Neil Osterweil

The treatment of bone sarcomas in adults is guided as much by experience as it is by medical evidence, say sarcoma experts who should know.

“[L]arge prospective clinical trials in adults with bone sarcomas are lacking. Although translation of findings in pediatric studies to adults is possible, it is not clear if findings from pediatric studies truly apply to adults,” Dr. Michael J. Wagner and his colleagues from the University of Texas MD Anderson Cancer Center in Houston said.

In a review article in the Journal of Oncology Practice, the investigators outline how they have melded lessons learned from pediatric clinical trials with clinical experience treating adults with bone sarcomas.

Adult osteosarcomas

Although the peak incidence of osteosarcoma occurs in adolescents and young adults, some studies of various chemotherapy regimens have included middle-aged adults and even some patients in their 90s, although many have excluded patients older than 30, the authors noted.

In adults, and in children and adolescents and young adults, chemotherapy and definitive surgical resection are the mainstays of treatment, with the exception of osteosarcomas of the jaw, which are generally treated with resection alone. For the past three decades, adults with high-grade osteosarcomas have been treated with chemotherapy containing doxorubicin, cisplatin, high-dose methotrexate, and ifosfamide.

“However, important differences to consider in the treatment of older patients include, but are not limited to, the increased incidence of histologic variants of osteosarcoma (including secondary osteosarcomas) and medical comorbidities that may limit tolerance of older adults to dose-intense chemotherapy,” wrote Dr. Wagner and his colleagues (J Oncol Pract. 2016 Mar. doi: 10.1200/JOP.2015.009944).

High-grade localized osteosarcoma is treated with neoadjuvant chemotherapy, followed by limb-sparing surgery and adjuvant chemotherapy.

A poor response to neoadjuvant chemotherapy, defined as tumor necrosis of less than 90% at resection, is a marker for poor prognosis.

The authors previously reported that for patients with a poor response following a regimen of doxorubicin intravenous infusion at 90 mg/m² over 96 hours plus cisplatin infused intra-arterially at 120-160 mg/m² over 2 to 24 hours, the addition of high-dose methotrexate and ifosfamide resulted in significant improvement in continuous relapse-free survival.

At MD Anderson, adults with osteosarcoma receive preoperative chemotherapy with doxorubicin and cisplatin for three to four cycles and then undergo surgical resection. Those who have a good response go on to receive adjuvant chemotherapy with doxorubicin 75 mg/m2 and ifosfamide 10g/m2 for four cycles. Patients who have a poor response to neoadjuvant chemotherapy receive alternating courses of ifosfamide 14 g/m², high-dose methotrexate 10 to 12 g/m², and doxorubicin 75 mg/m² and ifosfamide 10 g/m² for up to 12 cycles or until intolerable adverse events.

Patients with metastatic relapsed/refractory osteosarcoma have 5-year overall survival rates ranging from 15% to 20%, the authors noted, adding that chemotherapy has “limited efficacy” in this setting.

Targeted agents, including the tyrosine kinase inhibitor sorafenib (Nexavar) and the mammalian target of rapamycin (mTOR) inhibitor everolimus (Afinitor) have been evaluated in phase II trials.

Ewing sarcoma

Evidence from clinical trials of chemotherapy regimens in Ewing sarcoma show that patients 18 and older tend to have less favorable outcomes than younger patients when treated with dose-dense regimens, the authors noted.

Their practice is to treat adults with Ewing sarcoma with upfront vincristine 2 mg on day 1, doxorubicin 75 to 90 mg/m² in a continuous 72-hour infusion, and ifosfamide 2.5 g/m² given over 3 hours daily for four doses, followed by surgery, and adjuvant chemotherapy with an ifosfamide-based regimen.

Giant cell tumors of bone

These rare osteolytic tumors are treated with surgery as the primary therapy if they are resectable. Patients with metastases (which paradoxically, are usually histologically benign) as well as those who have tumors in areas where surgery may cause unacceptable morbidities may be treated with serial embolization, denosumab (Xgeva), interferon, or pegylated interferon.

Chondrosarcoma

The so-called “conventional” sub-type of chondrosarcomas are not generally responsive to cytotoxic chemotherapy and best managed with surgery alone, the authors say. However, patients with mesenchymal chondrosarcoma are treated similarly to patients with Ewing sarcoma, and those with the dedifferentiated subtype are treated with an osteosarcoma regimens.

The authors noted that point mutations in IDH1 and IDH2 have recently been discovered in chondrosarcomas, making them potential targets for an experimental IDH-1 inhibitor.

Dr. Wagner and coauthor Dr. J. Andrew Livingston reported no relevant disclosures. Coauthors Dr. Shreyaskumar R. Patel and Dr. Robert S. Benjamin reported consulting, advisory roles, research funding, or ownership interests in various pharmaceutical companies.

The treatment of bone sarcomas in adults is guided as much by experience as it is by medical evidence, say sarcoma experts who should know.

“[L]arge prospective clinical trials in adults with bone sarcomas are lacking. Although translation of findings in pediatric studies to adults is possible, it is not clear if findings from pediatric studies truly apply to adults,” Dr. Michael J. Wagner and his colleagues from the University of Texas MD Anderson Cancer Center in Houston said.

In a review article in the Journal of Oncology Practice, the investigators outline how they have melded lessons learned from pediatric clinical trials with clinical experience treating adults with bone sarcomas.

Adult osteosarcomas

Although the peak incidence of osteosarcoma occurs in adolescents and young adults, some studies of various chemotherapy regimens have included middle-aged adults and even some patients in their 90s, although many have excluded patients older than 30, the authors noted.

In adults, and in children and adolescents and young adults, chemotherapy and definitive surgical resection are the mainstays of treatment, with the exception of osteosarcomas of the jaw, which are generally treated with resection alone. For the past three decades, adults with high-grade osteosarcomas have been treated with chemotherapy containing doxorubicin, cisplatin, high-dose methotrexate, and ifosfamide.

“However, important differences to consider in the treatment of older patients include, but are not limited to, the increased incidence of histologic variants of osteosarcoma (including secondary osteosarcomas) and medical comorbidities that may limit tolerance of older adults to dose-intense chemotherapy,” wrote Dr. Wagner and his colleagues (J Oncol Pract. 2016 Mar. doi: 10.1200/JOP.2015.009944).

High-grade localized osteosarcoma is treated with neoadjuvant chemotherapy, followed by limb-sparing surgery and adjuvant chemotherapy.

A poor response to neoadjuvant chemotherapy, defined as tumor necrosis of less than 90% at resection, is a marker for poor prognosis.

The authors previously reported that for patients with a poor response following a regimen of doxorubicin intravenous infusion at 90 mg/m² over 96 hours plus cisplatin infused intra-arterially at 120-160 mg/m² over 2 to 24 hours, the addition of high-dose methotrexate and ifosfamide resulted in significant improvement in continuous relapse-free survival.

At MD Anderson, adults with osteosarcoma receive preoperative chemotherapy with doxorubicin and cisplatin for three to four cycles and then undergo surgical resection. Those who have a good response go on to receive adjuvant chemotherapy with doxorubicin 75 mg/m2 and ifosfamide 10g/m2 for four cycles. Patients who have a poor response to neoadjuvant chemotherapy receive alternating courses of ifosfamide 14 g/m², high-dose methotrexate 10 to 12 g/m², and doxorubicin 75 mg/m² and ifosfamide 10 g/m² for up to 12 cycles or until intolerable adverse events.

Patients with metastatic relapsed/refractory osteosarcoma have 5-year overall survival rates ranging from 15% to 20%, the authors noted, adding that chemotherapy has “limited efficacy” in this setting.

Targeted agents, including the tyrosine kinase inhibitor sorafenib (Nexavar) and the mammalian target of rapamycin (mTOR) inhibitor everolimus (Afinitor) have been evaluated in phase II trials.

