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Better GI, urinary function after pelvic radiation with IMRT
BOSTON – For women with cervical or endometrial cancers, postoperative pelvic irradiation with intensity-modulated radiation therapy (IMRT) is associated with a reduction in acute gastrointestinal or genitourinary side effects, better physical functioning, and better quality of life than standard four-field pelvic radiation therapy, investigators contend.
Five weeks after the start of radiation therapy, women treated with pelvic IMRT in a phase III multicenter randomized trial had significantly better bowel and urinary function scores on the Expanded Prostate Index Composite (EPIC) scale, a patient reported–outcomes instrument, said co-principal investigator Ann H. Klopp, MD, from the University of Texas MD Anderson Cancer in Houston.
The trial, nicknamed TIME-C, was specifically designed to determine whether IMRT could reduce acute GI toxicities relative to standard therapy in the 5th week of treatment, after 23 to 25 radiation fractions had been delivered, with urinary toxicities and quality of life measures as secondary endpoints.
Eligible patients were women with pathologically proven diagnoses of endometrial and/or cervical cancer who required postoperative radiation or chemoradiation and had good performance statuses.
Following stratification by dose level (45 or 50.4 Gy), chemotherapy (five cycles of weekly cisplatin 40 mg/m2) or no chemotherapy, and disease site, the patients were randomly assigned to undergo either IMRT (129 patients) or standard 4-field radiation (149) to the pelvis.
Patients were evaluated for symptoms at baseline, 3 and 5 weeks after the start of radiation, and 4-5 weeks after completion, and follow-up is planned for 1 and 3 years after the start of radiation therapy.
EPIC findings
For the primary endpoint of change in the composite of EPIC bowel function and bother score from baseline, patients in both arms had declines in scores, signaling increased symptoms, but the decline was significantly greater among patients treated with four-field radiation (mean 23.6 point decline) vs. IMRT (mean 18.6 point decline, P = .048). Viewed separately, bowel function but not bowel bother scores were significantly lower in the standard radiation group. By 4 to 6 weeks after therapy, however, scores in both groups had recovered to baseline levels, Dr. Klopp noted.
Similarly, bowel-related scores on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events measure (PRO-CTCAE), a secondary endpoint, were significantly worse among patients who underwent standard radiation for the domains of diarrhea, fecal frequency, and fecal interference. There were no significant differences between the groups in abdominal pain measures, however.
For the secondary endpoint of EPIC urinary scores, IMRT was also associated with lower toxicities, with a mean urinary summary score decline of 5.6 points, compared with a 10.4-point drop among patients treated with standard four-field radiation (P = .03)
Finally, patients on IMRT had a smaller comparative decline in the physical wellbeing scale of the Functional Assessment of Cancer Therapy cervical cancer scale (P = .03).
The results support what many radiation oncologists believe but have not been able to prove until now, commented Geraldine Jacobson, MD, MPH, professor and chair of radiation oncology at West Virginia University, Morgantown.
But Supriya Chopra, MD, a radiation oncologist at the Tata Memorial Centre in Mumbai, India, the invited discussant at the plenary, said that the evidence in favor of IMRT is not so clear.
At the 2015 ASTRO annual meeting, Dr. Chopra and colleagues presented interim results of the PARCER study, in which grade III or higher radiation-induced bowel toxicity was lower with IMRT than with 3D-conformal radiation therapy. However, the 14.6% absolute difference, while significant (P = .02) was an exploratory endpoint only, and the observed differences in grade II or greater toxicities was not significant.
Differences in results between PARCER and TIME-C may be explained by the fact that patients in the PARCER trial had a higher proportion of concurrent cisplatin-based chemotherapy (about 88%) than patients in TIME-C (about 75%), with the excess cisplatin in the former trial possibly contributing to a worse symptom burden, she suggested.
“Pooled data from both trials is needed to assess the impact of IMRT for at least physician-reported acute GI toxicity, which both trials have captured. Long-term data from TIME-C and the final analysis of PARCER is awaited to assess the impact of late GI toxicity, and in my opinion, postoperative IMRT for gynecological cancers continues to be investigational,” she said.
BOSTON – For women with cervical or endometrial cancers, postoperative pelvic irradiation with intensity-modulated radiation therapy (IMRT) is associated with a reduction in acute gastrointestinal or genitourinary side effects, better physical functioning, and better quality of life than standard four-field pelvic radiation therapy, investigators contend.
Five weeks after the start of radiation therapy, women treated with pelvic IMRT in a phase III multicenter randomized trial had significantly better bowel and urinary function scores on the Expanded Prostate Index Composite (EPIC) scale, a patient reported–outcomes instrument, said co-principal investigator Ann H. Klopp, MD, from the University of Texas MD Anderson Cancer in Houston.
The trial, nicknamed TIME-C, was specifically designed to determine whether IMRT could reduce acute GI toxicities relative to standard therapy in the 5th week of treatment, after 23 to 25 radiation fractions had been delivered, with urinary toxicities and quality of life measures as secondary endpoints.
Eligible patients were women with pathologically proven diagnoses of endometrial and/or cervical cancer who required postoperative radiation or chemoradiation and had good performance statuses.
Following stratification by dose level (45 or 50.4 Gy), chemotherapy (five cycles of weekly cisplatin 40 mg/m2) or no chemotherapy, and disease site, the patients were randomly assigned to undergo either IMRT (129 patients) or standard 4-field radiation (149) to the pelvis.
Patients were evaluated for symptoms at baseline, 3 and 5 weeks after the start of radiation, and 4-5 weeks after completion, and follow-up is planned for 1 and 3 years after the start of radiation therapy.
EPIC findings
For the primary endpoint of change in the composite of EPIC bowel function and bother score from baseline, patients in both arms had declines in scores, signaling increased symptoms, but the decline was significantly greater among patients treated with four-field radiation (mean 23.6 point decline) vs. IMRT (mean 18.6 point decline, P = .048). Viewed separately, bowel function but not bowel bother scores were significantly lower in the standard radiation group. By 4 to 6 weeks after therapy, however, scores in both groups had recovered to baseline levels, Dr. Klopp noted.
Similarly, bowel-related scores on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events measure (PRO-CTCAE), a secondary endpoint, were significantly worse among patients who underwent standard radiation for the domains of diarrhea, fecal frequency, and fecal interference. There were no significant differences between the groups in abdominal pain measures, however.
For the secondary endpoint of EPIC urinary scores, IMRT was also associated with lower toxicities, with a mean urinary summary score decline of 5.6 points, compared with a 10.4-point drop among patients treated with standard four-field radiation (P = .03)
Finally, patients on IMRT had a smaller comparative decline in the physical wellbeing scale of the Functional Assessment of Cancer Therapy cervical cancer scale (P = .03).
The results support what many radiation oncologists believe but have not been able to prove until now, commented Geraldine Jacobson, MD, MPH, professor and chair of radiation oncology at West Virginia University, Morgantown.
But Supriya Chopra, MD, a radiation oncologist at the Tata Memorial Centre in Mumbai, India, the invited discussant at the plenary, said that the evidence in favor of IMRT is not so clear.
At the 2015 ASTRO annual meeting, Dr. Chopra and colleagues presented interim results of the PARCER study, in which grade III or higher radiation-induced bowel toxicity was lower with IMRT than with 3D-conformal radiation therapy. However, the 14.6% absolute difference, while significant (P = .02) was an exploratory endpoint only, and the observed differences in grade II or greater toxicities was not significant.
Differences in results between PARCER and TIME-C may be explained by the fact that patients in the PARCER trial had a higher proportion of concurrent cisplatin-based chemotherapy (about 88%) than patients in TIME-C (about 75%), with the excess cisplatin in the former trial possibly contributing to a worse symptom burden, she suggested.
“Pooled data from both trials is needed to assess the impact of IMRT for at least physician-reported acute GI toxicity, which both trials have captured. Long-term data from TIME-C and the final analysis of PARCER is awaited to assess the impact of late GI toxicity, and in my opinion, postoperative IMRT for gynecological cancers continues to be investigational,” she said.
BOSTON – For women with cervical or endometrial cancers, postoperative pelvic irradiation with intensity-modulated radiation therapy (IMRT) is associated with a reduction in acute gastrointestinal or genitourinary side effects, better physical functioning, and better quality of life than standard four-field pelvic radiation therapy, investigators contend.
Five weeks after the start of radiation therapy, women treated with pelvic IMRT in a phase III multicenter randomized trial had significantly better bowel and urinary function scores on the Expanded Prostate Index Composite (EPIC) scale, a patient reported–outcomes instrument, said co-principal investigator Ann H. Klopp, MD, from the University of Texas MD Anderson Cancer in Houston.
The trial, nicknamed TIME-C, was specifically designed to determine whether IMRT could reduce acute GI toxicities relative to standard therapy in the 5th week of treatment, after 23 to 25 radiation fractions had been delivered, with urinary toxicities and quality of life measures as secondary endpoints.
Eligible patients were women with pathologically proven diagnoses of endometrial and/or cervical cancer who required postoperative radiation or chemoradiation and had good performance statuses.
Following stratification by dose level (45 or 50.4 Gy), chemotherapy (five cycles of weekly cisplatin 40 mg/m2) or no chemotherapy, and disease site, the patients were randomly assigned to undergo either IMRT (129 patients) or standard 4-field radiation (149) to the pelvis.
Patients were evaluated for symptoms at baseline, 3 and 5 weeks after the start of radiation, and 4-5 weeks after completion, and follow-up is planned for 1 and 3 years after the start of radiation therapy.
EPIC findings
For the primary endpoint of change in the composite of EPIC bowel function and bother score from baseline, patients in both arms had declines in scores, signaling increased symptoms, but the decline was significantly greater among patients treated with four-field radiation (mean 23.6 point decline) vs. IMRT (mean 18.6 point decline, P = .048). Viewed separately, bowel function but not bowel bother scores were significantly lower in the standard radiation group. By 4 to 6 weeks after therapy, however, scores in both groups had recovered to baseline levels, Dr. Klopp noted.
Similarly, bowel-related scores on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events measure (PRO-CTCAE), a secondary endpoint, were significantly worse among patients who underwent standard radiation for the domains of diarrhea, fecal frequency, and fecal interference. There were no significant differences between the groups in abdominal pain measures, however.
For the secondary endpoint of EPIC urinary scores, IMRT was also associated with lower toxicities, with a mean urinary summary score decline of 5.6 points, compared with a 10.4-point drop among patients treated with standard four-field radiation (P = .03)
Finally, patients on IMRT had a smaller comparative decline in the physical wellbeing scale of the Functional Assessment of Cancer Therapy cervical cancer scale (P = .03).
The results support what many radiation oncologists believe but have not been able to prove until now, commented Geraldine Jacobson, MD, MPH, professor and chair of radiation oncology at West Virginia University, Morgantown.
But Supriya Chopra, MD, a radiation oncologist at the Tata Memorial Centre in Mumbai, India, the invited discussant at the plenary, said that the evidence in favor of IMRT is not so clear.
At the 2015 ASTRO annual meeting, Dr. Chopra and colleagues presented interim results of the PARCER study, in which grade III or higher radiation-induced bowel toxicity was lower with IMRT than with 3D-conformal radiation therapy. However, the 14.6% absolute difference, while significant (P = .02) was an exploratory endpoint only, and the observed differences in grade II or greater toxicities was not significant.
Differences in results between PARCER and TIME-C may be explained by the fact that patients in the PARCER trial had a higher proportion of concurrent cisplatin-based chemotherapy (about 88%) than patients in TIME-C (about 75%), with the excess cisplatin in the former trial possibly contributing to a worse symptom burden, she suggested.
“Pooled data from both trials is needed to assess the impact of IMRT for at least physician-reported acute GI toxicity, which both trials have captured. Long-term data from TIME-C and the final analysis of PARCER is awaited to assess the impact of late GI toxicity, and in my opinion, postoperative IMRT for gynecological cancers continues to be investigational,” she said.
Key clinical point: Pelvic irradiation with intensity-modulated radiation therapy was associated with lower acute bowel toxicity than standard radiation.
Major finding: The decline in EPIC bowel summary scores was smaller with IMRT than with four-field pelvic irradiation.
Data source: Randomized phase III trial in 278 patients with cervical or endometrial cancers.
Disclosures: TIME-C was supported by the National Cancer Institute. Dr. Klopp, Dr. Jacobson, and Dr. Chopra reported no relevant conflicts of interest.
Prostate cancer recurrence rates low with SBRT
BOSTON – For men with newly diagnosed low- or intermediate-risk prostate cancer, stereotactic body radiotherapy (SBRT) in the right hands can be safe, with low radiation-associated toxicities and with cancer control rates that compare favorably with those produced with external-beam radiotherapy (EBRT), investigators in a multicenter study report.
At 5-year follow-up, there were no grade 4 toxicities, no treatment-related deaths, and just five grade 3 adverse events that occurred in 4 out of 309 patients treated with SBRT, said Robert Meier, MD, at the annual meeting of the American Society for Radiation Oncology.
Using a standard radiology definition of recurrence as a more than 2 ng/mL increase in prostate-specific antigen (PSA) levels over posttreatment nadir, 97.1% of all patients were recurrence free at 5 years.
Among 172 patients with low-risk disease (T1b-T2, Gleason 6 or less and PSA 10 ng/mL or less), 97.3% were recurrence-free at 5 years, which compares favorably with the 93% seen in combined data from three large clinical trials of dose-escalated EBRT, Dr. Meier said.
For the 137 patients with intermediate risk disease (T1B-T2b, Gleason = 7, and PSA of 10 or less, or Gleason 6 or lower with a PSA between 10 and 20), 97% were recurrence-free at 5 years, a result “that matches the best results in radiotherapy for intermediate-risk patients, and matches the best results for, for example, dose-escalated IMRT [intensity-modulated radiation therapy],” he commented.
“The data is very encouraging,” commented Colleen Lawton, MD, professor and vice chair of radiation oncology at the Medical College of Wisconsin in Milwaukee.
To determine the safety and efficacy of SBRT in men with newly diagnosed prostate cancer, Dr. Meier and coinvestigators at six centers in the United States designed a prospective study.
A total of 309 patients were enrolled, and all were treated with SBRT delivered in 5 fractions of 8 Gy each over 5 days with a robotic linear accelerator that tracks the prostate, and corrections for motion in three spatial dimension, as well as yaw, pitch, and roll.
The treatment-delivery pattern is shaped to constrain doses to the bladder, rectum, testes, and penile bulb.
