Melanoma

Melanoma patients who took high doses of glucocorticoids for hypophysitis induced by the checkpoint-inhibitor ipilimumab had a lower overall survival time and a shorter time to treatment failure than did patients taking low-dose steroids for the adverse event, according to a new retrospective analysis in Cancer.

“Treatment with high-dose glucocorticoids does not appear to confer any obvious advantage to patients with IH (ipilimumab-induced hypophysitis) and may negatively affect tumor response to CPI (checkpoint-inhibitor therapy),” wrote Alexander Faje, MD, a neuroendocrinologist at Massachusetts General Hospital, Boston. “We recommend against the routine use of higher doses in these patients and that such treatment should be reserved for clinical indications like visual compromise or perhaps for intractable headache.”

Hypophysitis after treatment with a CTLA-4 inhibitor, such as ipilimumab, can approach 12%, though it is much less common with the checkpoint inhibitors that target PD-1 and PD-L1. Past studies examining the effects of glucocorticoids for immune-related adverse events have compared patients with severe events to those with minimal or no events. Since emergence of hypophysitis correlates with better overall survival, this is a flawed approach, the researchers said.

For their study, the researchers compared groups of patients with the same immune-related adverse events who received treatment with varying amounts of glucocorticoids.

They reviewed outcomes for 64 melanoma patients who had received ipilimumab monotherapy and were diagnosed with ipilimumab-induced hypophysitis treated in the Partners Healthcare system. Fourteen patients had received low-dose glucocorticoids, defined as a maximum average daily dose of 7.5 mg of prednisone or the equivalent. Fifty patients received high-dose glucocorticoids, defined as anything above that amount.

Overall survival and time to treatment failure were significantly higher in the low-dose group than the high-dose group (P = .002 for OS and P = .001 for TTF). Median overall survival was 23.3 months and time to treatment failure was 11.4 months in those given high-dose steroids. Median overall survival had not been reached in those given low-dose steroids.

While the findings are preliminary, the authors noted they may have implications for managing other immune-related adverse events. “Although the use of lower doses of immunosuppressive medications may be less of an option in many circumstances for other (immune-related adverse events), therapeutic parsimony would seem desirable with more tailored regimens as the biologic mechanisms underpinning these processes are further elucidated.”

SOURCE: Faje AT et al. Cancer. 2018 Jul 5.

Melanoma patients who took high doses of glucocorticoids for hypophysitis induced by the checkpoint-inhibitor ipilimumab had a lower overall survival time and a shorter time to treatment failure than did patients taking low-dose steroids for the adverse event, according to a new retrospective analysis in Cancer.

“Treatment with high-dose glucocorticoids does not appear to confer any obvious advantage to patients with IH (ipilimumab-induced hypophysitis) and may negatively affect tumor response to CPI (checkpoint-inhibitor therapy),” wrote Alexander Faje, MD, a neuroendocrinologist at Massachusetts General Hospital, Boston. “We recommend against the routine use of higher doses in these patients and that such treatment should be reserved for clinical indications like visual compromise or perhaps for intractable headache.”

Hypophysitis after treatment with a CTLA-4 inhibitor, such as ipilimumab, can approach 12%, though it is much less common with the checkpoint inhibitors that target PD-1 and PD-L1. Past studies examining the effects of glucocorticoids for immune-related adverse events have compared patients with severe events to those with minimal or no events. Since emergence of hypophysitis correlates with better overall survival, this is a flawed approach, the researchers said.

For their study, the researchers compared groups of patients with the same immune-related adverse events who received treatment with varying amounts of glucocorticoids.

They reviewed outcomes for 64 melanoma patients who had received ipilimumab monotherapy and were diagnosed with ipilimumab-induced hypophysitis treated in the Partners Healthcare system. Fourteen patients had received low-dose glucocorticoids, defined as a maximum average daily dose of 7.5 mg of prednisone or the equivalent. Fifty patients received high-dose glucocorticoids, defined as anything above that amount.

Overall survival and time to treatment failure were significantly higher in the low-dose group than the high-dose group (P = .002 for OS and P = .001 for TTF). Median overall survival was 23.3 months and time to treatment failure was 11.4 months in those given high-dose steroids. Median overall survival had not been reached in those given low-dose steroids.

While the findings are preliminary, the authors noted they may have implications for managing other immune-related adverse events. “Although the use of lower doses of immunosuppressive medications may be less of an option in many circumstances for other (immune-related adverse events), therapeutic parsimony would seem desirable with more tailored regimens as the biologic mechanisms underpinning these processes are further elucidated.”

SOURCE: Faje AT et al. Cancer. 2018 Jul 5.

Melanoma patients who took high doses of glucocorticoids for hypophysitis induced by the checkpoint-inhibitor ipilimumab had a lower overall survival time and a shorter time to treatment failure than did patients taking low-dose steroids for the adverse event, according to a new retrospective analysis in Cancer.

“Treatment with high-dose glucocorticoids does not appear to confer any obvious advantage to patients with IH (ipilimumab-induced hypophysitis) and may negatively affect tumor response to CPI (checkpoint-inhibitor therapy),” wrote Alexander Faje, MD, a neuroendocrinologist at Massachusetts General Hospital, Boston. “We recommend against the routine use of higher doses in these patients and that such treatment should be reserved for clinical indications like visual compromise or perhaps for intractable headache.”

Hypophysitis after treatment with a CTLA-4 inhibitor, such as ipilimumab, can approach 12%, though it is much less common with the checkpoint inhibitors that target PD-1 and PD-L1. Past studies examining the effects of glucocorticoids for immune-related adverse events have compared patients with severe events to those with minimal or no events. Since emergence of hypophysitis correlates with better overall survival, this is a flawed approach, the researchers said.

For their study, the researchers compared groups of patients with the same immune-related adverse events who received treatment with varying amounts of glucocorticoids.

They reviewed outcomes for 64 melanoma patients who had received ipilimumab monotherapy and were diagnosed with ipilimumab-induced hypophysitis treated in the Partners Healthcare system. Fourteen patients had received low-dose glucocorticoids, defined as a maximum average daily dose of 7.5 mg of prednisone or the equivalent. Fifty patients received high-dose glucocorticoids, defined as anything above that amount.

Overall survival and time to treatment failure were significantly higher in the low-dose group than the high-dose group (P = .002 for OS and P = .001 for TTF). Median overall survival was 23.3 months and time to treatment failure was 11.4 months in those given high-dose steroids. Median overall survival had not been reached in those given low-dose steroids.

While the findings are preliminary, the authors noted they may have implications for managing other immune-related adverse events. “Although the use of lower doses of immunosuppressive medications may be less of an option in many circumstances for other (immune-related adverse events), therapeutic parsimony would seem desirable with more tailored regimens as the biologic mechanisms underpinning these processes are further elucidated.”

SOURCE: Faje AT et al. Cancer. 2018 Jul 5.