Ewing sarcoma

Evidence from clinical trials of chemotherapy regimens in Ewing sarcoma show that patients 18 and older tend to have less favorable outcomes than younger patients when treated with dose-dense regimens, the authors noted.

Their practice is to treat adults with Ewing sarcoma with upfront vincristine 2 mg on day 1, doxorubicin 75 to 90 mg/m² in a continuous 72-hour infusion, and ifosfamide 2.5 g/m² given over 3 hours daily for four doses, followed by surgery, and adjuvant chemotherapy with an ifosfamide-based regimen.

Giant cell tumors of bone

These rare osteolytic tumors are treated with surgery as the primary therapy if they are resectable. Patients with metastases (which paradoxically, are usually histologically benign) as well as those who have tumors in areas where surgery may cause unacceptable morbidities may be treated with serial embolization, denosumab (Xgeva), interferon, or pegylated interferon.

Chondrosarcoma

The so-called “conventional” sub-type of chondrosarcomas are not generally responsive to cytotoxic chemotherapy and best managed with surgery alone, the authors say. However, patients with mesenchymal chondrosarcoma are treated similarly to patients with Ewing sarcoma, and those with the dedifferentiated subtype are treated with an osteosarcoma regimens.

The authors noted that point mutations in IDH1 and IDH2 have recently been discovered in chondrosarcomas, making them potential targets for an experimental IDH-1 inhibitor.

Dr. Wagner and coauthor Dr. J. Andrew Livingston reported no relevant disclosures. Coauthors Dr. Shreyaskumar R. Patel and Dr. Robert S. Benjamin reported consulting, advisory roles, research funding, or ownership interests in various pharmaceutical companies.

The treatment of bone sarcomas in adults is guided as much by experience as it is by medical evidence, say sarcoma experts who should know.

“[L]arge prospective clinical trials in adults with bone sarcomas are lacking. Although translation of findings in pediatric studies to adults is possible, it is not clear if findings from pediatric studies truly apply to adults,” Dr. Michael J. Wagner and his colleagues from the University of Texas MD Anderson Cancer Center in Houston said.

In a review article in the Journal of Oncology Practice, the investigators outline how they have melded lessons learned from pediatric clinical trials with clinical experience treating adults with bone sarcomas.

Adult osteosarcomas

Although the peak incidence of osteosarcoma occurs in adolescents and young adults, some studies of various chemotherapy regimens have included middle-aged adults and even some patients in their 90s, although many have excluded patients older than 30, the authors noted.

In adults, and in children and adolescents and young adults, chemotherapy and definitive surgical resection are the mainstays of treatment, with the exception of osteosarcomas of the jaw, which are generally treated with resection alone. For the past three decades, adults with high-grade osteosarcomas have been treated with chemotherapy containing doxorubicin, cisplatin, high-dose methotrexate, and ifosfamide.

“However, important differences to consider in the treatment of older patients include, but are not limited to, the increased incidence of histologic variants of osteosarcoma (including secondary osteosarcomas) and medical comorbidities that may limit tolerance of older adults to dose-intense chemotherapy,” wrote Dr. Wagner and his colleagues (J Oncol Pract. 2016 Mar. doi: 10.1200/JOP.2015.009944).

High-grade localized osteosarcoma is treated with neoadjuvant chemotherapy, followed by limb-sparing surgery and adjuvant chemotherapy.

A poor response to neoadjuvant chemotherapy, defined as tumor necrosis of less than 90% at resection, is a marker for poor prognosis.

The authors previously reported that for patients with a poor response following a regimen of doxorubicin intravenous infusion at 90 mg/m² over 96 hours plus cisplatin infused intra-arterially at 120-160 mg/m² over 2 to 24 hours, the addition of high-dose methotrexate and ifosfamide resulted in significant improvement in continuous relapse-free survival.

At MD Anderson, adults with osteosarcoma receive preoperative chemotherapy with doxorubicin and cisplatin for three to four cycles and then undergo surgical resection. Those who have a good response go on to receive adjuvant chemotherapy with doxorubicin 75 mg/m2 and ifosfamide 10g/m2 for four cycles. Patients who have a poor response to neoadjuvant chemotherapy receive alternating courses of ifosfamide 14 g/m², high-dose methotrexate 10 to 12 g/m², and doxorubicin 75 mg/m² and ifosfamide 10 g/m² for up to 12 cycles or until intolerable adverse events.

Patients with metastatic relapsed/refractory osteosarcoma have 5-year overall survival rates ranging from 15% to 20%, the authors noted, adding that chemotherapy has “limited efficacy” in this setting.

Targeted agents, including the tyrosine kinase inhibitor sorafenib (Nexavar) and the mammalian target of rapamycin (mTOR) inhibitor everolimus (Afinitor) have been evaluated in phase II trials.

Ewing sarcoma

Evidence from clinical trials of chemotherapy regimens in Ewing sarcoma show that patients 18 and older tend to have less favorable outcomes than younger patients when treated with dose-dense regimens, the authors noted.

Their practice is to treat adults with Ewing sarcoma with upfront vincristine 2 mg on day 1, doxorubicin 75 to 90 mg/m² in a continuous 72-hour infusion, and ifosfamide 2.5 g/m² given over 3 hours daily for four doses, followed by surgery, and adjuvant chemotherapy with an ifosfamide-based regimen.

Giant cell tumors of bone

These rare osteolytic tumors are treated with surgery as the primary therapy if they are resectable. Patients with metastases (which paradoxically, are usually histologically benign) as well as those who have tumors in areas where surgery may cause unacceptable morbidities may be treated with serial embolization, denosumab (Xgeva), interferon, or pegylated interferon.

Chondrosarcoma

The so-called “conventional” sub-type of chondrosarcomas are not generally responsive to cytotoxic chemotherapy and best managed with surgery alone, the authors say. However, patients with mesenchymal chondrosarcoma are treated similarly to patients with Ewing sarcoma, and those with the dedifferentiated subtype are treated with an osteosarcoma regimens.

The authors noted that point mutations in IDH1 and IDH2 have recently been discovered in chondrosarcomas, making them potential targets for an experimental IDH-1 inhibitor.

Dr. Wagner and coauthor Dr. J. Andrew Livingston reported no relevant disclosures. Coauthors Dr. Shreyaskumar R. Patel and Dr. Robert S. Benjamin reported consulting, advisory roles, research funding, or ownership interests in various pharmaceutical companies.

BOSTON – Access to and acceptance of thyroid cancer surgery varies by race, with black patients in particular appearing to be disadvantaged, compared with whites, investigators reported.

A review of data on nearly 138,000 patients diagnosed with thyroid cancer showed that blacks were significantly less likely than were whites to be offered surgery – despite its generally excellent outcomes and low rates of morbidity and mortality, reported Dr. Herbert Castillo Valladares and his colleagues from the department of surgery at the Yale University in New Haven, Conn.

SciePro/Science Source

American Indians/Alaskan natives and Asian/Pacific Islanders were significantly more likely to refuse surgery than were whites, the investigators also reported in a poster session at the Society of Surgical Oncology annual cancer symposium.

“In this project, we wanted to focus on the provider-level factors that might be perpetuating these racial disparities, and it appears that we need to educate some providers about the recommendation of surgery or how to educate patients who refuse thyroid cancer surgery,” Dr. Valladares said in an interview.

The investigators noted that although incidence and prevalence rates of thyroid cancer are similar among various racial groups, survival differs by race, and they wanted to find out why. To do so, they polled the Surveillance, Epidemiology, and End Results (SEER) registry to identify 137,483 patients diagnosed with thyroid cancer during 1988-2012. Results were stratified by thyroid cancer type, either papillary, medullary, follicular, or anaplastic.

In all, 82% of the sample were white, 75% were female, 87% had a diagnosis of papillary thyroid cancer, and 95% underwent thyroid cancer surgery.

In logistic regression analysis that controlled for race, the investigators found that blacks, Asian/Pacific Islanders, and persons of unknown race were significantly less likely than whites were to have thyroid cancer surgery (odds ratios, 0.7, 0.82, and 0.34, respectively; P for each less than .0001).