Using standard dosimetry calculation, the total actual radiation dose delivered to the prostate is equivalent to approximately 100 Gy, Dr. Meier said.
The safety analysis was powered to consider a greater than 10% rate of grade 3-5 urinary or bowel side effects as excessive. The efficacy analysis was designed to ask whether 5-year recurrence-free rates in low-risk patients could equal or be superior to a historical control rate of 93%.
As noted before, there were no grade 4 toxicities and no treatment-related deaths, and the rate of grade 3 side effects was 2.7%. with two events occurring in low-risk patients, and three in intermediate-risk patients. The events, all genitourinary toxicities, occurred from 11 to 51 months after treatment. Grade 1 or 2 genitourinary toxicities at any time were seen in 53% and 35% of patients, respectively. Grade 1 or 2 GI toxicities were seen in 59% and 10%.
Five patients developed urinary retention which required temporary catheter placement.
The ideal candidate for the therapy is the unfavorable intermediate-risk patient, Dr. Meier said in the interview.
“These are the patients who, if they are going to get external-beam radiation, have to combine it with androgen ablation, and that has its own toxicities. SBRT did very well even in the unfavorable intermediate-risk patients, so I think that group, and for that matter any intermediate-risk patient, is ideally suited,” he said.
The study was supported by Accuray. Dr. Meier disclosed research grants from the company. Dr. Lawton reported no relevant financial disclosures.
BOSTON – For men with newly diagnosed low- or intermediate-risk prostate cancer, stereotactic body radiotherapy (SBRT) in the right hands can be safe, with low radiation-associated toxicities and with cancer control rates that compare favorably with those produced with external-beam radiotherapy (EBRT), investigators in a multicenter study report.
At 5-year follow-up, there were no grade 4 toxicities, no treatment-related deaths, and just five grade 3 adverse events that occurred in 4 out of 309 patients treated with SBRT, said Robert Meier, MD, at the annual meeting of the American Society for Radiation Oncology.
Using a standard radiology definition of recurrence as a more than 2 ng/mL increase in prostate-specific antigen (PSA) levels over posttreatment nadir, 97.1% of all patients were recurrence free at 5 years.
Among 172 patients with low-risk disease (T1b-T2, Gleason 6 or less and PSA 10 ng/mL or less), 97.3% were recurrence-free at 5 years, which compares favorably with the 93% seen in combined data from three large clinical trials of dose-escalated EBRT, Dr. Meier said.
For the 137 patients with intermediate risk disease (T1B-T2b, Gleason = 7, and PSA of 10 or less, or Gleason 6 or lower with a PSA between 10 and 20), 97% were recurrence-free at 5 years, a result “that matches the best results in radiotherapy for intermediate-risk patients, and matches the best results for, for example, dose-escalated IMRT [intensity-modulated radiation therapy],” he commented.
“The data is very encouraging,” commented Colleen Lawton, MD, professor and vice chair of radiation oncology at the Medical College of Wisconsin in Milwaukee.
To determine the safety and efficacy of SBRT in men with newly diagnosed prostate cancer, Dr. Meier and coinvestigators at six centers in the United States designed a prospective study.
A total of 309 patients were enrolled, and all were treated with SBRT delivered in 5 fractions of 8 Gy each over 5 days with a robotic linear accelerator that tracks the prostate, and corrections for motion in three spatial dimension, as well as yaw, pitch, and roll.
The treatment-delivery pattern is shaped to constrain doses to the bladder, rectum, testes, and penile bulb.
Using standard dosimetry calculation, the total actual radiation dose delivered to the prostate is equivalent to approximately 100 Gy, Dr. Meier said.
The safety analysis was powered to consider a greater than 10% rate of grade 3-5 urinary or bowel side effects as excessive. The efficacy analysis was designed to ask whether 5-year recurrence-free rates in low-risk patients could equal or be superior to a historical control rate of 93%.
As noted before, there were no grade 4 toxicities and no treatment-related deaths, and the rate of grade 3 side effects was 2.7%. with two events occurring in low-risk patients, and three in intermediate-risk patients. The events, all genitourinary toxicities, occurred from 11 to 51 months after treatment. Grade 1 or 2 genitourinary toxicities at any time were seen in 53% and 35% of patients, respectively. Grade 1 or 2 GI toxicities were seen in 59% and 10%.
Five patients developed urinary retention which required temporary catheter placement.
The ideal candidate for the therapy is the unfavorable intermediate-risk patient, Dr. Meier said in the interview.
“These are the patients who, if they are going to get external-beam radiation, have to combine it with androgen ablation, and that has its own toxicities. SBRT did very well even in the unfavorable intermediate-risk patients, so I think that group, and for that matter any intermediate-risk patient, is ideally suited,” he said.
The study was supported by Accuray. Dr. Meier disclosed research grants from the company. Dr. Lawton reported no relevant financial disclosures.
BOSTON – For men with newly diagnosed low- or intermediate-risk prostate cancer, stereotactic body radiotherapy (SBRT) in the right hands can be safe, with low radiation-associated toxicities and with cancer control rates that compare favorably with those produced with external-beam radiotherapy (EBRT), investigators in a multicenter study report.
At 5-year follow-up, there were no grade 4 toxicities, no treatment-related deaths, and just five grade 3 adverse events that occurred in 4 out of 309 patients treated with SBRT, said Robert Meier, MD, at the annual meeting of the American Society for Radiation Oncology.
Using a standard radiology definition of recurrence as a more than 2 ng/mL increase in prostate-specific antigen (PSA) levels over posttreatment nadir, 97.1% of all patients were recurrence free at 5 years.
Among 172 patients with low-risk disease (T1b-T2, Gleason 6 or less and PSA 10 ng/mL or less), 97.3% were recurrence-free at 5 years, which compares favorably with the 93% seen in combined data from three large clinical trials of dose-escalated EBRT, Dr. Meier said.
For the 137 patients with intermediate risk disease (T1B-T2b, Gleason = 7, and PSA of 10 or less, or Gleason 6 or lower with a PSA between 10 and 20), 97% were recurrence-free at 5 years, a result “that matches the best results in radiotherapy for intermediate-risk patients, and matches the best results for, for example, dose-escalated IMRT [intensity-modulated radiation therapy],” he commented.
“The data is very encouraging,” commented Colleen Lawton, MD, professor and vice chair of radiation oncology at the Medical College of Wisconsin in Milwaukee.
To determine the safety and efficacy of SBRT in men with newly diagnosed prostate cancer, Dr. Meier and coinvestigators at six centers in the United States designed a prospective study.
A total of 309 patients were enrolled, and all were treated with SBRT delivered in 5 fractions of 8 Gy each over 5 days with a robotic linear accelerator that tracks the prostate, and corrections for motion in three spatial dimension, as well as yaw, pitch, and roll.
The treatment-delivery pattern is shaped to constrain doses to the bladder, rectum, testes, and penile bulb.
Using standard dosimetry calculation, the total actual radiation dose delivered to the prostate is equivalent to approximately 100 Gy, Dr. Meier said.
The safety analysis was powered to consider a greater than 10% rate of grade 3-5 urinary or bowel side effects as excessive. The efficacy analysis was designed to ask whether 5-year recurrence-free rates in low-risk patients could equal or be superior to a historical control rate of 93%.
As noted before, there were no grade 4 toxicities and no treatment-related deaths, and the rate of grade 3 side effects was 2.7%. with two events occurring in low-risk patients, and three in intermediate-risk patients. The events, all genitourinary toxicities, occurred from 11 to 51 months after treatment. Grade 1 or 2 genitourinary toxicities at any time were seen in 53% and 35% of patients, respectively. Grade 1 or 2 GI toxicities were seen in 59% and 10%.
Five patients developed urinary retention which required temporary catheter placement.
The ideal candidate for the therapy is the unfavorable intermediate-risk patient, Dr. Meier said in the interview.
“These are the patients who, if they are going to get external-beam radiation, have to combine it with androgen ablation, and that has its own toxicities. SBRT did very well even in the unfavorable intermediate-risk patients, so I think that group, and for that matter any intermediate-risk patient, is ideally suited,” he said.
The study was supported by Accuray. Dr. Meier disclosed research grants from the company. Dr. Lawton reported no relevant financial disclosures.
Key clinical point:
Major finding: The 5-year recurrence-free rate for low-risk patients was 97.3%, surpassing the 93% seen with historic controls.
Data source: Prospective study in 309 patients treated at six U.S. centers.
Disclosures: The study was supported by Accuray. Dr. Meier disclosed research grants from the company. Dr. Lawton reported no relevant financial disclosures.
Less cognitive decline with stereotactic radiosurgery after brain metastases resection
BOSTON – For patients with resected brain metastases, stereotactic radiosurgery offers survival comparable with what’s seen with whole-brain radiotherapy, but with better quality of life and more effective preservation of cognitive function, investigators reported.
In the phase III N107C trial, there was no difference in overall survival between patients who were randomly assigned to undergo stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT), but patients who underwent WBRT had a twofold greater decline in cognitive function, compared with patients who underwent SRS, Paul D. Brown, MD, a radiation oncologist at the Mayo Clinic in Rochester, Minn., reported at the annual meeting of the American Society for Radiation Oncology.
In a similar prospective, randomized study, Anita Mahajan, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston compared postoperative SRS after complete resection with observation alone in 128 patients, and found that although there was no difference in either distant brain metastases or overall survival, SRS was associated with significant improvements in local control.
“I think that going forward with the next patient I see with this scenario, I’m going to be a bit better informed and be able to inform my patient better of the trade-offs involved with regards to the decision of SRS vs. whole-brain radiotherapy,” commented George Rodrigues, MD, from the London (Ontario) Health Sciences Center in Canada. Dr. Rodrigues moderated a briefing during which Dr. Brown and Dr. Mahajan presented their data.
WBRT has been the standard of care for improving local control following surgical resection of brain metastases, but it does not offer a survival benefit and comes at a significant cost in side effects, including alopecia, fatigue, erythema, and, most distressing to patients, significant decline in cognitive function.
The precision of radiosurgery, on the other hand, allows the radiation dose to be concentrated on the surgical bed, limiting exposure of surrounding tissues and structures. For this reason, many centers have begun to adopt SRS for patients with resected brain metastases, but there is not level I evidence to back it up, Dr. Brown said.
WBRT vs. SRS
To rectify this situation, Dr. Brown and his colleagues at the Mayo Clinic and 47 other institutions conducted a clinical trial in 194 patients with one to four brain metastases.
Following surgical resection, the patients were stratified by age, duration of extracranial disease control, number of preoperative metastases, histology, maximum diameter of the resection cavity, and institution, and then randomly assigned to undergo either WBRT or SRS.
Patients were assessed for cognitive function (a coprimary endpoint with overall survival) at baseline and approximately every 3 months thereafter for up to 24 months. Other assessments included MRI scans, and FACT-Br (Functional Assessment of Cancer Therapy-Brain), a quality-of-life instrument.
After a median follow-up of 18.7 months, there was no difference in median overall survival, which was 11.5 months for WBRT and 11.8 months for SRS.
There was, however, a significant difference in cognitive deterioration–free survival, which was 2.8 months for WBRT vs. 3.3 months for SRS. The hazard ratio for WBRT was 2.05 (P = .0001). Cognitive deterioration–free survival rates at 6 months were 5.4% and 22.9%, respectively (P = .0012).
The declines in cognitive function were accounted for by significant differences in the Hopkins Verbal Learning Test (HVLT) domains of total and delayed recall and in the Trail Making Test (Part A).
Overall brain disease control was significantly better with WBRT than with SRS at 3 months (P = .003) and at 6 and 12 months (P less than .001 for each time point).
Surgical bed control was similar between the treatment groups at 6 and 12 months, but was significantly better with WBRT at 12 months, with surgical bed relapse occurring in 21.8% and 44.4% of patients, respectively.
Patients treated with SRS reported significantly better physical well being at 3 and 6 months (P = .002 and .014, respectively). There were 18 grade 3 or greater radiation-related adverse events among patients treated with WBRT, compared with 7 among patients treated with SRS.
SRS vs. observation
In the MD Anderson study, 45% of patients who underwent observation alone had local control of disease at 12 months, compared with 72% treated with SRS. The hazard ratio for SRS was 0.46 (P = .01). The median time to local recurrence was 7.6 months among patients on observation only, but no time point was reached for SRS-treated patients.
The evidence from the two trials suggests that “radiosurgery is a, but not the, standard of care following resection for brain metastasis,” said Vinai Gondi, MD, of the Northwestern Medicine Cancer Center in Warrenville, Ill., the invited discussant.
“While the MD Anderson trial clearly demonstrated that radiosurgery reduces the risk of surgical bed relapse, the N107C trial demonstrated a 44% risk of surgical bed relapse, a rate that is arguably too high in regards to the long survival of resected brain metastasis patients, and it also challenges and risks the resection of surgical bed relapse following radiosurgery,” he said.
The N107C trial was sponsored by the National Cancer Institute and the Alliance for Clinical Trials in Oncology. The MD Anderson trial was funded by a Cancer Center Grant. Dr. Brown, Dr. Mahajan, and Dr. Rodrigues reported no conflicts of interest.
BOSTON – For patients with resected brain metastases, stereotactic radiosurgery offers survival comparable with what’s seen with whole-brain radiotherapy, but with better quality of life and more effective preservation of cognitive function, investigators reported.
In the phase III N107C trial, there was no difference in overall survival between patients who were randomly assigned to undergo stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT), but patients who underwent WBRT had a twofold greater decline in cognitive function, compared with patients who underwent SRS, Paul D. Brown, MD, a radiation oncologist at the Mayo Clinic in Rochester, Minn., reported at the annual meeting of the American Society for Radiation Oncology.
In a similar prospective, randomized study, Anita Mahajan, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston compared postoperative SRS after complete resection with observation alone in 128 patients, and found that although there was no difference in either distant brain metastases or overall survival, SRS was associated with significant improvements in local control.
“I think that going forward with the next patient I see with this scenario, I’m going to be a bit better informed and be able to inform my patient better of the trade-offs involved with regards to the decision of SRS vs. whole-brain radiotherapy,” commented George Rodrigues, MD, from the London (Ontario) Health Sciences Center in Canada. Dr. Rodrigues moderated a briefing during which Dr. Brown and Dr. Mahajan presented their data.
WBRT has been the standard of care for improving local control following surgical resection of brain metastases, but it does not offer a survival benefit and comes at a significant cost in side effects, including alopecia, fatigue, erythema, and, most distressing to patients, significant decline in cognitive function.
