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Poor-prognosis cancers linked to highest suicide risk in first year

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Suicide risk significantly increases within the first year of a cancer diagnosis, with risk varying by type of cancer, according to investigators who conducted a retrospective analysis representing nearly 4.7 million patients.

Risk of suicide in that first year after diagnosis was especially high in pancreatic and lung cancers, while by contrast, breast and prostate cancer did not increase suicide risk, reported the researchers, led by Hesham Hamoda, MD, MPH, of Boston Children’s Hospital/Harvard Medical School, and Ahmad Alfaar, MBBCh, MSc, of Charité–Universitätsmedizin Berlin.

That variation in suicide risk by cancer type suggests that prognosis and 5-year relative survival play a role in increasing suicide rates, according to Dr. Hamoda, Dr. Alfaar, and their coauthors.

“After the diagnosis, it is important that health care providers be vigilant in screening for suicide and ensuring that patients have access to social and emotional support,” they wrote in a report published in Cancer. Their analysis was based on 4,671,989 patients with a diagnosis of cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Out of 1,005,825 of those patients who died within the first year of diagnosis, the cause of death was suicide for 1,585, or 0.16%.

Overall, the risk of suicide increased significantly among cancer patients versus the general population, with an observed-to-expected (O/E) ratio of 2.51 per 10,000 person-years, the investigators found. The risk was highest in the first 6 months, with an O/E mortality of 3.13 versus 1.8 in the latter 6 months.

The highest ratios were seen for pancreatic cancer, with an O/E ratio of 8.01, and lung cancer, with a ratio of 6.05, the researchers found in further analysis.

Significant increases in suicide risk were also seen for colorectal cancer (2.08) and melanoma (1.45), though rates were not significantly different versus the general population for breast (1.23) and prostate (0.99), according to the reported data.

Suicide risk was relatively high for any cancer with distant metastases (5.63), though still significantly higher at 1.65 in persons with localized/regional disease, the data show.

The increased suicide risk persisted more than 1 year after the cancer diagnosis, though not to the degree observed within that first year, they added.

Most patients with suicide as a cause of death were white (90.2%) and male (87%). Nearly 60% were between the ages of 65 and 84 at the time of suicide.

Social support plays an integral role in suicide prevention among cancer patients, the researchers noted.

Previous studies suggest that support programs may decrease suicide risk by making patients better aware of their prognosis, receptive to decreased social stigma, or less likely to have stress related to cost of care, they said.

“Discussing the quality of life after diagnosis, the effectiveness of therapy, and the prognosis of the disease and maintaining a trusting relationship with health care professionals all decrease the likelihood of suicide immediately after a diagnosis of cancer,” they said.

Dr. Hamoda, Dr. Alfaar, and their coauthors reported no conflicts of interest. Funding for the study came in part from the German Academic Exchange Service (Dr. Alfaar).

SOURCE: Saad AM, et al. Cancer 2019 Jan 7. doi: 10.1002/cncr.31876.

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Suicide risk significantly increases within the first year of a cancer diagnosis, with risk varying by type of cancer, according to investigators who conducted a retrospective analysis representing nearly 4.7 million patients.

Risk of suicide in that first year after diagnosis was especially high in pancreatic and lung cancers, while by contrast, breast and prostate cancer did not increase suicide risk, reported the researchers, led by Hesham Hamoda, MD, MPH, of Boston Children’s Hospital/Harvard Medical School, and Ahmad Alfaar, MBBCh, MSc, of Charité–Universitätsmedizin Berlin.

That variation in suicide risk by cancer type suggests that prognosis and 5-year relative survival play a role in increasing suicide rates, according to Dr. Hamoda, Dr. Alfaar, and their coauthors.

“After the diagnosis, it is important that health care providers be vigilant in screening for suicide and ensuring that patients have access to social and emotional support,” they wrote in a report published in Cancer. Their analysis was based on 4,671,989 patients with a diagnosis of cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Out of 1,005,825 of those patients who died within the first year of diagnosis, the cause of death was suicide for 1,585, or 0.16%.

Overall, the risk of suicide increased significantly among cancer patients versus the general population, with an observed-to-expected (O/E) ratio of 2.51 per 10,000 person-years, the investigators found. The risk was highest in the first 6 months, with an O/E mortality of 3.13 versus 1.8 in the latter 6 months.

The highest ratios were seen for pancreatic cancer, with an O/E ratio of 8.01, and lung cancer, with a ratio of 6.05, the researchers found in further analysis.

Significant increases in suicide risk were also seen for colorectal cancer (2.08) and melanoma (1.45), though rates were not significantly different versus the general population for breast (1.23) and prostate (0.99), according to the reported data.

Suicide risk was relatively high for any cancer with distant metastases (5.63), though still significantly higher at 1.65 in persons with localized/regional disease, the data show.

The increased suicide risk persisted more than 1 year after the cancer diagnosis, though not to the degree observed within that first year, they added.

Most patients with suicide as a cause of death were white (90.2%) and male (87%). Nearly 60% were between the ages of 65 and 84 at the time of suicide.

Social support plays an integral role in suicide prevention among cancer patients, the researchers noted.

Previous studies suggest that support programs may decrease suicide risk by making patients better aware of their prognosis, receptive to decreased social stigma, or less likely to have stress related to cost of care, they said.

“Discussing the quality of life after diagnosis, the effectiveness of therapy, and the prognosis of the disease and maintaining a trusting relationship with health care professionals all decrease the likelihood of suicide immediately after a diagnosis of cancer,” they said.

Dr. Hamoda, Dr. Alfaar, and their coauthors reported no conflicts of interest. Funding for the study came in part from the German Academic Exchange Service (Dr. Alfaar).

SOURCE: Saad AM, et al. Cancer 2019 Jan 7. doi: 10.1002/cncr.31876.

 

Suicide risk significantly increases within the first year of a cancer diagnosis, with risk varying by type of cancer, according to investigators who conducted a retrospective analysis representing nearly 4.7 million patients.

Risk of suicide in that first year after diagnosis was especially high in pancreatic and lung cancers, while by contrast, breast and prostate cancer did not increase suicide risk, reported the researchers, led by Hesham Hamoda, MD, MPH, of Boston Children’s Hospital/Harvard Medical School, and Ahmad Alfaar, MBBCh, MSc, of Charité–Universitätsmedizin Berlin.

That variation in suicide risk by cancer type suggests that prognosis and 5-year relative survival play a role in increasing suicide rates, according to Dr. Hamoda, Dr. Alfaar, and their coauthors.

“After the diagnosis, it is important that health care providers be vigilant in screening for suicide and ensuring that patients have access to social and emotional support,” they wrote in a report published in Cancer. Their analysis was based on 4,671,989 patients with a diagnosis of cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Out of 1,005,825 of those patients who died within the first year of diagnosis, the cause of death was suicide for 1,585, or 0.16%.

Overall, the risk of suicide increased significantly among cancer patients versus the general population, with an observed-to-expected (O/E) ratio of 2.51 per 10,000 person-years, the investigators found. The risk was highest in the first 6 months, with an O/E mortality of 3.13 versus 1.8 in the latter 6 months.

The highest ratios were seen for pancreatic cancer, with an O/E ratio of 8.01, and lung cancer, with a ratio of 6.05, the researchers found in further analysis.

Significant increases in suicide risk were also seen for colorectal cancer (2.08) and melanoma (1.45), though rates were not significantly different versus the general population for breast (1.23) and prostate (0.99), according to the reported data.

Suicide risk was relatively high for any cancer with distant metastases (5.63), though still significantly higher at 1.65 in persons with localized/regional disease, the data show.

The increased suicide risk persisted more than 1 year after the cancer diagnosis, though not to the degree observed within that first year, they added.

Most patients with suicide as a cause of death were white (90.2%) and male (87%). Nearly 60% were between the ages of 65 and 84 at the time of suicide.

Social support plays an integral role in suicide prevention among cancer patients, the researchers noted.

Previous studies suggest that support programs may decrease suicide risk by making patients better aware of their prognosis, receptive to decreased social stigma, or less likely to have stress related to cost of care, they said.

“Discussing the quality of life after diagnosis, the effectiveness of therapy, and the prognosis of the disease and maintaining a trusting relationship with health care professionals all decrease the likelihood of suicide immediately after a diagnosis of cancer,” they said.

Dr. Hamoda, Dr. Alfaar, and their coauthors reported no conflicts of interest. Funding for the study came in part from the German Academic Exchange Service (Dr. Alfaar).

SOURCE: Saad AM, et al. Cancer 2019 Jan 7. doi: 10.1002/cncr.31876.

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Key clinical point: A cancer diagnosis significantly increases risk of suicide in comparison to the general population, particularly for poorer-prognosis cancers.

Major finding: The observed-to-expected mortality ratio was substantially higher for pancreatic cancer (8.01), and lung cancer (6.05), but not significantly increased for breast (1.23) and prostate (0.99).

Study details: A retrospective population-based study of 4,671,989 cancer patients.

Disclosures: The authors reported no conflicts of interest. Funding for the study came in part from the German Academic Exchange Service.

Source: Saad AM et al. Cancer. 2019 Jan 7. doi: 10.1002/cncr.31876.

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Pembrolizumab approved for Merkel cell carcinoma

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The Food and Drug Administration has granted accelerated approval for pembrolizumab (Keytruda) for the treatment of pediatric and adult Merkel cell carcinoma, specifically for recurrent locally advanced or metastatic disease.



In a nonrandomized, open-label trial of 50 patients with recurrent locally advanced or metastatic Merkel cell carcinoma who had not received systemic treatment for the advanced disease, the overall response rate was 56% with a complete response rate of 24%; median response duration was not reached. But responses lasting more than 6 months were achieved by 96% and more than 12 months by 54%. The most common adverse reactions included fatigue, musculoskeletal pain, and decreased appetite.



Because it is an accelerated approval, “continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials,” according to the FDA press release announcing the approval.



Pembrolizumab is a programmed death receptor-1 (PD-1)-blocking antibody that was previously approved for treatment of unresectable or metastatic melanoma.

More about the latest approval, as well as full prescribing information, can be found on the FDA’s website.

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The Food and Drug Administration has granted accelerated approval for pembrolizumab (Keytruda) for the treatment of pediatric and adult Merkel cell carcinoma, specifically for recurrent locally advanced or metastatic disease.



In a nonrandomized, open-label trial of 50 patients with recurrent locally advanced or metastatic Merkel cell carcinoma who had not received systemic treatment for the advanced disease, the overall response rate was 56% with a complete response rate of 24%; median response duration was not reached. But responses lasting more than 6 months were achieved by 96% and more than 12 months by 54%. The most common adverse reactions included fatigue, musculoskeletal pain, and decreased appetite.



Because it is an accelerated approval, “continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials,” according to the FDA press release announcing the approval.



Pembrolizumab is a programmed death receptor-1 (PD-1)-blocking antibody that was previously approved for treatment of unresectable or metastatic melanoma.

More about the latest approval, as well as full prescribing information, can be found on the FDA’s website.

 

The Food and Drug Administration has granted accelerated approval for pembrolizumab (Keytruda) for the treatment of pediatric and adult Merkel cell carcinoma, specifically for recurrent locally advanced or metastatic disease.



In a nonrandomized, open-label trial of 50 patients with recurrent locally advanced or metastatic Merkel cell carcinoma who had not received systemic treatment for the advanced disease, the overall response rate was 56% with a complete response rate of 24%; median response duration was not reached. But responses lasting more than 6 months were achieved by 96% and more than 12 months by 54%. The most common adverse reactions included fatigue, musculoskeletal pain, and decreased appetite.



Because it is an accelerated approval, “continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials,” according to the FDA press release announcing the approval.



Pembrolizumab is a programmed death receptor-1 (PD-1)-blocking antibody that was previously approved for treatment of unresectable or metastatic melanoma.

More about the latest approval, as well as full prescribing information, can be found on the FDA’s website.

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More data link severe sleep apnea and aggressive melanoma

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Severe sleep-disordered breathing was significantly associated with more aggressive skin cancer in a study of 443 adults.

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Sleep-disordered breathing (SDB) has been associated with increased cancer risk and mortality, but no large studies have examined the association in specific cancers, wrote Miguel Angel Martinez-Garcia, MD, of La Fe University and Polytechnic Hospital, Valencia, Spain, and his colleagues.

The researchers conducted a sleep study of 443 adults with melanoma within 6 months of their diagnoses. The findings were published in the journal CHEST®. Overall, patients with more severe sleep apnea were nearly twice as likely to have aggressive type melanoma, compared with those with less severe sleep apnea.

Sleep apnea was defined via the Apnea Hypopnea Index (AHI) and the desaturation indices (DI). Aggressive melanoma was defined as a Breslow index greater than 1 mm, compared with 1 mm or less.

Patients with AHI greater than 15.6 events per hour or in the DI4% tertile (more than 9.3 desaturations per hour) were approximately twice as likely (1.94 and 1.93 times, respectively) to have a more aggressive melanoma as were those with less severe sleep apnea, after adjustment for age, gender, body mass index, and melanoma location.

The average age of the patients was 60 years, 51% were male, and the average time between the melanoma diagnosis and the sleep study was 82 days. Sleep symptoms were not significantly different between the patients with aggressive or less aggressive melanoma. However, in addition to more severe sleep apnea, those with aggressive melanoma were significantly more likely to be older, male, and have a higher BMI than were those with less aggressive disease.

“Among the most salient findings were the dependence of the association between SDB and the markers of melanoma aggressiveness on both age and the actual indicators of tumor aggressiveness,” the researchers noted. The association was significant in patients younger than 55 years only if their Breslow index was greater than 2 mm, the researchers said.

The study findings were limited by the absence of full overnight polysomnography to assess SDB because not all participating centers had access to that option, the researchers noted. However, the results support an independent link between sleep apnea and common measures of aggressive melanoma, especially in younger patients, they said. “Future prospective studies are needed to confirm whether the presence and treatment of SDB and its evolution over time are also associated with poor melanoma outcomes, including death, the pathophysiological mechanisms underlying this association,” they added.

