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Matrilin-2 protein distinguished BCCs from benign tumors in study
ORLANDO – Matrilin-2 – a matrix protein found in peritumoral stroma – reliably distinguished invasive basal cell carcinoma from the often difficult-to-distinguish basaloid follicular hamartoma (BFH), in a study that evaluated the protein as a marker in this setting.
The protein marked 41 of 42 cancers and none of the hamartomas, Dr. Renato Goreshi reported at the annual meeting of the American College of Mohs Surgery. The one cancer it failed to identify was a superficial basal cell tumor – a finding that makes sense, since dermal fibroblasts appear to secrete matrilin-2 as a response to invasive skin tumors, said Dr. Goreshi of the Roger Williams Cancer Center, Providence, R.I.
Mohs surgery typically employs hematoxylin and eosin staining to delineate tumor boundary. But, Dr. Goreshi said, that stain doesn’t always reliably differentiate adnexal tumors from basal cell carcinomas. “Basaloid follicular hamartoma can be particularly difficult to distinguish from basal cell carcinoma,” he said.
BFH typically presents as individual or linearly arranged, small skin-colored to brown papules or plaques, or as multiple lesions in a generalized distribution on the face, scalp, and occasionally, the trunk (Arch Pathol Lab Med. 2010 Aug;134[8]:1215-9). These are often stable for many years. The differential diagnosis includes basal cell carcinoma and trichoepithelioma.
BFH sometimes occurs near a BCC, although there are no data on how often this happens.
Dr. Goreshi cited a 2007 case report of a young woman that illustrates this problem. The patient presented with a basal cell carcinoma on the side of her nose. The adjacent BFH was unrecognized, however. She underwent a multiple-stage Mohs that was unnecessarily extended because tumor margins included sections of the BFH.
“The lesion was interpreted as malignancy by both the Mohs surgeon and the dermatopathologist, but was later determined to have been a hamartoma. This highlights the importance of finding an effective marker,” Dr. Goreshi said.
He and his fellowship director, Dr. Satori Iwamoto, chief of Mohs micrographic surgery at Roger Williams, looked for a reliable way to differentiate these tumors, capitalizing on the invasive nature of BCC. The peritumoral stroma plays a role in tumor growth and invasion. It involves fibroblasts, inflammatory and endothelial cells, and extracellular matrix proteins. Matrilin-2, which is involved in the formation of filamentous networks, was a promising candidate and the initial investigations looked good, said Dr. Goreshi said.
Their confirmatory study comprised 42 BCC and seven BFH sections that were obtained during Mohs surgery. All were stained for matrilin-2 and scored for location and intensity of staining by two reviewers. The investigators also conducted flow cytometry to determine the source of the protein.
The BCC set consisted of 11 morpheaform/infiltrative BCCs, 25 nodular BCCs, and 6 superficial BCCs. With the exception of one superficial lesion, all of these stained positive for matrilin-2 in the peritumoral stroma. None of the BFH sections stained positive for the protein, however. Flow cytometry determined that the protein was coming from dermal fibroblasts in the stroma.
This is actually a key point, Dr. Goreshi noted. “Matrilin-2 is not acting as a conventional tumor marker would, but as a marker of invasion.”
This was again played out in the variation of staining intensity in the tumor subtypes. It was most intense around the infiltrative subtypes. There was also adnexal staining, but it was significantly less than what was seen in the peritumoral stroma. There was virtually no staining in or around the hamartoma.
Staining was not as intense around the superficial BCC subtypes. In fact, it was not significantly different from what was seen in the adnexal structures. Again, however, there was no staining in or around the hamartoma.
“Now we are looking at the staining patterns of other lesions, including melanoma and squamous cell carcinoma, and trying to figure out why the dermal fibroblasts are secreting matrilin-2,” Dr. Goreshi said.
The study was the winner of the 2016 Theodore Tromovitch Award, presented for original research conducted by a fellow-in-training during his or her year of training.
Neither Dr. Goreshi nor Dr. Iwamoto had any relevant financial disclosures.
ORLANDO – Matrilin-2 – a matrix protein found in peritumoral stroma – reliably distinguished invasive basal cell carcinoma from the often difficult-to-distinguish basaloid follicular hamartoma (BFH), in a study that evaluated the protein as a marker in this setting.
The protein marked 41 of 42 cancers and none of the hamartomas, Dr. Renato Goreshi reported at the annual meeting of the American College of Mohs Surgery. The one cancer it failed to identify was a superficial basal cell tumor – a finding that makes sense, since dermal fibroblasts appear to secrete matrilin-2 as a response to invasive skin tumors, said Dr. Goreshi of the Roger Williams Cancer Center, Providence, R.I.
Mohs surgery typically employs hematoxylin and eosin staining to delineate tumor boundary. But, Dr. Goreshi said, that stain doesn’t always reliably differentiate adnexal tumors from basal cell carcinomas. “Basaloid follicular hamartoma can be particularly difficult to distinguish from basal cell carcinoma,” he said.
BFH typically presents as individual or linearly arranged, small skin-colored to brown papules or plaques, or as multiple lesions in a generalized distribution on the face, scalp, and occasionally, the trunk (Arch Pathol Lab Med. 2010 Aug;134[8]:1215-9). These are often stable for many years. The differential diagnosis includes basal cell carcinoma and trichoepithelioma.
BFH sometimes occurs near a BCC, although there are no data on how often this happens.
Dr. Goreshi cited a 2007 case report of a young woman that illustrates this problem. The patient presented with a basal cell carcinoma on the side of her nose. The adjacent BFH was unrecognized, however. She underwent a multiple-stage Mohs that was unnecessarily extended because tumor margins included sections of the BFH.
“The lesion was interpreted as malignancy by both the Mohs surgeon and the dermatopathologist, but was later determined to have been a hamartoma. This highlights the importance of finding an effective marker,” Dr. Goreshi said.
He and his fellowship director, Dr. Satori Iwamoto, chief of Mohs micrographic surgery at Roger Williams, looked for a reliable way to differentiate these tumors, capitalizing on the invasive nature of BCC. The peritumoral stroma plays a role in tumor growth and invasion. It involves fibroblasts, inflammatory and endothelial cells, and extracellular matrix proteins. Matrilin-2, which is involved in the formation of filamentous networks, was a promising candidate and the initial investigations looked good, said Dr. Goreshi said.
Their confirmatory study comprised 42 BCC and seven BFH sections that were obtained during Mohs surgery. All were stained for matrilin-2 and scored for location and intensity of staining by two reviewers. The investigators also conducted flow cytometry to determine the source of the protein.
The BCC set consisted of 11 morpheaform/infiltrative BCCs, 25 nodular BCCs, and 6 superficial BCCs. With the exception of one superficial lesion, all of these stained positive for matrilin-2 in the peritumoral stroma. None of the BFH sections stained positive for the protein, however. Flow cytometry determined that the protein was coming from dermal fibroblasts in the stroma.
This is actually a key point, Dr. Goreshi noted. “Matrilin-2 is not acting as a conventional tumor marker would, but as a marker of invasion.”
This was again played out in the variation of staining intensity in the tumor subtypes. It was most intense around the infiltrative subtypes. There was also adnexal staining, but it was significantly less than what was seen in the peritumoral stroma. There was virtually no staining in or around the hamartoma.
Staining was not as intense around the superficial BCC subtypes. In fact, it was not significantly different from what was seen in the adnexal structures. Again, however, there was no staining in or around the hamartoma.
“Now we are looking at the staining patterns of other lesions, including melanoma and squamous cell carcinoma, and trying to figure out why the dermal fibroblasts are secreting matrilin-2,” Dr. Goreshi said.
The study was the winner of the 2016 Theodore Tromovitch Award, presented for original research conducted by a fellow-in-training during his or her year of training.
Neither Dr. Goreshi nor Dr. Iwamoto had any relevant financial disclosures.
ORLANDO – Matrilin-2 – a matrix protein found in peritumoral stroma – reliably distinguished invasive basal cell carcinoma from the often difficult-to-distinguish basaloid follicular hamartoma (BFH), in a study that evaluated the protein as a marker in this setting.
The protein marked 41 of 42 cancers and none of the hamartomas, Dr. Renato Goreshi reported at the annual meeting of the American College of Mohs Surgery. The one cancer it failed to identify was a superficial basal cell tumor – a finding that makes sense, since dermal fibroblasts appear to secrete matrilin-2 as a response to invasive skin tumors, said Dr. Goreshi of the Roger Williams Cancer Center, Providence, R.I.