The precision of radiosurgery, on the other hand, allows the radiation dose to be concentrated on the surgical bed, limiting exposure of surrounding tissues and structures. For this reason, many centers have begun to adopt SRS for patients with resected brain metastases, but there is not level I evidence to back it up, Dr. Brown said.
WBRT vs. SRS
To rectify this situation, Dr. Brown and his colleagues at the Mayo Clinic and 47 other institutions conducted a clinical trial in 194 patients with one to four brain metastases.
Following surgical resection, the patients were stratified by age, duration of extracranial disease control, number of preoperative metastases, histology, maximum diameter of the resection cavity, and institution, and then randomly assigned to undergo either WBRT or SRS.
Patients were assessed for cognitive function (a coprimary endpoint with overall survival) at baseline and approximately every 3 months thereafter for up to 24 months. Other assessments included MRI scans, and FACT-Br (Functional Assessment of Cancer Therapy-Brain), a quality-of-life instrument.
After a median follow-up of 18.7 months, there was no difference in median overall survival, which was 11.5 months for WBRT and 11.8 months for SRS.
There was, however, a significant difference in cognitive deterioration–free survival, which was 2.8 months for WBRT vs. 3.3 months for SRS. The hazard ratio for WBRT was 2.05 (P = .0001). Cognitive deterioration–free survival rates at 6 months were 5.4% and 22.9%, respectively (P = .0012).
The declines in cognitive function were accounted for by significant differences in the Hopkins Verbal Learning Test (HVLT) domains of total and delayed recall and in the Trail Making Test (Part A).
Overall brain disease control was significantly better with WBRT than with SRS at 3 months (P = .003) and at 6 and 12 months (P less than .001 for each time point).
Surgical bed control was similar between the treatment groups at 6 and 12 months, but was significantly better with WBRT at 12 months, with surgical bed relapse occurring in 21.8% and 44.4% of patients, respectively.
Patients treated with SRS reported significantly better physical well being at 3 and 6 months (P = .002 and .014, respectively). There were 18 grade 3 or greater radiation-related adverse events among patients treated with WBRT, compared with 7 among patients treated with SRS.
SRS vs. observation
In the MD Anderson study, 45% of patients who underwent observation alone had local control of disease at 12 months, compared with 72% treated with SRS. The hazard ratio for SRS was 0.46 (P = .01). The median time to local recurrence was 7.6 months among patients on observation only, but no time point was reached for SRS-treated patients.
The evidence from the two trials suggests that “radiosurgery is a, but not the, standard of care following resection for brain metastasis,” said Vinai Gondi, MD, of the Northwestern Medicine Cancer Center in Warrenville, Ill., the invited discussant.
“While the MD Anderson trial clearly demonstrated that radiosurgery reduces the risk of surgical bed relapse, the N107C trial demonstrated a 44% risk of surgical bed relapse, a rate that is arguably too high in regards to the long survival of resected brain metastasis patients, and it also challenges and risks the resection of surgical bed relapse following radiosurgery,” he said.
The N107C trial was sponsored by the National Cancer Institute and the Alliance for Clinical Trials in Oncology. The MD Anderson trial was funded by a Cancer Center Grant. Dr. Brown, Dr. Mahajan, and Dr. Rodrigues reported no conflicts of interest.
BOSTON – For patients with resected brain metastases, stereotactic radiosurgery offers survival comparable with what’s seen with whole-brain radiotherapy, but with better quality of life and more effective preservation of cognitive function, investigators reported.
In the phase III N107C trial, there was no difference in overall survival between patients who were randomly assigned to undergo stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT), but patients who underwent WBRT had a twofold greater decline in cognitive function, compared with patients who underwent SRS, Paul D. Brown, MD, a radiation oncologist at the Mayo Clinic in Rochester, Minn., reported at the annual meeting of the American Society for Radiation Oncology.
In a similar prospective, randomized study, Anita Mahajan, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston compared postoperative SRS after complete resection with observation alone in 128 patients, and found that although there was no difference in either distant brain metastases or overall survival, SRS was associated with significant improvements in local control.
“I think that going forward with the next patient I see with this scenario, I’m going to be a bit better informed and be able to inform my patient better of the trade-offs involved with regards to the decision of SRS vs. whole-brain radiotherapy,” commented George Rodrigues, MD, from the London (Ontario) Health Sciences Center in Canada. Dr. Rodrigues moderated a briefing during which Dr. Brown and Dr. Mahajan presented their data.
WBRT has been the standard of care for improving local control following surgical resection of brain metastases, but it does not offer a survival benefit and comes at a significant cost in side effects, including alopecia, fatigue, erythema, and, most distressing to patients, significant decline in cognitive function.
The precision of radiosurgery, on the other hand, allows the radiation dose to be concentrated on the surgical bed, limiting exposure of surrounding tissues and structures. For this reason, many centers have begun to adopt SRS for patients with resected brain metastases, but there is not level I evidence to back it up, Dr. Brown said.
WBRT vs. SRS
To rectify this situation, Dr. Brown and his colleagues at the Mayo Clinic and 47 other institutions conducted a clinical trial in 194 patients with one to four brain metastases.
Following surgical resection, the patients were stratified by age, duration of extracranial disease control, number of preoperative metastases, histology, maximum diameter of the resection cavity, and institution, and then randomly assigned to undergo either WBRT or SRS.
Patients were assessed for cognitive function (a coprimary endpoint with overall survival) at baseline and approximately every 3 months thereafter for up to 24 months. Other assessments included MRI scans, and FACT-Br (Functional Assessment of Cancer Therapy-Brain), a quality-of-life instrument.
After a median follow-up of 18.7 months, there was no difference in median overall survival, which was 11.5 months for WBRT and 11.8 months for SRS.
There was, however, a significant difference in cognitive deterioration–free survival, which was 2.8 months for WBRT vs. 3.3 months for SRS. The hazard ratio for WBRT was 2.05 (P = .0001). Cognitive deterioration–free survival rates at 6 months were 5.4% and 22.9%, respectively (P = .0012).
The declines in cognitive function were accounted for by significant differences in the Hopkins Verbal Learning Test (HVLT) domains of total and delayed recall and in the Trail Making Test (Part A).
Overall brain disease control was significantly better with WBRT than with SRS at 3 months (P = .003) and at 6 and 12 months (P less than .001 for each time point).
Surgical bed control was similar between the treatment groups at 6 and 12 months, but was significantly better with WBRT at 12 months, with surgical bed relapse occurring in 21.8% and 44.4% of patients, respectively.
Patients treated with SRS reported significantly better physical well being at 3 and 6 months (P = .002 and .014, respectively). There were 18 grade 3 or greater radiation-related adverse events among patients treated with WBRT, compared with 7 among patients treated with SRS.
SRS vs. observation
In the MD Anderson study, 45% of patients who underwent observation alone had local control of disease at 12 months, compared with 72% treated with SRS. The hazard ratio for SRS was 0.46 (P = .01). The median time to local recurrence was 7.6 months among patients on observation only, but no time point was reached for SRS-treated patients.
The evidence from the two trials suggests that “radiosurgery is a, but not the, standard of care following resection for brain metastasis,” said Vinai Gondi, MD, of the Northwestern Medicine Cancer Center in Warrenville, Ill., the invited discussant.
“While the MD Anderson trial clearly demonstrated that radiosurgery reduces the risk of surgical bed relapse, the N107C trial demonstrated a 44% risk of surgical bed relapse, a rate that is arguably too high in regards to the long survival of resected brain metastasis patients, and it also challenges and risks the resection of surgical bed relapse following radiosurgery,” he said.
The N107C trial was sponsored by the National Cancer Institute and the Alliance for Clinical Trials in Oncology. The MD Anderson trial was funded by a Cancer Center Grant. Dr. Brown, Dr. Mahajan, and Dr. Rodrigues reported no conflicts of interest.
AT ASTRO ANNUAL MEETING 2016
Key clinical point: Stereotactic radiosurgery following brain metastases resection was associated with similar survival but less toxicity than was whole-brain radiation therapy.
Major finding: WBRT was associated with a twofold greater risk for cognitive deterioration than SRS in one study, and SRS provided better local control than observation alone in another study.
Data source: A randomized, phase III trial in 194 patients from 48 centers in the United States and Canada, and a randomized trial in 128 patients from the MD Anderson Cancer Center.
Disclosures: The N107C trial was sponsored by the National Cancer Institute and the Alliance for Clinical Trials in Oncology. The MD Anderson trial was funded by a Cancer Center Grant. Dr. Brown, Dr. Mahajan, and Dr. Rodrigues reported no conflicts of interest.
Planning, education smooth transition to longer-acting clotting factors
ORLANDO – Transitioning patients with hemophilia from standard clotting factor concentrates to newer extended half-life products takes planning, education, and a little patience, but the payoff can be better hemostasis, a hemophilia treatment specialist said.
“Real-world experience shows us that you can maintain effective protection with less infusion with these new products, but we also know that each person should be evaluated individually when determining what their specific optimal treatment is,” said Jennifer Maahs, a hemophilia nurse practitioner at the Indiana Hemophilia and Thrombosis Center in Indianapolis.
Staff and patient education about the proper use of newer extended half-life (EHL) products is the key to success, she added in an oral session at the World Federation of Hemophilia World Congress.
The new EHL products allow for longer intervals between doses, especially with EHL recombinant factor IX used to treat hemophilia B. Prophylaxis with standard factor IX concentrates requires doses of 25-40 IU/kg twice weekly; in contrasts, EHL products can be given in various doses based on patient responses of either 50 IU/kg every 7 days, 100 IU/kg every 10 days, 25-40 IU/kg every 7 days, or 50-75 IU/kg every 14 days.
In general, the longer intervals between dosing occur in adults; young children tend to require more frequent dosing and have lower levels of factor recovery, she noted.
Extended Experience
Her center currently has more than 100 patients maintained on prolonged half-life factor VIII and factor IX products.
“We have really learned a lot of lessons along the way, and we have had to modify our approach based on these lessons,” she said. “Each patient situation is unique, and everything needs to be individualized.”
Staff review the published literature to educate themselves on the EHL products and prepare answers to expected questions from patients. Ms. Maahs suggested identifying key staff who are best equipped to answer specific questions.
“From a patient standpoint, we’ve developed a patient notification letter, so for any new product that comes out – for example a new factor VIII product – the notification gets sent out factor VIII patients, and we do that for every new product that comes out,” she said.
PK OK
Pharmacokinetic (PK) analyses may also be helpful in transitioning patients to EHL products.
To test patient responses to new products, her center tests patients for recovery from 15 minutes to 1 hour post-infusion, which will provide information about how the patient may respond to the product during a bleeding episode.
If the patient is on prophylaxis they will evaluate trough effectiveness to determine that patient’s responsiveness at the lowest level prior to the next infusion. Testing at other time points may be required based on the patient’s individual clinical history.
Center staff talk with each patient to discuss his needs and capabilities. If the patient is currently being managed with on-demand therapy, the talk may center on obstacles to utilization of prophylaxis and the patient’s desired infusion interval.
For patients currently on prophylaxis, they discuss the current regimen frequency and dose and assess how well it’s working. Staff members also provide information about alternative approaches to therapy, and ask patients specifically about their activity levels and dates of activity, compared with currently scheduled infusion days.
Patients are also educated about the reconstitution requirements for the new product, and are told to use up any remaining concentrates before switching over to the new product.
“As we move forward, within 2 to 4 weeks of starting a new therapy, we like to obtain a trough to see how their prophylaxis is working. At that time we ask how have you been doing on the new product, are you having any breakthrough bleeding, and how are you feeling about it,” Ms. Maahs said.
Weekly phone calls to the patient during the first month are also very helpful for reinforcing information about dosing regimens for bleeding episodes, reminding patients to call in if they experience a lead, and encouraging them to keep a treatment log. The phone call can also be helpful in identifying potential product-related reactions or other issues, she said.
‘Big impact’
“What’s the impact that we’ve seen? With factor IX, it has been really big. Previous on-demand patients have agreed that, ‘gosh, I’m infusing a couple of times a month anyway,’ so starting an every 14-day prophylactic regimen seems pretty reasonable,” she said.
“We’ve had infusion schedules in children change from twice weekly to once weekly and that has really decreased the burden of disease,” she added.
A few adults, however, have gone back to standard half-life products because of concerns that they would not be able to infuse when they thought they needed treatment, she noted.
The impact of the EHL factor VIII products has been smaller, although it has allowed slight increases in the dosing intervals (from every other day to every third day in children, for example), and has overall decreased the average number of monthly infusions from about 15 to about 10.
Some adolescents and young adults, who often have been on prophylaxis for all of their lives, have experienced absent or only minimal joint disease, and some have been able to extend their dosing intervals from every 4 to every 5 to 7 days, she said.
Ms. Maahs disclosed serving on advisory committees to Baxalta, Novo Nordisk, Biogen, Genentech, and CSL, and receiving honoraria related to those activities.
ORLANDO – Transitioning patients with hemophilia from standard clotting factor concentrates to newer extended half-life products takes planning, education, and a little patience, but the payoff can be better hemostasis, a hemophilia treatment specialist said.
“Real-world experience shows us that you can maintain effective protection with less infusion with these new products, but we also know that each person should be evaluated individually when determining what their specific optimal treatment is,” said Jennifer Maahs, a hemophilia nurse practitioner at the Indiana Hemophilia and Thrombosis Center in Indianapolis.
Staff and patient education about the proper use of newer extended half-life (EHL) products is the key to success, she added in an oral session at the World Federation of Hemophilia World Congress.
The new EHL products allow for longer intervals between doses, especially with EHL recombinant factor IX used to treat hemophilia B. Prophylaxis with standard factor IX concentrates requires doses of 25-40 IU/kg twice weekly; in contrasts, EHL products can be given in various doses based on patient responses of either 50 IU/kg every 7 days, 100 IU/kg every 10 days, 25-40 IU/kg every 7 days, or 50-75 IU/kg every 14 days.
In general, the longer intervals between dosing occur in adults; young children tend to require more frequent dosing and have lower levels of factor recovery, she noted.
Extended Experience
Her center currently has more than 100 patients maintained on prolonged half-life factor VIII and factor IX products.
“We have really learned a lot of lessons along the way, and we have had to modify our approach based on these lessons,” she said. “Each patient situation is unique, and everything needs to be individualized.”