The study was supported in part by Fondo de Investigation Sanitaria, SEPAR, Red Respira, and Sociedad Valenciana de Neumología. The researchers had no financial conflicts to disclose

SOURCE: Martinez-Garcia M et al. CHEST. 2018; doi: 10.1016/j.chest.2018.07.015.

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Severe sleep-disordered breathing was significantly associated with more aggressive skin cancer in a study of 443 adults.

Dlumen/Thinkstock

Sleep-disordered breathing (SDB) has been associated with increased cancer risk and mortality, but no large studies have examined the association in specific cancers, wrote Miguel Angel Martinez-Garcia, MD, of La Fe University and Polytechnic Hospital, Valencia, Spain, and his colleagues.

The researchers conducted a sleep study of 443 adults with melanoma within 6 months of their diagnoses. The findings were published in the journal CHEST®. Overall, patients with more severe sleep apnea were nearly twice as likely to have aggressive type melanoma, compared with those with less severe sleep apnea.

Sleep apnea was defined via the Apnea Hypopnea Index (AHI) and the desaturation indices (DI). Aggressive melanoma was defined as a Breslow index greater than 1 mm, compared with 1 mm or less.

Patients with AHI greater than 15.6 events per hour or in the DI4% tertile (more than 9.3 desaturations per hour) were approximately twice as likely (1.94 and 1.93 times, respectively) to have a more aggressive melanoma as were those with less severe sleep apnea, after adjustment for age, gender, body mass index, and melanoma location.

The average age of the patients was 60 years, 51% were male, and the average time between the melanoma diagnosis and the sleep study was 82 days. Sleep symptoms were not significantly different between the patients with aggressive or less aggressive melanoma. However, in addition to more severe sleep apnea, those with aggressive melanoma were significantly more likely to be older, male, and have a higher BMI than were those with less aggressive disease.

“Among the most salient findings were the dependence of the association between SDB and the markers of melanoma aggressiveness on both age and the actual indicators of tumor aggressiveness,” the researchers noted. The association was significant in patients younger than 55 years only if their Breslow index was greater than 2 mm, the researchers said.

The study findings were limited by the absence of full overnight polysomnography to assess SDB because not all participating centers had access to that option, the researchers noted. However, the results support an independent link between sleep apnea and common measures of aggressive melanoma, especially in younger patients, they said. “Future prospective studies are needed to confirm whether the presence and treatment of SDB and its evolution over time are also associated with poor melanoma outcomes, including death, the pathophysiological mechanisms underlying this association,” they added.

The study was supported in part by Fondo de Investigation Sanitaria, SEPAR, Red Respira, and Sociedad Valenciana de Neumología. The researchers had no financial conflicts to disclose

SOURCE: Martinez-Garcia M et al. CHEST. 2018; doi: 10.1016/j.chest.2018.07.015.

 

Severe sleep-disordered breathing was significantly associated with more aggressive skin cancer in a study of 443 adults.

Dlumen/Thinkstock

Sleep-disordered breathing (SDB) has been associated with increased cancer risk and mortality, but no large studies have examined the association in specific cancers, wrote Miguel Angel Martinez-Garcia, MD, of La Fe University and Polytechnic Hospital, Valencia, Spain, and his colleagues.

The researchers conducted a sleep study of 443 adults with melanoma within 6 months of their diagnoses. The findings were published in the journal CHEST®. Overall, patients with more severe sleep apnea were nearly twice as likely to have aggressive type melanoma, compared with those with less severe sleep apnea.

Sleep apnea was defined via the Apnea Hypopnea Index (AHI) and the desaturation indices (DI). Aggressive melanoma was defined as a Breslow index greater than 1 mm, compared with 1 mm or less.

Patients with AHI greater than 15.6 events per hour or in the DI4% tertile (more than 9.3 desaturations per hour) were approximately twice as likely (1.94 and 1.93 times, respectively) to have a more aggressive melanoma as were those with less severe sleep apnea, after adjustment for age, gender, body mass index, and melanoma location.

The average age of the patients was 60 years, 51% were male, and the average time between the melanoma diagnosis and the sleep study was 82 days. Sleep symptoms were not significantly different between the patients with aggressive or less aggressive melanoma. However, in addition to more severe sleep apnea, those with aggressive melanoma were significantly more likely to be older, male, and have a higher BMI than were those with less aggressive disease.

“Among the most salient findings were the dependence of the association between SDB and the markers of melanoma aggressiveness on both age and the actual indicators of tumor aggressiveness,” the researchers noted. The association was significant in patients younger than 55 years only if their Breslow index was greater than 2 mm, the researchers said.

The study findings were limited by the absence of full overnight polysomnography to assess SDB because not all participating centers had access to that option, the researchers noted. However, the results support an independent link between sleep apnea and common measures of aggressive melanoma, especially in younger patients, they said. “Future prospective studies are needed to confirm whether the presence and treatment of SDB and its evolution over time are also associated with poor melanoma outcomes, including death, the pathophysiological mechanisms underlying this association,” they added.

The study was supported in part by Fondo de Investigation Sanitaria, SEPAR, Red Respira, and Sociedad Valenciana de Neumología. The researchers had no financial conflicts to disclose

SOURCE: Martinez-Garcia M et al. CHEST. 2018; doi: 10.1016/j.chest.2018.07.015.

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Key clinical point: Severe sleep disordered breathing is independently associated with more severe melanoma.

Major finding: Patients in the upper tertiles of AHI or DI4% were 1.94 and 1.93 times more likely, respectively, to have aggressive melanoma compared with patients with less severe sleep apnea.

Study details: The data come from an observational study of 443 adults diagnosed with melanoma.

Disclosures: The study was supported in part by Fondo de Investigation Sanitaria, SEPAR, Red Respira, and Sociedad Valenciana de Neumología. The researchers had no financial conflicts to disclose.

Source: Martinez-Garcia M et al. Chest. 2018. doi: 10.1016/j.chest.2018.07.015.

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RCC strongly linked to melanoma, and vice versa

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A review of registry data from a major cancer center revealed a strong, bidirectional association between renal cell carcinoma (RCC) and melanoma.

A greater than twofold risk of melanoma in patients with RCC, and a nearly threefold risk of RCC in melanoma patients, were found in the review of the International Tumor Registry Database at The University of Texas MD Anderson Cancer Center.

The incidence of subsequent melanomas or RCCs in this study was in line with other recent reports from cancer registry analyses, reported Kevin B. Kim, MD, and his coinvestigators.

“Clinicians should be more watchful for these secondary cancers in patients with a history of melanoma or RCC,” they wrote. The report is in Cancer Epidemiology.

They found a total of 13,879 patients with melanoma and 7,597 patients with RCC in their review. Of those patients, 89 had both a melanoma and an RCC diagnosis. About 30% were first diagnosed with RCC, 61% were first diagnosed with melanoma, and 9% had both diagnoses around the same time.

Among the RCC-first patients, the standardized incidence ratio for developing a second primary melanoma was 2.31 (95% confidence interval, 1.52-3.37; P less than .001), while for melanoma-first patients, for developing a second primary RCC, it was 2.87 (95% CI, 2.16-3.74; P less than .001).

Those statistics were consistent with other registry reports, according to Dr. Kim and his colleagues, who wrote that the standardized incidence ratios in those studies ranged from 1.28 to 2.5.

In the MD Anderson registry study, nearly one-third of patients with secondary primary melanoma or RCC had a history of additional secondary cancers, according to the researchers. Those diagnoses included nonmelanoma skin cancers, leukemias, prostate cancer, breast cancer, and colon cancer, among others.

That suggested the presence of possible common risk factors that may have included abnormal genetics, though the database lacked the genetic sequencing and family history data to explore that hypothesis further.

“It would be highly desirable to assess germline genetic information on patients and their families, and also somatic gene aberrations in the tumor lesions, in a more systematic way in order to better elucidate the contribution of the genetics in the association between melanoma and RCC,” Dr. Kim and his colleagues said.

They reported that they had no conflicts of interest.

SOURCE: Kim KB et al. Cancer Epidemiol. 2018 Oct 19;57:80-4.

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A review of registry data from a major cancer center revealed a strong, bidirectional association between renal cell carcinoma (RCC) and melanoma.

A greater than twofold risk of melanoma in patients with RCC, and a nearly threefold risk of RCC in melanoma patients, were found in the review of the International Tumor Registry Database at The University of Texas MD Anderson Cancer Center.

The incidence of subsequent melanomas or RCCs in this study was in line with other recent reports from cancer registry analyses, reported Kevin B. Kim, MD, and his coinvestigators.

“Clinicians should be more watchful for these secondary cancers in patients with a history of melanoma or RCC,” they wrote. The report is in Cancer Epidemiology.

They found a total of 13,879 patients with melanoma and 7,597 patients with RCC in their review. Of those patients, 89 had both a melanoma and an RCC diagnosis. About 30% were first diagnosed with RCC, 61% were first diagnosed with melanoma, and 9% had both diagnoses around the same time.

Among the RCC-first patients, the standardized incidence ratio for developing a second primary melanoma was 2.31 (95% confidence interval, 1.52-3.37; P less than .001), while for melanoma-first patients, for developing a second primary RCC, it was 2.87 (95% CI, 2.16-3.74; P less than .001).

Those statistics were consistent with other registry reports, according to Dr. Kim and his colleagues, who wrote that the standardized incidence ratios in those studies ranged from 1.28 to 2.5.

In the MD Anderson registry study, nearly one-third of patients with secondary primary melanoma or RCC had a history of additional secondary cancers, according to the researchers. Those diagnoses included nonmelanoma skin cancers, leukemias, prostate cancer, breast cancer, and colon cancer, among others.

That suggested the presence of possible common risk factors that may have included abnormal genetics, though the database lacked the genetic sequencing and family history data to explore that hypothesis further.

“It would be highly desirable to assess germline genetic information on patients and their families, and also somatic gene aberrations in the tumor lesions, in a more systematic way in order to better elucidate the contribution of the genetics in the association between melanoma and RCC,” Dr. Kim and his colleagues said.

They reported that they had no conflicts of interest.

SOURCE: Kim KB et al. Cancer Epidemiol. 2018 Oct 19;57:80-4.

A review of registry data from a major cancer center revealed a strong, bidirectional association between renal cell carcinoma (RCC) and melanoma.

A greater than twofold risk of melanoma in patients with RCC, and a nearly threefold risk of RCC in melanoma patients, were found in the review of the International Tumor Registry Database at The University of Texas MD Anderson Cancer Center.

The incidence of subsequent melanomas or RCCs in this study was in line with other recent reports from cancer registry analyses, reported Kevin B. Kim, MD, and his coinvestigators.

“Clinicians should be more watchful for these secondary cancers in patients with a history of melanoma or RCC,” they wrote. The report is in Cancer Epidemiology.

They found a total of 13,879 patients with melanoma and 7,597 patients with RCC in their review. Of those patients, 89 had both a melanoma and an RCC diagnosis. About 30% were first diagnosed with RCC, 61% were first diagnosed with melanoma, and 9% had both diagnoses around the same time.

Among the RCC-first patients, the standardized incidence ratio for developing a second primary melanoma was 2.31 (95% confidence interval, 1.52-3.37; P less than .001), while for melanoma-first patients, for developing a second primary RCC, it was 2.87 (95% CI, 2.16-3.74; P less than .001).

Those statistics were consistent with other registry reports, according to Dr. Kim and his colleagues, who wrote that the standardized incidence ratios in those studies ranged from 1.28 to 2.5.

In the MD Anderson registry study, nearly one-third of patients with secondary primary melanoma or RCC had a history of additional secondary cancers, according to the researchers. Those diagnoses included nonmelanoma skin cancers, leukemias, prostate cancer, breast cancer, and colon cancer, among others.

That suggested the presence of possible common risk factors that may have included abnormal genetics, though the database lacked the genetic sequencing and family history data to explore that hypothesis further.

“It would be highly desirable to assess germline genetic information on patients and their families, and also somatic gene aberrations in the tumor lesions, in a more systematic way in order to better elucidate the contribution of the genetics in the association between melanoma and RCC,” Dr. Kim and his colleagues said.

They reported that they had no conflicts of interest.

SOURCE: Kim KB et al. Cancer Epidemiol. 2018 Oct 19;57:80-4.

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Key clinical point: Review of international tumor registry data demonstrated a strong and bidirectional association between renal cell carcinoma (RCC) and melanoma.

Major finding: Standardized incidence ratios were 2.31 for developing a second primary melanoma in patients who first had an RCC diagnosis, and 2.87 for developing a second primary RCC in patients who had melanoma first.

Study details: Analysis of 13,879 patients with melanoma and 7,597 patients with RCC in the International Tumor Registry Database at The University of Texas MD Anderson Cancer Center.

Disclosures: The authors reported that they had no conflicts of interest.

Source: Kim KB et al. Cancer Epidemiol. 2018 Oct 19;57:80-4.

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BRAF-MEK inhibitor combo approved for adjuvant melanoma therapy

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On April 30, 2018, the US Food and Drug Administration expanded the indication for the combined use of dabrafenib and trametinib to include adjuvant treatment of BRAF-mutant melanoma following complete surgical resection. Dabrafenib is an inhibitor of the BRAF kinase, and trametinib is an inhibitor of the MEK kinase, both of which are components of the mitogen-activated protein kinase (MAPK) signaling pathway. The 2 drugs are already approved as both single agents and in combination for the treatment of BRAF-mutated metastatic melanoma.

The current approval was based on data from a phase 3, international, multicenter, randomized, double-blind, placebo-controlled trial. The COMBI-AD trial was carried out from January 2013 through December 2014 at 169 sites in 26 countries. A total of 870 patients with stage III melanoma and BRAF V600E/K mutations and pathologic involvement of regional lymph nodes following complete resection were randomly assigned to receive dabrafenib 150 mg twice daily in combination with trametinib 2 mg once daily, or 2 matched placebos for up to 1 year. Randomization was stratified according to BRAF mutation status (V600E or V600K) and disease stage (IIIA, IIIB or IIIC).

Eligible patients were aged 18 years or older and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (on a scale of 1-5, with higher scores indicating greater disability). Patients who had undergone previous systemic anticancer therapy or radiotherapy were excluded from the study.