Since the Food and Drug Administration first approved checkpoint blockade immunotherapy (CBI) and BRAF^V600-targeted therapy in 2011, survival times for patients with melanoma brain metastases (MBMs) have significantly improved, with a 91% increase in 4-year overall survival (OS) from 7.4% to 14.1%.

“The management of advanced melanoma has traditionally been tempered by limited responses to conventional therapies, resulting in a median overall survival (OS) of less than 1 year,” wrote J. Bryan Iorgulescu, MD, of Brigham and Women’s Hospital in Boston, and his colleagues. The report was published in Cancer Immunology Research. “The landscape of advanced melanoma treatment was revolutionized” by the approval of immunotherapy agents, beginning in 2011.

The current, retrospective study involved 2,753 patients with stage IV melanoma. Patient data were drawn from the National Cancer Database, with diagnoses made between 2010 and 2015. Patient management, overall survival, and disease characteristics were evaluated.

During initial review, the researchers found that 35.8% of patients with stage IV melanoma had brain involvement. These patients were further categorized by those with MBM only (39.7%) versus those with extracranial metastatic disease (60.3%), which included involvement of lung (82.9%), liver (8.1%), bone (6.0%), and lymph nodes or distant subcutaneous skin (3%). MBM-only disease was independently predicted by both younger age and geographic location.

Patients receiving first-line CBI therapy demonstrated improved 4-year OS (28.1% vs. 11.1%; P less than.001) and median OS (12.4 months vs. 5.2 months; P less than .001).

Improvements with CBI were most dramatic in patients with MBM-only disease. In these cases, 4-year OS improved from 16.9% to 51.5% (P less than .001), while median OS jumped from 7.7 months to 56.4 months (P less than .001).

Improved OS was also associated with fewer comorbidities, younger age, management at an academic cancer center, single-fraction stereotactic radiosurgery, and resection of the MBM.

“Our findings help bridge the gaps in early clinical trials of CBIs that largely excluded stage IV melanoma patients with MBMs, with checkpoint immunotherapy demonstrating a more than doubling of the median and 4-year OS of MBMs,” the authors concluded.

SOURCE: Iorgulescu et al. Cancer Immunol Res. 2018 July 12 doi: 10.1158/2326-6066.CIR-18-0067.

Since the Food and Drug Administration first approved checkpoint blockade immunotherapy (CBI) and BRAF^V600-targeted therapy in 2011, survival times for patients with melanoma brain metastases (MBMs) have significantly improved, with a 91% increase in 4-year overall survival (OS) from 7.4% to 14.1%.

“The management of advanced melanoma has traditionally been tempered by limited responses to conventional therapies, resulting in a median overall survival (OS) of less than 1 year,” wrote J. Bryan Iorgulescu, MD, of Brigham and Women’s Hospital in Boston, and his colleagues. The report was published in Cancer Immunology Research. “The landscape of advanced melanoma treatment was revolutionized” by the approval of immunotherapy agents, beginning in 2011.

The current, retrospective study involved 2,753 patients with stage IV melanoma. Patient data were drawn from the National Cancer Database, with diagnoses made between 2010 and 2015. Patient management, overall survival, and disease characteristics were evaluated.

During initial review, the researchers found that 35.8% of patients with stage IV melanoma had brain involvement. These patients were further categorized by those with MBM only (39.7%) versus those with extracranial metastatic disease (60.3%), which included involvement of lung (82.9%), liver (8.1%), bone (6.0%), and lymph nodes or distant subcutaneous skin (3%). MBM-only disease was independently predicted by both younger age and geographic location.

Patients receiving first-line CBI therapy demonstrated improved 4-year OS (28.1% vs. 11.1%; P less than.001) and median OS (12.4 months vs. 5.2 months; P less than .001).

Improvements with CBI were most dramatic in patients with MBM-only disease. In these cases, 4-year OS improved from 16.9% to 51.5% (P less than .001), while median OS jumped from 7.7 months to 56.4 months (P less than .001).

Improved OS was also associated with fewer comorbidities, younger age, management at an academic cancer center, single-fraction stereotactic radiosurgery, and resection of the MBM.

“Our findings help bridge the gaps in early clinical trials of CBIs that largely excluded stage IV melanoma patients with MBMs, with checkpoint immunotherapy demonstrating a more than doubling of the median and 4-year OS of MBMs,” the authors concluded.

SOURCE: Iorgulescu et al. Cancer Immunol Res. 2018 July 12 doi: 10.1158/2326-6066.CIR-18-0067.

Since the Food and Drug Administration first approved checkpoint blockade immunotherapy (CBI) and BRAF^V600-targeted therapy in 2011, survival times for patients with melanoma brain metastases (MBMs) have significantly improved, with a 91% increase in 4-year overall survival (OS) from 7.4% to 14.1%.

“The management of advanced melanoma has traditionally been tempered by limited responses to conventional therapies, resulting in a median overall survival (OS) of less than 1 year,” wrote J. Bryan Iorgulescu, MD, of Brigham and Women’s Hospital in Boston, and his colleagues. The report was published in Cancer Immunology Research. “The landscape of advanced melanoma treatment was revolutionized” by the approval of immunotherapy agents, beginning in 2011.

The current, retrospective study involved 2,753 patients with stage IV melanoma. Patient data were drawn from the National Cancer Database, with diagnoses made between 2010 and 2015. Patient management, overall survival, and disease characteristics were evaluated.

During initial review, the researchers found that 35.8% of patients with stage IV melanoma had brain involvement. These patients were further categorized by those with MBM only (39.7%) versus those with extracranial metastatic disease (60.3%), which included involvement of lung (82.9%), liver (8.1%), bone (6.0%), and lymph nodes or distant subcutaneous skin (3%). MBM-only disease was independently predicted by both younger age and geographic location.

Patients receiving first-line CBI therapy demonstrated improved 4-year OS (28.1% vs. 11.1%; P less than.001) and median OS (12.4 months vs. 5.2 months; P less than .001).

Improvements with CBI were most dramatic in patients with MBM-only disease. In these cases, 4-year OS improved from 16.9% to 51.5% (P less than .001), while median OS jumped from 7.7 months to 56.4 months (P less than .001).

Improved OS was also associated with fewer comorbidities, younger age, management at an academic cancer center, single-fraction stereotactic radiosurgery, and resection of the MBM.

“Our findings help bridge the gaps in early clinical trials of CBIs that largely excluded stage IV melanoma patients with MBMs, with checkpoint immunotherapy demonstrating a more than doubling of the median and 4-year OS of MBMs,” the authors concluded.

SOURCE: Iorgulescu et al. Cancer Immunol Res. 2018 July 12 doi: 10.1158/2326-6066.CIR-18-0067.

In a study of more than 5,000 fifth graders, fewer than a quarter of participants almost always used sunscreen, and the figures were much lower for non-Hispanic black children.