Staff review the published literature to educate themselves on the EHL products and prepare answers to expected questions from patients. Ms. Maahs suggested identifying key staff who are best equipped to answer specific questions.
“From a patient standpoint, we’ve developed a patient notification letter, so for any new product that comes out – for example a new factor VIII product – the notification gets sent out factor VIII patients, and we do that for every new product that comes out,” she said.
PK OK
Pharmacokinetic (PK) analyses may also be helpful in transitioning patients to EHL products.
To test patient responses to new products, her center tests patients for recovery from 15 minutes to 1 hour post-infusion, which will provide information about how the patient may respond to the product during a bleeding episode.
If the patient is on prophylaxis they will evaluate trough effectiveness to determine that patient’s responsiveness at the lowest level prior to the next infusion. Testing at other time points may be required based on the patient’s individual clinical history.
Center staff talk with each patient to discuss his needs and capabilities. If the patient is currently being managed with on-demand therapy, the talk may center on obstacles to utilization of prophylaxis and the patient’s desired infusion interval.
For patients currently on prophylaxis, they discuss the current regimen frequency and dose and assess how well it’s working. Staff members also provide information about alternative approaches to therapy, and ask patients specifically about their activity levels and dates of activity, compared with currently scheduled infusion days.
Patients are also educated about the reconstitution requirements for the new product, and are told to use up any remaining concentrates before switching over to the new product.
“As we move forward, within 2 to 4 weeks of starting a new therapy, we like to obtain a trough to see how their prophylaxis is working. At that time we ask how have you been doing on the new product, are you having any breakthrough bleeding, and how are you feeling about it,” Ms. Maahs said.
Weekly phone calls to the patient during the first month are also very helpful for reinforcing information about dosing regimens for bleeding episodes, reminding patients to call in if they experience a lead, and encouraging them to keep a treatment log. The phone call can also be helpful in identifying potential product-related reactions or other issues, she said.
‘Big impact’
“What’s the impact that we’ve seen? With factor IX, it has been really big. Previous on-demand patients have agreed that, ‘gosh, I’m infusing a couple of times a month anyway,’ so starting an every 14-day prophylactic regimen seems pretty reasonable,” she said.
“We’ve had infusion schedules in children change from twice weekly to once weekly and that has really decreased the burden of disease,” she added.
A few adults, however, have gone back to standard half-life products because of concerns that they would not be able to infuse when they thought they needed treatment, she noted.
The impact of the EHL factor VIII products has been smaller, although it has allowed slight increases in the dosing intervals (from every other day to every third day in children, for example), and has overall decreased the average number of monthly infusions from about 15 to about 10.
Some adolescents and young adults, who often have been on prophylaxis for all of their lives, have experienced absent or only minimal joint disease, and some have been able to extend their dosing intervals from every 4 to every 5 to 7 days, she said.
Ms. Maahs disclosed serving on advisory committees to Baxalta, Novo Nordisk, Biogen, Genentech, and CSL, and receiving honoraria related to those activities.
ORLANDO – Transitioning patients with hemophilia from standard clotting factor concentrates to newer extended half-life products takes planning, education, and a little patience, but the payoff can be better hemostasis, a hemophilia treatment specialist said.
“Real-world experience shows us that you can maintain effective protection with less infusion with these new products, but we also know that each person should be evaluated individually when determining what their specific optimal treatment is,” said Jennifer Maahs, a hemophilia nurse practitioner at the Indiana Hemophilia and Thrombosis Center in Indianapolis.
Staff and patient education about the proper use of newer extended half-life (EHL) products is the key to success, she added in an oral session at the World Federation of Hemophilia World Congress.
The new EHL products allow for longer intervals between doses, especially with EHL recombinant factor IX used to treat hemophilia B. Prophylaxis with standard factor IX concentrates requires doses of 25-40 IU/kg twice weekly; in contrasts, EHL products can be given in various doses based on patient responses of either 50 IU/kg every 7 days, 100 IU/kg every 10 days, 25-40 IU/kg every 7 days, or 50-75 IU/kg every 14 days.
In general, the longer intervals between dosing occur in adults; young children tend to require more frequent dosing and have lower levels of factor recovery, she noted.
Extended Experience
Her center currently has more than 100 patients maintained on prolonged half-life factor VIII and factor IX products.
“We have really learned a lot of lessons along the way, and we have had to modify our approach based on these lessons,” she said. “Each patient situation is unique, and everything needs to be individualized.”
Staff review the published literature to educate themselves on the EHL products and prepare answers to expected questions from patients. Ms. Maahs suggested identifying key staff who are best equipped to answer specific questions.
“From a patient standpoint, we’ve developed a patient notification letter, so for any new product that comes out – for example a new factor VIII product – the notification gets sent out factor VIII patients, and we do that for every new product that comes out,” she said.
PK OK
Pharmacokinetic (PK) analyses may also be helpful in transitioning patients to EHL products.
To test patient responses to new products, her center tests patients for recovery from 15 minutes to 1 hour post-infusion, which will provide information about how the patient may respond to the product during a bleeding episode.
If the patient is on prophylaxis they will evaluate trough effectiveness to determine that patient’s responsiveness at the lowest level prior to the next infusion. Testing at other time points may be required based on the patient’s individual clinical history.
Center staff talk with each patient to discuss his needs and capabilities. If the patient is currently being managed with on-demand therapy, the talk may center on obstacles to utilization of prophylaxis and the patient’s desired infusion interval.
For patients currently on prophylaxis, they discuss the current regimen frequency and dose and assess how well it’s working. Staff members also provide information about alternative approaches to therapy, and ask patients specifically about their activity levels and dates of activity, compared with currently scheduled infusion days.
Patients are also educated about the reconstitution requirements for the new product, and are told to use up any remaining concentrates before switching over to the new product.
“As we move forward, within 2 to 4 weeks of starting a new therapy, we like to obtain a trough to see how their prophylaxis is working. At that time we ask how have you been doing on the new product, are you having any breakthrough bleeding, and how are you feeling about it,” Ms. Maahs said.
Weekly phone calls to the patient during the first month are also very helpful for reinforcing information about dosing regimens for bleeding episodes, reminding patients to call in if they experience a lead, and encouraging them to keep a treatment log. The phone call can also be helpful in identifying potential product-related reactions or other issues, she said.
‘Big impact’
“What’s the impact that we’ve seen? With factor IX, it has been really big. Previous on-demand patients have agreed that, ‘gosh, I’m infusing a couple of times a month anyway,’ so starting an every 14-day prophylactic regimen seems pretty reasonable,” she said.
“We’ve had infusion schedules in children change from twice weekly to once weekly and that has really decreased the burden of disease,” she added.
A few adults, however, have gone back to standard half-life products because of concerns that they would not be able to infuse when they thought they needed treatment, she noted.
The impact of the EHL factor VIII products has been smaller, although it has allowed slight increases in the dosing intervals (from every other day to every third day in children, for example), and has overall decreased the average number of monthly infusions from about 15 to about 10.
Some adolescents and young adults, who often have been on prophylaxis for all of their lives, have experienced absent or only minimal joint disease, and some have been able to extend their dosing intervals from every 4 to every 5 to 7 days, she said.
Ms. Maahs disclosed serving on advisory committees to Baxalta, Novo Nordisk, Biogen, Genentech, and CSL, and receiving honoraria related to those activities.
EXPERT ANALYSIS AT WFH 2016 WORLD CONGRESS
Key clinical point: Transitioning patients to extended half-life clotting factor concentrates requires tailoring treatment to individual patients.
Major finding: Many patients can transition from on-demand dosing with factor IX to prophylaxis infusions once every 2 weeks.
Data source: Review of a hemophilia treatment center experience transitioning patients to extended half-life products.
Disclosures: Jennifer Maahs, RN-BC, disclosed serving on advisory committees to Baxalta, Novo Nordisk, Biogen, Genentech, and CSL, and receiving honoraria related to those activities.
Early intensive prophylaxis provides better QoL in hemophilia
ORLANDO – Boys with hemophilia have a better quality of life when they are managed with intensive bleeding prophylaxis with clotting factor concentrates rather than on-demand therapy, results of an international study suggest.
An analysis of pooled data from six studies conducted in eight countries showed that boys with severe hemophilia who received limited on-demand factor replacement had significantly lower health-related quality of life (HRQoL) scores than did boys treated prophylactically, reported Victoria Price, MB, of Dalhousie University, Halifax, N.S., and colleagues.
“Early initiation of intensive prophylaxis has the greatest impact on HRQoL in boys with severe hemophilia. HRQoL in boys with severe hemophilia exposed to early initiation of intensive prophylaxis is comparable to boys with mild hemophilia receiving on-demand therapy,” they wrote in a scientific poster presented at the World Federation of Hemophilia World Congress.
In countries where patients have access to safe clotting factor concentrates, prophylaxis has become the standard of care for management of hemophilia A and B, because it has been shown to reduce the frequency of bleeds. But because of the small sample sizes in most studies of hemophilia, it has been difficult to determine whether prophylaxis actually has a significant effect on HRQoL, the investigators noted.
To get an answer to that question, they looked at data from six studies in boys younger than 18 that measured HRQoL using the same standard instrument, the Canadian Haemophilia Outcomes–Kids’ Life Assessment Tool (CHO-KLAT). The studies were conducted in Brazil, Canada, China, France, Germany, the Netherlands, Spain, and the United Kingdom.
Patients in the studies were grouped into one of five categories:
• Early initiation with intensive prophylaxis (Germany, the Netherlands, Spain, UK)
• Gradual initiation with intensive prophylaxis (Canada, France)
• Late initiation with limited prophylaxis (Brazil, China)
• On-demand with good access to factor (Canada and European nations)
• On-demand with variable or limited access to factor (Brazil and China).
Data on a total of 254 boys with severe hemophilia were analyzed and compared with estimated scores from boys with mild hemophilia in the pooled dataset.
Of the boys with severe hemophilia, 220 (86.6% had hemophilia A, and 34 (13.4%) had hemophilia B. They ranged in age from 4.4 to 17.9 years; 21 of the boys were younger than 7 years.
The investigators found that in a linear regression model, patients with early initiation and intensive prophylaxis had the highest CHO-KLAT scores, followed by those who had gradual initiation with intensive prophylaxis (P = .003), late initiation/limited prophylaxis (P = .005), on-demand with good access (P = .008) and, lastly, on-demand with limited access to factor (P less than .001)
The authors noted that the differences by treatment group in the analysis were defined by expert consensus, and may not reflect changes in treatment protocols over the last 10 years. The studies were published between 2006 and 2016.
“Despite this limitation, important differences were observed between groups,” they wrote.
The studies were supported by grants from the Canadian Haemophilia Society and the Society of Haemophilia Clinic Directors of Canada, Bayer, Baxalta, and CSL Behring. The authors did not report conflict of interest disclosures.
ORLANDO – Boys with hemophilia have a better quality of life when they are managed with intensive bleeding prophylaxis with clotting factor concentrates rather than on-demand therapy, results of an international study suggest.
An analysis of pooled data from six studies conducted in eight countries showed that boys with severe hemophilia who received limited on-demand factor replacement had significantly lower health-related quality of life (HRQoL) scores than did boys treated prophylactically, reported Victoria Price, MB, of Dalhousie University, Halifax, N.S., and colleagues.
“Early initiation of intensive prophylaxis has the greatest impact on HRQoL in boys with severe hemophilia. HRQoL in boys with severe hemophilia exposed to early initiation of intensive prophylaxis is comparable to boys with mild hemophilia receiving on-demand therapy,” they wrote in a scientific poster presented at the World Federation of Hemophilia World Congress.
In countries where patients have access to safe clotting factor concentrates, prophylaxis has become the standard of care for management of hemophilia A and B, because it has been shown to reduce the frequency of bleeds. But because of the small sample sizes in most studies of hemophilia, it has been difficult to determine whether prophylaxis actually has a significant effect on HRQoL, the investigators noted.
To get an answer to that question, they looked at data from six studies in boys younger than 18 that measured HRQoL using the same standard instrument, the Canadian Haemophilia Outcomes–Kids’ Life Assessment Tool (CHO-KLAT). The studies were conducted in Brazil, Canada, China, France, Germany, the Netherlands, Spain, and the United Kingdom.
Patients in the studies were grouped into one of five categories:
• Early initiation with intensive prophylaxis (Germany, the Netherlands, Spain, UK)
• Gradual initiation with intensive prophylaxis (Canada, France)
• Late initiation with limited prophylaxis (Brazil, China)
• On-demand with good access to factor (Canada and European nations)
• On-demand with variable or limited access to factor (Brazil and China).
Data on a total of 254 boys with severe hemophilia were analyzed and compared with estimated scores from boys with mild hemophilia in the pooled dataset.
Of the boys with severe hemophilia, 220 (86.6% had hemophilia A, and 34 (13.4%) had hemophilia B. They ranged in age from 4.4 to 17.9 years; 21 of the boys were younger than 7 years.
The investigators found that in a linear regression model, patients with early initiation and intensive prophylaxis had the highest CHO-KLAT scores, followed by those who had gradual initiation with intensive prophylaxis (P = .003), late initiation/limited prophylaxis (P = .005), on-demand with good access (P = .008) and, lastly, on-demand with limited access to factor (P less than .001)
The authors noted that the differences by treatment group in the analysis were defined by expert consensus, and may not reflect changes in treatment protocols over the last 10 years. The studies were published between 2006 and 2016.
“Despite this limitation, important differences were observed between groups,” they wrote.
The studies were supported by grants from the Canadian Haemophilia Society and the Society of Haemophilia Clinic Directors of Canada, Bayer, Baxalta, and CSL Behring. The authors did not report conflict of interest disclosures.
ORLANDO – Boys with hemophilia have a better quality of life when they are managed with intensive bleeding prophylaxis with clotting factor concentrates rather than on-demand therapy, results of an international study suggest.
An analysis of pooled data from six studies conducted in eight countries showed that boys with severe hemophilia who received limited on-demand factor replacement had significantly lower health-related quality of life (HRQoL) scores than did boys treated prophylactically, reported Victoria Price, MB, of Dalhousie University, Halifax, N.S., and colleagues.
“Early initiation of intensive prophylaxis has the greatest impact on HRQoL in boys with severe hemophilia. HRQoL in boys with severe hemophilia exposed to early initiation of intensive prophylaxis is comparable to boys with mild hemophilia receiving on-demand therapy,” they wrote in a scientific poster presented at the World Federation of Hemophilia World Congress.