Similarly, surgery was more frequently not recommended for blacks (OR, 1.34; P less than .0001), Asian/Pacific Islanders (OR, 1.2; P = .004) and those of unknown race (OR, 3.06; P less than .0001).

American Indians/Alaskan natives and Asian/Pacific Islanders were also significantly more likely than were whites to refuse surgery (OR, 4.45; P = .0001; OR, 2.96; P less than .0001, respectively).

Compared with whites, blacks – but not other races – had significantly worse 5-year survival (hazard ratio, 1.14; P = .0002).

In an analysis by cancer type, the investigators saw that race was not a predictor for surgery recommendation or refusal of surgery by patients with medullary or anaplastic cancer. However, among patients with papillary thyroid cancer, the most common type, surgery was recommended less often for blacks (OR, 1.2), Asian/Pacific Islanders (OR, 1.3), and patients of unknown race (OR, 3.1; all comparisons significant by 95% confidence interval).

Among patients with follicular histology, patients of unknown race were significantly less likely than were whites to have the surgery recommended (OR, 2.7; significant by 95% CI).

Dr. Valladares explained that the SEER data set does not include information about provider type, such as those in community based versus academic settings, so the next step will be to find a method for analyzing factors at both the patient level and the provider level that might influence recommendations for surgery or patient refusals to accept surgery.

The study was supported by the Paul H. Lavietes, M.D., Summer Research Fellowship of Yale University. The investigators reported no relevant conflicts of interest.

BOSTON – Access to and acceptance of thyroid cancer surgery varies by race, with black patients in particular appearing to be disadvantaged, compared with whites, investigators reported.

A review of data on nearly 138,000 patients diagnosed with thyroid cancer showed that blacks were significantly less likely than were whites to be offered surgery – despite its generally excellent outcomes and low rates of morbidity and mortality, reported Dr. Herbert Castillo Valladares and his colleagues from the department of surgery at the Yale University in New Haven, Conn.

SciePro/Science Source

American Indians/Alaskan natives and Asian/Pacific Islanders were significantly more likely to refuse surgery than were whites, the investigators also reported in a poster session at the Society of Surgical Oncology annual cancer symposium.

“In this project, we wanted to focus on the provider-level factors that might be perpetuating these racial disparities, and it appears that we need to educate some providers about the recommendation of surgery or how to educate patients who refuse thyroid cancer surgery,” Dr. Valladares said in an interview.

The investigators noted that although incidence and prevalence rates of thyroid cancer are similar among various racial groups, survival differs by race, and they wanted to find out why. To do so, they polled the Surveillance, Epidemiology, and End Results (SEER) registry to identify 137,483 patients diagnosed with thyroid cancer during 1988-2012. Results were stratified by thyroid cancer type, either papillary, medullary, follicular, or anaplastic.

In all, 82% of the sample were white, 75% were female, 87% had a diagnosis of papillary thyroid cancer, and 95% underwent thyroid cancer surgery.

In logistic regression analysis that controlled for race, the investigators found that blacks, Asian/Pacific Islanders, and persons of unknown race were significantly less likely than whites were to have thyroid cancer surgery (odds ratios, 0.7, 0.82, and 0.34, respectively; P for each less than .0001).

Similarly, surgery was more frequently not recommended for blacks (OR, 1.34; P less than .0001), Asian/Pacific Islanders (OR, 1.2; P = .004) and those of unknown race (OR, 3.06; P less than .0001).

American Indians/Alaskan natives and Asian/Pacific Islanders were also significantly more likely than were whites to refuse surgery (OR, 4.45; P = .0001; OR, 2.96; P less than .0001, respectively).

Compared with whites, blacks – but not other races – had significantly worse 5-year survival (hazard ratio, 1.14; P = .0002).

In an analysis by cancer type, the investigators saw that race was not a predictor for surgery recommendation or refusal of surgery by patients with medullary or anaplastic cancer. However, among patients with papillary thyroid cancer, the most common type, surgery was recommended less often for blacks (OR, 1.2), Asian/Pacific Islanders (OR, 1.3), and patients of unknown race (OR, 3.1; all comparisons significant by 95% confidence interval).

Among patients with follicular histology, patients of unknown race were significantly less likely than were whites to have the surgery recommended (OR, 2.7; significant by 95% CI).

Dr. Valladares explained that the SEER data set does not include information about provider type, such as those in community based versus academic settings, so the next step will be to find a method for analyzing factors at both the patient level and the provider level that might influence recommendations for surgery or patient refusals to accept surgery.

The study was supported by the Paul H. Lavietes, M.D., Summer Research Fellowship of Yale University. The investigators reported no relevant conflicts of interest.

BOSTON – Access to and acceptance of thyroid cancer surgery varies by race, with black patients in particular appearing to be disadvantaged, compared with whites, investigators reported.

A review of data on nearly 138,000 patients diagnosed with thyroid cancer showed that blacks were significantly less likely than were whites to be offered surgery – despite its generally excellent outcomes and low rates of morbidity and mortality, reported Dr. Herbert Castillo Valladares and his colleagues from the department of surgery at the Yale University in New Haven, Conn.

SciePro/Science Source

American Indians/Alaskan natives and Asian/Pacific Islanders were significantly more likely to refuse surgery than were whites, the investigators also reported in a poster session at the Society of Surgical Oncology annual cancer symposium.

“In this project, we wanted to focus on the provider-level factors that might be perpetuating these racial disparities, and it appears that we need to educate some providers about the recommendation of surgery or how to educate patients who refuse thyroid cancer surgery,” Dr. Valladares said in an interview.

The investigators noted that although incidence and prevalence rates of thyroid cancer are similar among various racial groups, survival differs by race, and they wanted to find out why. To do so, they polled the Surveillance, Epidemiology, and End Results (SEER) registry to identify 137,483 patients diagnosed with thyroid cancer during 1988-2012. Results were stratified by thyroid cancer type, either papillary, medullary, follicular, or anaplastic.

In all, 82% of the sample were white, 75% were female, 87% had a diagnosis of papillary thyroid cancer, and 95% underwent thyroid cancer surgery.

In logistic regression analysis that controlled for race, the investigators found that blacks, Asian/Pacific Islanders, and persons of unknown race were significantly less likely than whites were to have thyroid cancer surgery (odds ratios, 0.7, 0.82, and 0.34, respectively; P for each less than .0001).

Similarly, surgery was more frequently not recommended for blacks (OR, 1.34; P less than .0001), Asian/Pacific Islanders (OR, 1.2; P = .004) and those of unknown race (OR, 3.06; P less than .0001).

American Indians/Alaskan natives and Asian/Pacific Islanders were also significantly more likely than were whites to refuse surgery (OR, 4.45; P = .0001; OR, 2.96; P less than .0001, respectively).

Compared with whites, blacks – but not other races – had significantly worse 5-year survival (hazard ratio, 1.14; P = .0002).

In an analysis by cancer type, the investigators saw that race was not a predictor for surgery recommendation or refusal of surgery by patients with medullary or anaplastic cancer. However, among patients with papillary thyroid cancer, the most common type, surgery was recommended less often for blacks (OR, 1.2), Asian/Pacific Islanders (OR, 1.3), and patients of unknown race (OR, 3.1; all comparisons significant by 95% confidence interval).

Among patients with follicular histology, patients of unknown race were significantly less likely than were whites to have the surgery recommended (OR, 2.7; significant by 95% CI).

Dr. Valladares explained that the SEER data set does not include information about provider type, such as those in community based versus academic settings, so the next step will be to find a method for analyzing factors at both the patient level and the provider level that might influence recommendations for surgery or patient refusals to accept surgery.

The study was supported by the Paul H. Lavietes, M.D., Summer Research Fellowship of Yale University. The investigators reported no relevant conflicts of interest.

BOSTON – The operation was a success, but the patient died.