Mohs surgery typically employs hematoxylin and eosin staining to delineate tumor boundary. But, Dr. Goreshi said, that stain doesn’t always reliably differentiate adnexal tumors from basal cell carcinomas. “Basaloid follicular hamartoma can be particularly difficult to distinguish from basal cell carcinoma,” he said.
BFH typically presents as individual or linearly arranged, small skin-colored to brown papules or plaques, or as multiple lesions in a generalized distribution on the face, scalp, and occasionally, the trunk (Arch Pathol Lab Med. 2010 Aug;134[8]:1215-9). These are often stable for many years. The differential diagnosis includes basal cell carcinoma and trichoepithelioma.
BFH sometimes occurs near a BCC, although there are no data on how often this happens.
Dr. Goreshi cited a 2007 case report of a young woman that illustrates this problem. The patient presented with a basal cell carcinoma on the side of her nose. The adjacent BFH was unrecognized, however. She underwent a multiple-stage Mohs that was unnecessarily extended because tumor margins included sections of the BFH.
“The lesion was interpreted as malignancy by both the Mohs surgeon and the dermatopathologist, but was later determined to have been a hamartoma. This highlights the importance of finding an effective marker,” Dr. Goreshi said.
He and his fellowship director, Dr. Satori Iwamoto, chief of Mohs micrographic surgery at Roger Williams, looked for a reliable way to differentiate these tumors, capitalizing on the invasive nature of BCC. The peritumoral stroma plays a role in tumor growth and invasion. It involves fibroblasts, inflammatory and endothelial cells, and extracellular matrix proteins. Matrilin-2, which is involved in the formation of filamentous networks, was a promising candidate and the initial investigations looked good, said Dr. Goreshi said.
Their confirmatory study comprised 42 BCC and seven BFH sections that were obtained during Mohs surgery. All were stained for matrilin-2 and scored for location and intensity of staining by two reviewers. The investigators also conducted flow cytometry to determine the source of the protein.
The BCC set consisted of 11 morpheaform/infiltrative BCCs, 25 nodular BCCs, and 6 superficial BCCs. With the exception of one superficial lesion, all of these stained positive for matrilin-2 in the peritumoral stroma. None of the BFH sections stained positive for the protein, however. Flow cytometry determined that the protein was coming from dermal fibroblasts in the stroma.
This is actually a key point, Dr. Goreshi noted. “Matrilin-2 is not acting as a conventional tumor marker would, but as a marker of invasion.”
This was again played out in the variation of staining intensity in the tumor subtypes. It was most intense around the infiltrative subtypes. There was also adnexal staining, but it was significantly less than what was seen in the peritumoral stroma. There was virtually no staining in or around the hamartoma.
Staining was not as intense around the superficial BCC subtypes. In fact, it was not significantly different from what was seen in the adnexal structures. Again, however, there was no staining in or around the hamartoma.
“Now we are looking at the staining patterns of other lesions, including melanoma and squamous cell carcinoma, and trying to figure out why the dermal fibroblasts are secreting matrilin-2,” Dr. Goreshi said.
The study was the winner of the 2016 Theodore Tromovitch Award, presented for original research conducted by a fellow-in-training during his or her year of training.
Neither Dr. Goreshi nor Dr. Iwamoto had any relevant financial disclosures.
AT THE ACMS ANNUAL MEETING
Key clinical point: Matrilin-2 is the first marker of tumor invasion to be used in skin cancers.
Major finding: The protein bound to 41 of 42 BCCs, and to none of the hamartoma lesions studied, reliably distinguishing the two.
Data source: 42 frozen section BCCs and seven basaloid follicular hamartomas.
Disclosures: Neither Dr. Goreshi nor Dr. Iwamoto had any relevant financial disclosures.
For preventing AKs, 5-FU beats placebo for up to 3 years
SCOTTSDALE – A single course of topical 5-fluorouracil (5-FU) prevented 62% more actinic keratoses than placebo, and this chemopreventive effect persisted for up to 3 years, according to an analysis of the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial (VAKCCT) trial.
Other studies have shown that 5-FU effectively treats precancerous AKs, but have not examined whether 5-FU can prevent AKs, Dr. Joanna Walker said in an interview at the annual meeting of the Society for Investigative Dermatology.
Clinicians should consider preventive 5-FU in patients who are at high risk for basal cell and squamous cell carcinomas, especially if a skin check reveals multiple AKs, said Dr. Walker of the department of dermatology, Brown University, Providence, RI.
The VAKCCT was a randomized, double-blind, placebo-controlled study conducted at 12 Veterans Affairs dermatology clinics. The 319 patients in the analysis were nearly all elderly men with extensive sun damage, with a total of 2,386 AKs at baseline, for an average of five lesions per patient. Patients also had a history of at least two keratinocyte carcinomas in the past 5 years, including at least one lesion on the face or ears, and no recent history of 5-FU exposure.
The clinically and demographically similar study arms were randomized to either 5% topical 5-FU cream or a vehicle control cream, applied twice daily for 2-4 weeks. Both groups received cryotherapy for existing AKs, and were given free SPF 30 sunscreen. At each 6-month follow-up visit, the researchers counted existing AKs and new lesions.
At month 6, the treatment group had 62% fewer new AKs than the placebo group (average per patient, 1.78 and 4.73, respectively), a statistically significant difference. At months 12, 18, 24, 30, and 36, respectively, the treatment group had 50%, 40%, 41%, 25%, and 35% fewer new AKs than the placebo group, and these differences all were statistically significant. Furthermore, at month 6, only 56% of treated patients had at least one new AK, compared with 78% of the control group (incidence rate ratio, 0.72; 95% confidence interval, 0.54-0.95).
This chemopreventive effect remained significant for 24 months, the investigators reported. “Individuals with at least five AKs at the time of 5-FU treatment had an even more dramatic reduction in new AKs,” Dr. Walker noted. “There is now high-quality evidence supporting the use of topical 5-FU for AK chemoprevention. I think this is important information that we can take back to the clinic when we are trying to convince our patients to go through a course of 5-FU.”
The rate of new AKs in the placebo group fell during the first 2.5 years of the study and then stabilized. “For both groups, there was a dramatic increase in the use of sunscreen during the trial, and we hypothesized that the decrease in AKs in the control group was due to increased use of sun-protective measures,” Dr. Walker said.
The research was funded by the Cooperative Studies Program of the U.S. Department of Veterans Affairs. Dr. Walker had no disclosures.
SCOTTSDALE – A single course of topical 5-fluorouracil (5-FU) prevented 62% more actinic keratoses than placebo, and this chemopreventive effect persisted for up to 3 years, according to an analysis of the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial (VAKCCT) trial.
Other studies have shown that 5-FU effectively treats precancerous AKs, but have not examined whether 5-FU can prevent AKs, Dr. Joanna Walker said in an interview at the annual meeting of the Society for Investigative Dermatology.
Clinicians should consider preventive 5-FU in patients who are at high risk for basal cell and squamous cell carcinomas, especially if a skin check reveals multiple AKs, said Dr. Walker of the department of dermatology, Brown University, Providence, RI.
The VAKCCT was a randomized, double-blind, placebo-controlled study conducted at 12 Veterans Affairs dermatology clinics. The 319 patients in the analysis were nearly all elderly men with extensive sun damage, with a total of 2,386 AKs at baseline, for an average of five lesions per patient. Patients also had a history of at least two keratinocyte carcinomas in the past 5 years, including at least one lesion on the face or ears, and no recent history of 5-FU exposure.
The clinically and demographically similar study arms were randomized to either 5% topical 5-FU cream or a vehicle control cream, applied twice daily for 2-4 weeks. Both groups received cryotherapy for existing AKs, and were given free SPF 30 sunscreen. At each 6-month follow-up visit, the researchers counted existing AKs and new lesions.
At month 6, the treatment group had 62% fewer new AKs than the placebo group (average per patient, 1.78 and 4.73, respectively), a statistically significant difference. At months 12, 18, 24, 30, and 36, respectively, the treatment group had 50%, 40%, 41%, 25%, and 35% fewer new AKs than the placebo group, and these differences all were statistically significant. Furthermore, at month 6, only 56% of treated patients had at least one new AK, compared with 78% of the control group (incidence rate ratio, 0.72; 95% confidence interval, 0.54-0.95).