In countries where patients have access to safe clotting factor concentrates, prophylaxis has become the standard of care for management of hemophilia A and B, because it has been shown to reduce the frequency of bleeds. But because of the small sample sizes in most studies of hemophilia, it has been difficult to determine whether prophylaxis actually has a significant effect on HRQoL, the investigators noted.
To get an answer to that question, they looked at data from six studies in boys younger than 18 that measured HRQoL using the same standard instrument, the Canadian Haemophilia Outcomes–Kids’ Life Assessment Tool (CHO-KLAT). The studies were conducted in Brazil, Canada, China, France, Germany, the Netherlands, Spain, and the United Kingdom.
Patients in the studies were grouped into one of five categories:
• Early initiation with intensive prophylaxis (Germany, the Netherlands, Spain, UK)
• Gradual initiation with intensive prophylaxis (Canada, France)
• Late initiation with limited prophylaxis (Brazil, China)
• On-demand with good access to factor (Canada and European nations)
• On-demand with variable or limited access to factor (Brazil and China).
Data on a total of 254 boys with severe hemophilia were analyzed and compared with estimated scores from boys with mild hemophilia in the pooled dataset.
Of the boys with severe hemophilia, 220 (86.6% had hemophilia A, and 34 (13.4%) had hemophilia B. They ranged in age from 4.4 to 17.9 years; 21 of the boys were younger than 7 years.
The investigators found that in a linear regression model, patients with early initiation and intensive prophylaxis had the highest CHO-KLAT scores, followed by those who had gradual initiation with intensive prophylaxis (P = .003), late initiation/limited prophylaxis (P = .005), on-demand with good access (P = .008) and, lastly, on-demand with limited access to factor (P less than .001)
The authors noted that the differences by treatment group in the analysis were defined by expert consensus, and may not reflect changes in treatment protocols over the last 10 years. The studies were published between 2006 and 2016.
“Despite this limitation, important differences were observed between groups,” they wrote.
The studies were supported by grants from the Canadian Haemophilia Society and the Society of Haemophilia Clinic Directors of Canada, Bayer, Baxalta, and CSL Behring. The authors did not report conflict of interest disclosures.
AT WFH 2016 WORLD CONGRESS
Key clinical point: Early initiation of intensive bleeding prophylaxis was associated with significantly better health-related quality of life (HRQoL).
Major finding: Boys with severe hemophilia started early on intensive prophylaxis had HRQoL comparable to that of boys with mild hemophilia with good access to factor.
Data source: Pooled analysis of six studies comprising 254 boys with severe hemophilia.
Disclosures: The studies were supported by grants from the Canadian Haemophilia Society and the Society of Haemophilia Clinic Directors of Canada, Bayer, Baxalta, and CSL Behring. The authors did not report conflict of interest disclosures.
Better survival with primary surgery in stage IIIC ovarian ca
Although the use of neoadjuvant chemotherapy for treatment of women with advanced ovarian cancer has grown significantly in recent years, a new study shows that it is associated with worse overall survival for women with stage IIIC disease, compared with primary cytoreductive surgery.
Among 594 women with advanced ovarian cancer treated at one of six major comprehensive cancer centers, median overall survival (OS) for women with stage IIIC cancers treated with neoadjuvant chemotherapy (NACT) was 33 months, compared with 43 months for women treated with primary cytoreductive surgery (PCS), reported Larissa A. Meyer, MD, of the University of Texas M.D. Anderson Cancer Center in Houston, and her colleagues.
There were no significant survival differences between chemotherapy and surgery for women with stage IV disease, however, and for these patients neoadjuvant chemotherapy was associated with fewer morbidities, and may be a better therapeutic option, the investigators reported.
“Although additional biases may persist despite propensity-score matching, our results suggest that in carefully selected patients with stage IIIC disease, PCS is associated with a survival advantage, with overall low rates of surgical morbidity. In contrast, for patients with stage IV disease, our results confirm that NACT is noninferior to PCS for survival, with fewer ICU admissions and rehospitalizations, which suggests that NACT may be preferable for patients with stage IV ovarian cancer,” they wrote in the Journal of Clinical Oncology (2016. doi: 10.1200/JCO.2016.68.1239).
The increase in the use of NACT in women with advanced ovarian cancer in the United States was spurred by two randomized clinical trials, the investigators noted. The first, published in 2010 showed that survival was similar for women with stage IIIC or IV ovarian cancer treated with either neoadjuvant chemotherapy followed by interval debulking surgery or with primary surgery followed by chemotherapy. The second study, published in 2015, found that “in women with stage III or IV ovarian cancer, survival with primary chemotherapy is noninferior to primary surgery. In this study population, the researchers stated that “giving primary chemotherapy before surgery is an acceptable standard of care for women with advanced ovarian cancer.”
To see what effect these trials had on clinical practice and outcomes in the United States, the authors conducted an observational study of patients treated at six National Cancer Institute–designated cancer centers, looking at NACT use in 1,538 women diagnosed with ovarian cancer from 2003 through 2012, and at OS, morbidity, and postoperative residual disease in a propensity score–matched sample of 594 patients.
They found that for women with stage IIIC disease, NACT use increased from 16% during the period 2003-2010, to 34% during 2011-2012. For women with stage IV disease, NACT use grew from 41% to 62% during the respective time periods (P for trend for both comparisons = .001).
As noted before, median overall survival among women with stage IIIC disease in the propensity score–matched sample was significantly shorter for those treated with primary NACT vs. PCS.
For women with stage IV disease, however, there was no significant difference in OS between those treated with NACT (median 31 months) vs. those treated with PCS (median 36 months, hazard ratio 1.16, not significant).
Women with stages IIIC and IV disease who received NACT were less likely to have one or more centimeters of residual disease postoperatively and were less likely to have an ICU admission or rehospitalization (P for all comparisons = .04). However, overall survival was lower among women with stage IIIC disease who had only microscopic residual disease or residual disease measuring 1 cm or less (HR, 1.49; P = .04).
“Future studies should prospectively consider the efficacy of NACT by extent of residual disease in unselected patients,” the authors recommended.
The study was supported by grants from the National Cancer Institute and Cancer Prevention and Research Institute of Texas. Dr. Meyer and multiple coauthors disclosed honoraria, research funding, and/or advising/consulting with various pharmaceutical companies.
Although the use of neoadjuvant chemotherapy for treatment of women with advanced ovarian cancer has grown significantly in recent years, a new study shows that it is associated with worse overall survival for women with stage IIIC disease, compared with primary cytoreductive surgery.
Among 594 women with advanced ovarian cancer treated at one of six major comprehensive cancer centers, median overall survival (OS) for women with stage IIIC cancers treated with neoadjuvant chemotherapy (NACT) was 33 months, compared with 43 months for women treated with primary cytoreductive surgery (PCS), reported Larissa A. Meyer, MD, of the University of Texas M.D. Anderson Cancer Center in Houston, and her colleagues.
There were no significant survival differences between chemotherapy and surgery for women with stage IV disease, however, and for these patients neoadjuvant chemotherapy was associated with fewer morbidities, and may be a better therapeutic option, the investigators reported.
“Although additional biases may persist despite propensity-score matching, our results suggest that in carefully selected patients with stage IIIC disease, PCS is associated with a survival advantage, with overall low rates of surgical morbidity. In contrast, for patients with stage IV disease, our results confirm that NACT is noninferior to PCS for survival, with fewer ICU admissions and rehospitalizations, which suggests that NACT may be preferable for patients with stage IV ovarian cancer,” they wrote in the Journal of Clinical Oncology (2016. doi: 10.1200/JCO.2016.68.1239).
The increase in the use of NACT in women with advanced ovarian cancer in the United States was spurred by two randomized clinical trials, the investigators noted. The first, published in 2010 showed that survival was similar for women with stage IIIC or IV ovarian cancer treated with either neoadjuvant chemotherapy followed by interval debulking surgery or with primary surgery followed by chemotherapy. The second study, published in 2015, found that “in women with stage III or IV ovarian cancer, survival with primary chemotherapy is noninferior to primary surgery. In this study population, the researchers stated that “giving primary chemotherapy before surgery is an acceptable standard of care for women with advanced ovarian cancer.”
To see what effect these trials had on clinical practice and outcomes in the United States, the authors conducted an observational study of patients treated at six National Cancer Institute–designated cancer centers, looking at NACT use in 1,538 women diagnosed with ovarian cancer from 2003 through 2012, and at OS, morbidity, and postoperative residual disease in a propensity score–matched sample of 594 patients.
They found that for women with stage IIIC disease, NACT use increased from 16% during the period 2003-2010, to 34% during 2011-2012. For women with stage IV disease, NACT use grew from 41% to 62% during the respective time periods (P for trend for both comparisons = .001).
As noted before, median overall survival among women with stage IIIC disease in the propensity score–matched sample was significantly shorter for those treated with primary NACT vs. PCS.
For women with stage IV disease, however, there was no significant difference in OS between those treated with NACT (median 31 months) vs. those treated with PCS (median 36 months, hazard ratio 1.16, not significant).
Women with stages IIIC and IV disease who received NACT were less likely to have one or more centimeters of residual disease postoperatively and were less likely to have an ICU admission or rehospitalization (P for all comparisons = .04). However, overall survival was lower among women with stage IIIC disease who had only microscopic residual disease or residual disease measuring 1 cm or less (HR, 1.49; P = .04).
“Future studies should prospectively consider the efficacy of NACT by extent of residual disease in unselected patients,” the authors recommended.
The study was supported by grants from the National Cancer Institute and Cancer Prevention and Research Institute of Texas. Dr. Meyer and multiple coauthors disclosed honoraria, research funding, and/or advising/consulting with various pharmaceutical companies.
Although the use of neoadjuvant chemotherapy for treatment of women with advanced ovarian cancer has grown significantly in recent years, a new study shows that it is associated with worse overall survival for women with stage IIIC disease, compared with primary cytoreductive surgery.
Among 594 women with advanced ovarian cancer treated at one of six major comprehensive cancer centers, median overall survival (OS) for women with stage IIIC cancers treated with neoadjuvant chemotherapy (NACT) was 33 months, compared with 43 months for women treated with primary cytoreductive surgery (PCS), reported Larissa A. Meyer, MD, of the University of Texas M.D. Anderson Cancer Center in Houston, and her colleagues.
There were no significant survival differences between chemotherapy and surgery for women with stage IV disease, however, and for these patients neoadjuvant chemotherapy was associated with fewer morbidities, and may be a better therapeutic option, the investigators reported.
“Although additional biases may persist despite propensity-score matching, our results suggest that in carefully selected patients with stage IIIC disease, PCS is associated with a survival advantage, with overall low rates of surgical morbidity. In contrast, for patients with stage IV disease, our results confirm that NACT is noninferior to PCS for survival, with fewer ICU admissions and rehospitalizations, which suggests that NACT may be preferable for patients with stage IV ovarian cancer,” they wrote in the Journal of Clinical Oncology (2016. doi: 10.1200/JCO.2016.68.1239).
The increase in the use of NACT in women with advanced ovarian cancer in the United States was spurred by two randomized clinical trials, the investigators noted. The first, published in 2010 showed that survival was similar for women with stage IIIC or IV ovarian cancer treated with either neoadjuvant chemotherapy followed by interval debulking surgery or with primary surgery followed by chemotherapy. The second study, published in 2015, found that “in women with stage III or IV ovarian cancer, survival with primary chemotherapy is noninferior to primary surgery. In this study population, the researchers stated that “giving primary chemotherapy before surgery is an acceptable standard of care for women with advanced ovarian cancer.”
To see what effect these trials had on clinical practice and outcomes in the United States, the authors conducted an observational study of patients treated at six National Cancer Institute–designated cancer centers, looking at NACT use in 1,538 women diagnosed with ovarian cancer from 2003 through 2012, and at OS, morbidity, and postoperative residual disease in a propensity score–matched sample of 594 patients.
They found that for women with stage IIIC disease, NACT use increased from 16% during the period 2003-2010, to 34% during 2011-2012. For women with stage IV disease, NACT use grew from 41% to 62% during the respective time periods (P for trend for both comparisons = .001).
As noted before, median overall survival among women with stage IIIC disease in the propensity score–matched sample was significantly shorter for those treated with primary NACT vs. PCS.
For women with stage IV disease, however, there was no significant difference in OS between those treated with NACT (median 31 months) vs. those treated with PCS (median 36 months, hazard ratio 1.16, not significant).
Women with stages IIIC and IV disease who received NACT were less likely to have one or more centimeters of residual disease postoperatively and were less likely to have an ICU admission or rehospitalization (P for all comparisons = .04). However, overall survival was lower among women with stage IIIC disease who had only microscopic residual disease or residual disease measuring 1 cm or less (HR, 1.49; P = .04).
“Future studies should prospectively consider the efficacy of NACT by extent of residual disease in unselected patients,” the authors recommended.
The study was supported by grants from the National Cancer Institute and Cancer Prevention and Research Institute of Texas. Dr. Meyer and multiple coauthors disclosed honoraria, research funding, and/or advising/consulting with various pharmaceutical companies.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Neoadjuvant chemotherapy was associated with lower overall survival of stage IIIC but not stage IV ovarian cancer.
Major finding: Median OS was 33 months with neoadjuvant chemotherapy vs. 43 months with primary cytoreductive surgery.
Data source: Observational study of 1,538 patients with ovarian cancer, and propensity score–matched sample of 594 patients for clinical outcomes.
Disclosures: The study was supported by grants from the National Cancer Institute and Cancer Prevention and Research Institute of Texas. Larissa A. Meyer and multiple coauthors disclosed honoraria, research funding, and/or advising/consulting with various pharmaceutical companies.
September 2016: Click for Credit
Here are 5 articles in the August issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Women With BRCA1 Mutations at Higher Risk for Endometrial Cancers
To take the posttest, go to: http://bit.ly/2t6SPIY
Expires June 30, 2017
VITALSKey clinical point: Clinicians may wish to discuss the option of hysterectomy at the time of salpingo-oophorectomy in women with deleterious BRCA1 mutations.
Major finding: Among women with BRCA1 but not BRCA2 mutations there was increased risk for serous/serous-like endometrial carcinomas.
Data source: Prospective multicenter follow-up study of 1,083 women with BRCA mutations who underwent salpingo-oophorectomy without hysterectomy.
Disclosures: The study was supported by grants from the Department of Defense, National Institutes of Health, and public and private foundations. Coauthor Robert Soslow, MD, disclosed consulting for EMD Serono. No others reported conflicts of interest. The editorialists reported no conflicts of interest related to the study.