It’s an old chestnut for sure, but there is a painful kernel of truth in it, say investigators who found that patients who undergo complex cancer surgery and have serious complications are at significantly increased risk for death for at least 6 months after surgery, compared with patients who undergo the same procedure with few or no complications.

“Our work has important implications for quality assessment. I think in cancer surgery in particular we have to get away from the short-term metrics of survival, and we have to think about the implications of complications for long-term survival, even if at a very high-quality hospital we’re good at salvaging those patients who do experience those complications,” said Dr. Hari Nathan of the University of Michigan, Ann Arbor.

In a retrospective study, results of which were presented at the annual Society of Surgical Oncology Cancer Symposium, Dr. Nathan and colleagues showed that patients who underwent surgery for cancers of the esophagus and lung who had serious complications but survived at least 30 days after surgery had a more than twofold greater risk for death than did patients who had no complications, and patients with serious complications following surgery for cancer of the pancreas had a nearly twofold greater risk.

The effects of serious complications on survival persisted out to at least 180 days after surgery for each of the three procedures.

The findings suggest that just getting the patient through the operation and keeping him or her alive in the ICU is not sufficient cause for celebration by surgeons, Dr. Nathan said.

The investigators conducted the study to examine the incidence of complications following cancer surgery in older patients, the relationship between surgical complications and long-term survival, and whether the effects of complications would diminish or “wash out” over time. They reviewed Surveillance, Epidemiology and End Results–Medicare data on patients aged 65 years and older who underwent surgery with curative intent for esophageal cancer, non–small cell lung cancer, or pancreatic adenocarcinoma from 2005 through 2009.

They defined serious complications as “the appearance of a complication associated with a hospital length of stay greater than the 75th percentile for that procedure.”

The cohort included 965 patients who underwent esophageal surgery, 12,395 who had lung surgery, and 1,966 who underwent pancreatic resection. The proportion of patients over 80 years who underwent the procedures, respectively, were 12%, 18%, and 19%.

Serious complications occurred in 17% of patients with esophageal cancer, 10% of those with lung cancer, and 12% of those with cancer of the pancreas. The respective 30-day mortality rates were 6.%, 3.3%, and 3.9%.

Looking only at those patients with lung cancer who survived at least 30 days after surgery, the investigators found that median survival among those who had no complications was 79 months, compared with 60 months for those who had mild complications, and 33 months for patients who had serious complications (P less than .001)

“And indeed, when we performed adjusted survival analyses looking at all three disease sites, we saw a very consistent story: that those patients who had serious complications had decreased long-term survival for all three malignancies we looked at,” Dr. Nathan said.

Specifically, in survival analyses adjusted for sex, age, and procedure code, hazard ratios for patients with serious complications compared with those who had no complications were 2.55 for esophageal cancer patients, 2.13 for lung cancer patients, and 1.57 for pancreatic cancer patients (all comparisons significant as shown by 95% confidence intervals).

The investigators questioned whether the differences in mortality were due to the late effects of perioperative complications.

“In modern ICUs, we can keep virtually anybody alive for 30 days, and there has been a lot interest in longer-term metrics for perioperative mortality, for example, at 30 or 90 days, so we thought maybe that’s what we were seeing here,” he said. To test this idea, the investigators looked at the effects of complications on patient who survived lung cancer surgery for at least 90 days, and those who lived for at least 180 days after surgery, and they saw that the survival curves were similar to those seen with the 30-day survivors, showing significantly and persistently worse survival for patients with serious complications (P less than .001).

For each of the disease states, patients with serious complications were also significantly less likely than were those with no or mild complications to receive adjuvant chemotherapy, even after adjustment for patient age and cancer stage, two significant determinants of the likelihood of receiving chemotherapy.

And even when the effect of chemotherapy for those who did receive it was added into the survival models, patients with serious complications still had significantly worse overall survival, Dr. Nathan noted.

“Serious complications after these three cancer resections are common and they are associated with dramatically inferior long-term survival. Thirty, 60, 90, and even 180-day measures of mortality do not capture the full impact of complications on long-term survival,” he said.

Asked whether it may be possible to identify those patients at higher risk for serious complications due to comorbidities or other factors, and perhaps suggest withholding surgery from such patients, Dr. Nathan agreed, but added that “the best chance for survival for all of these patients is a high-quality surgical resection, so it’s hard to deny a patient that chance unless you think they have a really high risk of perioperative death.”

The study was internally funded. Dr. Nathan reported no significant disclosures.

BOSTON – The operation was a success, but the patient died.

It’s an old chestnut for sure, but there is a painful kernel of truth in it, say investigators who found that patients who undergo complex cancer surgery and have serious complications are at significantly increased risk for death for at least 6 months after surgery, compared with patients who undergo the same procedure with few or no complications.

“Our work has important implications for quality assessment. I think in cancer surgery in particular we have to get away from the short-term metrics of survival, and we have to think about the implications of complications for long-term survival, even if at a very high-quality hospital we’re good at salvaging those patients who do experience those complications,” said Dr. Hari Nathan of the University of Michigan, Ann Arbor.

In a retrospective study, results of which were presented at the annual Society of Surgical Oncology Cancer Symposium, Dr. Nathan and colleagues showed that patients who underwent surgery for cancers of the esophagus and lung who had serious complications but survived at least 30 days after surgery had a more than twofold greater risk for death than did patients who had no complications, and patients with serious complications following surgery for cancer of the pancreas had a nearly twofold greater risk.

The effects of serious complications on survival persisted out to at least 180 days after surgery for each of the three procedures.

The findings suggest that just getting the patient through the operation and keeping him or her alive in the ICU is not sufficient cause for celebration by surgeons, Dr. Nathan said.

The investigators conducted the study to examine the incidence of complications following cancer surgery in older patients, the relationship between surgical complications and long-term survival, and whether the effects of complications would diminish or “wash out” over time. They reviewed Surveillance, Epidemiology and End Results–Medicare data on patients aged 65 years and older who underwent surgery with curative intent for esophageal cancer, non–small cell lung cancer, or pancreatic adenocarcinoma from 2005 through 2009.

They defined serious complications as “the appearance of a complication associated with a hospital length of stay greater than the 75th percentile for that procedure.”

The cohort included 965 patients who underwent esophageal surgery, 12,395 who had lung surgery, and 1,966 who underwent pancreatic resection. The proportion of patients over 80 years who underwent the procedures, respectively, were 12%, 18%, and 19%.

Serious complications occurred in 17% of patients with esophageal cancer, 10% of those with lung cancer, and 12% of those with cancer of the pancreas. The respective 30-day mortality rates were 6.%, 3.3%, and 3.9%.

Looking only at those patients with lung cancer who survived at least 30 days after surgery, the investigators found that median survival among those who had no complications was 79 months, compared with 60 months for those who had mild complications, and 33 months for patients who had serious complications (P less than .001)

“And indeed, when we performed adjusted survival analyses looking at all three disease sites, we saw a very consistent story: that those patients who had serious complications had decreased long-term survival for all three malignancies we looked at,” Dr. Nathan said.

Specifically, in survival analyses adjusted for sex, age, and procedure code, hazard ratios for patients with serious complications compared with those who had no complications were 2.55 for esophageal cancer patients, 2.13 for lung cancer patients, and 1.57 for pancreatic cancer patients (all comparisons significant as shown by 95% confidence intervals).

The investigators questioned whether the differences in mortality were due to the late effects of perioperative complications.

“In modern ICUs, we can keep virtually anybody alive for 30 days, and there has been a lot interest in longer-term metrics for perioperative mortality, for example, at 30 or 90 days, so we thought maybe that’s what we were seeing here,” he said. To test this idea, the investigators looked at the effects of complications on patient who survived lung cancer surgery for at least 90 days, and those who lived for at least 180 days after surgery, and they saw that the survival curves were similar to those seen with the 30-day survivors, showing significantly and persistently worse survival for patients with serious complications (P less than .001).