This chemopreventive effect remained significant for 24 months, the investigators reported. “Individuals with at least five AKs at the time of 5-FU treatment had an even more dramatic reduction in new AKs,” Dr. Walker noted. “There is now high-quality evidence supporting the use of topical 5-FU for AK chemoprevention. I think this is important information that we can take back to the clinic when we are trying to convince our patients to go through a course of 5-FU.”
The rate of new AKs in the placebo group fell during the first 2.5 years of the study and then stabilized. “For both groups, there was a dramatic increase in the use of sunscreen during the trial, and we hypothesized that the decrease in AKs in the control group was due to increased use of sun-protective measures,” Dr. Walker said.
The research was funded by the Cooperative Studies Program of the U.S. Department of Veterans Affairs. Dr. Walker had no disclosures.
SCOTTSDALE – A single course of topical 5-fluorouracil (5-FU) prevented 62% more actinic keratoses than placebo, and this chemopreventive effect persisted for up to 3 years, according to an analysis of the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial (VAKCCT) trial.
Other studies have shown that 5-FU effectively treats precancerous AKs, but have not examined whether 5-FU can prevent AKs, Dr. Joanna Walker said in an interview at the annual meeting of the Society for Investigative Dermatology.
Clinicians should consider preventive 5-FU in patients who are at high risk for basal cell and squamous cell carcinomas, especially if a skin check reveals multiple AKs, said Dr. Walker of the department of dermatology, Brown University, Providence, RI.
The VAKCCT was a randomized, double-blind, placebo-controlled study conducted at 12 Veterans Affairs dermatology clinics. The 319 patients in the analysis were nearly all elderly men with extensive sun damage, with a total of 2,386 AKs at baseline, for an average of five lesions per patient. Patients also had a history of at least two keratinocyte carcinomas in the past 5 years, including at least one lesion on the face or ears, and no recent history of 5-FU exposure.
The clinically and demographically similar study arms were randomized to either 5% topical 5-FU cream or a vehicle control cream, applied twice daily for 2-4 weeks. Both groups received cryotherapy for existing AKs, and were given free SPF 30 sunscreen. At each 6-month follow-up visit, the researchers counted existing AKs and new lesions.
At month 6, the treatment group had 62% fewer new AKs than the placebo group (average per patient, 1.78 and 4.73, respectively), a statistically significant difference. At months 12, 18, 24, 30, and 36, respectively, the treatment group had 50%, 40%, 41%, 25%, and 35% fewer new AKs than the placebo group, and these differences all were statistically significant. Furthermore, at month 6, only 56% of treated patients had at least one new AK, compared with 78% of the control group (incidence rate ratio, 0.72; 95% confidence interval, 0.54-0.95).
This chemopreventive effect remained significant for 24 months, the investigators reported. “Individuals with at least five AKs at the time of 5-FU treatment had an even more dramatic reduction in new AKs,” Dr. Walker noted. “There is now high-quality evidence supporting the use of topical 5-FU for AK chemoprevention. I think this is important information that we can take back to the clinic when we are trying to convince our patients to go through a course of 5-FU.”
The rate of new AKs in the placebo group fell during the first 2.5 years of the study and then stabilized. “For both groups, there was a dramatic increase in the use of sunscreen during the trial, and we hypothesized that the decrease in AKs in the control group was due to increased use of sun-protective measures,” Dr. Walker said.
The research was funded by the Cooperative Studies Program of the U.S. Department of Veterans Affairs. Dr. Walker had no disclosures.
AT THE 2016 SID ANNUAL MEETING
Key clinical point: One course of topical 5-fluorouracil was effective and durable in preventing new actinic keratoses in high-risk patients.
Major finding: At month 6, the treatment group had 62% fewer new AKs than the placebo group, and the difference remained significant at month 36.
Data source: The double-blind controlled study evaluated 5-FU vs. a vehicle cream in 319 veterans, most of whom were elderly men.
Disclosures: The study was funded by the Cooperative Studies Program of the U.S. Department of Veterans Affairs. Dr. Walker had no disclosures.
Liquid biopsy–based test detects BRAF mutations
Analysis of plasma-derived cell-free DNA can identify BRAF mutations as accurately as formalin-fixed paraffin-embedded tumor sample analysis, investigators report.
Of 160 patients with advanced solid tumors, BRAF V600 mutations were detected in 62 (39%) archival formalin-fixed paraffin-embedded (FFPE) tumor samples and 47 (29%) plasma cell-free (cf) DNA samples. The two methods had overall agreement in 141 patients (88%; kappa coefficient, 0.74; SE, 0.06; 95% confidence interval, 0.63-0.85), Dr. Filip Janku of the University of Texas and his associates reported (Mol Cancer Ther. 2016 May 20. doi: 10.1158/1535-7163.MCT-15-0712).
BRAF mutations are prevalent in many types of advanced cancers, and targeting these mutations has demonstrated efficacy, but current assessment of BRAF mutations is limited by a lack of tissue samples and complicated by constantly changing mutation status.
cfDNA is secreted into the circulation by tumor cells and cells in the tumor microenvironment that are undergoing apoptosis or necroptosis and might serve as an alternate source for determining BRAF mutation.
“Collecting plasma cfDNA is a minimally invasive procedure that can be repeated at multiple times for diagnostic and disease-monitoring purposes,” Dr. Janku and associates said.
The investigators analyzed plasma samples from 160 patients with advanced solid tumors – most commonly colorectal cancer and melanoma –who had available archival FFPE tumor samples. cfDNA was isolated and extracted from whole blood and analyzed using the Idylla BRAF Mutation Test, a fully integrated real-time polymerase chain reaction–based test with a turnaround time of about 90 minutes.
Dr. Janku and associates found that a higher amount of mutant cfDNA was associated with shorter overall survival. Mean overall survival for patients with a BRAF-mutant cfDNA percentage of less than 2% (10.7 months; 95% CI, 9-12.4) was significantly longer than patients with a BRAF-mutant cfDNA percentage of greater than 2% (4.4 months; 95% CI, 3.2-5.6). Similar results were observed using different percentage cutoffs.
“Our study shows that the Idylla system can detect BRAF V600 mutations in plasma-derived cfDNA from patients with advanced cancers and has acceptable concordance (baseline, 88%; any time point, 90%); sensitivity (baseline, 73%; any time, 77%); and specificity (baseline, 98%; any time, 98%), compared with CLIA-certified laboratory testing of FFPE tumor tissue obtained at different times during routine care,” investigators wrote.
This study was supported by Biocartis, the Elsa U. Pardee Foundation, and the Sidney Kimmel Foundation for Cancer Research. Five of the investigators reported serving in an advisory role for, having ownership interest in, or receiving financial compensation or honoraria from multiple companies. The other investigators reported having no disclosures.
On Twitter @JessCraig_OP
Analysis of plasma-derived cell-free DNA can identify BRAF mutations as accurately as formalin-fixed paraffin-embedded tumor sample analysis, investigators report.
Of 160 patients with advanced solid tumors, BRAF V600 mutations were detected in 62 (39%) archival formalin-fixed paraffin-embedded (FFPE) tumor samples and 47 (29%) plasma cell-free (cf) DNA samples. The two methods had overall agreement in 141 patients (88%; kappa coefficient, 0.74; SE, 0.06; 95% confidence interval, 0.63-0.85), Dr. Filip Janku of the University of Texas and his associates reported (Mol Cancer Ther. 2016 May 20. doi: 10.1158/1535-7163.MCT-15-0712).
BRAF mutations are prevalent in many types of advanced cancers, and targeting these mutations has demonstrated efficacy, but current assessment of BRAF mutations is limited by a lack of tissue samples and complicated by constantly changing mutation status.
cfDNA is secreted into the circulation by tumor cells and cells in the tumor microenvironment that are undergoing apoptosis or necroptosis and might serve as an alternate source for determining BRAF mutation.
“Collecting plasma cfDNA is a minimally invasive procedure that can be repeated at multiple times for diagnostic and disease-monitoring purposes,” Dr. Janku and associates said.
The investigators analyzed plasma samples from 160 patients with advanced solid tumors – most commonly colorectal cancer and melanoma –who had available archival FFPE tumor samples. cfDNA was isolated and extracted from whole blood and analyzed using the Idylla BRAF Mutation Test, a fully integrated real-time polymerase chain reaction–based test with a turnaround time of about 90 minutes.