2. Cochrane Review: Topical Steroid—Vitamin D Combo Best for Scalp Psoriasis
To take the posttest, go to: http://bit.ly/2sIyLNI
Expires July 14, 2017
VITALSKey clinical point: The combination of a topical steroid and topical vitamin D is marginally better but with a similar safety profile to steroids alone as a treatment for psoriasis on the scalp.
Major finding: The combination of a topical steroid and vitamin D showed a small but statistically significant advantage over steroids alone, and a greater advantage over vitamin D alone.
Data source: A systematic review of 59 randomized controlled studies in 11,561 patients.
Disclosures: The study was supported by the Universidade Federal de São Paulo, Brazil; the Universidade Federal do Rio Grande do Norte, Brazil; and the National Institute for Health Research, United Kingdom. Six authors and one clinical referee declared speakers' fees, research grants, and funding from the pharmaceutical industry. One author had no conflicts of interest to disclose.
3. Study Finds Emergence of Azithromycin-resistant Gonorrhea
To take the posttest, go to: http://bit.ly/2u1nMmb
Expires July 16, 2017
VITALSKey clinical point:Resistance to azithromycin is emerging among patients diagnosed with gonorrhea.
Major finding: Among patients with gonorrhea, resistance to azithromycin increased from 0.6% in 2013 to 2.5% in 2014, predominantly in the Midwest.
Data source: An analysis of 5,093 Neisseria gonorrhoeae isolates from 27 clinics as part of the CDC's Gonococcal Isolate Surveillance Project.
Disclosures: The researchers had no financial disclosures.
4. Statins Improve Ovarian Cancer Survival
To take the posttest, go to: http://bit.ly/2t6swCF
Expires June 16, 2017
VITALSKey clinical point: The risk of all-cause mortality in ovarian cancer patients on statin therapy was reduced by one-third.
Major finding: Mean survival in a large cohort of women with stage III ovarian cancer was 5.8 months longer among those on statin therapy.
Data source: A retrospective study of 1,510 women diagnosed with epithelial ovarian cancer during 2007-2009.
Disclosures: Dr. Vogel reported having no financial conflicts regarding this study, conducted without commercial support.
5. Common Surgeries Linked to Chronic Opioid Use Among Opioid-naive Patients
To take the posttest, go to: http://bit.ly/2ub9fFg
Expires June 18, 2017
VITALSKey clinical point: Common surgeries increase the risk of chronic opioid use in opioid-naive adults, especially among those using antidepressants or benzodiazepines before their operations, and those with substance abuse histories.
Major finding: After adjustment for potential confounders, knee replacement increased the risk fivefold; open cholecystectomy almost fourfold; and total hip replacement and simple mastectomy almost threefold.
Data source: Insurance claims of more than 18 million people.
Disclosures: The authors had no disclosures. The work was funded in part by the Foundation for Anesthesia Education and Research and the Anesthesia Quality Institute. Claims data came from MarketScan (Truven Health Analytics).
Here are 5 articles in the August issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Women With BRCA1 Mutations at Higher Risk for Endometrial Cancers
To take the posttest, go to: http://bit.ly/2t6SPIY
Expires June 30, 2017
VITALSKey clinical point: Clinicians may wish to discuss the option of hysterectomy at the time of salpingo-oophorectomy in women with deleterious BRCA1 mutations.
Major finding: Among women with BRCA1 but not BRCA2 mutations there was increased risk for serous/serous-like endometrial carcinomas.
Data source: Prospective multicenter follow-up study of 1,083 women with BRCA mutations who underwent salpingo-oophorectomy without hysterectomy.
Disclosures: The study was supported by grants from the Department of Defense, National Institutes of Health, and public and private foundations. Coauthor Robert Soslow, MD, disclosed consulting for EMD Serono. No others reported conflicts of interest. The editorialists reported no conflicts of interest related to the study.
2. Cochrane Review: Topical Steroid—Vitamin D Combo Best for Scalp Psoriasis
To take the posttest, go to: http://bit.ly/2sIyLNI
Expires July 14, 2017
VITALSKey clinical point: The combination of a topical steroid and topical vitamin D is marginally better but with a similar safety profile to steroids alone as a treatment for psoriasis on the scalp.
Major finding: The combination of a topical steroid and vitamin D showed a small but statistically significant advantage over steroids alone, and a greater advantage over vitamin D alone.
Data source: A systematic review of 59 randomized controlled studies in 11,561 patients.
Disclosures: The study was supported by the Universidade Federal de São Paulo, Brazil; the Universidade Federal do Rio Grande do Norte, Brazil; and the National Institute for Health Research, United Kingdom. Six authors and one clinical referee declared speakers' fees, research grants, and funding from the pharmaceutical industry. One author had no conflicts of interest to disclose.
3. Study Finds Emergence of Azithromycin-resistant Gonorrhea
To take the posttest, go to: http://bit.ly/2u1nMmb
Expires July 16, 2017
VITALSKey clinical point:Resistance to azithromycin is emerging among patients diagnosed with gonorrhea.
Major finding: Among patients with gonorrhea, resistance to azithromycin increased from 0.6% in 2013 to 2.5% in 2014, predominantly in the Midwest.
Data source: An analysis of 5,093 Neisseria gonorrhoeae isolates from 27 clinics as part of the CDC's Gonococcal Isolate Surveillance Project.
Disclosures: The researchers had no financial disclosures.
4. Statins Improve Ovarian Cancer Survival
To take the posttest, go to: http://bit.ly/2t6swCF
Expires June 16, 2017
VITALSKey clinical point: The risk of all-cause mortality in ovarian cancer patients on statin therapy was reduced by one-third.
Major finding: Mean survival in a large cohort of women with stage III ovarian cancer was 5.8 months longer among those on statin therapy.
Data source: A retrospective study of 1,510 women diagnosed with epithelial ovarian cancer during 2007-2009.
Disclosures: Dr. Vogel reported having no financial conflicts regarding this study, conducted without commercial support.
5. Common Surgeries Linked to Chronic Opioid Use Among Opioid-naive Patients
To take the posttest, go to: http://bit.ly/2ub9fFg
Expires June 18, 2017
VITALSKey clinical point: Common surgeries increase the risk of chronic opioid use in opioid-naive adults, especially among those using antidepressants or benzodiazepines before their operations, and those with substance abuse histories.
Major finding: After adjustment for potential confounders, knee replacement increased the risk fivefold; open cholecystectomy almost fourfold; and total hip replacement and simple mastectomy almost threefold.
Data source: Insurance claims of more than 18 million people.
Disclosures: The authors had no disclosures. The work was funded in part by the Foundation for Anesthesia Education and Research and the Anesthesia Quality Institute. Claims data came from MarketScan (Truven Health Analytics).
Here are 5 articles in the August issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Women With BRCA1 Mutations at Higher Risk for Endometrial Cancers
To take the posttest, go to: http://bit.ly/2t6SPIY
Expires June 30, 2017
VITALSKey clinical point: Clinicians may wish to discuss the option of hysterectomy at the time of salpingo-oophorectomy in women with deleterious BRCA1 mutations.
Major finding: Among women with BRCA1 but not BRCA2 mutations there was increased risk for serous/serous-like endometrial carcinomas.
Data source: Prospective multicenter follow-up study of 1,083 women with BRCA mutations who underwent salpingo-oophorectomy without hysterectomy.
Disclosures: The study was supported by grants from the Department of Defense, National Institutes of Health, and public and private foundations. Coauthor Robert Soslow, MD, disclosed consulting for EMD Serono. No others reported conflicts of interest. The editorialists reported no conflicts of interest related to the study.
2. Cochrane Review: Topical Steroid—Vitamin D Combo Best for Scalp Psoriasis
To take the posttest, go to: http://bit.ly/2sIyLNI
Expires July 14, 2017
VITALSKey clinical point: The combination of a topical steroid and topical vitamin D is marginally better but with a similar safety profile to steroids alone as a treatment for psoriasis on the scalp.
Major finding: The combination of a topical steroid and vitamin D showed a small but statistically significant advantage over steroids alone, and a greater advantage over vitamin D alone.
Data source: A systematic review of 59 randomized controlled studies in 11,561 patients.
Disclosures: The study was supported by the Universidade Federal de São Paulo, Brazil; the Universidade Federal do Rio Grande do Norte, Brazil; and the National Institute for Health Research, United Kingdom. Six authors and one clinical referee declared speakers' fees, research grants, and funding from the pharmaceutical industry. One author had no conflicts of interest to disclose.
3. Study Finds Emergence of Azithromycin-resistant Gonorrhea
To take the posttest, go to: http://bit.ly/2u1nMmb
Expires July 16, 2017
VITALSKey clinical point:Resistance to azithromycin is emerging among patients diagnosed with gonorrhea.
Major finding: Among patients with gonorrhea, resistance to azithromycin increased from 0.6% in 2013 to 2.5% in 2014, predominantly in the Midwest.
Data source: An analysis of 5,093 Neisseria gonorrhoeae isolates from 27 clinics as part of the CDC's Gonococcal Isolate Surveillance Project.
Disclosures: The researchers had no financial disclosures.
4. Statins Improve Ovarian Cancer Survival
To take the posttest, go to: http://bit.ly/2t6swCF
Expires June 16, 2017
VITALSKey clinical point: The risk of all-cause mortality in ovarian cancer patients on statin therapy was reduced by one-third.
Major finding: Mean survival in a large cohort of women with stage III ovarian cancer was 5.8 months longer among those on statin therapy.
Data source: A retrospective study of 1,510 women diagnosed with epithelial ovarian cancer during 2007-2009.
Disclosures: Dr. Vogel reported having no financial conflicts regarding this study, conducted without commercial support.
5. Common Surgeries Linked to Chronic Opioid Use Among Opioid-naive Patients
To take the posttest, go to: http://bit.ly/2ub9fFg
Expires June 18, 2017
VITALSKey clinical point: Common surgeries increase the risk of chronic opioid use in opioid-naive adults, especially among those using antidepressants or benzodiazepines before their operations, and those with substance abuse histories.
Major finding: After adjustment for potential confounders, knee replacement increased the risk fivefold; open cholecystectomy almost fourfold; and total hip replacement and simple mastectomy almost threefold.
Data source: Insurance claims of more than 18 million people.
Disclosures: The authors had no disclosures. The work was funded in part by the Foundation for Anesthesia Education and Research and the Anesthesia Quality Institute. Claims data came from MarketScan (Truven Health Analytics).
FDG-PET gives early indication of response to therapy for Ewing sarcoma
Among patients with Ewing sarcoma, functional imaging with 18fluorodeoxyglucose (FDG)–PET was a better predictor of response 9 days after the start of therapy than anatomic imaging modalities were at 6 weeks, results of a retrospective analysis suggest.
A study comparing the predictive ability of functional imaging modalities such as FDG-PET with that of anatomic imaging modalities such as CT or MRI showed that an early signal with FDG-PET was superior to anatomic imaging, and that newly defined tumor volume criteria were better at predicting response and clinical benefit than either World Health Organization (WHO) criteria or Response Evaluation Criteria in Solid Tumors (RECIST), reported Vadim S. Koshkin, MD, of the Cleveland Clinic and colleagues.
“The time needed to assess tumors volumetrically is slightly greater than to do so unidimensionally or bidimensionally, but the process is now automated. The analysis presented here suggests that assessment of tumor volume is superior to predict response in clinical trials, compared with the currently widely used RECIST and WHO criteria. This requires additional validation with prospective clinical trials,” they wrote (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.68.1858].
To get a better idea of the relative benefits of FDG-PET and anatomic imaging for assessing clinical outcomes, the investigators took a retrospective look at patients with Ewing sarcoma who were enrolled in the SARC 011 trial, a single-arm, multicenter, multicohort phase II study of patients with recurrent Ewing sarcoma treated with the investigational insulinlike growth factor–1 receptor antibody R1507.
Of the 115 patients enrolled, 76 had available anatomic imaging at baseline and at 6 weeks after the start of treatment. The imaging studies were assessed by the treating oncologist according to WHO criteria and by a central, external group of radiologists blinded to clinical outcomes of individual patients. FDG-PET studies were performed at baseline and on day 9 and were assessed by central reviewers using PET Response Criteria in Solid Tumors (PERCIST).
The authors compared PERCIST 1.0 criteria for functional imaging with FDG-PET, and for anatomic imaging, WHO and RECIST criteria were assessed independently, and newly defined volumetric criteria were based on measurements done by the central radiology group using semi-automated solid tumor segmentation software.
As noted before, the investigators found results of day 9 FDG-PET scans were associated with reduced overall survival (OS) in patients with disease progression, compared with those without progression (P = .001), and with improved OS among patients with responses to the antibody, compared with those without responses.
“There was no significance in median survival between patients who responded to treatment and patients with stable disease for any of the imaging criteria. However, for all of the criteria, there was a trend toward longer survival for patients in the response group, compared with the stable disease group,” the authors wrote.
They found that the anatomic imaging criteria (WHO local and centralized assessments, RECIST, and volume) identified fewer patients in the response group than PERCIST (FDG-PET) criteria did.
When they looked at the subgroup of 66 patients who had both interpretable functional and anatomic imaging, they found that PERCIST identified 43.9% of patients as responders, and 90.9% as nonprogressors.
The authors acknowledged that their study was hampered by the retrospective design, small sample size relative to the trial population, and lack of FDG-PET standardization to common criteria across the treatment centers.
Among patients with Ewing sarcoma, functional imaging with 18fluorodeoxyglucose (FDG)–PET was a better predictor of response 9 days after the start of therapy than anatomic imaging modalities were at 6 weeks, results of a retrospective analysis suggest.
A study comparing the predictive ability of functional imaging modalities such as FDG-PET with that of anatomic imaging modalities such as CT or MRI showed that an early signal with FDG-PET was superior to anatomic imaging, and that newly defined tumor volume criteria were better at predicting response and clinical benefit than either World Health Organization (WHO) criteria or Response Evaluation Criteria in Solid Tumors (RECIST), reported Vadim S. Koshkin, MD, of the Cleveland Clinic and colleagues.
“The time needed to assess tumors volumetrically is slightly greater than to do so unidimensionally or bidimensionally, but the process is now automated. The analysis presented here suggests that assessment of tumor volume is superior to predict response in clinical trials, compared with the currently widely used RECIST and WHO criteria. This requires additional validation with prospective clinical trials,” they wrote (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.68.1858].