For each of the disease states, patients with serious complications were also significantly less likely than were those with no or mild complications to receive adjuvant chemotherapy, even after adjustment for patient age and cancer stage, two significant determinants of the likelihood of receiving chemotherapy.

And even when the effect of chemotherapy for those who did receive it was added into the survival models, patients with serious complications still had significantly worse overall survival, Dr. Nathan noted.

“Serious complications after these three cancer resections are common and they are associated with dramatically inferior long-term survival. Thirty, 60, 90, and even 180-day measures of mortality do not capture the full impact of complications on long-term survival,” he said.

Asked whether it may be possible to identify those patients at higher risk for serious complications due to comorbidities or other factors, and perhaps suggest withholding surgery from such patients, Dr. Nathan agreed, but added that “the best chance for survival for all of these patients is a high-quality surgical resection, so it’s hard to deny a patient that chance unless you think they have a really high risk of perioperative death.”

The study was internally funded. Dr. Nathan reported no significant disclosures.

BOSTON – The operation was a success, but the patient died.

It’s an old chestnut for sure, but there is a painful kernel of truth in it, say investigators who found that patients who undergo complex cancer surgery and have serious complications are at significantly increased risk for death for at least 6 months after surgery, compared with patients who undergo the same procedure with few or no complications.

“Our work has important implications for quality assessment. I think in cancer surgery in particular we have to get away from the short-term metrics of survival, and we have to think about the implications of complications for long-term survival, even if at a very high-quality hospital we’re good at salvaging those patients who do experience those complications,” said Dr. Hari Nathan of the University of Michigan, Ann Arbor.

In a retrospective study, results of which were presented at the annual Society of Surgical Oncology Cancer Symposium, Dr. Nathan and colleagues showed that patients who underwent surgery for cancers of the esophagus and lung who had serious complications but survived at least 30 days after surgery had a more than twofold greater risk for death than did patients who had no complications, and patients with serious complications following surgery for cancer of the pancreas had a nearly twofold greater risk.

The effects of serious complications on survival persisted out to at least 180 days after surgery for each of the three procedures.

The findings suggest that just getting the patient through the operation and keeping him or her alive in the ICU is not sufficient cause for celebration by surgeons, Dr. Nathan said.

The investigators conducted the study to examine the incidence of complications following cancer surgery in older patients, the relationship between surgical complications and long-term survival, and whether the effects of complications would diminish or “wash out” over time. They reviewed Surveillance, Epidemiology and End Results–Medicare data on patients aged 65 years and older who underwent surgery with curative intent for esophageal cancer, non–small cell lung cancer, or pancreatic adenocarcinoma from 2005 through 2009.

They defined serious complications as “the appearance of a complication associated with a hospital length of stay greater than the 75th percentile for that procedure.”

The cohort included 965 patients who underwent esophageal surgery, 12,395 who had lung surgery, and 1,966 who underwent pancreatic resection. The proportion of patients over 80 years who underwent the procedures, respectively, were 12%, 18%, and 19%.

Serious complications occurred in 17% of patients with esophageal cancer, 10% of those with lung cancer, and 12% of those with cancer of the pancreas. The respective 30-day mortality rates were 6.%, 3.3%, and 3.9%.

Looking only at those patients with lung cancer who survived at least 30 days after surgery, the investigators found that median survival among those who had no complications was 79 months, compared with 60 months for those who had mild complications, and 33 months for patients who had serious complications (P less than .001)

“And indeed, when we performed adjusted survival analyses looking at all three disease sites, we saw a very consistent story: that those patients who had serious complications had decreased long-term survival for all three malignancies we looked at,” Dr. Nathan said.

Specifically, in survival analyses adjusted for sex, age, and procedure code, hazard ratios for patients with serious complications compared with those who had no complications were 2.55 for esophageal cancer patients, 2.13 for lung cancer patients, and 1.57 for pancreatic cancer patients (all comparisons significant as shown by 95% confidence intervals).

The investigators questioned whether the differences in mortality were due to the late effects of perioperative complications.

“In modern ICUs, we can keep virtually anybody alive for 30 days, and there has been a lot interest in longer-term metrics for perioperative mortality, for example, at 30 or 90 days, so we thought maybe that’s what we were seeing here,” he said. To test this idea, the investigators looked at the effects of complications on patient who survived lung cancer surgery for at least 90 days, and those who lived for at least 180 days after surgery, and they saw that the survival curves were similar to those seen with the 30-day survivors, showing significantly and persistently worse survival for patients with serious complications (P less than .001).

For each of the disease states, patients with serious complications were also significantly less likely than were those with no or mild complications to receive adjuvant chemotherapy, even after adjustment for patient age and cancer stage, two significant determinants of the likelihood of receiving chemotherapy.

And even when the effect of chemotherapy for those who did receive it was added into the survival models, patients with serious complications still had significantly worse overall survival, Dr. Nathan noted.

“Serious complications after these three cancer resections are common and they are associated with dramatically inferior long-term survival. Thirty, 60, 90, and even 180-day measures of mortality do not capture the full impact of complications on long-term survival,” he said.

Asked whether it may be possible to identify those patients at higher risk for serious complications due to comorbidities or other factors, and perhaps suggest withholding surgery from such patients, Dr. Nathan agreed, but added that “the best chance for survival for all of these patients is a high-quality surgical resection, so it’s hard to deny a patient that chance unless you think they have a really high risk of perioperative death.”

The study was internally funded. Dr. Nathan reported no significant disclosures.

Single-agent therapy with temsirolimus was active in patients with relapsed/refractory primary central nervous system lymphoma, but most of the responses were short lived, results of a phase II trial show.

Among 37 patients with primary CNS lymphoma (PCNSL) for whom firstline therapy had failed, there were five complete responses (CR), three CR unconfirmed, and 12 partial responses (PR), for an overall response rate (ORR) of 54%, reported Dr. Agnieszka Korfel from Charité University Medicine Berlin (Germany) and colleagues.

Creative Commons/Steven Fruitsmaak

The median progression-free survival (PFS), however, was just 2.1 months, although 1 patient had PFS of 15.8 months duration, and another had a response lasting for more than 44 months, the investigators noted in a study published online in the Journal of Clinical Oncology (doi: 10.1200/JCO.2015.64.9897).

The rationale for trying temsirolimus (Torisel), an inhibitor of the mammalian target of rapamycin (mTOR), came from studies showing the drug’s efficacy against relapsed/refractory mantle-cell lymphoma and against other, more aggressive forms of non-Hodgkin lymphoma. Patients with relapsed/refractory aggressive lymphomas tolerate temsirolimus relatively well, and the drug has the ability to penetrate brain tumor tissue, the authors noted.

They enrolled 37 patients with a median age of 70 years and a median time since their last treatment of 3.9 months into an open-label trial. The patients were all immuncompetent with histologically confirmed primary central nervous system lymphoma for whom high-dose methotrexate-based chemotherapy had failed and for whom high-dose chemotherapy with autologous stem cell transplant had either failed or was not an option.

The first six patients were treated with temsirolimus 25 mg intravenously once weekly, and the remaining 31 were treated with 75 mg IV once weekly until disease progression, intolerable toxicity, patient or physician decision to terminate, or death.

As noted before, ORR, the primary endpoint, was 54%. Median overall survival (OS), a secondary endpoint, was 3.7 months, and 1-year and 2-year OS were 19% and 16.2%, respectively.

The most frequently occurring toxicities include hyperglycemia, myelosuppression, pneumonias and other infections, and fatigue. A total of 28 severe adverse events occurred in 21 patients, including infectious episodes, hospitalizations because of disease progression, deep-vein thromboses, hyperglycemia, and one case each of seizures, grade 4 thrombocytopenia, drug fever, hyponatremia, renal insufficiency, and atrial fibrillation.

“Although most responses were short lived, some patients achieved long-term control. Thus, further evaluation in combination with other drugs seems reasonable. However, one has to be aware of the risk of hematotoxicity and infections necessitating primary antibiotic prophylaxis. Definition of biomarkers allowing identification of potential responders and those who are at particular risk for toxicity would be highly desirable,” the investigators concluded.