©Vesna Andjic/iStockphoto.com

koakes@mdedge.com

SOURCE: Correnti CM et al. Pediatr Dermatol. 2018. doi: 10.1111/pde.13550.

In a study of more than 5,000 fifth graders, fewer than a quarter of participants almost always used sunscreen, and the figures were much lower for non-Hispanic black children.

©Vesna Andjic/iStockphoto.com

koakes@mdedge.com

SOURCE: Correnti CM et al. Pediatr Dermatol. 2018. doi: 10.1111/pde.13550.

In a study of more than 5,000 fifth graders, fewer than a quarter of participants almost always used sunscreen, and the figures were much lower for non-Hispanic black children.

©Vesna Andjic/iStockphoto.com

koakes@mdedge.com

SOURCE: Correnti CM et al. Pediatr Dermatol. 2018. doi: 10.1111/pde.13550.

Practice Gap

Mohs micrographic surgery (MMS) is a highly curative tissue-sparing skin cancer treatment¹ and is a required component of dermatology residency training. According to the Accreditation Council for Graduate Medical Education, residents must have exposure “either through direct observation or as an assistant in Mohs micrographic surgery, and reconstruction of these defects, to include flaps and grafts.”² The MMS technique allows for complete circumferential peripheral and deep margin assessment of excised specimens; however, the conformation of a 3-dimensional gross tissue specimen into a 2-dimensional specimen as represented on a microscope slide is challenging to conceptualize.

Behavioral science research has shown that analogies and metaphors help integrate topics into a memorable format and produce deeper comprehension.³ As such, analogies can aid in the visualization of these complex spatial concepts. The MMS tissue-processing technique has been compared to flattening a pie pan.⁴ More recently, a peanut butter cup analogy was described as a visualization tool for explaining the various steps of MMS to patients.⁵ Although these analogies may help elucidate certain aspects of the MMS technique, none adequately account for the multilayered anatomy of the skin.

The Technique

To address this need, we developed the cantaloupe analogy, which provides visual representation of the 3 basic skin layers: (1) the rind represents the epidermis; (2) the flesh represents the dermis, and (3) the seed cavity represents the subcutaneous layer (Figures 1 and 2).

Image courtesy of Janna M. Vassantachart, MD.

Image courtesy of Janna M. Vassantachart, MD.

In MMS tissue processing, the peripheral margin of the ovoid excised skin specimen is pressed down into the same plane as the deepest layer through a process called relaxation.⁴ The cantaloupe represents the dome shape of the relaxed tissue, which is then serially sectioned in horizontal layers from deep to superficial (Figure 2). The first slice represents the deepest subcutaneous layer and most peripheral dermal and epidermal layers of the specimen (Figure 3). Using the cantaloupe analogy, subsequent stages (if warranted) would be guided by the location of the residual skin cancer. If the skin cancer is in the epidermis (rind) or dermis (flesh), then a skin specimen from the perimeter of the defect would be indicated. Residual skin cancer extending into the subcutaneous layer (seed cavity) would require a deeper resection.

Image courtesy of Janna M. Vassantachart, MD.

Practice Implications

The cantaloupe provides a simple analogy to conceptualize the transition from the multilayered 3-dimensional skin tissue specimen to the 2-dimensional histologic slide specimen. Use of this cantaloupe analogy will aid dermatology residents and others interested in gaining a clearer understanding of MMS.

Practice Gap

Mohs micrographic surgery (MMS) is a highly curative tissue-sparing skin cancer treatment¹ and is a required component of dermatology residency training. According to the Accreditation Council for Graduate Medical Education, residents must have exposure “either through direct observation or as an assistant in Mohs micrographic surgery, and reconstruction of these defects, to include flaps and grafts.”² The MMS technique allows for complete circumferential peripheral and deep margin assessment of excised specimens; however, the conformation of a 3-dimensional gross tissue specimen into a 2-dimensional specimen as represented on a microscope slide is challenging to conceptualize.

Behavioral science research has shown that analogies and metaphors help integrate topics into a memorable format and produce deeper comprehension.³ As such, analogies can aid in the visualization of these complex spatial concepts. The MMS tissue-processing technique has been compared to flattening a pie pan.⁴ More recently, a peanut butter cup analogy was described as a visualization tool for explaining the various steps of MMS to patients.⁵ Although these analogies may help elucidate certain aspects of the MMS technique, none adequately account for the multilayered anatomy of the skin.

The Technique

To address this need, we developed the cantaloupe analogy, which provides visual representation of the 3 basic skin layers: (1) the rind represents the epidermis; (2) the flesh represents the dermis, and (3) the seed cavity represents the subcutaneous layer (Figures 1 and 2).

Image courtesy of Janna M. Vassantachart, MD.

Image courtesy of Janna M. Vassantachart, MD.

In MMS tissue processing, the peripheral margin of the ovoid excised skin specimen is pressed down into the same plane as the deepest layer through a process called relaxation.⁴ The cantaloupe represents the dome shape of the relaxed tissue, which is then serially sectioned in horizontal layers from deep to superficial (Figure 2). The first slice represents the deepest subcutaneous layer and most peripheral dermal and epidermal layers of the specimen (Figure 3). Using the cantaloupe analogy, subsequent stages (if warranted) would be guided by the location of the residual skin cancer. If the skin cancer is in the epidermis (rind) or dermis (flesh), then a skin specimen from the perimeter of the defect would be indicated. Residual skin cancer extending into the subcutaneous layer (seed cavity) would require a deeper resection.

Image courtesy of Janna M. Vassantachart, MD.

Practice Implications

The cantaloupe provides a simple analogy to conceptualize the transition from the multilayered 3-dimensional skin tissue specimen to the 2-dimensional histologic slide specimen. Use of this cantaloupe analogy will aid dermatology residents and others interested in gaining a clearer understanding of MMS.

Practice Gap

Mohs micrographic surgery (MMS) is a highly curative tissue-sparing skin cancer treatment¹ and is a required component of dermatology residency training. According to the Accreditation Council for Graduate Medical Education, residents must have exposure “either through direct observation or as an assistant in Mohs micrographic surgery, and reconstruction of these defects, to include flaps and grafts.”² The MMS technique allows for complete circumferential peripheral and deep margin assessment of excised specimens; however, the conformation of a 3-dimensional gross tissue specimen into a 2-dimensional specimen as represented on a microscope slide is challenging to conceptualize.

Behavioral science research has shown that analogies and metaphors help integrate topics into a memorable format and produce deeper comprehension.³ As such, analogies can aid in the visualization of these complex spatial concepts. The MMS tissue-processing technique has been compared to flattening a pie pan.⁴ More recently, a peanut butter cup analogy was described as a visualization tool for explaining the various steps of MMS to patients.⁵ Although these analogies may help elucidate certain aspects of the MMS technique, none adequately account for the multilayered anatomy of the skin.

The Technique

To address this need, we developed the cantaloupe analogy, which provides visual representation of the 3 basic skin layers: (1) the rind represents the epidermis; (2) the flesh represents the dermis, and (3) the seed cavity represents the subcutaneous layer (Figures 1 and 2).