To get a better idea of the relative benefits of FDG-PET and anatomic imaging for assessing clinical outcomes, the investigators took a retrospective look at patients with Ewing sarcoma who were enrolled in the SARC 011 trial, a single-arm, multicenter, multicohort phase II study of patients with recurrent Ewing sarcoma treated with the investigational insulinlike growth factor–1 receptor antibody R1507.
Of the 115 patients enrolled, 76 had available anatomic imaging at baseline and at 6 weeks after the start of treatment. The imaging studies were assessed by the treating oncologist according to WHO criteria and by a central, external group of radiologists blinded to clinical outcomes of individual patients. FDG-PET studies were performed at baseline and on day 9 and were assessed by central reviewers using PET Response Criteria in Solid Tumors (PERCIST).
The authors compared PERCIST 1.0 criteria for functional imaging with FDG-PET, and for anatomic imaging, WHO and RECIST criteria were assessed independently, and newly defined volumetric criteria were based on measurements done by the central radiology group using semi-automated solid tumor segmentation software.
As noted before, the investigators found results of day 9 FDG-PET scans were associated with reduced overall survival (OS) in patients with disease progression, compared with those without progression (P = .001), and with improved OS among patients with responses to the antibody, compared with those without responses.
“There was no significance in median survival between patients who responded to treatment and patients with stable disease for any of the imaging criteria. However, for all of the criteria, there was a trend toward longer survival for patients in the response group, compared with the stable disease group,” the authors wrote.
They found that the anatomic imaging criteria (WHO local and centralized assessments, RECIST, and volume) identified fewer patients in the response group than PERCIST (FDG-PET) criteria did.
When they looked at the subgroup of 66 patients who had both interpretable functional and anatomic imaging, they found that PERCIST identified 43.9% of patients as responders, and 90.9% as nonprogressors.
The authors acknowledged that their study was hampered by the retrospective design, small sample size relative to the trial population, and lack of FDG-PET standardization to common criteria across the treatment centers.
Among patients with Ewing sarcoma, functional imaging with 18fluorodeoxyglucose (FDG)–PET was a better predictor of response 9 days after the start of therapy than anatomic imaging modalities were at 6 weeks, results of a retrospective analysis suggest.
A study comparing the predictive ability of functional imaging modalities such as FDG-PET with that of anatomic imaging modalities such as CT or MRI showed that an early signal with FDG-PET was superior to anatomic imaging, and that newly defined tumor volume criteria were better at predicting response and clinical benefit than either World Health Organization (WHO) criteria or Response Evaluation Criteria in Solid Tumors (RECIST), reported Vadim S. Koshkin, MD, of the Cleveland Clinic and colleagues.
“The time needed to assess tumors volumetrically is slightly greater than to do so unidimensionally or bidimensionally, but the process is now automated. The analysis presented here suggests that assessment of tumor volume is superior to predict response in clinical trials, compared with the currently widely used RECIST and WHO criteria. This requires additional validation with prospective clinical trials,” they wrote (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.68.1858].
To get a better idea of the relative benefits of FDG-PET and anatomic imaging for assessing clinical outcomes, the investigators took a retrospective look at patients with Ewing sarcoma who were enrolled in the SARC 011 trial, a single-arm, multicenter, multicohort phase II study of patients with recurrent Ewing sarcoma treated with the investigational insulinlike growth factor–1 receptor antibody R1507.
Of the 115 patients enrolled, 76 had available anatomic imaging at baseline and at 6 weeks after the start of treatment. The imaging studies were assessed by the treating oncologist according to WHO criteria and by a central, external group of radiologists blinded to clinical outcomes of individual patients. FDG-PET studies were performed at baseline and on day 9 and were assessed by central reviewers using PET Response Criteria in Solid Tumors (PERCIST).
The authors compared PERCIST 1.0 criteria for functional imaging with FDG-PET, and for anatomic imaging, WHO and RECIST criteria were assessed independently, and newly defined volumetric criteria were based on measurements done by the central radiology group using semi-automated solid tumor segmentation software.
As noted before, the investigators found results of day 9 FDG-PET scans were associated with reduced overall survival (OS) in patients with disease progression, compared with those without progression (P = .001), and with improved OS among patients with responses to the antibody, compared with those without responses.
“There was no significance in median survival between patients who responded to treatment and patients with stable disease for any of the imaging criteria. However, for all of the criteria, there was a trend toward longer survival for patients in the response group, compared with the stable disease group,” the authors wrote.
They found that the anatomic imaging criteria (WHO local and centralized assessments, RECIST, and volume) identified fewer patients in the response group than PERCIST (FDG-PET) criteria did.
When they looked at the subgroup of 66 patients who had both interpretable functional and anatomic imaging, they found that PERCIST identified 43.9% of patients as responders, and 90.9% as nonprogressors.
The authors acknowledged that their study was hampered by the retrospective design, small sample size relative to the trial population, and lack of FDG-PET standardization to common criteria across the treatment centers.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: FDG-PET predicted response to Ewing sarcoma therapy significantly earlier than MRI or CT.
Major finding: Day 9 FDG-PET scans were associated with reduced overall survival (OS) in patients with disease progression, compared with those without progression (P = .001).
Data source: Retrospective analysis of data on 76 patients enrolled in the SARC 011 trial.
Disclosures: The study was supported by the Radiological Society of North America; Quantitative Imaging Biomarker Alliance; the Sarcoma Alliance for Research Through Collaboration (SARC), and the National Institutes of Health. Vadim S. Koshkin and three coauthors reported no conflicts of interest. Seven coauthors reported financial relationships with various drug and/or device companies.
HIV infection linked with death from cervical cancer
HIV-infected women with cervical cancer have significantly lower survival rates than women with cervical cancer who are not infected, investigators found.
A study of 348 women with invasive cervical cancer in Botswana, a nation with robust and wide-reaching HIV prevention and antiretroviral therapy (ART) programs, showed that women who had HIV infections had a twofold greater risk for death within 3 years than women without HIV, reported Scott Dryden-Peterson, MD, from the Brigham and Women’s Hospital and Harvard TH Chan School of Public Health in Boston, and his colleagues.
“Even in the context of good access to and use of ART, HIV infection more than doubled the risk of death among women who received curative guideline-concordant therapy. Competing mortality from HIV-associated infections seemed to contribute minimally to the excess risk of death; rather, earlier oncologic progression among women with HIV seemed to account for the excess mortality,” they wrote (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.67.9613).
It is well known that HIV infection significantly increases the risk of cervical cancer, with HIV-infected women having a sixfold greater risk for the malignancy than women in the general population, the investigators stated.
Whether HIV has a detrimental effect on cervical cancer–specific survival was unclear, however, prompting them to investigate the question in a cohort of 348 women, 231 of whom were infected with HIV, 96 of whom were free of infection, and 21 of whom had unknown HIV status.
Of the women with HIV, 189 (81.8%) had started on ART before their cancers were diagnosed, and had been on therapy for a median of 4.8 years. Most of the HIV-infected women had CD4 cell counts that fell in the moderate or mildly immunosuppressed range (median 397 cells per microliter). Of this group, only 24 had CD4 counts below 200, the threshold for a diagnosis of AIDS.
After a median follow-up of 19.7 months, 157 participants had died, including 117 women with HIV infections and 40 without infections.
Three-year survival, the primary outcome, was 35% for women with HIV, compared with 48% for uninfected women.
In an analysis adjusted for age, cancer stage, CD4 cell counts, duration of ART, radiation dose received and treatment intent (curative or palliative), the hazard ratio for death among women with HIV was 1.95 (P = .007).
In an analysis restricted to women who received therapy with curative intent, the HR was 2.35 (P = .002), and an analysis restricted to women who received therapy with curative intent that adhered to clinical guidelines showed that the HR for death among HIV-infected women was 2.65 (P = .037).
Of note, the detrimental effect of HIV on survival was highest among women with stage I (HR, 4.03) and stage II (HR, 2.44) cancers, compared with stages III or IV (P = .035).
Among women with CD4 cell counts below 250, the HR for death was 2.75. This risk diminished with increasing cell counts, but remained significantly higher among women with near-normal counts (350 to 500 cells/microliter; HR, 1.87; significant according to confidence intervals).
“Advanced stage and poor treatment completion contributed to high mortality overall,” the investigators wrote.
Despite methodological concerns and the absence of detailed data about certain aspects, this study describes the importance of further research and investment into improving the outcomes of women with both HIV and cervical cancer. International collaboration through research networks, such as the recently established Cervix Cancer Research Network, that could provide infrastructure, quality assurance, financial support, data sharing, education, and expertise in conducting clinical trials can potentially help establish future initiatives to answer outstanding questions such as those highlighted by Dryden-Peterson et al. We commend these authors for their dedication to improve treatment for women with HIV and cervical cancer in this rising burden of disease that has had limited research to date.
One clear major barrier to optimal treatment of cervical cancer, and indeed many cancers, is access to radiation therapy. A recent analysis of radiation therapy infrastructure in 139 low- and middle-income countries found that only 4 (2.87%) have the requisite number of teletherapy units to manage the estimated burden of cancer in 2020 and that 55 (39.5%) have no radiation facilities. Another analysis of radiotherapy resources found that brachytherapy is available in only 20 of 52 African countries. If we are to reduce the number of deaths from cervical cancer in women with and without HIV, it is paramount that access to screening, vaccination, and treatment facilities in those areas of the world with the greatest burden of disease is addressed.
Linda R. Mileshkin, MD and Alison E. Freimund, MD are with the Peter MacCallum Cancer Centre, Melbourne. These comments are excerpted from an accompanying editorial (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.69.0784).
Despite methodological concerns and the absence of detailed data about certain aspects, this study describes the importance of further research and investment into improving the outcomes of women with both HIV and cervical cancer. International collaboration through research networks, such as the recently established Cervix Cancer Research Network, that could provide infrastructure, quality assurance, financial support, data sharing, education, and expertise in conducting clinical trials can potentially help establish future initiatives to answer outstanding questions such as those highlighted by Dryden-Peterson et al. We commend these authors for their dedication to improve treatment for women with HIV and cervical cancer in this rising burden of disease that has had limited research to date.
One clear major barrier to optimal treatment of cervical cancer, and indeed many cancers, is access to radiation therapy. A recent analysis of radiation therapy infrastructure in 139 low- and middle-income countries found that only 4 (2.87%) have the requisite number of teletherapy units to manage the estimated burden of cancer in 2020 and that 55 (39.5%) have no radiation facilities. Another analysis of radiotherapy resources found that brachytherapy is available in only 20 of 52 African countries. If we are to reduce the number of deaths from cervical cancer in women with and without HIV, it is paramount that access to screening, vaccination, and treatment facilities in those areas of the world with the greatest burden of disease is addressed.
Linda R. Mileshkin, MD and Alison E. Freimund, MD are with the Peter MacCallum Cancer Centre, Melbourne. These comments are excerpted from an accompanying editorial (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.69.0784).
Despite methodological concerns and the absence of detailed data about certain aspects, this study describes the importance of further research and investment into improving the outcomes of women with both HIV and cervical cancer. International collaboration through research networks, such as the recently established Cervix Cancer Research Network, that could provide infrastructure, quality assurance, financial support, data sharing, education, and expertise in conducting clinical trials can potentially help establish future initiatives to answer outstanding questions such as those highlighted by Dryden-Peterson et al. We commend these authors for their dedication to improve treatment for women with HIV and cervical cancer in this rising burden of disease that has had limited research to date.
One clear major barrier to optimal treatment of cervical cancer, and indeed many cancers, is access to radiation therapy. A recent analysis of radiation therapy infrastructure in 139 low- and middle-income countries found that only 4 (2.87%) have the requisite number of teletherapy units to manage the estimated burden of cancer in 2020 and that 55 (39.5%) have no radiation facilities. Another analysis of radiotherapy resources found that brachytherapy is available in only 20 of 52 African countries. If we are to reduce the number of deaths from cervical cancer in women with and without HIV, it is paramount that access to screening, vaccination, and treatment facilities in those areas of the world with the greatest burden of disease is addressed.
Linda R. Mileshkin, MD and Alison E. Freimund, MD are with the Peter MacCallum Cancer Centre, Melbourne. These comments are excerpted from an accompanying editorial (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.69.0784).
HIV-infected women with cervical cancer have significantly lower survival rates than women with cervical cancer who are not infected, investigators found.
A study of 348 women with invasive cervical cancer in Botswana, a nation with robust and wide-reaching HIV prevention and antiretroviral therapy (ART) programs, showed that women who had HIV infections had a twofold greater risk for death within 3 years than women without HIV, reported Scott Dryden-Peterson, MD, from the Brigham and Women’s Hospital and Harvard TH Chan School of Public Health in Boston, and his colleagues.
“Even in the context of good access to and use of ART, HIV infection more than doubled the risk of death among women who received curative guideline-concordant therapy. Competing mortality from HIV-associated infections seemed to contribute minimally to the excess risk of death; rather, earlier oncologic progression among women with HIV seemed to account for the excess mortality,” they wrote (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.67.9613).
It is well known that HIV infection significantly increases the risk of cervical cancer, with HIV-infected women having a sixfold greater risk for the malignancy than women in the general population, the investigators stated.
Whether HIV has a detrimental effect on cervical cancer–specific survival was unclear, however, prompting them to investigate the question in a cohort of 348 women, 231 of whom were infected with HIV, 96 of whom were free of infection, and 21 of whom had unknown HIV status.
Of the women with HIV, 189 (81.8%) had started on ART before their cancers were diagnosed, and had been on therapy for a median of 4.8 years. Most of the HIV-infected women had CD4 cell counts that fell in the moderate or mildly immunosuppressed range (median 397 cells per microliter). Of this group, only 24 had CD4 counts below 200, the threshold for a diagnosis of AIDS.
After a median follow-up of 19.7 months, 157 participants had died, including 117 women with HIV infections and 40 without infections.
Three-year survival, the primary outcome, was 35% for women with HIV, compared with 48% for uninfected women.
In an analysis adjusted for age, cancer stage, CD4 cell counts, duration of ART, radiation dose received and treatment intent (curative or palliative), the hazard ratio for death among women with HIV was 1.95 (P = .007).
In an analysis restricted to women who received therapy with curative intent, the HR was 2.35 (P = .002), and an analysis restricted to women who received therapy with curative intent that adhered to clinical guidelines showed that the HR for death among HIV-infected women was 2.65 (P = .037).