Single-agent therapy with temsirolimus was active in patients with relapsed/refractory primary central nervous system lymphoma, but most of the responses were short lived, results of a phase II trial show.

Among 37 patients with primary CNS lymphoma (PCNSL) for whom firstline therapy had failed, there were five complete responses (CR), three CR unconfirmed, and 12 partial responses (PR), for an overall response rate (ORR) of 54%, reported Dr. Agnieszka Korfel from Charité University Medicine Berlin (Germany) and colleagues.

Creative Commons/Steven Fruitsmaak

The median progression-free survival (PFS), however, was just 2.1 months, although 1 patient had PFS of 15.8 months duration, and another had a response lasting for more than 44 months, the investigators noted in a study published online in the Journal of Clinical Oncology (doi: 10.1200/JCO.2015.64.9897).

The rationale for trying temsirolimus (Torisel), an inhibitor of the mammalian target of rapamycin (mTOR), came from studies showing the drug’s efficacy against relapsed/refractory mantle-cell lymphoma and against other, more aggressive forms of non-Hodgkin lymphoma. Patients with relapsed/refractory aggressive lymphomas tolerate temsirolimus relatively well, and the drug has the ability to penetrate brain tumor tissue, the authors noted.

They enrolled 37 patients with a median age of 70 years and a median time since their last treatment of 3.9 months into an open-label trial. The patients were all immuncompetent with histologically confirmed primary central nervous system lymphoma for whom high-dose methotrexate-based chemotherapy had failed and for whom high-dose chemotherapy with autologous stem cell transplant had either failed or was not an option.

The first six patients were treated with temsirolimus 25 mg intravenously once weekly, and the remaining 31 were treated with 75 mg IV once weekly until disease progression, intolerable toxicity, patient or physician decision to terminate, or death.

As noted before, ORR, the primary endpoint, was 54%. Median overall survival (OS), a secondary endpoint, was 3.7 months, and 1-year and 2-year OS were 19% and 16.2%, respectively.

The most frequently occurring toxicities include hyperglycemia, myelosuppression, pneumonias and other infections, and fatigue. A total of 28 severe adverse events occurred in 21 patients, including infectious episodes, hospitalizations because of disease progression, deep-vein thromboses, hyperglycemia, and one case each of seizures, grade 4 thrombocytopenia, drug fever, hyponatremia, renal insufficiency, and atrial fibrillation.

“Although most responses were short lived, some patients achieved long-term control. Thus, further evaluation in combination with other drugs seems reasonable. However, one has to be aware of the risk of hematotoxicity and infections necessitating primary antibiotic prophylaxis. Definition of biomarkers allowing identification of potential responders and those who are at particular risk for toxicity would be highly desirable,” the investigators concluded.

Single-agent therapy with temsirolimus was active in patients with relapsed/refractory primary central nervous system lymphoma, but most of the responses were short lived, results of a phase II trial show.

Among 37 patients with primary CNS lymphoma (PCNSL) for whom firstline therapy had failed, there were five complete responses (CR), three CR unconfirmed, and 12 partial responses (PR), for an overall response rate (ORR) of 54%, reported Dr. Agnieszka Korfel from Charité University Medicine Berlin (Germany) and colleagues.

Creative Commons/Steven Fruitsmaak

The median progression-free survival (PFS), however, was just 2.1 months, although 1 patient had PFS of 15.8 months duration, and another had a response lasting for more than 44 months, the investigators noted in a study published online in the Journal of Clinical Oncology (doi: 10.1200/JCO.2015.64.9897).

The rationale for trying temsirolimus (Torisel), an inhibitor of the mammalian target of rapamycin (mTOR), came from studies showing the drug’s efficacy against relapsed/refractory mantle-cell lymphoma and against other, more aggressive forms of non-Hodgkin lymphoma. Patients with relapsed/refractory aggressive lymphomas tolerate temsirolimus relatively well, and the drug has the ability to penetrate brain tumor tissue, the authors noted.

They enrolled 37 patients with a median age of 70 years and a median time since their last treatment of 3.9 months into an open-label trial. The patients were all immuncompetent with histologically confirmed primary central nervous system lymphoma for whom high-dose methotrexate-based chemotherapy had failed and for whom high-dose chemotherapy with autologous stem cell transplant had either failed or was not an option.

The first six patients were treated with temsirolimus 25 mg intravenously once weekly, and the remaining 31 were treated with 75 mg IV once weekly until disease progression, intolerable toxicity, patient or physician decision to terminate, or death.

As noted before, ORR, the primary endpoint, was 54%. Median overall survival (OS), a secondary endpoint, was 3.7 months, and 1-year and 2-year OS were 19% and 16.2%, respectively.

The most frequently occurring toxicities include hyperglycemia, myelosuppression, pneumonias and other infections, and fatigue. A total of 28 severe adverse events occurred in 21 patients, including infectious episodes, hospitalizations because of disease progression, deep-vein thromboses, hyperglycemia, and one case each of seizures, grade 4 thrombocytopenia, drug fever, hyponatremia, renal insufficiency, and atrial fibrillation.

“Although most responses were short lived, some patients achieved long-term control. Thus, further evaluation in combination with other drugs seems reasonable. However, one has to be aware of the risk of hematotoxicity and infections necessitating primary antibiotic prophylaxis. Definition of biomarkers allowing identification of potential responders and those who are at particular risk for toxicity would be highly desirable,” the investigators concluded.

The International Myeloma Working Group has issued new recommendations for the diagnosis and management of multiple myeloma–related renal impairment. Depending on whether the condition is defined as elevated serum creatinine or decreased estimated glomerular filtration rate (eGFR), an estimated 20%-50% of patients with multiple myeloma have renal impairment at the time of diagnosis.

The guidelines recommend that all patients with multiple myeloma (MM) at diagnosis and at disease assessment should be tested for serum creatinine, eGFR, electrolytes, and serum free light chain, if available. Additionally, they recommend that all patients have urine electrophoresis of a sample from a 24-hour urine collection. All of the above are grade A recommendations (J Clin Oncol. 2016 Mar 14. doi: 10.1200/JCO.2015.65.0044).

©London_England/Thinkstock

Patients with nonselective proteinuria or significant albuminuria should undergo renal biopsy to determine the cause of the underlying impairment, the IMWG says (grade B recommendation).

For evaluation of eGFR in patients with stabilized serum creatinine, the IMWG favors the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, but also acknowledges that eGFR can be assessed with the Modification of Diet in Renal Disease (MDRD) formula (grade A).

“CKD-EPI seems to more accurately reflect GFR than does MDRD, mostly in higher levels of GFR,” the IMWG wrote.

Because the reversibility of renal dysfunction can affect treatment choice, the recommendations noted that for patients on dialysis, achieving independence from dialysis is “strong indication of improvement. For all other patients, IMWG criteria for renal response to therapy are recommended (grade B).

Management

“Acute renal impairment is a myeloma emergency. Diagnosis should be established as fast as possible, and antimyeloma therapy should be started immediately after confirmation of diagnosis to rapidly restore renal function,” working group members wrote.

Supportive care with increased hydration – at least 3 liters per day – is “mandatory” for all with suspected MM-related renal impairment, they add.

The recommendations also noted that antimyeloma therapy should be initiated immediately to reduce the load of toxic serum free light chains, which can help to improve renal function.

“Bortezomib [Velcade]-based regimens remain the cornerstone of the management of myeloma-related renal impairment (grade A). High-dose dexamethasone should be administered at least for the first month of therapy (grade B),” the working group members wrote.

Lenalidomide (Revlimid) can be given, but because it is excreted through the kidneys, the dose must be adjusted according to the degree of renal impairment. In contrast, thalidomide is not excreted and does not require dose modification in this population.