Image courtesy of Janna M. Vassantachart, MD.

Image courtesy of Janna M. Vassantachart, MD.

In MMS tissue processing, the peripheral margin of the ovoid excised skin specimen is pressed down into the same plane as the deepest layer through a process called relaxation.⁴ The cantaloupe represents the dome shape of the relaxed tissue, which is then serially sectioned in horizontal layers from deep to superficial (Figure 2). The first slice represents the deepest subcutaneous layer and most peripheral dermal and epidermal layers of the specimen (Figure 3). Using the cantaloupe analogy, subsequent stages (if warranted) would be guided by the location of the residual skin cancer. If the skin cancer is in the epidermis (rind) or dermis (flesh), then a skin specimen from the perimeter of the defect would be indicated. Residual skin cancer extending into the subcutaneous layer (seed cavity) would require a deeper resection.

Image courtesy of Janna M. Vassantachart, MD.

Practice Implications

The cantaloupe provides a simple analogy to conceptualize the transition from the multilayered 3-dimensional skin tissue specimen to the 2-dimensional histologic slide specimen. Use of this cantaloupe analogy will aid dermatology residents and others interested in gaining a clearer understanding of MMS.

The Food and Drug Administration has approved combination therapy of encorafenib (Braftovi) and binimetinib (Mektovi) for the treatment of unresectable or metastatic melanoma with BRAF V600E or BRAF V600K mutations; the FDA also has approved the THxID BRAF Kit as a companion diagnostic for this combination therapy.

The approval was based on results from the randomized, active-controlled, open-label, multicenter COLUMBUS trial, which included 517 patients. Progression-free survival, according to RECIST 1.1 criteria, was the major efficacy measure; the median progression-free survival was 14.9 months in the encorafenib/binimetinib combination arm versus 7.3 months in the vemurafenib (Zelboraf) monotherapy arm (hazard ratio, 0.54; 95% confidence interval, 0.41-0.71; P less than .0001).

Fatigue, nausea, diarrhea, vomiting, abdominal pain, and arthralgia were the most common adverse reactions. Discontinuation of therapy from adverse reactions occurred in 5% of patients receiving the combination, the FDA said in a press statement.

The full prescribing information for encorafenib and binimetinib can be found on the FDA website.






 

The Food and Drug Administration has approved combination therapy of encorafenib (Braftovi) and binimetinib (Mektovi) for the treatment of unresectable or metastatic melanoma with BRAF V600E or BRAF V600K mutations; the FDA also has approved the THxID BRAF Kit as a companion diagnostic for this combination therapy.

The approval was based on results from the randomized, active-controlled, open-label, multicenter COLUMBUS trial, which included 517 patients. Progression-free survival, according to RECIST 1.1 criteria, was the major efficacy measure; the median progression-free survival was 14.9 months in the encorafenib/binimetinib combination arm versus 7.3 months in the vemurafenib (Zelboraf) monotherapy arm (hazard ratio, 0.54; 95% confidence interval, 0.41-0.71; P less than .0001).

Fatigue, nausea, diarrhea, vomiting, abdominal pain, and arthralgia were the most common adverse reactions. Discontinuation of therapy from adverse reactions occurred in 5% of patients receiving the combination, the FDA said in a press statement.

The full prescribing information for encorafenib and binimetinib can be found on the FDA website.






 

The Food and Drug Administration has approved combination therapy of encorafenib (Braftovi) and binimetinib (Mektovi) for the treatment of unresectable or metastatic melanoma with BRAF V600E or BRAF V600K mutations; the FDA also has approved the THxID BRAF Kit as a companion diagnostic for this combination therapy.

The approval was based on results from the randomized, active-controlled, open-label, multicenter COLUMBUS trial, which included 517 patients. Progression-free survival, according to RECIST 1.1 criteria, was the major efficacy measure; the median progression-free survival was 14.9 months in the encorafenib/binimetinib combination arm versus 7.3 months in the vemurafenib (Zelboraf) monotherapy arm (hazard ratio, 0.54; 95% confidence interval, 0.41-0.71; P less than .0001).

Fatigue, nausea, diarrhea, vomiting, abdominal pain, and arthralgia were the most common adverse reactions. Discontinuation of therapy from adverse reactions occurred in 5% of patients receiving the combination, the FDA said in a press statement.

The full prescribing information for encorafenib and binimetinib can be found on the FDA website.






 

CHICAGO – Analysis of U.S. national cancer registry data shows that, contrary to expectation, the use of Mohs micrographic surgery for treatment of melanoma in situ did not increase following adoption of the Affordable Care Act, Sean Condon, MD, reported at the annual meeting of the American College of Mohs Surgery.

Ditto for the use of Mohs in patients with the rare cutaneous malignancies for which published evidence clearly demonstrates Mohs outperforms wide local excision, which is employed seven times more frequently than Mohs in such situations.

Bruce Jancin/MDedge News

“These rare cutaneous malignancies were historically treated with wide local excision. However, numerous studies have lately shown that lower recurrence rates were found with Mohs compared with wide local excision,” Dr. Condon noted.

Nonetheless, the proportion of the rare cutaneous malignancies treated using Mohs was unaffected by implementation of the ACA. Nor was it influenced one way or the other by publication of the joint Mohs appropriate use criteria in 2012: The Mohs-treated proportion of such cases was 15.25% in 2010-2011 and 14.6% in 2013-2014.

Similarly, even though the appropriate use criteria identified melanoma in situ as Mohs appropriate, the proportion of those malignancies treated via Mohs was the same before and after the 2012 release of the criteria.

“It’s commonly thought that Mohs is overused. However, our study and our data clearly identify that Mohs is being underutilized for melanoma in situ and for rare cutaneous malignancies. This represents a knowledge gap for other specialties regarding best-practice therapy,” Dr. Condon said.

He and his coinvestigators searched for socioeconomic predictors of Mohs utilization by matching the nationally representative SEER data with U.S. census data. They examined the impact of three metrics: insurance status, income, and poverty. They found that low-income patients and those in the highest quartile of poverty were significantly less likely to have Mohs surgery for their melanoma in situ and rare cutaneous malignancies throughout the study years. Lack of health insurance had no impact on Mohs utilization for melanoma in situ but was independently associated with decreased likelihood of Mohs for the rare cutaneous malignancies. White patients were 2-fold to 2.4-fold more likely to have Mohs surgery for their rare cutaneous malignancies than were black patients.

“One can conclude that Mohs micrographic surgery may be skewed toward more affluent patients, and lower socioeconomic status areas have less Mohs access. So our data from this study support a role for targeted education and improved patient access to Mohs,” Dr. Condon said.

He noted that because the SEER registries don’t track squamous or basal cell carcinomas, it’s unknown whether Mohs is also underutilized for the higher-risk forms of these most common of all skin cancers.