Dr. Janku and associates found that a higher amount of mutant cfDNA was associated with shorter overall survival. Mean overall survival for patients with a BRAF-mutant cfDNA percentage of less than 2% (10.7 months; 95% CI, 9-12.4) was significantly longer than patients with a BRAF-mutant cfDNA percentage of greater than 2% (4.4 months; 95% CI, 3.2-5.6). Similar results were observed using different percentage cutoffs.
“Our study shows that the Idylla system can detect BRAF V600 mutations in plasma-derived cfDNA from patients with advanced cancers and has acceptable concordance (baseline, 88%; any time point, 90%); sensitivity (baseline, 73%; any time, 77%); and specificity (baseline, 98%; any time, 98%), compared with CLIA-certified laboratory testing of FFPE tumor tissue obtained at different times during routine care,” investigators wrote.
This study was supported by Biocartis, the Elsa U. Pardee Foundation, and the Sidney Kimmel Foundation for Cancer Research. Five of the investigators reported serving in an advisory role for, having ownership interest in, or receiving financial compensation or honoraria from multiple companies. The other investigators reported having no disclosures.
On Twitter @JessCraig_OP
Analysis of plasma-derived cell-free DNA can identify BRAF mutations as accurately as formalin-fixed paraffin-embedded tumor sample analysis, investigators report.
Of 160 patients with advanced solid tumors, BRAF V600 mutations were detected in 62 (39%) archival formalin-fixed paraffin-embedded (FFPE) tumor samples and 47 (29%) plasma cell-free (cf) DNA samples. The two methods had overall agreement in 141 patients (88%; kappa coefficient, 0.74; SE, 0.06; 95% confidence interval, 0.63-0.85), Dr. Filip Janku of the University of Texas and his associates reported (Mol Cancer Ther. 2016 May 20. doi: 10.1158/1535-7163.MCT-15-0712).
BRAF mutations are prevalent in many types of advanced cancers, and targeting these mutations has demonstrated efficacy, but current assessment of BRAF mutations is limited by a lack of tissue samples and complicated by constantly changing mutation status.
cfDNA is secreted into the circulation by tumor cells and cells in the tumor microenvironment that are undergoing apoptosis or necroptosis and might serve as an alternate source for determining BRAF mutation.
“Collecting plasma cfDNA is a minimally invasive procedure that can be repeated at multiple times for diagnostic and disease-monitoring purposes,” Dr. Janku and associates said.
The investigators analyzed plasma samples from 160 patients with advanced solid tumors – most commonly colorectal cancer and melanoma –who had available archival FFPE tumor samples. cfDNA was isolated and extracted from whole blood and analyzed using the Idylla BRAF Mutation Test, a fully integrated real-time polymerase chain reaction–based test with a turnaround time of about 90 minutes.
Dr. Janku and associates found that a higher amount of mutant cfDNA was associated with shorter overall survival. Mean overall survival for patients with a BRAF-mutant cfDNA percentage of less than 2% (10.7 months; 95% CI, 9-12.4) was significantly longer than patients with a BRAF-mutant cfDNA percentage of greater than 2% (4.4 months; 95% CI, 3.2-5.6). Similar results were observed using different percentage cutoffs.
“Our study shows that the Idylla system can detect BRAF V600 mutations in plasma-derived cfDNA from patients with advanced cancers and has acceptable concordance (baseline, 88%; any time point, 90%); sensitivity (baseline, 73%; any time, 77%); and specificity (baseline, 98%; any time, 98%), compared with CLIA-certified laboratory testing of FFPE tumor tissue obtained at different times during routine care,” investigators wrote.
This study was supported by Biocartis, the Elsa U. Pardee Foundation, and the Sidney Kimmel Foundation for Cancer Research. Five of the investigators reported serving in an advisory role for, having ownership interest in, or receiving financial compensation or honoraria from multiple companies. The other investigators reported having no disclosures.
On Twitter @JessCraig_OP
FROM MOLECULAR CANCER THERAPEUTICS
Key clinical point: Analysis of plasma-derived cfDNA can identify BRAF mutations as accurately as FFPE tumor sample analysis.
Major finding: Concordance between mutation analysis of FFPE tumor samples and plasma cfDNA was in overall agreement (88%; kappa, 0.74; SE, 0.06; 95% CI, 0.63-0.85).
Data source: Analysis of FFPE tumor samples and plasma-derived cfDNA for 160 patients with advanced cancers.
Disclosures: This study was supported by Biocartis, the Elsa U. Pardee Foundation, and the Sidney Kimmel Foundation for Cancer Research. Five of the investigators reported serving in an advisory role for, having ownership interest in, or receiving financial compensation or honoraria from multiple companies. The other investigators reported having no disclosures.
Pembrolizumab benefit holds long-term for some melanoma patients
The anti–PD-1 immunotherapy pembrolizumab increases long-term survival in some patients with advanced melanoma, according to updated results of KEYNOTE-001.
Among the 655 patients studied in the phase 1b trial, the 3-year overall survival rate for advanced melanoma patients treated with pembrolizumab was 40%, Dr. Caroline Robert reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Median overall survival was 24.4 months. Before 2011, patients with advanced melanoma had a median overall survival of less than one year, said Dr. Robert, head of the dermatology unit at the Institut Gustave-Roussy in Paris.
Study participants received pembrolizumab at either 2 or 10 mg/kg every 3 weeks. During the trial, 2 mg/kg every 3 weeks was determined to be the optimal dosing regimen. Patients remained on the treatment until disease progression, intolerable toxicity, or investigator decision. Eight percent of patients stopped treatment due to drug-related symptoms, and there were no drug-related deaths.
Survival rates differed slightly based on prior melanoma treatment. Of the 655 patients in the study, 75% had received previous treatments; patients who had not received prior treatment had slightly higher survival at 45%.
Overall response rate was 33%. Responses were durable as 73% of patients had a response rate of two or more years. Ninety-five patients had a complete response, and 61 of those patients stopped treatment following the complete response.
“I really hope for a cure for these people,” Dr. Robert said.
Pembrolizumab was generally well tolerated with the most common adverse events being fatigue (40%), itchiness (28%), and rash (23%).
ASCO spokesperson and moderator, Dr. Don Dizon, said the results of this study are “incredibly exciting given they came from a phase I trial. This is a new treatment and the longest follow-up of people [with melanoma] who have received pembrolizumab.” Dr. Dizon hopes to “potentially see a cure [for] melanoma” given the reported durability and response rate to the drug.
On Twitter @JessCraig_OP
The anti–PD-1 immunotherapy pembrolizumab increases long-term survival in some patients with advanced melanoma, according to updated results of KEYNOTE-001.
Among the 655 patients studied in the phase 1b trial, the 3-year overall survival rate for advanced melanoma patients treated with pembrolizumab was 40%, Dr. Caroline Robert reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Median overall survival was 24.4 months. Before 2011, patients with advanced melanoma had a median overall survival of less than one year, said Dr. Robert, head of the dermatology unit at the Institut Gustave-Roussy in Paris.
Study participants received pembrolizumab at either 2 or 10 mg/kg every 3 weeks. During the trial, 2 mg/kg every 3 weeks was determined to be the optimal dosing regimen. Patients remained on the treatment until disease progression, intolerable toxicity, or investigator decision. Eight percent of patients stopped treatment due to drug-related symptoms, and there were no drug-related deaths.
Survival rates differed slightly based on prior melanoma treatment. Of the 655 patients in the study, 75% had received previous treatments; patients who had not received prior treatment had slightly higher survival at 45%.
Overall response rate was 33%. Responses were durable as 73% of patients had a response rate of two or more years. Ninety-five patients had a complete response, and 61 of those patients stopped treatment following the complete response.
“I really hope for a cure for these people,” Dr. Robert said.
Pembrolizumab was generally well tolerated with the most common adverse events being fatigue (40%), itchiness (28%), and rash (23%).
ASCO spokesperson and moderator, Dr. Don Dizon, said the results of this study are “incredibly exciting given they came from a phase I trial. This is a new treatment and the longest follow-up of people [with melanoma] who have received pembrolizumab.” Dr. Dizon hopes to “potentially see a cure [for] melanoma” given the reported durability and response rate to the drug.
On Twitter @JessCraig_OP
The anti–PD-1 immunotherapy pembrolizumab increases long-term survival in some patients with advanced melanoma, according to updated results of KEYNOTE-001.