Patients who are eligible for autologous stem cell transplant could receive bortezomib in a three-drug regimen with thalidomide and dexamethasone, or in combination with a conventional chemotherapeutic agent, either doxorubicin or cyclophosphamide. Patients who are not eligible for transplant can be treated with bortezomib, melphalan, and prednisone, the recommendations said, but add that there are no data on the use of this regimen in patients who are on dialysis.

Regarding newer proteasome inhibitors, the guidelines note that carfilzomib (Kyprolis) can be given safely to patients with creatinine clearance above 15 mL/min, and that the recently approved oral agent, ixazomib (Ninlaro), with lenalidomide and dexamethasone can be administered to patients with clearance rates above 30 mL/min (grade A).

The International Myeloma Working Group has issued new recommendations for the diagnosis and management of multiple myeloma–related renal impairment. Depending on whether the condition is defined as elevated serum creatinine or decreased estimated glomerular filtration rate (eGFR), an estimated 20%-50% of patients with multiple myeloma have renal impairment at the time of diagnosis.

The guidelines recommend that all patients with multiple myeloma (MM) at diagnosis and at disease assessment should be tested for serum creatinine, eGFR, electrolytes, and serum free light chain, if available. Additionally, they recommend that all patients have urine electrophoresis of a sample from a 24-hour urine collection. All of the above are grade A recommendations (J Clin Oncol. 2016 Mar 14. doi: 10.1200/JCO.2015.65.0044).

©London_England/Thinkstock

Patients with nonselective proteinuria or significant albuminuria should undergo renal biopsy to determine the cause of the underlying impairment, the IMWG says (grade B recommendation).

For evaluation of eGFR in patients with stabilized serum creatinine, the IMWG favors the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, but also acknowledges that eGFR can be assessed with the Modification of Diet in Renal Disease (MDRD) formula (grade A).

“CKD-EPI seems to more accurately reflect GFR than does MDRD, mostly in higher levels of GFR,” the IMWG wrote.

Because the reversibility of renal dysfunction can affect treatment choice, the recommendations noted that for patients on dialysis, achieving independence from dialysis is “strong indication of improvement. For all other patients, IMWG criteria for renal response to therapy are recommended (grade B).

Management

“Acute renal impairment is a myeloma emergency. Diagnosis should be established as fast as possible, and antimyeloma therapy should be started immediately after confirmation of diagnosis to rapidly restore renal function,” working group members wrote.

Supportive care with increased hydration – at least 3 liters per day – is “mandatory” for all with suspected MM-related renal impairment, they add.

The recommendations also noted that antimyeloma therapy should be initiated immediately to reduce the load of toxic serum free light chains, which can help to improve renal function.

“Bortezomib [Velcade]-based regimens remain the cornerstone of the management of myeloma-related renal impairment (grade A). High-dose dexamethasone should be administered at least for the first month of therapy (grade B),” the working group members wrote.

Lenalidomide (Revlimid) can be given, but because it is excreted through the kidneys, the dose must be adjusted according to the degree of renal impairment. In contrast, thalidomide is not excreted and does not require dose modification in this population.

Patients who are eligible for autologous stem cell transplant could receive bortezomib in a three-drug regimen with thalidomide and dexamethasone, or in combination with a conventional chemotherapeutic agent, either doxorubicin or cyclophosphamide. Patients who are not eligible for transplant can be treated with bortezomib, melphalan, and prednisone, the recommendations said, but add that there are no data on the use of this regimen in patients who are on dialysis.

Regarding newer proteasome inhibitors, the guidelines note that carfilzomib (Kyprolis) can be given safely to patients with creatinine clearance above 15 mL/min, and that the recently approved oral agent, ixazomib (Ninlaro), with lenalidomide and dexamethasone can be administered to patients with clearance rates above 30 mL/min (grade A).

The International Myeloma Working Group has issued new recommendations for the diagnosis and management of multiple myeloma–related renal impairment. Depending on whether the condition is defined as elevated serum creatinine or decreased estimated glomerular filtration rate (eGFR), an estimated 20%-50% of patients with multiple myeloma have renal impairment at the time of diagnosis.

The guidelines recommend that all patients with multiple myeloma (MM) at diagnosis and at disease assessment should be tested for serum creatinine, eGFR, electrolytes, and serum free light chain, if available. Additionally, they recommend that all patients have urine electrophoresis of a sample from a 24-hour urine collection. All of the above are grade A recommendations (J Clin Oncol. 2016 Mar 14. doi: 10.1200/JCO.2015.65.0044).

©London_England/Thinkstock

Patients with nonselective proteinuria or significant albuminuria should undergo renal biopsy to determine the cause of the underlying impairment, the IMWG says (grade B recommendation).

For evaluation of eGFR in patients with stabilized serum creatinine, the IMWG favors the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, but also acknowledges that eGFR can be assessed with the Modification of Diet in Renal Disease (MDRD) formula (grade A).

“CKD-EPI seems to more accurately reflect GFR than does MDRD, mostly in higher levels of GFR,” the IMWG wrote.

Because the reversibility of renal dysfunction can affect treatment choice, the recommendations noted that for patients on dialysis, achieving independence from dialysis is “strong indication of improvement. For all other patients, IMWG criteria for renal response to therapy are recommended (grade B).

Management

“Acute renal impairment is a myeloma emergency. Diagnosis should be established as fast as possible, and antimyeloma therapy should be started immediately after confirmation of diagnosis to rapidly restore renal function,” working group members wrote.

Supportive care with increased hydration – at least 3 liters per day – is “mandatory” for all with suspected MM-related renal impairment, they add.

The recommendations also noted that antimyeloma therapy should be initiated immediately to reduce the load of toxic serum free light chains, which can help to improve renal function.

“Bortezomib [Velcade]-based regimens remain the cornerstone of the management of myeloma-related renal impairment (grade A). High-dose dexamethasone should be administered at least for the first month of therapy (grade B),” the working group members wrote.

Lenalidomide (Revlimid) can be given, but because it is excreted through the kidneys, the dose must be adjusted according to the degree of renal impairment. In contrast, thalidomide is not excreted and does not require dose modification in this population.

Patients who are eligible for autologous stem cell transplant could receive bortezomib in a three-drug regimen with thalidomide and dexamethasone, or in combination with a conventional chemotherapeutic agent, either doxorubicin or cyclophosphamide. Patients who are not eligible for transplant can be treated with bortezomib, melphalan, and prednisone, the recommendations said, but add that there are no data on the use of this regimen in patients who are on dialysis.

Regarding newer proteasome inhibitors, the guidelines note that carfilzomib (Kyprolis) can be given safely to patients with creatinine clearance above 15 mL/min, and that the recently approved oral agent, ixazomib (Ninlaro), with lenalidomide and dexamethasone can be administered to patients with clearance rates above 30 mL/min (grade A).

Swapping lenalidomide for thalidomide in a standard regimen for transplant-ineligible patients with untreated multiple myeloma did not improve efficacy, but the toxicity profile may favor the use of lenalidomide in a maintenance regimen, results of a randomized trial suggest.

Among patients with previously untreated multiple myeloma who were not eligible for autologous stem cell transplant, neither median progression-free survival (PFS) nor overall survival (OS) were significantly different for patients treated with either melphalan, prednisone, and thalidomide (MPT-T) followed by thalidomide maintenance, or with the same regimen with lenalidomide (Revlimid) substituted for thalidomide (MPR-R), reported Dr. Sonja Zweegman of Vrije University Medical Center in Amsterdam.

“MPR-R has no advantage over MPT-T with respect to response rate, PFS, and OS. However, the use of thalidomide as maintenance therapy was associated with a high rate of clinically significant neuropathy and is therefore not preferred for maintenance strategies,” they wrote (Blood 2016;127[9];1109-16).

The investigators randomly assigned 637 transplant-ineligible patients with newly-diagnosed multiple myeloma to receive nine 4-week cycles of either MPT-T (318 patients) or MPR-R (319 patients). At 36 months’ median follow-up, median PFS, the primary endpoint, was 20 months for patients treated with MPT-T, compared with 23 months for those treated with MPR-R. This translated into a hazard ratio (HR) of 0.87, P = .12).