Dr. Condon reported having no financial conflicts regarding his study, conducted free of commercial support.

bjancin@mdedge.com

CHICAGO – Analysis of U.S. national cancer registry data shows that, contrary to expectation, the use of Mohs micrographic surgery for treatment of melanoma in situ did not increase following adoption of the Affordable Care Act, Sean Condon, MD, reported at the annual meeting of the American College of Mohs Surgery.

Ditto for the use of Mohs in patients with the rare cutaneous malignancies for which published evidence clearly demonstrates Mohs outperforms wide local excision, which is employed seven times more frequently than Mohs in such situations.

Bruce Jancin/MDedge News

“These rare cutaneous malignancies were historically treated with wide local excision. However, numerous studies have lately shown that lower recurrence rates were found with Mohs compared with wide local excision,” Dr. Condon noted.

Nonetheless, the proportion of the rare cutaneous malignancies treated using Mohs was unaffected by implementation of the ACA. Nor was it influenced one way or the other by publication of the joint Mohs appropriate use criteria in 2012: The Mohs-treated proportion of such cases was 15.25% in 2010-2011 and 14.6% in 2013-2014.

Similarly, even though the appropriate use criteria identified melanoma in situ as Mohs appropriate, the proportion of those malignancies treated via Mohs was the same before and after the 2012 release of the criteria.

“It’s commonly thought that Mohs is overused. However, our study and our data clearly identify that Mohs is being underutilized for melanoma in situ and for rare cutaneous malignancies. This represents a knowledge gap for other specialties regarding best-practice therapy,” Dr. Condon said.

He and his coinvestigators searched for socioeconomic predictors of Mohs utilization by matching the nationally representative SEER data with U.S. census data. They examined the impact of three metrics: insurance status, income, and poverty. They found that low-income patients and those in the highest quartile of poverty were significantly less likely to have Mohs surgery for their melanoma in situ and rare cutaneous malignancies throughout the study years. Lack of health insurance had no impact on Mohs utilization for melanoma in situ but was independently associated with decreased likelihood of Mohs for the rare cutaneous malignancies. White patients were 2-fold to 2.4-fold more likely to have Mohs surgery for their rare cutaneous malignancies than were black patients.

“One can conclude that Mohs micrographic surgery may be skewed toward more affluent patients, and lower socioeconomic status areas have less Mohs access. So our data from this study support a role for targeted education and improved patient access to Mohs,” Dr. Condon said.

He noted that because the SEER registries don’t track squamous or basal cell carcinomas, it’s unknown whether Mohs is also underutilized for the higher-risk forms of these most common of all skin cancers.

Dr. Condon reported having no financial conflicts regarding his study, conducted free of commercial support.

bjancin@mdedge.com

CHICAGO – Analysis of U.S. national cancer registry data shows that, contrary to expectation, the use of Mohs micrographic surgery for treatment of melanoma in situ did not increase following adoption of the Affordable Care Act, Sean Condon, MD, reported at the annual meeting of the American College of Mohs Surgery.

Ditto for the use of Mohs in patients with the rare cutaneous malignancies for which published evidence clearly demonstrates Mohs outperforms wide local excision, which is employed seven times more frequently than Mohs in such situations.

Bruce Jancin/MDedge News

“These rare cutaneous malignancies were historically treated with wide local excision. However, numerous studies have lately shown that lower recurrence rates were found with Mohs compared with wide local excision,” Dr. Condon noted.

Nonetheless, the proportion of the rare cutaneous malignancies treated using Mohs was unaffected by implementation of the ACA. Nor was it influenced one way or the other by publication of the joint Mohs appropriate use criteria in 2012: The Mohs-treated proportion of such cases was 15.25% in 2010-2011 and 14.6% in 2013-2014.

Similarly, even though the appropriate use criteria identified melanoma in situ as Mohs appropriate, the proportion of those malignancies treated via Mohs was the same before and after the 2012 release of the criteria.

“It’s commonly thought that Mohs is overused. However, our study and our data clearly identify that Mohs is being underutilized for melanoma in situ and for rare cutaneous malignancies. This represents a knowledge gap for other specialties regarding best-practice therapy,” Dr. Condon said.

He and his coinvestigators searched for socioeconomic predictors of Mohs utilization by matching the nationally representative SEER data with U.S. census data. They examined the impact of three metrics: insurance status, income, and poverty. They found that low-income patients and those in the highest quartile of poverty were significantly less likely to have Mohs surgery for their melanoma in situ and rare cutaneous malignancies throughout the study years. Lack of health insurance had no impact on Mohs utilization for melanoma in situ but was independently associated with decreased likelihood of Mohs for the rare cutaneous malignancies. White patients were 2-fold to 2.4-fold more likely to have Mohs surgery for their rare cutaneous malignancies than were black patients.

“One can conclude that Mohs micrographic surgery may be skewed toward more affluent patients, and lower socioeconomic status areas have less Mohs access. So our data from this study support a role for targeted education and improved patient access to Mohs,” Dr. Condon said.

He noted that because the SEER registries don’t track squamous or basal cell carcinomas, it’s unknown whether Mohs is also underutilized for the higher-risk forms of these most common of all skin cancers.

Dr. Condon reported having no financial conflicts regarding his study, conducted free of commercial support.

bjancin@mdedge.com

To the Editor:

An 81-year-old man presented with a nodular polypoid lesion that developed on a flat lesion on the back of 2 years’ duration. The lesion grew progressively over the course of 3 months prior to presentation. The patient had a history of melanoma in situ on the forehead that was treated with conventional surgery with clear surgical margins 6 years prior to the current presentation.

On physical examination the patient had a 4×2-cm ulcerated polypoid lesion on the back. The lesion was pink with a pigmented base. Additionally, 2 pink papules with superficial telangiectases were observed around the main lesion (Figure 1).

The gross section showed an exophytic tumor largely growing above the skin surface (Figure 2). Histopathologic analysis revealed an ulcerated lesion consisting of confluent nest and sheets of epithelioid and spindle atypical cells with numerous mitotic figures and necrotic foci (Figure 3). The thickness of the lesion was 2200 µm, and the mitotic count was 28 mitoses/mm². There also was peritumoral vascular invasion and satellite metastasis within the perilesional hypodermis measuring 0.4 mm. Immunohistochemistry staining for S-100, human melanoma black 45 (HMB-45)(Figure 4), and Melan-A was positive in neoplastic cells.

The dissemination study revealed multiple mediastinal and axillary lymphadenopathies and lesions with metastatic appearance in the brain, liver, pancreas, and muscle, together with peritoneal carcinomatosis. The patient was lost to follow-up and did not follow coadjuvant therapy with interferon alfa.