Among the 655 patients studied in the phase 1b trial, the 3-year overall survival rate for advanced melanoma patients treated with pembrolizumab was 40%, Dr. Caroline Robert reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Median overall survival was 24.4 months. Before 2011, patients with advanced melanoma had a median overall survival of less than one year, said Dr. Robert, head of the dermatology unit at the Institut Gustave-Roussy in Paris.
Study participants received pembrolizumab at either 2 or 10 mg/kg every 3 weeks. During the trial, 2 mg/kg every 3 weeks was determined to be the optimal dosing regimen. Patients remained on the treatment until disease progression, intolerable toxicity, or investigator decision. Eight percent of patients stopped treatment due to drug-related symptoms, and there were no drug-related deaths.
Survival rates differed slightly based on prior melanoma treatment. Of the 655 patients in the study, 75% had received previous treatments; patients who had not received prior treatment had slightly higher survival at 45%.
Overall response rate was 33%. Responses were durable as 73% of patients had a response rate of two or more years. Ninety-five patients had a complete response, and 61 of those patients stopped treatment following the complete response.
“I really hope for a cure for these people,” Dr. Robert said.
Pembrolizumab was generally well tolerated with the most common adverse events being fatigue (40%), itchiness (28%), and rash (23%).
ASCO spokesperson and moderator, Dr. Don Dizon, said the results of this study are “incredibly exciting given they came from a phase I trial. This is a new treatment and the longest follow-up of people [with melanoma] who have received pembrolizumab.” Dr. Dizon hopes to “potentially see a cure [for] melanoma” given the reported durability and response rate to the drug.
On Twitter @JessCraig_OP
FROM THE 2016 ASCO ANNUAL MEETING
Key clinical point: Pembrolizumab increases long-term survival in some patients with advanced melanoma.
Major finding: The 3-year overall survival rate for advanced melanoma patients treated with pembrolizumab was 40%. The median overall survival was 24.4 months.
Data source: A phase Ib clinical trial of 655 patients with advanced melanoma.
Disclosures: This study was funded by Merck. All of the investigators reported serving in advisory/consultatory roles for, having stock in, or receiving financial compensation or honoraria from several companies.
Early Detection of Melanoma in Men
Men do not know as much about skin cancer prevention and detection techniques as women, according to a recent survey conducted by the American Academy of Dermatology (AAD). This lack of knowledge may delay or prevent early diagnosis and treatment of melanoma and other nonmelanoma skin cancers in this patient population.
The survey results showed that only 56% of men versus 76% of women know there is no such thing as a healthy tan, and only 54% of men versus 70% of women know that getting a base tan is not a healthy way to protect skin from the sun. Furthermore, only 56% of men surveyed were aware that skin cancer could occur on areas of the skin not typically exposed to the sun compared to 65% of women.
“While our survey results indicate that men don’t know as much about skin cancer prevention and detection as women, men over 50 have a higher risk of developing melanoma, so it’s especially important for them to be vigilant about protecting and monitoring their skin,” said AAD President Abel Torres, MD, JD.
May is skin cancer awareness month and the AAD is encouraging patients to make sure their skin is “Looking Good in 2016” by using sun protection and regularly examining skin for signs of skin cancer. The campaign features a public service announcement encouraging men to check their skin for signs of skin cancer and find a partner to help. The AAD also released a new infographic with tips on performing a skin cancer self-examination that dermatologists can share with patients to promote early detection of skin cancer.
Dermatologist intervention in catching skin cancers when they are easier to treat also is key. At the 74th Annual Meeting of the American Academy of Dermatology in Washington, DC, Dr. Orit Markowitz discussed noninvasive imaging tools that can help dermatologists diagnose skin cancers earlier. She noted that even when a lesion looks very small, tools such as dermoscopy can reveal features that indicate it already has depth and therefore may progress to a more serious malignancy. Early detection is particularly crucial in cases of rare aggressive tumors such as amelanotic melanoma. “If something is very pink clinically and then suddenly has pigmentation dermoscopically, you really have to be considering biopsying that lesion because you may be looking at an early amelanotic melanoma,” Dr. Markowitz explained. By the time the lesion develops more obvious clinical features suggesting malignancy, the tumor progression may be far more advanced.
Men do not know as much about skin cancer prevention and detection techniques as women, according to a recent survey conducted by the American Academy of Dermatology (AAD). This lack of knowledge may delay or prevent early diagnosis and treatment of melanoma and other nonmelanoma skin cancers in this patient population.
The survey results showed that only 56% of men versus 76% of women know there is no such thing as a healthy tan, and only 54% of men versus 70% of women know that getting a base tan is not a healthy way to protect skin from the sun. Furthermore, only 56% of men surveyed were aware that skin cancer could occur on areas of the skin not typically exposed to the sun compared to 65% of women.
“While our survey results indicate that men don’t know as much about skin cancer prevention and detection as women, men over 50 have a higher risk of developing melanoma, so it’s especially important for them to be vigilant about protecting and monitoring their skin,” said AAD President Abel Torres, MD, JD.
May is skin cancer awareness month and the AAD is encouraging patients to make sure their skin is “Looking Good in 2016” by using sun protection and regularly examining skin for signs of skin cancer. The campaign features a public service announcement encouraging men to check their skin for signs of skin cancer and find a partner to help. The AAD also released a new infographic with tips on performing a skin cancer self-examination that dermatologists can share with patients to promote early detection of skin cancer.
Dermatologist intervention in catching skin cancers when they are easier to treat also is key. At the 74th Annual Meeting of the American Academy of Dermatology in Washington, DC, Dr. Orit Markowitz discussed noninvasive imaging tools that can help dermatologists diagnose skin cancers earlier. She noted that even when a lesion looks very small, tools such as dermoscopy can reveal features that indicate it already has depth and therefore may progress to a more serious malignancy. Early detection is particularly crucial in cases of rare aggressive tumors such as amelanotic melanoma. “If something is very pink clinically and then suddenly has pigmentation dermoscopically, you really have to be considering biopsying that lesion because you may be looking at an early amelanotic melanoma,” Dr. Markowitz explained. By the time the lesion develops more obvious clinical features suggesting malignancy, the tumor progression may be far more advanced.
Men do not know as much about skin cancer prevention and detection techniques as women, according to a recent survey conducted by the American Academy of Dermatology (AAD). This lack of knowledge may delay or prevent early diagnosis and treatment of melanoma and other nonmelanoma skin cancers in this patient population.
The survey results showed that only 56% of men versus 76% of women know there is no such thing as a healthy tan, and only 54% of men versus 70% of women know that getting a base tan is not a healthy way to protect skin from the sun. Furthermore, only 56% of men surveyed were aware that skin cancer could occur on areas of the skin not typically exposed to the sun compared to 65% of women.
“While our survey results indicate that men don’t know as much about skin cancer prevention and detection as women, men over 50 have a higher risk of developing melanoma, so it’s especially important for them to be vigilant about protecting and monitoring their skin,” said AAD President Abel Torres, MD, JD.
May is skin cancer awareness month and the AAD is encouraging patients to make sure their skin is “Looking Good in 2016” by using sun protection and regularly examining skin for signs of skin cancer. The campaign features a public service announcement encouraging men to check their skin for signs of skin cancer and find a partner to help. The AAD also released a new infographic with tips on performing a skin cancer self-examination that dermatologists can share with patients to promote early detection of skin cancer.
Dermatologist intervention in catching skin cancers when they are easier to treat also is key. At the 74th Annual Meeting of the American Academy of Dermatology in Washington, DC, Dr. Orit Markowitz discussed noninvasive imaging tools that can help dermatologists diagnose skin cancers earlier. She noted that even when a lesion looks very small, tools such as dermoscopy can reveal features that indicate it already has depth and therefore may progress to a more serious malignancy. Early detection is particularly crucial in cases of rare aggressive tumors such as amelanotic melanoma. “If something is very pink clinically and then suddenly has pigmentation dermoscopically, you really have to be considering biopsying that lesion because you may be looking at an early amelanotic melanoma,” Dr. Markowitz explained. By the time the lesion develops more obvious clinical features suggesting malignancy, the tumor progression may be far more advanced.
Mohs surgeons, dermatopathologists nearly always agree on frozen section analysis
ORLANDO – Mohs fellowship–trained surgeons are highly skilled at reading frozen section slides obtained during surgery, agreeing with the dermatopathologist’s assessment more than 99% of the time, according to a review of more than 4,000 cases.
Among 4,145 slides in five datasets, only 28 were discordant. The concordance of surgeons’ and dermatopathologists’ assessments was quite consistent, ranging from 95%-of 99.7%.