The overall response rates were 81% for MPT-T and 84% for MPR-R. Very good partial responses or better were seen in 47% and 45%, of patients, respectively. The complete response rate with MPT-T was 10%, compared with 13% for MPR-R. Median time to response and time to maximum response were similar between the arms.

OS at 2, 3, and 4 years in the MPT-T and MPR-R arms was 73% vs. 84%, 64% vs 69%, and 52% vs. 56%, respectively. These differences were not statistically significant.

The proportion of patients with one or more grade 3 or 4 adverse events was 81% with thalidomide and 86% with lenalidomide.

The investigators noted, however, that there was a high rate of discontinuation during induction therapy in each arm, with 49% of those starting on MPT-T and 41% of those starting on MPR-R halting therapy. Most of the patients who discontinued were older than age 75. Early treatment deaths (within three cycles) occurred in 13 patients on MPT-T, and 8 on MPR-R.

Among patients who started on maintenance therapy, significantly more patients on thalidomide had to discontinue thalidomide than did patients who started on lenalidomide maintenance (60% vs, 17%, P = .017).

The primary reason for the higher rate of discontinuation of MPT-T maintenance was neuropathy, which occurred in 87% of the discontinuations in this study arm, compared with 3% of those in the lenalidomide arm. Neuropathy of at least grade 3 was 16% in the MPT-T arm vs. 2% in MPR-R, resulting in a significantly shorter duration of maintenance therapy (5 vs. 17 months in MPR-R), irrespective of age.

Hematologic toxicities were higher in the MPR-R group, especially grades 3 and 4 neutropenia (64% vs 27%), but this did not translate into a higher clinical infection rate, and the toxicities were manageable in older patients, the investigators reported.

Swapping lenalidomide for thalidomide in a standard regimen for transplant-ineligible patients with untreated multiple myeloma did not improve efficacy, but the toxicity profile may favor the use of lenalidomide in a maintenance regimen, results of a randomized trial suggest.

Among patients with previously untreated multiple myeloma who were not eligible for autologous stem cell transplant, neither median progression-free survival (PFS) nor overall survival (OS) were significantly different for patients treated with either melphalan, prednisone, and thalidomide (MPT-T) followed by thalidomide maintenance, or with the same regimen with lenalidomide (Revlimid) substituted for thalidomide (MPR-R), reported Dr. Sonja Zweegman of Vrije University Medical Center in Amsterdam.

“MPR-R has no advantage over MPT-T with respect to response rate, PFS, and OS. However, the use of thalidomide as maintenance therapy was associated with a high rate of clinically significant neuropathy and is therefore not preferred for maintenance strategies,” they wrote (Blood 2016;127[9];1109-16).

The investigators randomly assigned 637 transplant-ineligible patients with newly-diagnosed multiple myeloma to receive nine 4-week cycles of either MPT-T (318 patients) or MPR-R (319 patients). At 36 months’ median follow-up, median PFS, the primary endpoint, was 20 months for patients treated with MPT-T, compared with 23 months for those treated with MPR-R. This translated into a hazard ratio (HR) of 0.87, P = .12).

The overall response rates were 81% for MPT-T and 84% for MPR-R. Very good partial responses or better were seen in 47% and 45%, of patients, respectively. The complete response rate with MPT-T was 10%, compared with 13% for MPR-R. Median time to response and time to maximum response were similar between the arms.

OS at 2, 3, and 4 years in the MPT-T and MPR-R arms was 73% vs. 84%, 64% vs 69%, and 52% vs. 56%, respectively. These differences were not statistically significant.

The proportion of patients with one or more grade 3 or 4 adverse events was 81% with thalidomide and 86% with lenalidomide.

The investigators noted, however, that there was a high rate of discontinuation during induction therapy in each arm, with 49% of those starting on MPT-T and 41% of those starting on MPR-R halting therapy. Most of the patients who discontinued were older than age 75. Early treatment deaths (within three cycles) occurred in 13 patients on MPT-T, and 8 on MPR-R.

Among patients who started on maintenance therapy, significantly more patients on thalidomide had to discontinue thalidomide than did patients who started on lenalidomide maintenance (60% vs, 17%, P = .017).

The primary reason for the higher rate of discontinuation of MPT-T maintenance was neuropathy, which occurred in 87% of the discontinuations in this study arm, compared with 3% of those in the lenalidomide arm. Neuropathy of at least grade 3 was 16% in the MPT-T arm vs. 2% in MPR-R, resulting in a significantly shorter duration of maintenance therapy (5 vs. 17 months in MPR-R), irrespective of age.

Hematologic toxicities were higher in the MPR-R group, especially grades 3 and 4 neutropenia (64% vs 27%), but this did not translate into a higher clinical infection rate, and the toxicities were manageable in older patients, the investigators reported.

Swapping lenalidomide for thalidomide in a standard regimen for transplant-ineligible patients with untreated multiple myeloma did not improve efficacy, but the toxicity profile may favor the use of lenalidomide in a maintenance regimen, results of a randomized trial suggest.

Among patients with previously untreated multiple myeloma who were not eligible for autologous stem cell transplant, neither median progression-free survival (PFS) nor overall survival (OS) were significantly different for patients treated with either melphalan, prednisone, and thalidomide (MPT-T) followed by thalidomide maintenance, or with the same regimen with lenalidomide (Revlimid) substituted for thalidomide (MPR-R), reported Dr. Sonja Zweegman of Vrije University Medical Center in Amsterdam.

“MPR-R has no advantage over MPT-T with respect to response rate, PFS, and OS. However, the use of thalidomide as maintenance therapy was associated with a high rate of clinically significant neuropathy and is therefore not preferred for maintenance strategies,” they wrote (Blood 2016;127[9];1109-16).

The investigators randomly assigned 637 transplant-ineligible patients with newly-diagnosed multiple myeloma to receive nine 4-week cycles of either MPT-T (318 patients) or MPR-R (319 patients). At 36 months’ median follow-up, median PFS, the primary endpoint, was 20 months for patients treated with MPT-T, compared with 23 months for those treated with MPR-R. This translated into a hazard ratio (HR) of 0.87, P = .12).

The overall response rates were 81% for MPT-T and 84% for MPR-R. Very good partial responses or better were seen in 47% and 45%, of patients, respectively. The complete response rate with MPT-T was 10%, compared with 13% for MPR-R. Median time to response and time to maximum response were similar between the arms.

OS at 2, 3, and 4 years in the MPT-T and MPR-R arms was 73% vs. 84%, 64% vs 69%, and 52% vs. 56%, respectively. These differences were not statistically significant.

The proportion of patients with one or more grade 3 or 4 adverse events was 81% with thalidomide and 86% with lenalidomide.

The investigators noted, however, that there was a high rate of discontinuation during induction therapy in each arm, with 49% of those starting on MPT-T and 41% of those starting on MPR-R halting therapy. Most of the patients who discontinued were older than age 75. Early treatment deaths (within three cycles) occurred in 13 patients on MPT-T, and 8 on MPR-R.

Among patients who started on maintenance therapy, significantly more patients on thalidomide had to discontinue thalidomide than did patients who started on lenalidomide maintenance (60% vs, 17%, P = .017).

The primary reason for the higher rate of discontinuation of MPT-T maintenance was neuropathy, which occurred in 87% of the discontinuations in this study arm, compared with 3% of those in the lenalidomide arm. Neuropathy of at least grade 3 was 16% in the MPT-T arm vs. 2% in MPR-R, resulting in a significantly shorter duration of maintenance therapy (5 vs. 17 months in MPR-R), irrespective of age.

Hematologic toxicities were higher in the MPR-R group, especially grades 3 and 4 neutropenia (64% vs 27%), but this did not translate into a higher clinical infection rate, and the toxicities were manageable in older patients, the investigators reported.