Polypoid melanoma initially was described as a type of melanoma characterized by an exophytic growth in which most of the tumor is located on the cutaneous surface, together with ulceration.¹ It usually occurs in patients aged 20 to 39 years,² and the reported incidence ranges from 1.9% to 43.3%.¹ It more commonly affects mucosae, including the upper respiratory tract, esophagus, and vagina. Polypoid melanoma has a rapid progression and a poor prognosis.³ Polypoid melanoma involving the skin primarily affects the back and has a 5-year survival rate of 32% to 42%.⁴ Poor prognosis has been attributed to the high risk for vascular embolization under the lesion.⁵ Histologically, there is marked cell atypia with nuclear and cellular pleomorphism and a high mitotic count. The tumor rarely involves the reticular dermis.^1,2

Polypoid melanomas are rare; however, reported frequency rates cover a wide range. These frequency rates may be due to the definition of polypoid melanoma used by the pathologist issuing the report. One of the most accepted definitions at present is a pigmented macule that progresses in months with a rapid vertical growth, invading the epidermis and the papillary dermis.² The differential diagnosis includes pyogenic granuloma, squamous cell carcinoma, basal cell carcinoma, soft tissue sarcomas, and hemangioma.

Although our patient had a history of melanoma and the polypoid lesion developed from a flat lesion, he was late to seek medical care. The diagnosis of melanoma is made on increasingly smaller lesions with better prognosis, but there still are reports of larger melanomas. This case highlights the role dermatologists serve in the education of patients on their diagnoses and risk factors so that we may be able to diagnose non–life-threatening small lesions. It is important to remember this morphologic variety of melanoma and highlight its rapid progression and poor prognosis.

To the Editor:

An 81-year-old man presented with a nodular polypoid lesion that developed on a flat lesion on the back of 2 years’ duration. The lesion grew progressively over the course of 3 months prior to presentation. The patient had a history of melanoma in situ on the forehead that was treated with conventional surgery with clear surgical margins 6 years prior to the current presentation.

On physical examination the patient had a 4×2-cm ulcerated polypoid lesion on the back. The lesion was pink with a pigmented base. Additionally, 2 pink papules with superficial telangiectases were observed around the main lesion (Figure 1).

The gross section showed an exophytic tumor largely growing above the skin surface (Figure 2). Histopathologic analysis revealed an ulcerated lesion consisting of confluent nest and sheets of epithelioid and spindle atypical cells with numerous mitotic figures and necrotic foci (Figure 3). The thickness of the lesion was 2200 µm, and the mitotic count was 28 mitoses/mm². There also was peritumoral vascular invasion and satellite metastasis within the perilesional hypodermis measuring 0.4 mm. Immunohistochemistry staining for S-100, human melanoma black 45 (HMB-45)(Figure 4), and Melan-A was positive in neoplastic cells.

The dissemination study revealed multiple mediastinal and axillary lymphadenopathies and lesions with metastatic appearance in the brain, liver, pancreas, and muscle, together with peritoneal carcinomatosis. The patient was lost to follow-up and did not follow coadjuvant therapy with interferon alfa.

Polypoid melanoma initially was described as a type of melanoma characterized by an exophytic growth in which most of the tumor is located on the cutaneous surface, together with ulceration.¹ It usually occurs in patients aged 20 to 39 years,² and the reported incidence ranges from 1.9% to 43.3%.¹ It more commonly affects mucosae, including the upper respiratory tract, esophagus, and vagina. Polypoid melanoma has a rapid progression and a poor prognosis.³ Polypoid melanoma involving the skin primarily affects the back and has a 5-year survival rate of 32% to 42%.⁴ Poor prognosis has been attributed to the high risk for vascular embolization under the lesion.⁵ Histologically, there is marked cell atypia with nuclear and cellular pleomorphism and a high mitotic count. The tumor rarely involves the reticular dermis.^1,2

Polypoid melanomas are rare; however, reported frequency rates cover a wide range. These frequency rates may be due to the definition of polypoid melanoma used by the pathologist issuing the report. One of the most accepted definitions at present is a pigmented macule that progresses in months with a rapid vertical growth, invading the epidermis and the papillary dermis.² The differential diagnosis includes pyogenic granuloma, squamous cell carcinoma, basal cell carcinoma, soft tissue sarcomas, and hemangioma.

Although our patient had a history of melanoma and the polypoid lesion developed from a flat lesion, he was late to seek medical care. The diagnosis of melanoma is made on increasingly smaller lesions with better prognosis, but there still are reports of larger melanomas. This case highlights the role dermatologists serve in the education of patients on their diagnoses and risk factors so that we may be able to diagnose non–life-threatening small lesions. It is important to remember this morphologic variety of melanoma and highlight its rapid progression and poor prognosis.

To the Editor:

An 81-year-old man presented with a nodular polypoid lesion that developed on a flat lesion on the back of 2 years’ duration. The lesion grew progressively over the course of 3 months prior to presentation. The patient had a history of melanoma in situ on the forehead that was treated with conventional surgery with clear surgical margins 6 years prior to the current presentation.

On physical examination the patient had a 4×2-cm ulcerated polypoid lesion on the back. The lesion was pink with a pigmented base. Additionally, 2 pink papules with superficial telangiectases were observed around the main lesion (Figure 1).

The gross section showed an exophytic tumor largely growing above the skin surface (Figure 2). Histopathologic analysis revealed an ulcerated lesion consisting of confluent nest and sheets of epithelioid and spindle atypical cells with numerous mitotic figures and necrotic foci (Figure 3). The thickness of the lesion was 2200 µm, and the mitotic count was 28 mitoses/mm². There also was peritumoral vascular invasion and satellite metastasis within the perilesional hypodermis measuring 0.4 mm. Immunohistochemistry staining for S-100, human melanoma black 45 (HMB-45)(Figure 4), and Melan-A was positive in neoplastic cells.

The dissemination study revealed multiple mediastinal and axillary lymphadenopathies and lesions with metastatic appearance in the brain, liver, pancreas, and muscle, together with peritoneal carcinomatosis. The patient was lost to follow-up and did not follow coadjuvant therapy with interferon alfa.

Polypoid melanoma initially was described as a type of melanoma characterized by an exophytic growth in which most of the tumor is located on the cutaneous surface, together with ulceration.¹ It usually occurs in patients aged 20 to 39 years,² and the reported incidence ranges from 1.9% to 43.3%.¹ It more commonly affects mucosae, including the upper respiratory tract, esophagus, and vagina. Polypoid melanoma has a rapid progression and a poor prognosis.³ Polypoid melanoma involving the skin primarily affects the back and has a 5-year survival rate of 32% to 42%.⁴ Poor prognosis has been attributed to the high risk for vascular embolization under the lesion.⁵ Histologically, there is marked cell atypia with nuclear and cellular pleomorphism and a high mitotic count. The tumor rarely involves the reticular dermis.^1,2

Polypoid melanomas are rare; however, reported frequency rates cover a wide range. These frequency rates may be due to the definition of polypoid melanoma used by the pathologist issuing the report. One of the most accepted definitions at present is a pigmented macule that progresses in months with a rapid vertical growth, invading the epidermis and the papillary dermis.² The differential diagnosis includes pyogenic granuloma, squamous cell carcinoma, basal cell carcinoma, soft tissue sarcomas, and hemangioma.