The primary endpoint was relapse-free survival (RFS), defined as the time from randomization to disease recurrence or death from any cause. Secondary endpoints included overall survival (OS), distant metastasis-free survival (DMFS), freedom from relapse (FFR), and safety. Clinical examination and imaging by computed tomography, magnetic resonance imaging, or both was performed every 3 months for the first 2 years and then every 6 months until disease recurrence or trial completion.

As of the data cut-off, the combination of dabrafenib and trametinib reduced the risk of disease recurrence or death by 53% compared with placebo (hazard ratio [HR], 0.47; P < .001). Median RFS was not yet reached in the combination arm, compared with 16.6 months in the placebo arm. The RFS benefit was observed across all prespecified subgroups, and the combination was also found to improve OS, DMFS, and FFR.

The most common adverse events (AEs) included pyrexia, fatigue, nausea, rash, vomiting, diarrhea, chills, and myalgia. Overall, 97% of patients experienced an AE, 41% experienced a grade 3/4 AE, and 26% had an AE that led to treatment discontinuation. In patients treated with placebo, those numbers were 88%, 14%, and 3%, respectively.



The separate prescribing information for dabrafenib and trametinib detail warnings and precautions relating to their combined use, including the need to confirm BRAF status before starting therapy (because use in BRAF wildtype tumors can promote tumor cell proliferation), new primary malignancies, hemorrhage, cardiomyopathy, uveitis, serious febrile reactions, serious skin toxicity, hyperglycemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, colitis and gastrointestinal perforation, venous thromboembolism, ocular toxicities, interstitial lung disease, and embryofetal toxicity.

Dermatologic evaluations should be completed before starting therapy, every 2 months during and for up to 6 months after completion of therapy, and patients should be monitored closely for the signs and symptoms of noncutaneous primary malignancies. Treatment should be discontinued for all grade 4 hemorrhagic events and for any grade 3 events that do not improve, and withheld for grade 3 events until they resolve, at which point treatment can be resumed at the next lowest dose as described in the prescribing information.

Left ventricular ejection fraction (LVEF) values should be assessed before initiating therapy, after 1 month, and then at intervals of 2-3 months. Treatment should be withheld for up to 4 weeks if absolute LVEF values decrease by 10% and are less than the lower limit of normal (LLN) and it should be permanently discontinued for symptomatic cardiomyopathy or persistent, asymptomatic left ventricular dysfunction of >20% from baseline that is below LLN and does not resolve within 4 weeks.

Treatment should be withheld for fevers higher than 104°F or for serious febrile reactions or fever accompanied by hypotension, rigors or chills, dehydration, or renal failure. Serum creatinine levels should be monitored, along with other evidence of renal function, during, and after severe pyrexia. Antipyretics should be administered as secondary prophylaxis when treatment is resumed if the patient had previous episodes of severe febrile reaction or if fever was associated with complications. Corticosteroids should be administered for at least 5 days for second or subsequent pyrexia if the body temperature dose not return to baseline within 3 days of fever onset or for pyrexia associated with complications and no evidence of active infection.

Treatment should also be withheld for intolerable or severe skin toxicity and resumed at a lower dose as per guidelines in patients who improve or recover within 3 weeks. Serum glucose levels should be monitored at the start of treatment and as clinically appropriate in patients with pre-existing diabetes or hyperglycemia. Patients with G6PD deficiency should be monitored closely for signs of hemolytic anemia.

Patients should be monitored closely for signs and symptoms of colitis and gastrointestinal perforation and should be advised to immediately seek medical care if they develop symptoms of deep vein thrombosis (DVT) or pulmonary embolism (PE). Treatment should be permanently discontinued for life-threatening PE, or withheld for uncomplicated DVT and PE for up to 3 weeks and then resumed at a lower dose if the patient improves.

Ophthalmological evaluations should be performed periodically and within 24 hours of patient-reported loss of vision or other visual disturbances. Treatment should be permanently discontinued in patients with documented retinal vein occlusion and withheld for retinal pigment epithelial detachment. Treatment should also be withheld in patients presenting with new or progressive pulmonary symptoms and findings and permanently discontinued for treatment-related interstitial lung disease or pneumonitis.

Both dabrafenib and trametinib can cause fetal harm and patients should be warned of this risk and the need for adequate contraceptive measures. Dabrafenib and trametinib are marketed as Tafinlar and Mekinist by Novartis.

References

1. US Food and Drug Administration Website. FDA approves dabrafenib plus trametinib for adjuvant treatment of melanoma with BRAF V600E or V600K mutations. https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm606165.htm. Last updated April 30, 2018. Accessed October 6, 2018.
2. Long GV, Hauschild A, Santinami M, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med. 2017;377:1913-1823.
3. Tafinlar (dabrafenib) capsules, for oral use. Prescribing information. Novartis. https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/tafinlar.pdf. May 2018. Accessed October 6, 2018.
4. Mekinist (trametinib) tablets, for oral use. Prescribing information. Novartis. https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/mekinist.pdf. May 2018. Accessed October 6th, 2018.

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On April 30, 2018, the US Food and Drug Administration expanded the indication for the combined use of dabrafenib and trametinib to include adjuvant treatment of BRAF-mutant melanoma following complete surgical resection. Dabrafenib is an inhibitor of the BRAF kinase, and trametinib is an inhibitor of the MEK kinase, both of which are components of the mitogen-activated protein kinase (MAPK) signaling pathway. The 2 drugs are already approved as both single agents and in combination for the treatment of BRAF-mutated metastatic melanoma.

The current approval was based on data from a phase 3, international, multicenter, randomized, double-blind, placebo-controlled trial. The COMBI-AD trial was carried out from January 2013 through December 2014 at 169 sites in 26 countries. A total of 870 patients with stage III melanoma and BRAF V600E/K mutations and pathologic involvement of regional lymph nodes following complete resection were randomly assigned to receive dabrafenib 150 mg twice daily in combination with trametinib 2 mg once daily, or 2 matched placebos for up to 1 year. Randomization was stratified according to BRAF mutation status (V600E or V600K) and disease stage (IIIA, IIIB or IIIC).

Eligible patients were aged 18 years or older and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (on a scale of 1-5, with higher scores indicating greater disability). Patients who had undergone previous systemic anticancer therapy or radiotherapy were excluded from the study.

The primary endpoint was relapse-free survival (RFS), defined as the time from randomization to disease recurrence or death from any cause. Secondary endpoints included overall survival (OS), distant metastasis-free survival (DMFS), freedom from relapse (FFR), and safety. Clinical examination and imaging by computed tomography, magnetic resonance imaging, or both was performed every 3 months for the first 2 years and then every 6 months until disease recurrence or trial completion.

As of the data cut-off, the combination of dabrafenib and trametinib reduced the risk of disease recurrence or death by 53% compared with placebo (hazard ratio [HR], 0.47; P < .001). Median RFS was not yet reached in the combination arm, compared with 16.6 months in the placebo arm. The RFS benefit was observed across all prespecified subgroups, and the combination was also found to improve OS, DMFS, and FFR.

The most common adverse events (AEs) included pyrexia, fatigue, nausea, rash, vomiting, diarrhea, chills, and myalgia. Overall, 97% of patients experienced an AE, 41% experienced a grade 3/4 AE, and 26% had an AE that led to treatment discontinuation. In patients treated with placebo, those numbers were 88%, 14%, and 3%, respectively.



The separate prescribing information for dabrafenib and trametinib detail warnings and precautions relating to their combined use, including the need to confirm BRAF status before starting therapy (because use in BRAF wildtype tumors can promote tumor cell proliferation), new primary malignancies, hemorrhage, cardiomyopathy, uveitis, serious febrile reactions, serious skin toxicity, hyperglycemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, colitis and gastrointestinal perforation, venous thromboembolism, ocular toxicities, interstitial lung disease, and embryofetal toxicity.

Dermatologic evaluations should be completed before starting therapy, every 2 months during and for up to 6 months after completion of therapy, and patients should be monitored closely for the signs and symptoms of noncutaneous primary malignancies. Treatment should be discontinued for all grade 4 hemorrhagic events and for any grade 3 events that do not improve, and withheld for grade 3 events until they resolve, at which point treatment can be resumed at the next lowest dose as described in the prescribing information.

Left ventricular ejection fraction (LVEF) values should be assessed before initiating therapy, after 1 month, and then at intervals of 2-3 months. Treatment should be withheld for up to 4 weeks if absolute LVEF values decrease by 10% and are less than the lower limit of normal (LLN) and it should be permanently discontinued for symptomatic cardiomyopathy or persistent, asymptomatic left ventricular dysfunction of >20% from baseline that is below LLN and does not resolve within 4 weeks.

Treatment should be withheld for fevers higher than 104°F or for serious febrile reactions or fever accompanied by hypotension, rigors or chills, dehydration, or renal failure. Serum creatinine levels should be monitored, along with other evidence of renal function, during, and after severe pyrexia. Antipyretics should be administered as secondary prophylaxis when treatment is resumed if the patient had previous episodes of severe febrile reaction or if fever was associated with complications. Corticosteroids should be administered for at least 5 days for second or subsequent pyrexia if the body temperature dose not return to baseline within 3 days of fever onset or for pyrexia associated with complications and no evidence of active infection.

Treatment should also be withheld for intolerable or severe skin toxicity and resumed at a lower dose as per guidelines in patients who improve or recover within 3 weeks. Serum glucose levels should be monitored at the start of treatment and as clinically appropriate in patients with pre-existing diabetes or hyperglycemia. Patients with G6PD deficiency should be monitored closely for signs of hemolytic anemia.

Patients should be monitored closely for signs and symptoms of colitis and gastrointestinal perforation and should be advised to immediately seek medical care if they develop symptoms of deep vein thrombosis (DVT) or pulmonary embolism (PE). Treatment should be permanently discontinued for life-threatening PE, or withheld for uncomplicated DVT and PE for up to 3 weeks and then resumed at a lower dose if the patient improves.

Ophthalmological evaluations should be performed periodically and within 24 hours of patient-reported loss of vision or other visual disturbances. Treatment should be permanently discontinued in patients with documented retinal vein occlusion and withheld for retinal pigment epithelial detachment. Treatment should also be withheld in patients presenting with new or progressive pulmonary symptoms and findings and permanently discontinued for treatment-related interstitial lung disease or pneumonitis.

Both dabrafenib and trametinib can cause fetal harm and patients should be warned of this risk and the need for adequate contraceptive measures. Dabrafenib and trametinib are marketed as Tafinlar and Mekinist by Novartis.

On April 30, 2018, the US Food and Drug Administration expanded the indication for the combined use of dabrafenib and trametinib to include adjuvant treatment of BRAF-mutant melanoma following complete surgical resection. Dabrafenib is an inhibitor of the BRAF kinase, and trametinib is an inhibitor of the MEK kinase, both of which are components of the mitogen-activated protein kinase (MAPK) signaling pathway. The 2 drugs are already approved as both single agents and in combination for the treatment of BRAF-mutated metastatic melanoma.

The current approval was based on data from a phase 3, international, multicenter, randomized, double-blind, placebo-controlled trial. The COMBI-AD trial was carried out from January 2013 through December 2014 at 169 sites in 26 countries. A total of 870 patients with stage III melanoma and BRAF V600E/K mutations and pathologic involvement of regional lymph nodes following complete resection were randomly assigned to receive dabrafenib 150 mg twice daily in combination with trametinib 2 mg once daily, or 2 matched placebos for up to 1 year. Randomization was stratified according to BRAF mutation status (V600E or V600K) and disease stage (IIIA, IIIB or IIIC).

Eligible patients were aged 18 years or older and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (on a scale of 1-5, with higher scores indicating greater disability). Patients who had undergone previous systemic anticancer therapy or radiotherapy were excluded from the study.

The primary endpoint was relapse-free survival (RFS), defined as the time from randomization to disease recurrence or death from any cause. Secondary endpoints included overall survival (OS), distant metastasis-free survival (DMFS), freedom from relapse (FFR), and safety. Clinical examination and imaging by computed tomography, magnetic resonance imaging, or both was performed every 3 months for the first 2 years and then every 6 months until disease recurrence or trial completion.

As of the data cut-off, the combination of dabrafenib and trametinib reduced the risk of disease recurrence or death by 53% compared with placebo (hazard ratio [HR], 0.47; P < .001). Median RFS was not yet reached in the combination arm, compared with 16.6 months in the placebo arm. The RFS benefit was observed across all prespecified subgroups, and the combination was also found to improve OS, DMFS, and FFR.

The most common adverse events (AEs) included pyrexia, fatigue, nausea, rash, vomiting, diarrhea, chills, and myalgia. Overall, 97% of patients experienced an AE, 41% experienced a grade 3/4 AE, and 26% had an AE that led to treatment discontinuation. In patients treated with placebo, those numbers were 88%, 14%, and 3%, respectively.



The separate prescribing information for dabrafenib and trametinib detail warnings and precautions relating to their combined use, including the need to confirm BRAF status before starting therapy (because use in BRAF wildtype tumors can promote tumor cell proliferation), new primary malignancies, hemorrhage, cardiomyopathy, uveitis, serious febrile reactions, serious skin toxicity, hyperglycemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, colitis and gastrointestinal perforation, venous thromboembolism, ocular toxicities, interstitial lung disease, and embryofetal toxicity.

Dermatologic evaluations should be completed before starting therapy, every 2 months during and for up to 6 months after completion of therapy, and patients should be monitored closely for the signs and symptoms of noncutaneous primary malignancies. Treatment should be discontinued for all grade 4 hemorrhagic events and for any grade 3 events that do not improve, and withheld for grade 3 events until they resolve, at which point treatment can be resumed at the next lowest dose as described in the prescribing information.

Left ventricular ejection fraction (LVEF) values should be assessed before initiating therapy, after 1 month, and then at intervals of 2-3 months. Treatment should be withheld for up to 4 weeks if absolute LVEF values decrease by 10% and are less than the lower limit of normal (LLN) and it should be permanently discontinued for symptomatic cardiomyopathy or persistent, asymptomatic left ventricular dysfunction of >20% from baseline that is below LLN and does not resolve within 4 weeks.