“There is absolutely no detriment to our interpretation of these frozen section slides,” Dr. James Highsmith said at the annual meeting of the American College of Mohs Surgery. “These numbers give credence as to why we have these good cure rates. We can say with 99% accuracy that yes, we are removing these tumors from our patients.”
Dr. Highsmith, a Mohs surgeon in Birmingham, Ala., reviewed 10 years of his own data (1,720 cases), as well as four published cohorts comprising another 2,425 cases. All of the studies examined the concordance of frozen section assessments between fellowship-trained Mohs surgeons and the dermatopathologists working with them. All of the series reported concordance, discordance, sensitivity, and specificity.
His own database is the largest one yet compiled, spanning the longest period of time. Of 1,720 cases, there were eight discrepancies: one in which the surgeon identified tumor that was not supported by dermatopathology, and seven in which the surgeon missed tumor that dermatopathology confirmed was present. The concordance rate was 99.5%. This worked out to a 99.4% sensitivity and 99.8% specificity, Dr. Highsmith said.
Results were similar with the other four studies.
The largest was a 2009 retrospective review of 1,156 slides collected over 10 years; they were part of a preexisting randomized, blinded study. Of these, 32 slides (2.8%) were discordant between the Mohs surgeon and the dermatopathologist, for a 99.7% concordance rate (J Am Acad Dermatol. 2009 Jan;[1]: 94-8).
The second largest cohort was published in 1989. It comprised 1,000 slides that were evaluated by the Mohs surgeon and a general pathologist; disputed slides were read by two other Mohs surgeons, two pathologists, and a dermatopathologist. The overall concordance rate was 98.9% (J Am Acad Dermatol. 1989;20[4]:670-4).
In 2013, a Mohs surgeon published a set of 170 slides that had been randomly selected from his cases as part of a quality assurance audit. There was one discordant interpretation, for an overall concordance rate of 99.4% (Dermatol Surg. 2013;39[11]:1648-52).
The smallest study, published in 2011, reviewed 99 slides assessed by a single Mohs surgeon. The concordance rate with dermatopathology was 95%.
An overall analysis of these four cohorts determined a sensitivity of 99.4%, specificity of 99.2% and negative predictive value of 99.2%, Dr. Highsmith said.
“When a fellowship-trained Mohs surgeon looks at a slide and says there’s no more tumor present, then there’s a greater-than-99% chance that is accurate,” he said.
Dr. Highsmith had no financial disclosures.
ORLANDO – Mohs fellowship–trained surgeons are highly skilled at reading frozen section slides obtained during surgery, agreeing with the dermatopathologist’s assessment more than 99% of the time, according to a review of more than 4,000 cases.
Among 4,145 slides in five datasets, only 28 were discordant. The concordance of surgeons’ and dermatopathologists’ assessments was quite consistent, ranging from 95%-of 99.7%.
“There is absolutely no detriment to our interpretation of these frozen section slides,” Dr. James Highsmith said at the annual meeting of the American College of Mohs Surgery. “These numbers give credence as to why we have these good cure rates. We can say with 99% accuracy that yes, we are removing these tumors from our patients.”
Dr. Highsmith, a Mohs surgeon in Birmingham, Ala., reviewed 10 years of his own data (1,720 cases), as well as four published cohorts comprising another 2,425 cases. All of the studies examined the concordance of frozen section assessments between fellowship-trained Mohs surgeons and the dermatopathologists working with them. All of the series reported concordance, discordance, sensitivity, and specificity.
His own database is the largest one yet compiled, spanning the longest period of time. Of 1,720 cases, there were eight discrepancies: one in which the surgeon identified tumor that was not supported by dermatopathology, and seven in which the surgeon missed tumor that dermatopathology confirmed was present. The concordance rate was 99.5%. This worked out to a 99.4% sensitivity and 99.8% specificity, Dr. Highsmith said.
Results were similar with the other four studies.
The largest was a 2009 retrospective review of 1,156 slides collected over 10 years; they were part of a preexisting randomized, blinded study. Of these, 32 slides (2.8%) were discordant between the Mohs surgeon and the dermatopathologist, for a 99.7% concordance rate (J Am Acad Dermatol. 2009 Jan;[1]: 94-8).
The second largest cohort was published in 1989. It comprised 1,000 slides that were evaluated by the Mohs surgeon and a general pathologist; disputed slides were read by two other Mohs surgeons, two pathologists, and a dermatopathologist. The overall concordance rate was 98.9% (J Am Acad Dermatol. 1989;20[4]:670-4).
In 2013, a Mohs surgeon published a set of 170 slides that had been randomly selected from his cases as part of a quality assurance audit. There was one discordant interpretation, for an overall concordance rate of 99.4% (Dermatol Surg. 2013;39[11]:1648-52).
The smallest study, published in 2011, reviewed 99 slides assessed by a single Mohs surgeon. The concordance rate with dermatopathology was 95%.
An overall analysis of these four cohorts determined a sensitivity of 99.4%, specificity of 99.2% and negative predictive value of 99.2%, Dr. Highsmith said.
“When a fellowship-trained Mohs surgeon looks at a slide and says there’s no more tumor present, then there’s a greater-than-99% chance that is accurate,” he said.
Dr. Highsmith had no financial disclosures.
ORLANDO – Mohs fellowship–trained surgeons are highly skilled at reading frozen section slides obtained during surgery, agreeing with the dermatopathologist’s assessment more than 99% of the time, according to a review of more than 4,000 cases.
Among 4,145 slides in five datasets, only 28 were discordant. The concordance of surgeons’ and dermatopathologists’ assessments was quite consistent, ranging from 95%-of 99.7%.
“There is absolutely no detriment to our interpretation of these frozen section slides,” Dr. James Highsmith said at the annual meeting of the American College of Mohs Surgery. “These numbers give credence as to why we have these good cure rates. We can say with 99% accuracy that yes, we are removing these tumors from our patients.”
Dr. Highsmith, a Mohs surgeon in Birmingham, Ala., reviewed 10 years of his own data (1,720 cases), as well as four published cohorts comprising another 2,425 cases. All of the studies examined the concordance of frozen section assessments between fellowship-trained Mohs surgeons and the dermatopathologists working with them. All of the series reported concordance, discordance, sensitivity, and specificity.
His own database is the largest one yet compiled, spanning the longest period of time. Of 1,720 cases, there were eight discrepancies: one in which the surgeon identified tumor that was not supported by dermatopathology, and seven in which the surgeon missed tumor that dermatopathology confirmed was present. The concordance rate was 99.5%. This worked out to a 99.4% sensitivity and 99.8% specificity, Dr. Highsmith said.
Results were similar with the other four studies.
The largest was a 2009 retrospective review of 1,156 slides collected over 10 years; they were part of a preexisting randomized, blinded study. Of these, 32 slides (2.8%) were discordant between the Mohs surgeon and the dermatopathologist, for a 99.7% concordance rate (J Am Acad Dermatol. 2009 Jan;[1]: 94-8).
The second largest cohort was published in 1989. It comprised 1,000 slides that were evaluated by the Mohs surgeon and a general pathologist; disputed slides were read by two other Mohs surgeons, two pathologists, and a dermatopathologist. The overall concordance rate was 98.9% (J Am Acad Dermatol. 1989;20[4]:670-4).
In 2013, a Mohs surgeon published a set of 170 slides that had been randomly selected from his cases as part of a quality assurance audit. There was one discordant interpretation, for an overall concordance rate of 99.4% (Dermatol Surg. 2013;39[11]:1648-52).
The smallest study, published in 2011, reviewed 99 slides assessed by a single Mohs surgeon. The concordance rate with dermatopathology was 95%.
An overall analysis of these four cohorts determined a sensitivity of 99.4%, specificity of 99.2% and negative predictive value of 99.2%, Dr. Highsmith said.
“When a fellowship-trained Mohs surgeon looks at a slide and says there’s no more tumor present, then there’s a greater-than-99% chance that is accurate,” he said.
Dr. Highsmith had no financial disclosures.
AT THE ACMS ANNUAL MEETING
Key clinical point: Fellowship-trained Mohs surgeons and dermatopathologists almost always agree on slide interpretation.
Major finding: The concordance rate between surgeons and dermatopathologists was over 99% in a pooled review of studies.
Data source: A review of 4,145 frozen section slides analyzed for concordance rates between Mohs surgeons and dermatopathologists.
Disclosures: Dr. James Highsmith had no financial disclosures.