Although our patient had a history of melanoma and the polypoid lesion developed from a flat lesion, he was late to seek medical care. The diagnosis of melanoma is made on increasingly smaller lesions with better prognosis, but there still are reports of larger melanomas. This case highlights the role dermatologists serve in the education of patients on their diagnoses and risk factors so that we may be able to diagnose non–life-threatening small lesions. It is important to remember this morphologic variety of melanoma and highlight its rapid progression and poor prognosis.

CHICAGO – Matched targeted therapy improved long-term survival in patients with advanced cancer, according to findings from a retrospective analysis of molecularly profiled patients.

Of 3,743 patients tested as part of IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy), 1,307 (34.9%) had at least one targetable molecular alteration. Of those, 711 (54.4%) received either matched targeted therapy that was being tested in a clinical trial or – in a small number of cases – therapy with an approved treatment used off label, and 596 (45.6%) received nonmatched therapy, Apostolia-Maria Tsimberidou, MD, reported during a press briefing at the annual meeting of the American Society of Clinical Oncology.

The objective response rates in 697 evaluable matched therapy patients was 16.2% versus 5.4% in 571 evaluable nonmatched patients, and stable disease for at least 6 months occurred in 18.7% and 14.7% of patients, respectively, for an overall disease control rate of 34.9% versus 20.1%, said Dr. Tsimberidou, a professor at the University of Texas MD Anderson Cancer Center, Houston.

Median progression-free survival in those who received matched versus nonmatched therapy was 4.0 months and 2.8 months, respectively (hazard ratio, 0.67), and median overall survival was 9.3 and 7.3 months, respectively (HR, 0.72), she said.

The 3-year overall survival rate was 15% versus 7%, respectively, and 10-year survival was 6% and 1%, respectively.

Patients included in IMPACT had a mean age of 57 years, and 39% were men. They were heavily pretreated (mean number of prior therapies was 4); only 2.8% of patients had no prior treatment. Cancers included gastrointestinal (24.2%), gynecologic (19.4%), breast (13.5%), melanoma (11.9%) and lung (8.7%).

In this video interview, Dr. Tsimberidou describes the rationale, methodology, and findings of IMPACT, including the use of a prognostic scoring system developed as part of the study to predict overall survival based on baseline characteristics, such as baseline p13K/AKT/mTOR pathway molecular alterations, which were shown on multivariate analysis in IMPACT to predict shorter overall survival versus other alterations. Other predictors of shorter survival included liver metastases, elevated lactate dehydrogenase levels, poor functional status, low albumin levels, elevated platelet counts, and age of 60 years or older.

SOURCE: Tsimberidou AM et al. ASCO 2018, Abstract LBA 2553.

CHICAGO – Matched targeted therapy improved long-term survival in patients with advanced cancer, according to findings from a retrospective analysis of molecularly profiled patients.

Of 3,743 patients tested as part of IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy), 1,307 (34.9%) had at least one targetable molecular alteration. Of those, 711 (54.4%) received either matched targeted therapy that was being tested in a clinical trial or – in a small number of cases – therapy with an approved treatment used off label, and 596 (45.6%) received nonmatched therapy, Apostolia-Maria Tsimberidou, MD, reported during a press briefing at the annual meeting of the American Society of Clinical Oncology.

The objective response rates in 697 evaluable matched therapy patients was 16.2% versus 5.4% in 571 evaluable nonmatched patients, and stable disease for at least 6 months occurred in 18.7% and 14.7% of patients, respectively, for an overall disease control rate of 34.9% versus 20.1%, said Dr. Tsimberidou, a professor at the University of Texas MD Anderson Cancer Center, Houston.

Median progression-free survival in those who received matched versus nonmatched therapy was 4.0 months and 2.8 months, respectively (hazard ratio, 0.67), and median overall survival was 9.3 and 7.3 months, respectively (HR, 0.72), she said.

The 3-year overall survival rate was 15% versus 7%, respectively, and 10-year survival was 6% and 1%, respectively.

Patients included in IMPACT had a mean age of 57 years, and 39% were men. They were heavily pretreated (mean number of prior therapies was 4); only 2.8% of patients had no prior treatment. Cancers included gastrointestinal (24.2%), gynecologic (19.4%), breast (13.5%), melanoma (11.9%) and lung (8.7%).

In this video interview, Dr. Tsimberidou describes the rationale, methodology, and findings of IMPACT, including the use of a prognostic scoring system developed as part of the study to predict overall survival based on baseline characteristics, such as baseline p13K/AKT/mTOR pathway molecular alterations, which were shown on multivariate analysis in IMPACT to predict shorter overall survival versus other alterations. Other predictors of shorter survival included liver metastases, elevated lactate dehydrogenase levels, poor functional status, low albumin levels, elevated platelet counts, and age of 60 years or older.

SOURCE: Tsimberidou AM et al. ASCO 2018, Abstract LBA 2553.

CHICAGO – Matched targeted therapy improved long-term survival in patients with advanced cancer, according to findings from a retrospective analysis of molecularly profiled patients.

Of 3,743 patients tested as part of IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy), 1,307 (34.9%) had at least one targetable molecular alteration. Of those, 711 (54.4%) received either matched targeted therapy that was being tested in a clinical trial or – in a small number of cases – therapy with an approved treatment used off label, and 596 (45.6%) received nonmatched therapy, Apostolia-Maria Tsimberidou, MD, reported during a press briefing at the annual meeting of the American Society of Clinical Oncology.

The objective response rates in 697 evaluable matched therapy patients was 16.2% versus 5.4% in 571 evaluable nonmatched patients, and stable disease for at least 6 months occurred in 18.7% and 14.7% of patients, respectively, for an overall disease control rate of 34.9% versus 20.1%, said Dr. Tsimberidou, a professor at the University of Texas MD Anderson Cancer Center, Houston.

Median progression-free survival in those who received matched versus nonmatched therapy was 4.0 months and 2.8 months, respectively (hazard ratio, 0.67), and median overall survival was 9.3 and 7.3 months, respectively (HR, 0.72), she said.

The 3-year overall survival rate was 15% versus 7%, respectively, and 10-year survival was 6% and 1%, respectively.

Patients included in IMPACT had a mean age of 57 years, and 39% were men. They were heavily pretreated (mean number of prior therapies was 4); only 2.8% of patients had no prior treatment. Cancers included gastrointestinal (24.2%), gynecologic (19.4%), breast (13.5%), melanoma (11.9%) and lung (8.7%).