Treatment should be withheld for fevers higher than 104°F or for serious febrile reactions or fever accompanied by hypotension, rigors or chills, dehydration, or renal failure. Serum creatinine levels should be monitored, along with other evidence of renal function, during, and after severe pyrexia. Antipyretics should be administered as secondary prophylaxis when treatment is resumed if the patient had previous episodes of severe febrile reaction or if fever was associated with complications. Corticosteroids should be administered for at least 5 days for second or subsequent pyrexia if the body temperature dose not return to baseline within 3 days of fever onset or for pyrexia associated with complications and no evidence of active infection.

Treatment should also be withheld for intolerable or severe skin toxicity and resumed at a lower dose as per guidelines in patients who improve or recover within 3 weeks. Serum glucose levels should be monitored at the start of treatment and as clinically appropriate in patients with pre-existing diabetes or hyperglycemia. Patients with G6PD deficiency should be monitored closely for signs of hemolytic anemia.

Patients should be monitored closely for signs and symptoms of colitis and gastrointestinal perforation and should be advised to immediately seek medical care if they develop symptoms of deep vein thrombosis (DVT) or pulmonary embolism (PE). Treatment should be permanently discontinued for life-threatening PE, or withheld for uncomplicated DVT and PE for up to 3 weeks and then resumed at a lower dose if the patient improves.

Ophthalmological evaluations should be performed periodically and within 24 hours of patient-reported loss of vision or other visual disturbances. Treatment should be permanently discontinued in patients with documented retinal vein occlusion and withheld for retinal pigment epithelial detachment. Treatment should also be withheld in patients presenting with new or progressive pulmonary symptoms and findings and permanently discontinued for treatment-related interstitial lung disease or pneumonitis.

Both dabrafenib and trametinib can cause fetal harm and patients should be warned of this risk and the need for adequate contraceptive measures. Dabrafenib and trametinib are marketed as Tafinlar and Mekinist by Novartis.

References

1. US Food and Drug Administration Website. FDA approves dabrafenib plus trametinib for adjuvant treatment of melanoma with BRAF V600E or V600K mutations. https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm606165.htm. Last updated April 30, 2018. Accessed October 6, 2018.
2. Long GV, Hauschild A, Santinami M, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med. 2017;377:1913-1823.
3. Tafinlar (dabrafenib) capsules, for oral use. Prescribing information. Novartis. https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/tafinlar.pdf. May 2018. Accessed October 6, 2018.
4. Mekinist (trametinib) tablets, for oral use. Prescribing information. Novartis. https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/mekinist.pdf. May 2018. Accessed October 6th, 2018.

References

1. US Food and Drug Administration Website. FDA approves dabrafenib plus trametinib for adjuvant treatment of melanoma with BRAF V600E or V600K mutations. https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm606165.htm. Last updated April 30, 2018. Accessed October 6, 2018.
2. Long GV, Hauschild A, Santinami M, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med. 2017;377:1913-1823.
3. Tafinlar (dabrafenib) capsules, for oral use. Prescribing information. Novartis. https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/tafinlar.pdf. May 2018. Accessed October 6, 2018.
4. Mekinist (trametinib) tablets, for oral use. Prescribing information. Novartis. https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/mekinist.pdf. May 2018. Accessed October 6th, 2018.

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A novel tracer shows promise for detecting CD8 T-cells in advanced solid tumors

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Positron emission tomography (PET) using the CD8-tracer 89Zr-IAB22M2C was safe and provided detailed whole-body information on the biodistribution of CD8 T-cells in advanced solid tumors and reference tissue in an open-label, phase 1, first-in-human study.

The findings demonstrate the ability of the tracer–an anti-CD8 zirconium-labeled minibody–to noninvasively detect CD8 distribution in patients with metastatic solid tumors, potentially providing more information – and more quickly – than is possible with a single biopsy, Michael S. Gordon, MD, reported during a late-breaking abstract session at the annual meeting of the Society for Immunotherapy of Cancer.

During a dose escalation period (stage 1) of the study, six patients received 3 mCi of 89Zr-IAB22M2C once intravenously followed by serial PET scans over a period of 5-7 days. The patients received increasing protein doses of 0.2 through 10 mg to establish safety and determine a “recommended protein dose and scanning parameters for subsequent trials,” explained Dr. Gordon of HonorHealth Research Institute, Scottsdale, Ariz.

Stage 1 was followed by a dose expansion period (stage 2) in which an additional nine subjects were scanned to better delineate the recommended phase 2 study dose, he said.

All patients were monitored for drug-related adverse events and evaluated with blood chemistry, hematology, cytokine assay, and anti-drug antibodies. Biodistribution, radiodosimetry and semi-quantitative evaluation of CD8-tracer uptake were performed in all patients.

“We saw rapid clearance with excretion through the hepatobiliary mechanism, uptake in T-cell rich tissues, and no uptake in background normal tissues – so no uptake in muscle, heart, brain, or lungs,” he said, adding that “tumor uptake was variable and was clearly seen in 10 out of 15 patients.

“The protein dose that was considered to have favorable biodistribution was the range between 0.5 and 1.5, and based upon the analysis, the most favorable imaging time point ... was deemed to be 24 hours,” he said, noting that changes could be seen in as early as 6 hours.

 

 


The estimated mean effective radiation dose was 2.4 rem/mCi, “which is consistent with other zirconium-labeled antibody or minibody technologies,” Dr. Gordon said.

Study subjects ranged in age from 31 to 82 years and included nine men and six women with solid tumor malignancies who were eligible to receive checkpoint inhibitor therapy. Their primary cancer types were melanoma (eight patients), non–small-cell lung cancer (six patients), and hepatocellular carcinoma (one patient).

Two patients had received no prior treatment, three had discontinued prior checkpoint inhibitor therapy, and 10 were on immunotherapy.

No drug-related adverse events occurred during the course of the study, although one patient had a transient increase in anti-drug antibodies, Dr. Gordon said.

“Immunotherapy, and specifically checkpoint inhibitors (CPIs), have transformed the landscape of cancer care. Antitumor activity of CPIs is mediated by the CD8-positive T-cell cytotoxic effects, with preclinical and translational clinical studies demonstrating the importance of activated CD8-positive cells within the tumor microenvironment,” he explained, adding that currently available technology is limited in its ability to continually assess the presence of and change in the CD8 infiltrate; one biopsy may fail to capture the immunologic heterogeneity that exists among various tumors in an individual patient.

“As CPI therapy moves into front-line and earlier settings, the ability to have a noninvasive technology to assess whole body and intratumoral changes in CD8 trafficking or expansion in response to therapy is viewed as being crucial,” he said.

A phase 2 study to look closer at the potential for PET + 89Zr-IAB22M2C to fulfill that role will begin soon. The study will focus on correlating imaging with synchronous biopsies before and after primary immunotherapy to look for any predictive potential for this technology, he said.

This study was supported by ImaginAb and Parker Institute for Cancer Immunotherapy. Dr. Gordon reported having no disclosures.

SOURCE: Gordon M et al., SITC 2018: Abstract LB49.

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Positron emission tomography (PET) using the CD8-tracer 89Zr-IAB22M2C was safe and provided detailed whole-body information on the biodistribution of CD8 T-cells in advanced solid tumors and reference tissue in an open-label, phase 1, first-in-human study.

The findings demonstrate the ability of the tracer–an anti-CD8 zirconium-labeled minibody–to noninvasively detect CD8 distribution in patients with metastatic solid tumors, potentially providing more information – and more quickly – than is possible with a single biopsy, Michael S. Gordon, MD, reported during a late-breaking abstract session at the annual meeting of the Society for Immunotherapy of Cancer.

During a dose escalation period (stage 1) of the study, six patients received 3 mCi of 89Zr-IAB22M2C once intravenously followed by serial PET scans over a period of 5-7 days. The patients received increasing protein doses of 0.2 through 10 mg to establish safety and determine a “recommended protein dose and scanning parameters for subsequent trials,” explained Dr. Gordon of HonorHealth Research Institute, Scottsdale, Ariz.

Stage 1 was followed by a dose expansion period (stage 2) in which an additional nine subjects were scanned to better delineate the recommended phase 2 study dose, he said.

All patients were monitored for drug-related adverse events and evaluated with blood chemistry, hematology, cytokine assay, and anti-drug antibodies. Biodistribution, radiodosimetry and semi-quantitative evaluation of CD8-tracer uptake were performed in all patients.

“We saw rapid clearance with excretion through the hepatobiliary mechanism, uptake in T-cell rich tissues, and no uptake in background normal tissues – so no uptake in muscle, heart, brain, or lungs,” he said, adding that “tumor uptake was variable and was clearly seen in 10 out of 15 patients.

“The protein dose that was considered to have favorable biodistribution was the range between 0.5 and 1.5, and based upon the analysis, the most favorable imaging time point ... was deemed to be 24 hours,” he said, noting that changes could be seen in as early as 6 hours.

 

 


The estimated mean effective radiation dose was 2.4 rem/mCi, “which is consistent with other zirconium-labeled antibody or minibody technologies,” Dr. Gordon said.

Study subjects ranged in age from 31 to 82 years and included nine men and six women with solid tumor malignancies who were eligible to receive checkpoint inhibitor therapy. Their primary cancer types were melanoma (eight patients), non–small-cell lung cancer (six patients), and hepatocellular carcinoma (one patient).

Two patients had received no prior treatment, three had discontinued prior checkpoint inhibitor therapy, and 10 were on immunotherapy.

No drug-related adverse events occurred during the course of the study, although one patient had a transient increase in anti-drug antibodies, Dr. Gordon said.

“Immunotherapy, and specifically checkpoint inhibitors (CPIs), have transformed the landscape of cancer care. Antitumor activity of CPIs is mediated by the CD8-positive T-cell cytotoxic effects, with preclinical and translational clinical studies demonstrating the importance of activated CD8-positive cells within the tumor microenvironment,” he explained, adding that currently available technology is limited in its ability to continually assess the presence of and change in the CD8 infiltrate; one biopsy may fail to capture the immunologic heterogeneity that exists among various tumors in an individual patient.

“As CPI therapy moves into front-line and earlier settings, the ability to have a noninvasive technology to assess whole body and intratumoral changes in CD8 trafficking or expansion in response to therapy is viewed as being crucial,” he said.

A phase 2 study to look closer at the potential for PET + 89Zr-IAB22M2C to fulfill that role will begin soon. The study will focus on correlating imaging with synchronous biopsies before and after primary immunotherapy to look for any predictive potential for this technology, he said.

This study was supported by ImaginAb and Parker Institute for Cancer Immunotherapy. Dr. Gordon reported having no disclosures.

SOURCE: Gordon M et al., SITC 2018: Abstract LB49.

Positron emission tomography (PET) using the CD8-tracer 89Zr-IAB22M2C was safe and provided detailed whole-body information on the biodistribution of CD8 T-cells in advanced solid tumors and reference tissue in an open-label, phase 1, first-in-human study.

The findings demonstrate the ability of the tracer–an anti-CD8 zirconium-labeled minibody–to noninvasively detect CD8 distribution in patients with metastatic solid tumors, potentially providing more information – and more quickly – than is possible with a single biopsy, Michael S. Gordon, MD, reported during a late-breaking abstract session at the annual meeting of the Society for Immunotherapy of Cancer.

During a dose escalation period (stage 1) of the study, six patients received 3 mCi of 89Zr-IAB22M2C once intravenously followed by serial PET scans over a period of 5-7 days. The patients received increasing protein doses of 0.2 through 10 mg to establish safety and determine a “recommended protein dose and scanning parameters for subsequent trials,” explained Dr. Gordon of HonorHealth Research Institute, Scottsdale, Ariz.

Stage 1 was followed by a dose expansion period (stage 2) in which an additional nine subjects were scanned to better delineate the recommended phase 2 study dose, he said.

All patients were monitored for drug-related adverse events and evaluated with blood chemistry, hematology, cytokine assay, and anti-drug antibodies. Biodistribution, radiodosimetry and semi-quantitative evaluation of CD8-tracer uptake were performed in all patients.

“We saw rapid clearance with excretion through the hepatobiliary mechanism, uptake in T-cell rich tissues, and no uptake in background normal tissues – so no uptake in muscle, heart, brain, or lungs,” he said, adding that “tumor uptake was variable and was clearly seen in 10 out of 15 patients.

“The protein dose that was considered to have favorable biodistribution was the range between 0.5 and 1.5, and based upon the analysis, the most favorable imaging time point ... was deemed to be 24 hours,” he said, noting that changes could be seen in as early as 6 hours.

 

 


The estimated mean effective radiation dose was 2.4 rem/mCi, “which is consistent with other zirconium-labeled antibody or minibody technologies,” Dr. Gordon said.

Study subjects ranged in age from 31 to 82 years and included nine men and six women with solid tumor malignancies who were eligible to receive checkpoint inhibitor therapy. Their primary cancer types were melanoma (eight patients), non–small-cell lung cancer (six patients), and hepatocellular carcinoma (one patient).

Two patients had received no prior treatment, three had discontinued prior checkpoint inhibitor therapy, and 10 were on immunotherapy.

No drug-related adverse events occurred during the course of the study, although one patient had a transient increase in anti-drug antibodies, Dr. Gordon said.

“Immunotherapy, and specifically checkpoint inhibitors (CPIs), have transformed the landscape of cancer care. Antitumor activity of CPIs is mediated by the CD8-positive T-cell cytotoxic effects, with preclinical and translational clinical studies demonstrating the importance of activated CD8-positive cells within the tumor microenvironment,” he explained, adding that currently available technology is limited in its ability to continually assess the presence of and change in the CD8 infiltrate; one biopsy may fail to capture the immunologic heterogeneity that exists among various tumors in an individual patient.

“As CPI therapy moves into front-line and earlier settings, the ability to have a noninvasive technology to assess whole body and intratumoral changes in CD8 trafficking or expansion in response to therapy is viewed as being crucial,” he said.

A phase 2 study to look closer at the potential for PET + 89Zr-IAB22M2C to fulfill that role will begin soon. The study will focus on correlating imaging with synchronous biopsies before and after primary immunotherapy to look for any predictive potential for this technology, he said.