En bloc excision may be viable amputation alternative for nail melanoma
ORLANDO – En bloc excision can cure melanoma in situ of the nail apparatus without amputation, while also preserving function and quality of life, according to the results of a retrospective study of patients treated with this approach.
At 3 years’ follow-up, there were no melanoma recurrences in any of 29 patients treated with the digit-sparing excision, Dr. Thomas Knackstedt said at the annual meeting of the American College of Mohs Surgery. Follow-up telephone interviews found that patients retained full function of the affected finger, and reported virtually no quality of life impairment.
“Because treatment without disarticulation or amputation can provide these excellent long-term cure rates in nail apparatus melanoma in situ, it should be the first-line treatment whenever possible,” said Dr. Knackstedt, a Mohs surgeon in East Greenwich, R.I.
Although similar excellent outcomes have been reported with wide local excision, Dr. Knackstedt said it remains a controversial treatment for nail apparatus melanoma in situ (NAMis).
He reviewed his institution’s experience with treating 29 cases of NAMis with en bloc excision: removal of nail folds, matrix, bed, hyponychium, and margins. All of the surgeries were performed between 2005 and 2015. The current mean follow-up time is 35.5 months for clinic visits and 39 months for telephone contact. The longest follow-up is 103 months. There have been no melanoma recurrences.
The patients were a mean of 39 years old. Melanoma appeared most often on the thumb (seven patients) and hallux (six). The average duration of the lesion was almost 5 years, although that varied from 6 months to 13 years.
Twenty-four patients (83%) presented with longitudinal melanonychia, with an average diameter of 4.1 mm. Four patients (14%) had complete melanonychia, and one patient had erythronychia.
Most of the cases were repaired with a full-thickness skin graft. One was left to heal by second intention, and one case was repaired by a dorsal metacarpal artery flap.
There were two wound infections, one case of delayed graft necrosis, seven nail spicules, and two cysts. There were no cases of tendon injury. One patient complained about temperature sensitivity in the affected finger. There were no cases of disease recurrence, although one patient with a nail spicule did show disease persistence. The spicule was excised, and that patient remains disease free 5 years later, Dr. Knackstedt said.
The telephone survey collected data from 23 patients (79%). Patients were unanimous in reporting that they were “very satisfied” with their treatment. In an 11-question quality of life survey, 78% said that the surgery affected their quality of life “only a little” or “not at all.” On a 10-point Likert scale with 10 being most affected by the surgery, the mean rating was 1.3.
“In light of these results, and when we consider that even a distal joint amputation can reduce the functionality of a finger by 40%-80%, we conclude that en bloc excision must be considered as a viable alternative to amputation for NAMis,” Dr. Knackstedt said.
He had no relevant financial disclosures.
ORLANDO – En bloc excision can cure melanoma in situ of the nail apparatus without amputation, while also preserving function and quality of life, according to the results of a retrospective study of patients treated with this approach.
At 3 years’ follow-up, there were no melanoma recurrences in any of 29 patients treated with the digit-sparing excision, Dr. Thomas Knackstedt said at the annual meeting of the American College of Mohs Surgery. Follow-up telephone interviews found that patients retained full function of the affected finger, and reported virtually no quality of life impairment.
“Because treatment without disarticulation or amputation can provide these excellent long-term cure rates in nail apparatus melanoma in situ, it should be the first-line treatment whenever possible,” said Dr. Knackstedt, a Mohs surgeon in East Greenwich, R.I.
Although similar excellent outcomes have been reported with wide local excision, Dr. Knackstedt said it remains a controversial treatment for nail apparatus melanoma in situ (NAMis).
He reviewed his institution’s experience with treating 29 cases of NAMis with en bloc excision: removal of nail folds, matrix, bed, hyponychium, and margins. All of the surgeries were performed between 2005 and 2015. The current mean follow-up time is 35.5 months for clinic visits and 39 months for telephone contact. The longest follow-up is 103 months. There have been no melanoma recurrences.
The patients were a mean of 39 years old. Melanoma appeared most often on the thumb (seven patients) and hallux (six). The average duration of the lesion was almost 5 years, although that varied from 6 months to 13 years.
Twenty-four patients (83%) presented with longitudinal melanonychia, with an average diameter of 4.1 mm. Four patients (14%) had complete melanonychia, and one patient had erythronychia.
Most of the cases were repaired with a full-thickness skin graft. One was left to heal by second intention, and one case was repaired by a dorsal metacarpal artery flap.
There were two wound infections, one case of delayed graft necrosis, seven nail spicules, and two cysts. There were no cases of tendon injury. One patient complained about temperature sensitivity in the affected finger. There were no cases of disease recurrence, although one patient with a nail spicule did show disease persistence. The spicule was excised, and that patient remains disease free 5 years later, Dr. Knackstedt said.
The telephone survey collected data from 23 patients (79%). Patients were unanimous in reporting that they were “very satisfied” with their treatment. In an 11-question quality of life survey, 78% said that the surgery affected their quality of life “only a little” or “not at all.” On a 10-point Likert scale with 10 being most affected by the surgery, the mean rating was 1.3.
“In light of these results, and when we consider that even a distal joint amputation can reduce the functionality of a finger by 40%-80%, we conclude that en bloc excision must be considered as a viable alternative to amputation for NAMis,” Dr. Knackstedt said.
He had no relevant financial disclosures.
ORLANDO – En bloc excision can cure melanoma in situ of the nail apparatus without amputation, while also preserving function and quality of life, according to the results of a retrospective study of patients treated with this approach.
At 3 years’ follow-up, there were no melanoma recurrences in any of 29 patients treated with the digit-sparing excision, Dr. Thomas Knackstedt said at the annual meeting of the American College of Mohs Surgery. Follow-up telephone interviews found that patients retained full function of the affected finger, and reported virtually no quality of life impairment.
“Because treatment without disarticulation or amputation can provide these excellent long-term cure rates in nail apparatus melanoma in situ, it should be the first-line treatment whenever possible,” said Dr. Knackstedt, a Mohs surgeon in East Greenwich, R.I.
Although similar excellent outcomes have been reported with wide local excision, Dr. Knackstedt said it remains a controversial treatment for nail apparatus melanoma in situ (NAMis).
He reviewed his institution’s experience with treating 29 cases of NAMis with en bloc excision: removal of nail folds, matrix, bed, hyponychium, and margins. All of the surgeries were performed between 2005 and 2015. The current mean follow-up time is 35.5 months for clinic visits and 39 months for telephone contact. The longest follow-up is 103 months. There have been no melanoma recurrences.
The patients were a mean of 39 years old. Melanoma appeared most often on the thumb (seven patients) and hallux (six). The average duration of the lesion was almost 5 years, although that varied from 6 months to 13 years.
Twenty-four patients (83%) presented with longitudinal melanonychia, with an average diameter of 4.1 mm. Four patients (14%) had complete melanonychia, and one patient had erythronychia.
Most of the cases were repaired with a full-thickness skin graft. One was left to heal by second intention, and one case was repaired by a dorsal metacarpal artery flap.
There were two wound infections, one case of delayed graft necrosis, seven nail spicules, and two cysts. There were no cases of tendon injury. One patient complained about temperature sensitivity in the affected finger. There were no cases of disease recurrence, although one patient with a nail spicule did show disease persistence. The spicule was excised, and that patient remains disease free 5 years later, Dr. Knackstedt said.
The telephone survey collected data from 23 patients (79%). Patients were unanimous in reporting that they were “very satisfied” with their treatment. In an 11-question quality of life survey, 78% said that the surgery affected their quality of life “only a little” or “not at all.” On a 10-point Likert scale with 10 being most affected by the surgery, the mean rating was 1.3.
“In light of these results, and when we consider that even a distal joint amputation can reduce the functionality of a finger by 40%-80%, we conclude that en bloc excision must be considered as a viable alternative to amputation for NAMis,” Dr. Knackstedt said.
He had no relevant financial disclosures.
AT THE ACMS ANNUAL MEETING
Key clinical point: En bloc removal of the nail apparatus effected good clinical and quality of life outcomes in nail melanoma.
Major finding: There have been no recurrences of melanoma over a mean follow-up of 39 months.
Data source: A review evaluated 29 cases of nail apparatus melanoma in situ treated with en bloc excision at one institution.
Disclosures: Dr. Knackstedt had no relevant financial disclosures.
What’s Less Noticeable: A Straight Scar or a Zigzag Scar?