In this video interview, Dr. Tsimberidou describes the rationale, methodology, and findings of IMPACT, including the use of a prognostic scoring system developed as part of the study to predict overall survival based on baseline characteristics, such as baseline p13K/AKT/mTOR pathway molecular alterations, which were shown on multivariate analysis in IMPACT to predict shorter overall survival versus other alterations. Other predictors of shorter survival included liver metastases, elevated lactate dehydrogenase levels, poor functional status, low albumin levels, elevated platelet counts, and age of 60 years or older.

SOURCE: Tsimberidou AM et al. ASCO 2018, Abstract LBA 2553.

Use of the recently updated AJCC Cancer Staging Manual, 8th edition, produced about 10% better accuracy when interpreting T1a invasive melanomas in a national study.

For stage T1b or greater cases, using the AJCC 8 instead of the AJCC 7 yielded about 6% higher concordance between interpretations and consensus reference diagnoses, said Joann G. Elmore, MD, MPH, of the David Geffen School of Medicine at the University of California, Los Angeles, and her associates. “Intraobserver reproducibility of diagnoses also improved,” but “concordance and reproducibility remain low,” the researchers wrote. The report was published in JAMA Open Network.

For the study, 187 pathologists each interpreted one of five glass slide sets of melanocytic skin biopsies. At least 8 months later, they interpreted the same set again, both times recording their interpretations on the online Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx). Researchers then used AJCC 7 and AJCC 8 criteria to group these interpretations into one of five MPATH-Dx classes. The final analysis included only the 116 cases of invasive melanoma, because changes in the AJCC 8 criteria affected only MPATH-Dx classes IV (T1a) and V (T1b and higher), the investigators explained.

For T1a invasive melanomas, overall concordance between interpretations and consensus diagnoses rose from 44% (95% confidence interval, 41%-48%) under the AJCC 7 criteria to 54% (95% CI, 51%-57%) under the AJCC 8 criteria. For stage T1b or higher lesions, concordance rose from 72% to 78%. Intrapathologist reproducibility improved from 59% to 64% for T1a cases and from 74% to 77% for T1b or higher cases. Thus, the AJCC 8 produced “modest” improvements in concordance and reproducibility over the AJCC 7, the researchers said.

One of the most likely explanations is that the AJCC 8 eliminated dermal mitotic activity as a criterion for T1b melanomas, which is “potentially unreliable” in thin lesions, they added. Persistently low concordance and reproducibility “suggest that conventional histopathology has been parsed to a degree that falls below the limits of reliability,” they concluded.

The National Cancer Institute provided funding. Dr. Elmore disclosed ties to Myriad Genetics, SciBase, and the National Institutes of Health.

SOURCE: Elmore JG et al. JAMA Network Open. 2018 May 18. doi: 10.1001/jamanetworkopen.2018.0083.

Use of the recently updated AJCC Cancer Staging Manual, 8th edition, produced about 10% better accuracy when interpreting T1a invasive melanomas in a national study.

For stage T1b or greater cases, using the AJCC 8 instead of the AJCC 7 yielded about 6% higher concordance between interpretations and consensus reference diagnoses, said Joann G. Elmore, MD, MPH, of the David Geffen School of Medicine at the University of California, Los Angeles, and her associates. “Intraobserver reproducibility of diagnoses also improved,” but “concordance and reproducibility remain low,” the researchers wrote. The report was published in JAMA Open Network.

For the study, 187 pathologists each interpreted one of five glass slide sets of melanocytic skin biopsies. At least 8 months later, they interpreted the same set again, both times recording their interpretations on the online Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx). Researchers then used AJCC 7 and AJCC 8 criteria to group these interpretations into one of five MPATH-Dx classes. The final analysis included only the 116 cases of invasive melanoma, because changes in the AJCC 8 criteria affected only MPATH-Dx classes IV (T1a) and V (T1b and higher), the investigators explained.

For T1a invasive melanomas, overall concordance between interpretations and consensus diagnoses rose from 44% (95% confidence interval, 41%-48%) under the AJCC 7 criteria to 54% (95% CI, 51%-57%) under the AJCC 8 criteria. For stage T1b or higher lesions, concordance rose from 72% to 78%. Intrapathologist reproducibility improved from 59% to 64% for T1a cases and from 74% to 77% for T1b or higher cases. Thus, the AJCC 8 produced “modest” improvements in concordance and reproducibility over the AJCC 7, the researchers said.

One of the most likely explanations is that the AJCC 8 eliminated dermal mitotic activity as a criterion for T1b melanomas, which is “potentially unreliable” in thin lesions, they added. Persistently low concordance and reproducibility “suggest that conventional histopathology has been parsed to a degree that falls below the limits of reliability,” they concluded.

The National Cancer Institute provided funding. Dr. Elmore disclosed ties to Myriad Genetics, SciBase, and the National Institutes of Health.

SOURCE: Elmore JG et al. JAMA Network Open. 2018 May 18. doi: 10.1001/jamanetworkopen.2018.0083.

Use of the recently updated AJCC Cancer Staging Manual, 8th edition, produced about 10% better accuracy when interpreting T1a invasive melanomas in a national study.

For stage T1b or greater cases, using the AJCC 8 instead of the AJCC 7 yielded about 6% higher concordance between interpretations and consensus reference diagnoses, said Joann G. Elmore, MD, MPH, of the David Geffen School of Medicine at the University of California, Los Angeles, and her associates. “Intraobserver reproducibility of diagnoses also improved,” but “concordance and reproducibility remain low,” the researchers wrote. The report was published in JAMA Open Network.

For the study, 187 pathologists each interpreted one of five glass slide sets of melanocytic skin biopsies. At least 8 months later, they interpreted the same set again, both times recording their interpretations on the online Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx). Researchers then used AJCC 7 and AJCC 8 criteria to group these interpretations into one of five MPATH-Dx classes. The final analysis included only the 116 cases of invasive melanoma, because changes in the AJCC 8 criteria affected only MPATH-Dx classes IV (T1a) and V (T1b and higher), the investigators explained.

For T1a invasive melanomas, overall concordance between interpretations and consensus diagnoses rose from 44% (95% confidence interval, 41%-48%) under the AJCC 7 criteria to 54% (95% CI, 51%-57%) under the AJCC 8 criteria. For stage T1b or higher lesions, concordance rose from 72% to 78%. Intrapathologist reproducibility improved from 59% to 64% for T1a cases and from 74% to 77% for T1b or higher cases. Thus, the AJCC 8 produced “modest” improvements in concordance and reproducibility over the AJCC 7, the researchers said.

One of the most likely explanations is that the AJCC 8 eliminated dermal mitotic activity as a criterion for T1b melanomas, which is “potentially unreliable” in thin lesions, they added. Persistently low concordance and reproducibility “suggest that conventional histopathology has been parsed to a degree that falls below the limits of reliability,” they concluded.

The National Cancer Institute provided funding. Dr. Elmore disclosed ties to Myriad Genetics, SciBase, and the National Institutes of Health.

SOURCE: Elmore JG et al. JAMA Network Open. 2018 May 18. doi: 10.1001/jamanetworkopen.2018.0083.