This study was supported by ImaginAb and Parker Institute for Cancer Immunotherapy. Dr. Gordon reported having no disclosures.

SOURCE: Gordon M et al., SITC 2018: Abstract LB49.

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Key clinical point: PET with CD8-tracer 89Zr-IAB22M2C is safe, provides detailed CD8 T-cell information.

Major finding: Tumor uptake of the CD8-tracer was seen in 10 of 15 subjects.

Study details: An open-label phase 1 study of 15 patients.

Disclosures: This study was supported by ImaginAb and Parker Institute for Cancer Immunotherapy. Dr. Gordon reported having no disclosures.

Source: Gordon M et al. SITC 2018: Abstract LB49.

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Strategies to Reduce Youth Indoor Tanning Injuries

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Strategies to Reduce Youth Indoor Tanning Injuries

Perusal of any lifestyle magazine reveals photographs of movie stars with sun-kissed skin. One can imagine their carefree lives afford ample time outdoors, a vast departure from the pasty masses trapped in their office cubicles. Our cultural norms dictate that a glowing look is a sign of health and attractiveness. Light-skinned individuals must receive regular exposure to sunlight to maintain their bronzed color. Over the last century, the indoor tanning industry has expanded to fill the niche created by the ceaseless pursuit of the ideal complexion.

 


Indoor tanning use causes up to 170,000 cases of skin cancer per year worldwide.1 Accumulating sunburns early in life is a leading risk factor for melanoma, the deadliest form of skin cancer. Campaigns to spread awareness about the link between UV radiation and skin cancer are ubiquitous. The US Food and Drug Administration (FDA) recommends against the use of tanning beds by minors, and several states have passed laws restricting their access. However, adolescents continue to engage. White female high school students remain frequenters of this practice, with more than 15% reporting current use of indoor tanning facilities.2 It seems targeted outreach and media campaigns are unsuccessful in influencing their behavior, and new approaches are needed.

Tanning-Related Injuries

Concentrated exposure to UV radiation during indoor tanning sessions carries the potential for immediate harm. Public health campaigns have focused on long-term skin cancer risk while overlooking thousands of injuries that occur annually at tanning salons across the country. The US Consumer Product Safety Commission first noted injuries associated with the largely unregulated tanning industry in 1974.3 In response, the FDA limited radiation levels, required indoor tanning devices to have timers and manual off switches, and mandated the use of protective eyewear. These changes sparked industry backlash due to the cost of compliance. The Indoor Tanning Association (no longer in operation) hired a lobbying firm in 2009 that successfully fought to resist further regulation.3

More than 3000 indoor tanning–related injuries are treated in emergency departments annually.4 White women aged 18 to 24 years who visit tanning salons are most likely to sustain injuries. In one study, severe skin burns accounted for 80% of emergency department visits, while the rest were due to fainting, eye injuries, and infections from unsanitary equipment.Timer malfunctions may play a role in tanning bed injuries, as several injured patients have reported falling asleep while tanning.4 Only 5% of tanning salons in North Carolina complied with FDA-recommended exposure schedules in 2003, suggesting that neglect or deliberate override of safety features also may contribute to injury.5

Challenges in Changing Tanning Behaviors

Use of indoor tanning facilities by adolescents is boosted by their misperceptions of peer engagement. Many teenagers overestimate the number of their peers who tan, which influences their own behavior.6 This phenomenon illustrates the importance of perceived social norms in this demographic group. Motivating adolescents to take actions that violate these norms poses a considerable challenge.

To teenagers, the perceived immediate benefits of indoor tanning far outweigh perceived costs. The immediate benefit of indoor tanning is having attractive skin, which may improve social standing and perceived self-worth. When adolescents weigh costs and benefits at different points in time, the present value of future events is discounted when compared to current events. For example, an immediate loss of $1000 is more impactful than losing $1000 ten years down the road. Adolescents are motivated to succeed in the short-term and may heavily discount future adverse effects such as the risk for developing cancer or premature aging of the skin. Therefore, getting a tan may be the “rational” decision even if there is an increased risk of future skin cancer.7

The addiction theory of tanning seeks to explain why individuals continue to tan despite knowledge of the associated risks. Exposure to UV radiation releases endorphins, producing a natural narcotic effect.8 The relaxing feeling sunbathers experience may lead to a phenomenon similar to addictions to opioids, alcohol, tobacco, and sugar. Behavior change is a process that unfolds over time. The 5 stages are precontemplation, contemplation, preparation, action, and maintenance.9 Education falls on deaf ears when the recipients are not ready to consider change. Individuals who are already thinking about cutting back on tanning fall into the category of contemplators and are the most open to educational techniques.9

 

 

Potential Solutions

Despite the dire long-term consequences of melanoma, warning adolescents of the increased cancer risk from tanning is an ineffective dissuasion strategy.10 Solutions that aim to limit tanning behaviors in this population should instead center on decreasing the present utility of a tan. Emphasis on the risk of immediate injury may be one effective route. The costs of potential damage to current appearance, vision, and overall health are not readily discounted by adolescents. Teens who devote time and money to the pursuit of a golden glow place high value on attractiveness. Such individuals respond best to loss-framed messages that focus on the impact of UV exposure on appearance, not just their health.11 However, appearance-motivated individuals may feel threatened by interventions that aim to reduce their decision freedom and display high reactance, leading them to reassert their freedom by resisting antitanning messages.12 Another strategy is altering media messaging to support a wider swathe of skin tones, reducing the social benefits of a tan. To swing the needle on our cultural norms, this intervention will require an enduring effort with backing from media outlets and celebrities.

Taxes on tanning salons and devices provide a basic economic disincentive to adolescents who typically have limited funds. State cigarette tax increases successfully reduced youth consumption of tobacco in the 1990s.13 A provision of the Patient Protection and Affordable Care Act levied a 10% excise tax on tanning salons with promising early results.14 Further taxation may generate revenue for educational campaigns on the injury risks of tanning. Continued safety improvements that limit user exposure to UV radiation and enforcement of FDA regulations also will decrease injury rates. Minimizing the UV output of tanning beds and designing protective equipment for tanners are 2 potential objectives. Improvement of over-the-counter sunless tanning agents also will provide alternatives to catching rays for adolescents who wish to attain a bronzed complexion.

Final Thoughts

Health care providers must assess a patient’s readiness for change and tailor interventions accordingly. Regardless of the method, new approaches to combat adolescent tanning injuries may reduce health care costs and minimize serious public health concerns for the next generation.

References
  1. Firger J. Indoor tanning injuries send thousands to the ER each year. CBS News. December 16, 2014. https://www.cbsnews.com/news/skin-cancer-burns-indoor-tanning-salon-injuries/. Accessed November 7, 2018.
  2. Guy GP, Berkowitz Z, Everett Jones S, et al. Prevalence of indoor tanning and association with sunburn among youth in the United States. JAMA Dermatol. 2017;153:387-390.
  3. Pulley MK. Government tan lines: examining the reach and effectiveness of federal and state efforts to protect consumers from the dangers of indoor tanning. Pepperdine Law Review. 2009;36:1163-1181.
  4. Guy GP Jr, Watson M, Haileyesus T, et al. Indoor tanning–related injuries treated in a national sample of US hospital emergency departments. JAMA Intern Med. 2015;175:309-311.
  5. Hornung RL, Magee KH, Lee WJ, et al. Tanning facility use: are we exceeding Food and Drug Administration limits? J Am Acad Dermatol. 2003;49:655-661.
  6. Hoerster KD, Mayer JA, Woodruff SI, et al. The influence of parents and peers on adolescent indoor tanning behavior: findings from a multi-city sample. J Am Acad Dermatol. 2007;57:990-997.
  7. Feldman SR, Dempsey JR, Grummer S, et al. Implications of a utility model for ultraviolet exposure behavior. J Am Acad Dermatol. 2001;45:718-722.
  8. Okhovat J, Feldman SR. Tanning: an addiction? The Melanoma Letter. 2013 Winter;31:5-7. https://www.skincancer.org/Media/Default/File/File/SCF_ML_31-3.pdf. Accessed November 11, 2017.
  9. Prochaska JO, DiClemente CC, Norcross JC. In search of how people change. applications to addictive behaviors. Am Psychol. 1992;47:1102-1114.
  10. Baker MK. Preventing Skin Cancer in Adolescent Girls Through Intervention With Their Mothers [dissertation]. Johnson City, TN: East Tennessee State University; 2013.
  11. Thomas K, Hevey D, Pertl M, et al. Appearance matters: the frame and focus of health messages influences beliefs about skin cancer. Br J Health Psychol. 2011;16(pt 2):418-429.
  12. Jones JL, Leary MR. Effects of appearance-based admonitions against sun exposure on tanning intentions in young adults. Health Psychol. 1994;13:86-90.
  13. Carpenter C, Cook PJ. Cigarette taxes and youth smoking: new evidence from national, state, and local youth risk behavior surveys. J Health Econ. 2008;27:287-99.
  14. Ryan E. The ‘tanning tax’ is a public health success story. Health Affairs website. https://www.healthaffairs.org/do/10.1377/hblog20170815.061547/full/. Published August 15, 2017. Accessed November 7, 2018.
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Mr. Hamid and Dr. Feldman are from the Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina. Dr. Feldman also is from the Departments of Pathology and Public Health Sciences. Dr. Fleischer is from the Department of Dermatology, University of Cincinnati, Ohio. Dr. Siegel is from the Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, and the Brooklyn VA Hospital, New York.

The authors report no conflict of interest.

Correspondence: Ramiz N. Hamid, MPH, Department of Dermatology, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1071 (hamid0615@gmail.com).

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Mr. Hamid and Dr. Feldman are from the Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina. Dr. Feldman also is from the Departments of Pathology and Public Health Sciences. Dr. Fleischer is from the Department of Dermatology, University of Cincinnati, Ohio. Dr. Siegel is from the Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, and the Brooklyn VA Hospital, New York.

The authors report no conflict of interest.

Correspondence: Ramiz N. Hamid, MPH, Department of Dermatology, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1071 (hamid0615@gmail.com).

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Mr. Hamid and Dr. Feldman are from the Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, North Carolina. Dr. Feldman also is from the Departments of Pathology and Public Health Sciences. Dr. Fleischer is from the Department of Dermatology, University of Cincinnati, Ohio. Dr. Siegel is from the Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, and the Brooklyn VA Hospital, New York.

The authors report no conflict of interest.

Correspondence: Ramiz N. Hamid, MPH, Department of Dermatology, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1071 (hamid0615@gmail.com).

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Perusal of any lifestyle magazine reveals photographs of movie stars with sun-kissed skin. One can imagine their carefree lives afford ample time outdoors, a vast departure from the pasty masses trapped in their office cubicles. Our cultural norms dictate that a glowing look is a sign of health and attractiveness. Light-skinned individuals must receive regular exposure to sunlight to maintain their bronzed color. Over the last century, the indoor tanning industry has expanded to fill the niche created by the ceaseless pursuit of the ideal complexion.

 


Indoor tanning use causes up to 170,000 cases of skin cancer per year worldwide.1 Accumulating sunburns early in life is a leading risk factor for melanoma, the deadliest form of skin cancer. Campaigns to spread awareness about the link between UV radiation and skin cancer are ubiquitous. The US Food and Drug Administration (FDA) recommends against the use of tanning beds by minors, and several states have passed laws restricting their access. However, adolescents continue to engage. White female high school students remain frequenters of this practice, with more than 15% reporting current use of indoor tanning facilities.2 It seems targeted outreach and media campaigns are unsuccessful in influencing their behavior, and new approaches are needed.

Tanning-Related Injuries

Concentrated exposure to UV radiation during indoor tanning sessions carries the potential for immediate harm. Public health campaigns have focused on long-term skin cancer risk while overlooking thousands of injuries that occur annually at tanning salons across the country. The US Consumer Product Safety Commission first noted injuries associated with the largely unregulated tanning industry in 1974.3 In response, the FDA limited radiation levels, required indoor tanning devices to have timers and manual off switches, and mandated the use of protective eyewear. These changes sparked industry backlash due to the cost of compliance. The Indoor Tanning Association (no longer in operation) hired a lobbying firm in 2009 that successfully fought to resist further regulation.3

More than 3000 indoor tanning–related injuries are treated in emergency departments annually.4 White women aged 18 to 24 years who visit tanning salons are most likely to sustain injuries. In one study, severe skin burns accounted for 80% of emergency department visits, while the rest were due to fainting, eye injuries, and infections from unsanitary equipment.Timer malfunctions may play a role in tanning bed injuries, as several injured patients have reported falling asleep while tanning.4 Only 5% of tanning salons in North Carolina complied with FDA-recommended exposure schedules in 2003, suggesting that neglect or deliberate override of safety features also may contribute to injury.5

Challenges in Changing Tanning Behaviors

Use of indoor tanning facilities by adolescents is boosted by their misperceptions of peer engagement. Many teenagers overestimate the number of their peers who tan, which influences their own behavior.6 This phenomenon illustrates the importance of perceived social norms in this demographic group. Motivating adolescents to take actions that violate these norms poses a considerable challenge.