Of note, the detrimental effect of HIV on survival was highest among women with stage I (HR, 4.03) and stage II (HR, 2.44) cancers, compared with stages III or IV (P = .035).
Among women with CD4 cell counts below 250, the HR for death was 2.75. This risk diminished with increasing cell counts, but remained significantly higher among women with near-normal counts (350 to 500 cells/microliter; HR, 1.87; significant according to confidence intervals).
“Advanced stage and poor treatment completion contributed to high mortality overall,” the investigators wrote.
HIV-infected women with cervical cancer have significantly lower survival rates than women with cervical cancer who are not infected, investigators found.
A study of 348 women with invasive cervical cancer in Botswana, a nation with robust and wide-reaching HIV prevention and antiretroviral therapy (ART) programs, showed that women who had HIV infections had a twofold greater risk for death within 3 years than women without HIV, reported Scott Dryden-Peterson, MD, from the Brigham and Women’s Hospital and Harvard TH Chan School of Public Health in Boston, and his colleagues.
“Even in the context of good access to and use of ART, HIV infection more than doubled the risk of death among women who received curative guideline-concordant therapy. Competing mortality from HIV-associated infections seemed to contribute minimally to the excess risk of death; rather, earlier oncologic progression among women with HIV seemed to account for the excess mortality,” they wrote (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.67.9613).
It is well known that HIV infection significantly increases the risk of cervical cancer, with HIV-infected women having a sixfold greater risk for the malignancy than women in the general population, the investigators stated.
Whether HIV has a detrimental effect on cervical cancer–specific survival was unclear, however, prompting them to investigate the question in a cohort of 348 women, 231 of whom were infected with HIV, 96 of whom were free of infection, and 21 of whom had unknown HIV status.
Of the women with HIV, 189 (81.8%) had started on ART before their cancers were diagnosed, and had been on therapy for a median of 4.8 years. Most of the HIV-infected women had CD4 cell counts that fell in the moderate or mildly immunosuppressed range (median 397 cells per microliter). Of this group, only 24 had CD4 counts below 200, the threshold for a diagnosis of AIDS.
After a median follow-up of 19.7 months, 157 participants had died, including 117 women with HIV infections and 40 without infections.
Three-year survival, the primary outcome, was 35% for women with HIV, compared with 48% for uninfected women.
In an analysis adjusted for age, cancer stage, CD4 cell counts, duration of ART, radiation dose received and treatment intent (curative or palliative), the hazard ratio for death among women with HIV was 1.95 (P = .007).
In an analysis restricted to women who received therapy with curative intent, the HR was 2.35 (P = .002), and an analysis restricted to women who received therapy with curative intent that adhered to clinical guidelines showed that the HR for death among HIV-infected women was 2.65 (P = .037).
Of note, the detrimental effect of HIV on survival was highest among women with stage I (HR, 4.03) and stage II (HR, 2.44) cancers, compared with stages III or IV (P = .035).
Among women with CD4 cell counts below 250, the HR for death was 2.75. This risk diminished with increasing cell counts, but remained significantly higher among women with near-normal counts (350 to 500 cells/microliter; HR, 1.87; significant according to confidence intervals).
“Advanced stage and poor treatment completion contributed to high mortality overall,” the investigators wrote.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: HIV infection appears to be an independent risk factor for worse survival among women with invasive cervical cancer.
Major finding: Three-year survival was 35% for women with HIV, compared with 48% for uninfected women.
Data source: Prospective study of 348 women with invasive cervical cancer treated in Botswana.
Disclosures: The study was supported by grants from the US National Institutes of Health and the Paul G. Allen Family Foundation. Dr. Dryden-Peterson disclosed royalties for articles, two co-authors, and editorialists Dr. Mileshkin and Dr. Freimund disclosed relationships with various pharmaceutical companies.
Hemophilia carriers are at risk for abnormal bleeding
ORLANDO – The traditional view that women who are hemophilia carriers are unaffected by the disease may not be accurate, because many hemophilia carriers experience abnormal bleeding, a hemophilia specialist contends.
“We do know that hemophilia carriers have increased bleeding scores compared to controls,” said Michelle Sholzberg, MD, a hematologist and medical director of the coagulation laboratory at St. Michael’s Hospital in Toronto.
Bleeding in carriers is predominantly mucocutaneous bleeding, and may include epistaxis, heavy menstrual bleeding, bleeding with interventional procedures, and postpartum hemorrhage, she said at the World Federation of Hemophilia World Congress.
The majority of women who carry a factor VIII or factor IX mutation on one X chromosome have factor levels ranging from 0.40 to 0.60 IU/mL, which are generally considered to be adequate for hemostasis.
Yet, “we know that many carriers bleed, and in fact there are carriers who bleed with higher factor levels that are truly in the normal range,” Dr. Sholzberg said.
Normal coagulation factor levels in the general population range from about 0.50 to 1.50 IU/mL. By this standard, approximately 30% of hemophilia carriers have low factor levels, she said.
Joint damage
In addition, 14%-19% of hemophilia A carriers report hemarthrosis, and there is an association in factor VIII or IX deficiencies among hemophilia carriers and reduced joint range of motion. In one study, this decreased range of motion was evident as early as the preteen years, and was suggestive of subclinical musculoskeletal bleeding among carriers. In a separate study, investigators found evidence that hemophilia A carriers have pathologic and radiologic evidence of structural joint damage.
Variability in factor levels among carriers may be caused by lyonization (the inactivation of one of the X-chromosomes), ABO blood type, the presence of mutations in genes encoding for von Willebrand factor, compound heterozygosity or homozygosity, or Turner’s mosaicism.
Clotting factor levels can also change with pregnancy, with hemophilia A carriers experiencing an increase in mean factor VIII levels from 0.46 IU/mL prepregnancy to 1.21 IU/mL in the third trimester, and hemophilia B carriers having a corresponding rise in factor IX levels from 0.31 IU/mL to 0.48 IU/mL, and many carriers still have suboptimal factor levels at pregnancy, Dr. Sholzberg said.
Postpartum hemorrhagic complications among carriers can lead to iron-deficiency anemia. The Centers for Disease Control and Prevention recommends testing all nonpregnant women for anemia every 5-10 years throughout their childbearing years, and annual objective testing for women with risk factors, she noted.
“I think we can all appreciate now that the multidisciplinary approach is important for women with bleeding disorders, and carriers of hemophilia can be safely cared for at HTCs [hemophilia treatment centers],” she said.
Carriers should be treated with a multimodal approach that enhances patient education and awareness, with an emphasis on self-report of symptoms and communication with health care providers.
“It’s also critical never to start a conversation with a woman who has a bleeding disorder with ‘Do you have heavy menstrual bleeding?’ I think we all know that the answer is almost always ‘No, I don’t,’ and that’s because if she has bled heavily for her entire life, she doesn’t know what normal is,” Dr. Sholzberg said.
She described a typical comprehensive care plan for a pregnant hemophilia A carrier. The plan will include information about the diagnosis, recommendations to the obstetricians to avoid the use of invasive instrumentation, anesthesia recommendations, recommendations for care of the mother regarding hemostatic agents, postpartum tranexamic acid, and factor levels, and hematology recommendations for the newborn.
Dr. Sholzberg disclosed research support and/or honoraria from Shire (previously Baxter, Baxalta), Octapharma, CSL Behring, Pfizer, and Novo Nordisk, and advisory committee activity for Shire.
ORLANDO – The traditional view that women who are hemophilia carriers are unaffected by the disease may not be accurate, because many hemophilia carriers experience abnormal bleeding, a hemophilia specialist contends.
“We do know that hemophilia carriers have increased bleeding scores compared to controls,” said Michelle Sholzberg, MD, a hematologist and medical director of the coagulation laboratory at St. Michael’s Hospital in Toronto.
Bleeding in carriers is predominantly mucocutaneous bleeding, and may include epistaxis, heavy menstrual bleeding, bleeding with interventional procedures, and postpartum hemorrhage, she said at the World Federation of Hemophilia World Congress.
The majority of women who carry a factor VIII or factor IX mutation on one X chromosome have factor levels ranging from 0.40 to 0.60 IU/mL, which are generally considered to be adequate for hemostasis.
Yet, “we know that many carriers bleed, and in fact there are carriers who bleed with higher factor levels that are truly in the normal range,” Dr. Sholzberg said.
Normal coagulation factor levels in the general population range from about 0.50 to 1.50 IU/mL. By this standard, approximately 30% of hemophilia carriers have low factor levels, she said.
Joint damage
In addition, 14%-19% of hemophilia A carriers report hemarthrosis, and there is an association in factor VIII or IX deficiencies among hemophilia carriers and reduced joint range of motion. In one study, this decreased range of motion was evident as early as the preteen years, and was suggestive of subclinical musculoskeletal bleeding among carriers. In a separate study, investigators found evidence that hemophilia A carriers have pathologic and radiologic evidence of structural joint damage.
Variability in factor levels among carriers may be caused by lyonization (the inactivation of one of the X-chromosomes), ABO blood type, the presence of mutations in genes encoding for von Willebrand factor, compound heterozygosity or homozygosity, or Turner’s mosaicism.
Clotting factor levels can also change with pregnancy, with hemophilia A carriers experiencing an increase in mean factor VIII levels from 0.46 IU/mL prepregnancy to 1.21 IU/mL in the third trimester, and hemophilia B carriers having a corresponding rise in factor IX levels from 0.31 IU/mL to 0.48 IU/mL, and many carriers still have suboptimal factor levels at pregnancy, Dr. Sholzberg said.
Postpartum hemorrhagic complications among carriers can lead to iron-deficiency anemia. The Centers for Disease Control and Prevention recommends testing all nonpregnant women for anemia every 5-10 years throughout their childbearing years, and annual objective testing for women with risk factors, she noted.
“I think we can all appreciate now that the multidisciplinary approach is important for women with bleeding disorders, and carriers of hemophilia can be safely cared for at HTCs [hemophilia treatment centers],” she said.
Carriers should be treated with a multimodal approach that enhances patient education and awareness, with an emphasis on self-report of symptoms and communication with health care providers.
“It’s also critical never to start a conversation with a woman who has a bleeding disorder with ‘Do you have heavy menstrual bleeding?’ I think we all know that the answer is almost always ‘No, I don’t,’ and that’s because if she has bled heavily for her entire life, she doesn’t know what normal is,” Dr. Sholzberg said.
She described a typical comprehensive care plan for a pregnant hemophilia A carrier. The plan will include information about the diagnosis, recommendations to the obstetricians to avoid the use of invasive instrumentation, anesthesia recommendations, recommendations for care of the mother regarding hemostatic agents, postpartum tranexamic acid, and factor levels, and hematology recommendations for the newborn.
Dr. Sholzberg disclosed research support and/or honoraria from Shire (previously Baxter, Baxalta), Octapharma, CSL Behring, Pfizer, and Novo Nordisk, and advisory committee activity for Shire.
ORLANDO – The traditional view that women who are hemophilia carriers are unaffected by the disease may not be accurate, because many hemophilia carriers experience abnormal bleeding, a hemophilia specialist contends.
“We do know that hemophilia carriers have increased bleeding scores compared to controls,” said Michelle Sholzberg, MD, a hematologist and medical director of the coagulation laboratory at St. Michael’s Hospital in Toronto.
Bleeding in carriers is predominantly mucocutaneous bleeding, and may include epistaxis, heavy menstrual bleeding, bleeding with interventional procedures, and postpartum hemorrhage, she said at the World Federation of Hemophilia World Congress.
The majority of women who carry a factor VIII or factor IX mutation on one X chromosome have factor levels ranging from 0.40 to 0.60 IU/mL, which are generally considered to be adequate for hemostasis.
Yet, “we know that many carriers bleed, and in fact there are carriers who bleed with higher factor levels that are truly in the normal range,” Dr. Sholzberg said.
Normal coagulation factor levels in the general population range from about 0.50 to 1.50 IU/mL. By this standard, approximately 30% of hemophilia carriers have low factor levels, she said.
Joint damage
In addition, 14%-19% of hemophilia A carriers report hemarthrosis, and there is an association in factor VIII or IX deficiencies among hemophilia carriers and reduced joint range of motion. In one study, this decreased range of motion was evident as early as the preteen years, and was suggestive of subclinical musculoskeletal bleeding among carriers. In a separate study, investigators found evidence that hemophilia A carriers have pathologic and radiologic evidence of structural joint damage.
Variability in factor levels among carriers may be caused by lyonization (the inactivation of one of the X-chromosomes), ABO blood type, the presence of mutations in genes encoding for von Willebrand factor, compound heterozygosity or homozygosity, or Turner’s mosaicism.
Clotting factor levels can also change with pregnancy, with hemophilia A carriers experiencing an increase in mean factor VIII levels from 0.46 IU/mL prepregnancy to 1.21 IU/mL in the third trimester, and hemophilia B carriers having a corresponding rise in factor IX levels from 0.31 IU/mL to 0.48 IU/mL, and many carriers still have suboptimal factor levels at pregnancy, Dr. Sholzberg said.
Postpartum hemorrhagic complications among carriers can lead to iron-deficiency anemia. The Centers for Disease Control and Prevention recommends testing all nonpregnant women for anemia every 5-10 years throughout their childbearing years, and annual objective testing for women with risk factors, she noted.
“I think we can all appreciate now that the multidisciplinary approach is important for women with bleeding disorders, and carriers of hemophilia can be safely cared for at HTCs [hemophilia treatment centers],” she said.
Carriers should be treated with a multimodal approach that enhances patient education and awareness, with an emphasis on self-report of symptoms and communication with health care providers.
“It’s also critical never to start a conversation with a woman who has a bleeding disorder with ‘Do you have heavy menstrual bleeding?’ I think we all know that the answer is almost always ‘No, I don’t,’ and that’s because if she has bled heavily for her entire life, she doesn’t know what normal is,” Dr. Sholzberg said.
She described a typical comprehensive care plan for a pregnant hemophilia A carrier. The plan will include information about the diagnosis, recommendations to the obstetricians to avoid the use of invasive instrumentation, anesthesia recommendations, recommendations for care of the mother regarding hemostatic agents, postpartum tranexamic acid, and factor levels, and hematology recommendations for the newborn.
Dr. Sholzberg disclosed research support and/or honoraria from Shire (previously Baxter, Baxalta), Octapharma, CSL Behring, Pfizer, and Novo Nordisk, and advisory committee activity for Shire.
EXPERT ANALYSIS FROM WFH 2016 WORLD CONGRESS