To teenagers, the perceived immediate benefits of indoor tanning far outweigh perceived costs. The immediate benefit of indoor tanning is having attractive skin, which may improve social standing and perceived self-worth. When adolescents weigh costs and benefits at different points in time, the present value of future events is discounted when compared to current events. For example, an immediate loss of $1000 is more impactful than losing $1000 ten years down the road. Adolescents are motivated to succeed in the short-term and may heavily discount future adverse effects such as the risk for developing cancer or premature aging of the skin. Therefore, getting a tan may be the “rational” decision even if there is an increased risk of future skin cancer.7

The addiction theory of tanning seeks to explain why individuals continue to tan despite knowledge of the associated risks. Exposure to UV radiation releases endorphins, producing a natural narcotic effect.8 The relaxing feeling sunbathers experience may lead to a phenomenon similar to addictions to opioids, alcohol, tobacco, and sugar. Behavior change is a process that unfolds over time. The 5 stages are precontemplation, contemplation, preparation, action, and maintenance.9 Education falls on deaf ears when the recipients are not ready to consider change. Individuals who are already thinking about cutting back on tanning fall into the category of contemplators and are the most open to educational techniques.9

 

 

Potential Solutions

Despite the dire long-term consequences of melanoma, warning adolescents of the increased cancer risk from tanning is an ineffective dissuasion strategy.10 Solutions that aim to limit tanning behaviors in this population should instead center on decreasing the present utility of a tan. Emphasis on the risk of immediate injury may be one effective route. The costs of potential damage to current appearance, vision, and overall health are not readily discounted by adolescents. Teens who devote time and money to the pursuit of a golden glow place high value on attractiveness. Such individuals respond best to loss-framed messages that focus on the impact of UV exposure on appearance, not just their health.11 However, appearance-motivated individuals may feel threatened by interventions that aim to reduce their decision freedom and display high reactance, leading them to reassert their freedom by resisting antitanning messages.12 Another strategy is altering media messaging to support a wider swathe of skin tones, reducing the social benefits of a tan. To swing the needle on our cultural norms, this intervention will require an enduring effort with backing from media outlets and celebrities.

Taxes on tanning salons and devices provide a basic economic disincentive to adolescents who typically have limited funds. State cigarette tax increases successfully reduced youth consumption of tobacco in the 1990s.13 A provision of the Patient Protection and Affordable Care Act levied a 10% excise tax on tanning salons with promising early results.14 Further taxation may generate revenue for educational campaigns on the injury risks of tanning. Continued safety improvements that limit user exposure to UV radiation and enforcement of FDA regulations also will decrease injury rates. Minimizing the UV output of tanning beds and designing protective equipment for tanners are 2 potential objectives. Improvement of over-the-counter sunless tanning agents also will provide alternatives to catching rays for adolescents who wish to attain a bronzed complexion.

Final Thoughts

Health care providers must assess a patient’s readiness for change and tailor interventions accordingly. Regardless of the method, new approaches to combat adolescent tanning injuries may reduce health care costs and minimize serious public health concerns for the next generation.

Perusal of any lifestyle magazine reveals photographs of movie stars with sun-kissed skin. One can imagine their carefree lives afford ample time outdoors, a vast departure from the pasty masses trapped in their office cubicles. Our cultural norms dictate that a glowing look is a sign of health and attractiveness. Light-skinned individuals must receive regular exposure to sunlight to maintain their bronzed color. Over the last century, the indoor tanning industry has expanded to fill the niche created by the ceaseless pursuit of the ideal complexion.

 


Indoor tanning use causes up to 170,000 cases of skin cancer per year worldwide.1 Accumulating sunburns early in life is a leading risk factor for melanoma, the deadliest form of skin cancer. Campaigns to spread awareness about the link between UV radiation and skin cancer are ubiquitous. The US Food and Drug Administration (FDA) recommends against the use of tanning beds by minors, and several states have passed laws restricting their access. However, adolescents continue to engage. White female high school students remain frequenters of this practice, with more than 15% reporting current use of indoor tanning facilities.2 It seems targeted outreach and media campaigns are unsuccessful in influencing their behavior, and new approaches are needed.

Tanning-Related Injuries

Concentrated exposure to UV radiation during indoor tanning sessions carries the potential for immediate harm. Public health campaigns have focused on long-term skin cancer risk while overlooking thousands of injuries that occur annually at tanning salons across the country. The US Consumer Product Safety Commission first noted injuries associated with the largely unregulated tanning industry in 1974.3 In response, the FDA limited radiation levels, required indoor tanning devices to have timers and manual off switches, and mandated the use of protective eyewear. These changes sparked industry backlash due to the cost of compliance. The Indoor Tanning Association (no longer in operation) hired a lobbying firm in 2009 that successfully fought to resist further regulation.3

More than 3000 indoor tanning–related injuries are treated in emergency departments annually.4 White women aged 18 to 24 years who visit tanning salons are most likely to sustain injuries. In one study, severe skin burns accounted for 80% of emergency department visits, while the rest were due to fainting, eye injuries, and infections from unsanitary equipment.Timer malfunctions may play a role in tanning bed injuries, as several injured patients have reported falling asleep while tanning.4 Only 5% of tanning salons in North Carolina complied with FDA-recommended exposure schedules in 2003, suggesting that neglect or deliberate override of safety features also may contribute to injury.5

Challenges in Changing Tanning Behaviors

Use of indoor tanning facilities by adolescents is boosted by their misperceptions of peer engagement. Many teenagers overestimate the number of their peers who tan, which influences their own behavior.6 This phenomenon illustrates the importance of perceived social norms in this demographic group. Motivating adolescents to take actions that violate these norms poses a considerable challenge.

To teenagers, the perceived immediate benefits of indoor tanning far outweigh perceived costs. The immediate benefit of indoor tanning is having attractive skin, which may improve social standing and perceived self-worth. When adolescents weigh costs and benefits at different points in time, the present value of future events is discounted when compared to current events. For example, an immediate loss of $1000 is more impactful than losing $1000 ten years down the road. Adolescents are motivated to succeed in the short-term and may heavily discount future adverse effects such as the risk for developing cancer or premature aging of the skin. Therefore, getting a tan may be the “rational” decision even if there is an increased risk of future skin cancer.7

The addiction theory of tanning seeks to explain why individuals continue to tan despite knowledge of the associated risks. Exposure to UV radiation releases endorphins, producing a natural narcotic effect.8 The relaxing feeling sunbathers experience may lead to a phenomenon similar to addictions to opioids, alcohol, tobacco, and sugar. Behavior change is a process that unfolds over time. The 5 stages are precontemplation, contemplation, preparation, action, and maintenance.9 Education falls on deaf ears when the recipients are not ready to consider change. Individuals who are already thinking about cutting back on tanning fall into the category of contemplators and are the most open to educational techniques.9

 

 

Potential Solutions

Despite the dire long-term consequences of melanoma, warning adolescents of the increased cancer risk from tanning is an ineffective dissuasion strategy.10 Solutions that aim to limit tanning behaviors in this population should instead center on decreasing the present utility of a tan. Emphasis on the risk of immediate injury may be one effective route. The costs of potential damage to current appearance, vision, and overall health are not readily discounted by adolescents. Teens who devote time and money to the pursuit of a golden glow place high value on attractiveness. Such individuals respond best to loss-framed messages that focus on the impact of UV exposure on appearance, not just their health.11 However, appearance-motivated individuals may feel threatened by interventions that aim to reduce their decision freedom and display high reactance, leading them to reassert their freedom by resisting antitanning messages.12 Another strategy is altering media messaging to support a wider swathe of skin tones, reducing the social benefits of a tan. To swing the needle on our cultural norms, this intervention will require an enduring effort with backing from media outlets and celebrities.

Taxes on tanning salons and devices provide a basic economic disincentive to adolescents who typically have limited funds. State cigarette tax increases successfully reduced youth consumption of tobacco in the 1990s.13 A provision of the Patient Protection and Affordable Care Act levied a 10% excise tax on tanning salons with promising early results.14 Further taxation may generate revenue for educational campaigns on the injury risks of tanning. Continued safety improvements that limit user exposure to UV radiation and enforcement of FDA regulations also will decrease injury rates. Minimizing the UV output of tanning beds and designing protective equipment for tanners are 2 potential objectives. Improvement of over-the-counter sunless tanning agents also will provide alternatives to catching rays for adolescents who wish to attain a bronzed complexion.

Final Thoughts

Health care providers must assess a patient’s readiness for change and tailor interventions accordingly. Regardless of the method, new approaches to combat adolescent tanning injuries may reduce health care costs and minimize serious public health concerns for the next generation.

References
  1. Firger J. Indoor tanning injuries send thousands to the ER each year. CBS News. December 16, 2014. https://www.cbsnews.com/news/skin-cancer-burns-indoor-tanning-salon-injuries/. Accessed November 7, 2018.
  2. Guy GP, Berkowitz Z, Everett Jones S, et al. Prevalence of indoor tanning and association with sunburn among youth in the United States. JAMA Dermatol. 2017;153:387-390.
  3. Pulley MK. Government tan lines: examining the reach and effectiveness of federal and state efforts to protect consumers from the dangers of indoor tanning. Pepperdine Law Review. 2009;36:1163-1181.
  4. Guy GP Jr, Watson M, Haileyesus T, et al. Indoor tanning–related injuries treated in a national sample of US hospital emergency departments. JAMA Intern Med. 2015;175:309-311.
  5. Hornung RL, Magee KH, Lee WJ, et al. Tanning facility use: are we exceeding Food and Drug Administration limits? J Am Acad Dermatol. 2003;49:655-661.
  6. Hoerster KD, Mayer JA, Woodruff SI, et al. The influence of parents and peers on adolescent indoor tanning behavior: findings from a multi-city sample. J Am Acad Dermatol. 2007;57:990-997.
  7. Feldman SR, Dempsey JR, Grummer S, et al. Implications of a utility model for ultraviolet exposure behavior. J Am Acad Dermatol. 2001;45:718-722.
  8. Okhovat J, Feldman SR. Tanning: an addiction? The Melanoma Letter. 2013 Winter;31:5-7. https://www.skincancer.org/Media/Default/File/File/SCF_ML_31-3.pdf. Accessed November 11, 2017.
  9. Prochaska JO, DiClemente CC, Norcross JC. In search of how people change. applications to addictive behaviors. Am Psychol. 1992;47:1102-1114.
  10. Baker MK. Preventing Skin Cancer in Adolescent Girls Through Intervention With Their Mothers [dissertation]. Johnson City, TN: East Tennessee State University; 2013.
  11. Thomas K, Hevey D, Pertl M, et al. Appearance matters: the frame and focus of health messages influences beliefs about skin cancer. Br J Health Psychol. 2011;16(pt 2):418-429.
  12. Jones JL, Leary MR. Effects of appearance-based admonitions against sun exposure on tanning intentions in young adults. Health Psychol. 1994;13:86-90.
  13. Carpenter C, Cook PJ. Cigarette taxes and youth smoking: new evidence from national, state, and local youth risk behavior surveys. J Health Econ. 2008;27:287-99.
  14. Ryan E. The ‘tanning tax’ is a public health success story. Health Affairs website. https://www.healthaffairs.org/do/10.1377/hblog20170815.061547/full/. Published August 15, 2017. Accessed November 7, 2018.
References
  1. Firger J. Indoor tanning injuries send thousands to the ER each year. CBS News. December 16, 2014. https://www.cbsnews.com/news/skin-cancer-burns-indoor-tanning-salon-injuries/. Accessed November 7, 2018.
  2. Guy GP, Berkowitz Z, Everett Jones S, et al. Prevalence of indoor tanning and association with sunburn among youth in the United States. JAMA Dermatol. 2017;153:387-390.
  3. Pulley MK. Government tan lines: examining the reach and effectiveness of federal and state efforts to protect consumers from the dangers of indoor tanning. Pepperdine Law Review. 2009;36:1163-1181.
  4. Guy GP Jr, Watson M, Haileyesus T, et al. Indoor tanning–related injuries treated in a national sample of US hospital emergency departments. JAMA Intern Med. 2015;175:309-311.
  5. Hornung RL, Magee KH, Lee WJ, et al. Tanning facility use: are we exceeding Food and Drug Administration limits? J Am Acad Dermatol. 2003;49:655-661.
  6. Hoerster KD, Mayer JA, Woodruff SI, et al. The influence of parents and peers on adolescent indoor tanning behavior: findings from a multi-city sample. J Am Acad Dermatol. 2007;57:990-997.
  7. Feldman SR, Dempsey JR, Grummer S, et al. Implications of a utility model for ultraviolet exposure behavior. J Am Acad Dermatol. 2001;45:718-722.
  8. Okhovat J, Feldman SR. Tanning: an addiction? The Melanoma Letter. 2013 Winter;31:5-7. https://www.skincancer.org/Media/Default/File/File/SCF_ML_31-3.pdf. Accessed November 11, 2017.
  9. Prochaska JO, DiClemente CC, Norcross JC. In search of how people change. applications to addictive behaviors. Am Psychol. 1992;47:1102-1114.
  10. Baker MK. Preventing Skin Cancer in Adolescent Girls Through Intervention With Their Mothers [dissertation]. Johnson City, TN: East Tennessee State University; 2013.
  11. Thomas K, Hevey D, Pertl M, et al. Appearance matters: the frame and focus of health messages influences beliefs about skin cancer. Br J Health Psychol. 2011;16(pt 2):418-429.
  12. Jones JL, Leary MR. Effects of appearance-based admonitions against sun exposure on tanning intentions in young adults. Health Psychol. 1994;13:86-90.
  13. Carpenter C, Cook PJ. Cigarette taxes and youth smoking: new evidence from national, state, and local youth risk behavior surveys. J Health Econ. 2008;27:287-99.
  14. Ryan E. The ‘tanning tax’ is a public health success story. Health Affairs website. https://www.healthaffairs.org/do/10.1377/hblog20170815.061547/full/. Published August 15, 2017. Accessed November 7, 2018.
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Second-melanoma risk higher with indoor tanning

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Patients who use indoor tanning beds are more likely to develop a second primary melanoma, and do it more quickly, than those who avoid indoor tanning, according to a retrospective study involving 434 melanoma patients.

Over the course of the study, 88 patients developed multiple primary melanomas. In the year after the original diagnosis, 56% of the patients exposed to artificial UV radiation (UVR) were diagnosed with a second primary melanoma versus 18% of the nonexposed subjects, Yang Li of Washington University, St. Louis, and her associates said in the Journal of the American Academy of Dermatology.

The incidence of second melanomas over the entire 16-year course of the study was 25.2% among the tanning-bed users and 18.6% for nonusers. Among these study subjects – 27 with tanning-bed exposure and 61 without – median time to the second tumor was 225 days (0.62 years) for exposed patients and 1,280 days (3.50 years) for those with no exposure, the investigators reported.

This study, they wrote, is the first to show that “patients who had second primary melanoma diagnoses were more likely to have had” exposure to artificial UVR. The increased radiation intensity of tanning beds, “as opposed to UVR from ambient sunlight, in a physiologically vulnerable patient population [fair-skinned persons] at an early age contributes to our findings of decreased tumor lag time.”

SOURCE: Li Y et al. J Am Acad Dermatol. 2018;79(6):1101-8.

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Patients who use indoor tanning beds are more likely to develop a second primary melanoma, and do it more quickly, than those who avoid indoor tanning, according to a retrospective study involving 434 melanoma patients.

Over the course of the study, 88 patients developed multiple primary melanomas. In the year after the original diagnosis, 56% of the patients exposed to artificial UV radiation (UVR) were diagnosed with a second primary melanoma versus 18% of the nonexposed subjects, Yang Li of Washington University, St. Louis, and her associates said in the Journal of the American Academy of Dermatology.

The incidence of second melanomas over the entire 16-year course of the study was 25.2% among the tanning-bed users and 18.6% for nonusers. Among these study subjects – 27 with tanning-bed exposure and 61 without – median time to the second tumor was 225 days (0.62 years) for exposed patients and 1,280 days (3.50 years) for those with no exposure, the investigators reported.

This study, they wrote, is the first to show that “patients who had second primary melanoma diagnoses were more likely to have had” exposure to artificial UVR. The increased radiation intensity of tanning beds, “as opposed to UVR from ambient sunlight, in a physiologically vulnerable patient population [fair-skinned persons] at an early age contributes to our findings of decreased tumor lag time.”

SOURCE: Li Y et al. J Am Acad Dermatol. 2018;79(6):1101-8.

 

Patients who use indoor tanning beds are more likely to develop a second primary melanoma, and do it more quickly, than those who avoid indoor tanning, according to a retrospective study involving 434 melanoma patients.

Over the course of the study, 88 patients developed multiple primary melanomas. In the year after the original diagnosis, 56% of the patients exposed to artificial UV radiation (UVR) were diagnosed with a second primary melanoma versus 18% of the nonexposed subjects, Yang Li of Washington University, St. Louis, and her associates said in the Journal of the American Academy of Dermatology.

The incidence of second melanomas over the entire 16-year course of the study was 25.2% among the tanning-bed users and 18.6% for nonusers. Among these study subjects – 27 with tanning-bed exposure and 61 without – median time to the second tumor was 225 days (0.62 years) for exposed patients and 1,280 days (3.50 years) for those with no exposure, the investigators reported.

This study, they wrote, is the first to show that “patients who had second primary melanoma diagnoses were more likely to have had” exposure to artificial UVR. The increased radiation intensity of tanning beds, “as opposed to UVR from ambient sunlight, in a physiologically vulnerable patient population [fair-skinned persons] at an early age contributes to our findings of decreased tumor lag time.”

SOURCE: Li Y et al. J Am Acad Dermatol. 2018;79(6):1101-8.

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SRS beats surgery in early control of brain mets, advantage fades with time

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tereotactic radiosurgery (SRS) provides better early local control of brain metastases than complete surgical resection, but this advantage fades with time, according to investigators.

By 6 months, lower risks associated with SRS shifted in favor of those who had surgical resection, reported lead author Thomas Churilla, MD, of Fox Chase Cancer Center in Philadelphia and his colleagues.

“Outside recognized indications for surgery such as establishing diagnosis or relieving mass effect, little evidence is available to guide the therapeutic choice of SRS vs. surgical resection in the treatment of patients with limited brain metastases,” the investigators wrote in JAMA Oncology.

The investigators performed an exploratory analysis of data from the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial, which was designed to evaluate whole-brain radiotherapy for patients with one to three brain metastases who had undergone SRS or complete surgical resection. The present analysis involved 268 patients, of whom 154 had SRS and 114 had complete surgical resection.

Primary tumors included lung, breast, colorectum, kidney, and melanoma. Initial analysis showed that patients undergoing surgical resection, compared with those who had SRS, typically had larger brain metastases (median, 28 mm vs. 20 mm) and more often had 1 brain metastasis (98.2% vs. 74.0%). Mass locality also differed between groups; compared with patients receiving SRS, surgical patients more often had metastases in the posterior fossa (26.3% vs. 7.8%) and less often in the parietal lobe (18.4% vs. 39.6%).

After median follow-up of 39.9 months, risks of local recurrence were similar between surgical and SRS groups (hazard ratio, 1.15). Stratifying by interval, however, showed that surgical patients were at much higher risk of local recurrence in the first 3 months following treatment (HR for 0-3 months, 5.94). Of note, this risk faded with time (HR for 3-6 months, 1.37; HR for 6-9 months, 0.75; HR for 9 months or longer, 0.36). From the 6-9 months interval onward, surgical patients had lower risk of recurrence, compared with SRS patients, and the risk even decreased after the 6-9 month interval.

“Prospective controlled trials are warranted to direct the optimal local approach for patients with brain metastases and to define whether any population may benefit from escalation in local therapy,” the investigators concluded.

The study was funded by the National Cancer Institute, National Institutes of Health, and Fonds Cancer in Belgium. One author reported receiving financial compensation from Pfizer via her institution.

SOURCE: Churilla T et al. JAMA Onc. 2018. doi: 10.1001/jamaoncol.2018.4610.
 

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tereotactic radiosurgery (SRS) provides better early local control of brain metastases than complete surgical resection, but this advantage fades with time, according to investigators.

By 6 months, lower risks associated with SRS shifted in favor of those who had surgical resection, reported lead author Thomas Churilla, MD, of Fox Chase Cancer Center in Philadelphia and his colleagues.

“Outside recognized indications for surgery such as establishing diagnosis or relieving mass effect, little evidence is available to guide the therapeutic choice of SRS vs. surgical resection in the treatment of patients with limited brain metastases,” the investigators wrote in JAMA Oncology.

The investigators performed an exploratory analysis of data from the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial, which was designed to evaluate whole-brain radiotherapy for patients with one to three brain metastases who had undergone SRS or complete surgical resection. The present analysis involved 268 patients, of whom 154 had SRS and 114 had complete surgical resection.

Primary tumors included lung, breast, colorectum, kidney, and melanoma. Initial analysis showed that patients undergoing surgical resection, compared with those who had SRS, typically had larger brain metastases (median, 28 mm vs. 20 mm) and more often had 1 brain metastasis (98.2% vs. 74.0%). Mass locality also differed between groups; compared with patients receiving SRS, surgical patients more often had metastases in the posterior fossa (26.3% vs. 7.8%) and less often in the parietal lobe (18.4% vs. 39.6%).

After median follow-up of 39.9 months, risks of local recurrence were similar between surgical and SRS groups (hazard ratio, 1.15). Stratifying by interval, however, showed that surgical patients were at much higher risk of local recurrence in the first 3 months following treatment (HR for 0-3 months, 5.94). Of note, this risk faded with time (HR for 3-6 months, 1.37; HR for 6-9 months, 0.75; HR for 9 months or longer, 0.36). From the 6-9 months interval onward, surgical patients had lower risk of recurrence, compared with SRS patients, and the risk even decreased after the 6-9 month interval.

“Prospective controlled trials are warranted to direct the optimal local approach for patients with brain metastases and to define whether any population may benefit from escalation in local therapy,” the investigators concluded.

The study was funded by the National Cancer Institute, National Institutes of Health, and Fonds Cancer in Belgium. One author reported receiving financial compensation from Pfizer via her institution.

SOURCE: Churilla T et al. JAMA Onc. 2018. doi: 10.1001/jamaoncol.2018.4610.
 

 

tereotactic radiosurgery (SRS) provides better early local control of brain metastases than complete surgical resection, but this advantage fades with time, according to investigators.

By 6 months, lower risks associated with SRS shifted in favor of those who had surgical resection, reported lead author Thomas Churilla, MD, of Fox Chase Cancer Center in Philadelphia and his colleagues.

“Outside recognized indications for surgery such as establishing diagnosis or relieving mass effect, little evidence is available to guide the therapeutic choice of SRS vs. surgical resection in the treatment of patients with limited brain metastases,” the investigators wrote in JAMA Oncology.

The investigators performed an exploratory analysis of data from the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial, which was designed to evaluate whole-brain radiotherapy for patients with one to three brain metastases who had undergone SRS or complete surgical resection. The present analysis involved 268 patients, of whom 154 had SRS and 114 had complete surgical resection.

Primary tumors included lung, breast, colorectum, kidney, and melanoma. Initial analysis showed that patients undergoing surgical resection, compared with those who had SRS, typically had larger brain metastases (median, 28 mm vs. 20 mm) and more often had 1 brain metastasis (98.2% vs. 74.0%). Mass locality also differed between groups; compared with patients receiving SRS, surgical patients more often had metastases in the posterior fossa (26.3% vs. 7.8%) and less often in the parietal lobe (18.4% vs. 39.6%).

After median follow-up of 39.9 months, risks of local recurrence were similar between surgical and SRS groups (hazard ratio, 1.15). Stratifying by interval, however, showed that surgical patients were at much higher risk of local recurrence in the first 3 months following treatment (HR for 0-3 months, 5.94). Of note, this risk faded with time (HR for 3-6 months, 1.37; HR for 6-9 months, 0.75; HR for 9 months or longer, 0.36). From the 6-9 months interval onward, surgical patients had lower risk of recurrence, compared with SRS patients, and the risk even decreased after the 6-9 month interval.

“Prospective controlled trials are warranted to direct the optimal local approach for patients with brain metastases and to define whether any population may benefit from escalation in local therapy,” the investigators concluded.

The study was funded by the National Cancer Institute, National Institutes of Health, and Fonds Cancer in Belgium. One author reported receiving financial compensation from Pfizer via her institution.

SOURCE: Churilla T et al. JAMA Onc. 2018. doi: 10.1001/jamaoncol.2018.4610.
 

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Key clinical point: Stereotactic radiosurgery (SRS) provides better early local control of brain metastases than surgical resection, but this advantage fades with time.

Major finding: Patients treated with surgery were more likely to have local recurrence in the first 3 months following treatment, compared with patients treated with SRS (hazard ratio, 5.94).

Study details: An exploratory analysis of data from the European Organization for the Research and Treatment of Cancer (EORTC) 22952-26001 phase 3 trial. Analysis involved 268 patients with one to three brain metastases who underwent whole-brain radiotherapy or observation after SRS (n = 154) or complete surgical resection (n = 114).

Disclosures: The study was funded by the National Cancer Institute, National Institutes of Health, and Fonds Cancer in Belgium. Dr. Handorf reported financial compensation from Pfizer, via her institution.

Source: Churilla T et al. JAMA Onc. 2018. doi: 10.1001/jamaoncol.2018.4610.

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New pregnancy, genetic testing guidance added to AAD’s melanoma guidelines

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Pregnancy does not necessarily increase a woman’s risk for melanoma, nor is it clear that becoming pregnant affects melanoma’s disease course, according to current evidence. This guidance is among several updates added to newly released guidelines for managing patients with primary cutaneous melanoma.

Dr. Susan Swetter

The American Academy of Dermatology, which formed a working group to develop the updated cutaneous melanoma (CM) treatment guidelines, also addressed the burgeoning field of genetic testing for cancer in the guidelines, which were published online on Nov. 1. Although there may be a hereditary component to some melanomas, genetic testing may not be appropriate for all patients, and any formal genetic testing should be carried out only after individualized education and counseling, according to the updates.

However, the guidelines make it clear that all patients whose family history includes melanoma should be counseled about their genetic risk.

As with genetic testing, counseling regarding future pregnancies for women with melanoma, or a history of melanoma, should be personalized and account for individual history and melanoma risk, according to the new guidelines. Since evidence is lacking that pregnancy affects the course of melanoma, physicians caring for pregnant women with melanoma should first look at patient and the disease characteristics. The addition of detailed guidance regarding pregnancy reflects research showing that CM is the most common malignancy seen in pregnancy, amounting to nearly one-third of the malignancies that arise in pregnancy. “Although the incidence of CM is generally higher in men, it is higher in younger women than in men, most notably during women’s reproductive years,” wrote Susan M. Swetter, MD, and her guideline coauthors.

The National Cancer Institute

“Melanoma is the deadliest form of skin cancer, and we hope these guidelines will help dermatologists and other physicians enhance their delivery of life-saving treatment to patients,” Dr. Swetter said in a press release announcing the guideline updates. Dr. Swetter, professor of dermatology and director of the pigmented lesion and melanoma program at Stanford (Calif.) University Medical Center and Cancer Institute, led the working group that developed the guidelines. “In order to provide the best possible resource for practitioners, we reviewed the latest scientific data and addressed certain topics that weren’t covered in the AAD’s previous melanoma guidelines,” she said.

A cornerstone of cutaneous melanoma care remains unchanged in the guidelines: Surgical excision is still the preferred method for treating melanoma. Adjuvant topical therapies or radiation, say the guidelines, can be considered as second-line care, but only in limited situations in which surgery is not feasible. Staged excision techniques, such as Mohs surgery, also may be considered for certain types of melanoma and in certain body areas.

 

 


In an interview, Dr. Swetter also said that is critical that the updated guidelines have been harmonized with changes made in the American Joint Committee on Cancer’s 8th edition of its melanoma staging manual. Key points for dermatologists to understand that reporting of Breslow thickness to the nearest 1/10th decimal point (over the nearest 1/100th), such that a melanoma measuring 0.75-0.84 mm in thickness would be reported as 0.8 mm depth and one between 0.95-1.04 mm would be rounded to 1 mm.

The main changes regarding staging of thin (T1) melanoma – that is less than or equal to 1 mm – is that the 0.8 mm thickness is the threshold for a T1a melanoma (now classified as less than 0.8 mm without ulceration), whereas T1b is now 0.8 – 1.0 mm thickness with or w/out ulceration or less than 0.8 mm thickness with ulceration. A T1a melanoma generally is not considered appropriate for staging of the regional lymph nodes with sentinel lymph node biopsy (with exceptions noted in the guideline), whereas a T1b melanoma may be considered for SLNB staging – though rates of SLN positivity remain relatively low in the T1b group.”

Dr. Swetter also emphasized that histologic ulceration of the primary tumor was affirmed as an indicator of worse prognosis; mitotic rate, although removed from T1 staging, is still tracked by pathologists and still seen as an independent predictor of worse prognosis, according to the 8th edition, she said.

A cornerstone of cutaneous melanoma care remains unchanged in the guidelines: Surgical excision is still the preferred method for treating melanoma. “Mohs micrographic surgery and other staged excision techniques can provide exhaustive peripheral margin histologic assessment for melanoma in situ, lentigo maligna type and tissue sparing in anatomically constrained sites,” Dr. Swetter said. “Current data are insufficient to recommend Mohs surgery for invasive cutaneous melanoma, in which the use of surgical margins less than 1 cm has not been adequately studied,” she cautioned.

Reinforcing the importance of surgery as the primary treatment for melanoma, Dr. Swetter clarified that “Nonsurgical approaches (imiquimod and traditional forms of radiation therapy) should be considered [only] if surgery is impractical or contraindicated, and only for melanoma in situ, lentigo maligna type, as cure rates are lower.”

In terms of other therapies, the guideline working group found insufficient evidence to recommend electronic brachytherapy for melanoma.

Assessment of novel diagnostic and molecular imaging modalities was not the primary focus of the AAD guidelines, Dr. Swetter pointed out. Looking to the future, though, she added that the hope is “that these prebiopsy modalities can one day reduce unnecessary biopsies from being done” in the clinic.

Other knowledge gaps cited by the working group included several related to pathology, including determination of appropriate margin control in some lesion types, and the quest to reduce inter-reader variability in histopathologic diagnosis of melanocytic tissue samples. However, noted Dr. Swetter and her coauthors, the rapid pace of genomic medicine advances “may make many of the aforementioned issues obsolete” before the next guideline update.

In the interview, Dr. Swetter said that the guidelines reflect evolving thinking about melanoma in the context of a rapidly growing field. “Only in the last year have effective, more tolerable adjuvant therapies been [Food and Drug Administration] approved for patients with resected stage III melanoma, including patients with regional lymph node disease detected via sentinel lymph node biopsy. The hope is that less invasive procedures for melanoma will be performed in the future, and replaced by better drugs and novel techniques.”

Dr. Swetter reported that she had no relevant financial disclosures; several working group members reported multiple financial relationships with pharmaceutical, diagnostic, and imaging companies. Working group members were recused from discussion of guidelines where their particular relationships might pose a conflict of interest.

SOURCE: Swetter S. et al. J Am Acad Dermatol. 2011 Nov;65(5):1032-47.

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Pregnancy does not necessarily increase a woman’s risk for melanoma, nor is it clear that becoming pregnant affects melanoma’s disease course, according to current evidence. This guidance is among several updates added to newly released guidelines for managing patients with primary cutaneous melanoma.

Dr. Susan Swetter

The American Academy of Dermatology, which formed a working group to develop the updated cutaneous melanoma (CM) treatment guidelines, also addressed the burgeoning field of genetic testing for cancer in the guidelines, which were published online on Nov. 1. Although there may be a hereditary component to some melanomas, genetic testing may not be appropriate for all patients, and any formal genetic testing should be carried out only after individualized education and counseling, according to the updates.

However, the guidelines make it clear that all patients whose family history includes melanoma should be counseled about their genetic risk.

As with genetic testing, counseling regarding future pregnancies for women with melanoma, or a history of melanoma, should be personalized and account for individual history and melanoma risk, according to the new guidelines. Since evidence is lacking that pregnancy affects the course of melanoma, physicians caring for pregnant women with melanoma should first look at patient and the disease characteristics. The addition of detailed guidance regarding pregnancy reflects research showing that CM is the most common malignancy seen in pregnancy, amounting to nearly one-third of the malignancies that arise in pregnancy. “Although the incidence of CM is generally higher in men, it is higher in younger women than in men, most notably during women’s reproductive years,” wrote Susan M. Swetter, MD, and her guideline coauthors.

The National Cancer Institute

“Melanoma is the deadliest form of skin cancer, and we hope these guidelines will help dermatologists and other physicians enhance their delivery of life-saving treatment to patients,” Dr. Swetter said in a press release announcing the guideline updates. Dr. Swetter, professor of dermatology and director of the pigmented lesion and melanoma program at Stanford (Calif.) University Medical Center and Cancer Institute, led the working group that developed the guidelines. “In order to provide the best possible resource for practitioners, we reviewed the latest scientific data and addressed certain topics that weren’t covered in the AAD’s previous melanoma guidelines,” she said.

A cornerstone of cutaneous melanoma care remains unchanged in the guidelines: Surgical excision is still the preferred method for treating melanoma. Adjuvant topical therapies or radiation, say the guidelines, can be considered as second-line care, but only in limited situations in which surgery is not feasible. Staged excision techniques, such as Mohs surgery, also may be considered for certain types of melanoma and in certain body areas.

 

 


In an interview, Dr. Swetter also said that is critical that the updated guidelines have been harmonized with changes made in the American Joint Committee on Cancer’s 8th edition of its melanoma staging manual. Key points for dermatologists to understand that reporting of Breslow thickness to the nearest 1/10th decimal point (over the nearest 1/100th), such that a melanoma measuring 0.75-0.84 mm in thickness would be reported as 0.8 mm depth and one between 0.95-1.04 mm would be rounded to 1 mm.

The main changes regarding staging of thin (T1) melanoma – that is less than or equal to 1 mm – is that the 0.8 mm thickness is the threshold for a T1a melanoma (now classified as less than 0.8 mm without ulceration), whereas T1b is now 0.8 – 1.0 mm thickness with or w/out ulceration or less than 0.8 mm thickness with ulceration. A T1a melanoma generally is not considered appropriate for staging of the regional lymph nodes with sentinel lymph node biopsy (with exceptions noted in the guideline), whereas a T1b melanoma may be considered for SLNB staging – though rates of SLN positivity remain relatively low in the T1b group.”

Dr. Swetter also emphasized that histologic ulceration of the primary tumor was affirmed as an indicator of worse prognosis; mitotic rate, although removed from T1 staging, is still tracked by pathologists and still seen as an independent predictor of worse prognosis, according to the 8th edition, she said.

A cornerstone of cutaneous melanoma care remains unchanged in the guidelines: Surgical excision is still the preferred method for treating melanoma. “Mohs micrographic surgery and other staged excision techniques can provide exhaustive peripheral margin histologic assessment for melanoma in situ, lentigo maligna type and tissue sparing in anatomically constrained sites,” Dr. Swetter said. “Current data are insufficient to recommend Mohs surgery for invasive cutaneous melanoma, in which the use of surgical margins less than 1 cm has not been adequately studied,” she cautioned.

Reinforcing the importance of surgery as the primary treatment for melanoma, Dr. Swetter clarified that “Nonsurgical approaches (imiquimod and traditional forms of radiation therapy) should be considered [only] if surgery is impractical or contraindicated, and only for melanoma in situ, lentigo maligna type, as cure rates are lower.”

In terms of other therapies, the guideline working group found insufficient evidence to recommend electronic brachytherapy for melanoma.

Assessment of novel diagnostic and molecular imaging modalities was not the primary focus of the AAD guidelines, Dr. Swetter pointed out. Looking to the future, though, she added that the hope is “that these prebiopsy modalities can one day reduce unnecessary biopsies from being done” in the clinic.

Other knowledge gaps cited by the working group included several related to pathology, including determination of appropriate margin control in some lesion types, and the quest to reduce inter-reader variability in histopathologic diagnosis of melanocytic tissue samples. However, noted Dr. Swetter and her coauthors, the rapid pace of genomic medicine advances “may make many of the aforementioned issues obsolete” before the next guideline update.

In the interview, Dr. Swetter said that the guidelines reflect evolving thinking about melanoma in the context of a rapidly growing field. “Only in the last year have effective, more tolerable adjuvant therapies been [Food and Drug Administration] approved for patients with resected stage III melanoma, including patients with regional lymph node disease detected via sentinel lymph node biopsy. The hope is that less invasive procedures for melanoma will be performed in the future, and replaced by better drugs and novel techniques.”

Dr. Swetter reported that she had no relevant financial disclosures; several working group members reported multiple financial relationships with pharmaceutical, diagnostic, and imaging companies. Working group members were recused from discussion of guidelines where their particular relationships might pose a conflict of interest.

SOURCE: Swetter S. et al. J Am Acad Dermatol. 2011 Nov;65(5):1032-47.

 

Pregnancy does not necessarily increase a woman’s risk for melanoma, nor is it clear that becoming pregnant affects melanoma’s disease course, according to current evidence. This guidance is among several updates added to newly released guidelines for managing patients with primary cutaneous melanoma.

Dr. Susan Swetter

The American Academy of Dermatology, which formed a working group to develop the updated cutaneous melanoma (CM) treatment guidelines, also addressed the burgeoning field of genetic testing for cancer in the guidelines, which were published online on Nov. 1. Although there may be a hereditary component to some melanomas, genetic testing may not be appropriate for all patients, and any formal genetic testing should be carried out only after individualized education and counseling, according to the updates.

However, the guidelines make it clear that all patients whose family history includes melanoma should be counseled about their genetic risk.

As with genetic testing, counseling regarding future pregnancies for women with melanoma, or a history of melanoma, should be personalized and account for individual history and melanoma risk, according to the new guidelines. Since evidence is lacking that pregnancy affects the course of melanoma, physicians caring for pregnant women with melanoma should first look at patient and the disease characteristics. The addition of detailed guidance regarding pregnancy reflects research showing that CM is the most common malignancy seen in pregnancy, amounting to nearly one-third of the malignancies that arise in pregnancy. “Although the incidence of CM is generally higher in men, it is higher in younger women than in men, most notably during women’s reproductive years,” wrote Susan M. Swetter, MD, and her guideline coauthors.

The National Cancer Institute

“Melanoma is the deadliest form of skin cancer, and we hope these guidelines will help dermatologists and other physicians enhance their delivery of life-saving treatment to patients,” Dr. Swetter said in a press release announcing the guideline updates. Dr. Swetter, professor of dermatology and director of the pigmented lesion and melanoma program at Stanford (Calif.) University Medical Center and Cancer Institute, led the working group that developed the guidelines. “In order to provide the best possible resource for practitioners, we reviewed the latest scientific data and addressed certain topics that weren’t covered in the AAD’s previous melanoma guidelines,” she said.

A cornerstone of cutaneous melanoma care remains unchanged in the guidelines: Surgical excision is still the preferred method for treating melanoma. Adjuvant topical therapies or radiation, say the guidelines, can be considered as second-line care, but only in limited situations in which surgery is not feasible. Staged excision techniques, such as Mohs surgery, also may be considered for certain types of melanoma and in certain body areas.

 

 


In an interview, Dr. Swetter also said that is critical that the updated guidelines have been harmonized with changes made in the American Joint Committee on Cancer’s 8th edition of its melanoma staging manual. Key points for dermatologists to understand that reporting of Breslow thickness to the nearest 1/10th decimal point (over the nearest 1/100th), such that a melanoma measuring 0.75-0.84 mm in thickness would be reported as 0.8 mm depth and one between 0.95-1.04 mm would be rounded to 1 mm.

The main changes regarding staging of thin (T1) melanoma – that is less than or equal to 1 mm – is that the 0.8 mm thickness is the threshold for a T1a melanoma (now classified as less than 0.8 mm without ulceration), whereas T1b is now 0.8 – 1.0 mm thickness with or w/out ulceration or less than 0.8 mm thickness with ulceration. A T1a melanoma generally is not considered appropriate for staging of the regional lymph nodes with sentinel lymph node biopsy (with exceptions noted in the guideline), whereas a T1b melanoma may be considered for SLNB staging – though rates of SLN positivity remain relatively low in the T1b group.”

Dr. Swetter also emphasized that histologic ulceration of the primary tumor was affirmed as an indicator of worse prognosis; mitotic rate, although removed from T1 staging, is still tracked by pathologists and still seen as an independent predictor of worse prognosis, according to the 8th edition, she said.

A cornerstone of cutaneous melanoma care remains unchanged in the guidelines: Surgical excision is still the preferred method for treating melanoma. “Mohs micrographic surgery and other staged excision techniques can provide exhaustive peripheral margin histologic assessment for melanoma in situ, lentigo maligna type and tissue sparing in anatomically constrained sites,” Dr. Swetter said. “Current data are insufficient to recommend Mohs surgery for invasive cutaneous melanoma, in which the use of surgical margins less than 1 cm has not been adequately studied,” she cautioned.

Reinforcing the importance of surgery as the primary treatment for melanoma, Dr. Swetter clarified that “Nonsurgical approaches (imiquimod and traditional forms of radiation therapy) should be considered [only] if surgery is impractical or contraindicated, and only for melanoma in situ, lentigo maligna type, as cure rates are lower.”

In terms of other therapies, the guideline working group found insufficient evidence to recommend electronic brachytherapy for melanoma.

Assessment of novel diagnostic and molecular imaging modalities was not the primary focus of the AAD guidelines, Dr. Swetter pointed out. Looking to the future, though, she added that the hope is “that these prebiopsy modalities can one day reduce unnecessary biopsies from being done” in the clinic.

Other knowledge gaps cited by the working group included several related to pathology, including determination of appropriate margin control in some lesion types, and the quest to reduce inter-reader variability in histopathologic diagnosis of melanocytic tissue samples. However, noted Dr. Swetter and her coauthors, the rapid pace of genomic medicine advances “may make many of the aforementioned issues obsolete” before the next guideline update.

In the interview, Dr. Swetter said that the guidelines reflect evolving thinking about melanoma in the context of a rapidly growing field. “Only in the last year have effective, more tolerable adjuvant therapies been [Food and Drug Administration] approved for patients with resected stage III melanoma, including patients with regional lymph node disease detected via sentinel lymph node biopsy. The hope is that less invasive procedures for melanoma will be performed in the future, and replaced by better drugs and novel techniques.”

Dr. Swetter reported that she had no relevant financial disclosures; several working group members reported multiple financial relationships with pharmaceutical, diagnostic, and imaging companies. Working group members were recused from discussion of guidelines where their particular relationships might pose a conflict of interest.

SOURCE: Swetter S. et al. J Am Acad Dermatol. 2011 Nov;65(5):1032-47.

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