One of the determinants of a successful surgical outcome is the perception, on the part of the patient, of the cosmesis of a scar. The use of Z-plasty is an accepted means by which to break a scar up into smaller geometric segments. In some instances, a Z-plasty is used for scar revision to elongate a scar that may be pulling. However, a study published online in JAMA Facial Plastic Surgery on April 7 mentions the lack of studies measuring the perception of these scars among the normal population after surgery.
Ratnarathorn et al designed a prospective Internet-based survey with a goal of 580 responses to give a power of 90%. The survey was distributed to a diverse sample of the US population. Using editing software, Ratnarathorn et al superimposed a mature linear scar and a mature zigzag scar onto the faces of standardized headshots from 4 individuals (2 males, 2 females). Each individual had 1 image of the linear scar and 1 image of the zigzag scars superimposed onto each of 3 anatomical areas—forehead (flat surface), cheek (convex surface), and temple (concave surface)—yielding 24 images for the respondents to assess.
A 24.5% (n=876) response rate was achieved with 3575 surveys distributed. Of the 876 respondents, 810 (92.5%) completed the survey (46.1% male, 53.9% female). Respondents were asked to rate the scars on a scale of 1 to 10 (1=normal skin; 10=worst scar imaginable).
Results were statistically significantly lower (better) for the linear scars compared to the zigzag scars in all 3 anatomic areas and across both male and female groups with a mean score of 2.9 versus 4.5 (P<.001). A multivariable regression model of respondent age, sex, educational level, and income showed no statistically significant effect on the rating of the scars.
What’s the issue?
This study highlights some interesting points. Coming from an academic practice, we oftentimes find ourselves teaching residents a variety of skin closure techniques to deal with defects from skin cancer excisions. It is both challenging and fun to design complex closures; however, we must keep in mind what is in the best interest of the patient. One of the points I try to emphasize is that we must understand that there are no true straight lines on the face. In fact, when scars from procedures appear as geometric shapes on the face, our eyes tend to be drawn to them. For this reason, it often is best to use curvilinear lines wherever possible. Ratnarathorn et al highlights that point exactly. More studies of this nature are needed to assess what is perceived as a successful outcome, by both physicians and patients.
As you follow your patients for the long-term, have you noticed that you perform more or fewer zigzag scars?
One of the determinants of a successful surgical outcome is the perception, on the part of the patient, of the cosmesis of a scar. The use of Z-plasty is an accepted means by which to break a scar up into smaller geometric segments. In some instances, a Z-plasty is used for scar revision to elongate a scar that may be pulling. However, a study published online in JAMA Facial Plastic Surgery on April 7 mentions the lack of studies measuring the perception of these scars among the normal population after surgery.
Ratnarathorn et al designed a prospective Internet-based survey with a goal of 580 responses to give a power of 90%. The survey was distributed to a diverse sample of the US population. Using editing software, Ratnarathorn et al superimposed a mature linear scar and a mature zigzag scar onto the faces of standardized headshots from 4 individuals (2 males, 2 females). Each individual had 1 image of the linear scar and 1 image of the zigzag scars superimposed onto each of 3 anatomical areas—forehead (flat surface), cheek (convex surface), and temple (concave surface)—yielding 24 images for the respondents to assess.
A 24.5% (n=876) response rate was achieved with 3575 surveys distributed. Of the 876 respondents, 810 (92.5%) completed the survey (46.1% male, 53.9% female). Respondents were asked to rate the scars on a scale of 1 to 10 (1=normal skin; 10=worst scar imaginable).
Results were statistically significantly lower (better) for the linear scars compared to the zigzag scars in all 3 anatomic areas and across both male and female groups with a mean score of 2.9 versus 4.5 (P<.001). A multivariable regression model of respondent age, sex, educational level, and income showed no statistically significant effect on the rating of the scars.
What’s the issue?
This study highlights some interesting points. Coming from an academic practice, we oftentimes find ourselves teaching residents a variety of skin closure techniques to deal with defects from skin cancer excisions. It is both challenging and fun to design complex closures; however, we must keep in mind what is in the best interest of the patient. One of the points I try to emphasize is that we must understand that there are no true straight lines on the face. In fact, when scars from procedures appear as geometric shapes on the face, our eyes tend to be drawn to them. For this reason, it often is best to use curvilinear lines wherever possible. Ratnarathorn et al highlights that point exactly. More studies of this nature are needed to assess what is perceived as a successful outcome, by both physicians and patients.
As you follow your patients for the long-term, have you noticed that you perform more or fewer zigzag scars?
One of the determinants of a successful surgical outcome is the perception, on the part of the patient, of the cosmesis of a scar. The use of Z-plasty is an accepted means by which to break a scar up into smaller geometric segments. In some instances, a Z-plasty is used for scar revision to elongate a scar that may be pulling. However, a study published online in JAMA Facial Plastic Surgery on April 7 mentions the lack of studies measuring the perception of these scars among the normal population after surgery.
Ratnarathorn et al designed a prospective Internet-based survey with a goal of 580 responses to give a power of 90%. The survey was distributed to a diverse sample of the US population. Using editing software, Ratnarathorn et al superimposed a mature linear scar and a mature zigzag scar onto the faces of standardized headshots from 4 individuals (2 males, 2 females). Each individual had 1 image of the linear scar and 1 image of the zigzag scars superimposed onto each of 3 anatomical areas—forehead (flat surface), cheek (convex surface), and temple (concave surface)—yielding 24 images for the respondents to assess.
A 24.5% (n=876) response rate was achieved with 3575 surveys distributed. Of the 876 respondents, 810 (92.5%) completed the survey (46.1% male, 53.9% female). Respondents were asked to rate the scars on a scale of 1 to 10 (1=normal skin; 10=worst scar imaginable).
Results were statistically significantly lower (better) for the linear scars compared to the zigzag scars in all 3 anatomic areas and across both male and female groups with a mean score of 2.9 versus 4.5 (P<.001). A multivariable regression model of respondent age, sex, educational level, and income showed no statistically significant effect on the rating of the scars.
What’s the issue?
This study highlights some interesting points. Coming from an academic practice, we oftentimes find ourselves teaching residents a variety of skin closure techniques to deal with defects from skin cancer excisions. It is both challenging and fun to design complex closures; however, we must keep in mind what is in the best interest of the patient. One of the points I try to emphasize is that we must understand that there are no true straight lines on the face. In fact, when scars from procedures appear as geometric shapes on the face, our eyes tend to be drawn to them. For this reason, it often is best to use curvilinear lines wherever possible. Ratnarathorn et al highlights that point exactly. More studies of this nature are needed to assess what is perceived as a successful outcome, by both physicians and patients.
As you follow your patients for the long-term, have you noticed that you perform more or fewer zigzag scars?
Search is on for cases of aggressive, ruxolitinib-associated skin cancers
ORLANDO – The hematologic cancer drug ruxolitinib seems to be associated with cases of aggressive nonmelanoma skin cancer.
After treating a very aggressive squamous cell carcinoma in a 55-year-old man treated with ruxolitinib for polycythemia vera, and hearing firsthand of three other similar cases, Dr. Fiona Zwald is collecting additional data on the association. She intends to publish these cases in a monograph as a warning to dermatologists, hematologists, oncologists, and other physicians who manage patients with hematologic malignancies, she said at the annual meeting of the American College of Mohs Surgery.
The prescribing information for ruxolitinib (Jakafi, Incyte Pharmaceuticals; Jakavi, Novartis) was updated in 2014 to warn that patients taking the drug face an increased risk of nonmelanoma skin cancers. The label also recommends that physicians inspect the skin regularly and urge patients to be alert for and report any new or changing lesions.
Despite the warnings and recommendations, cases are occurring – and some are quite serious, said Dr. Zwald, a Mohs surgeon in Atlanta.
“People should know this is actually happening. If you have experience with this medication, please let us know so we can compile this report. We are trying to assess the number of skin cancers before and after initiating this medication,” she said.
Ruxolitinib is an inhibitor of Janus kinase with a special affinity for the JAK1 and JAK2 subtypes. Like other cytokine-signaling molecules, their function depends on cell context; it may inhibit cell growth in one setting, and, in another, stimulate it. Ruxolitinib was initially approved in 2011 for the treatment of intermediate- and high-risk myelofibrosis, including primary myelofibrosis, post–polycythemia vera myelofibrosis, and post–essential thrombocythemia myelofibrosis.
In 2014, indications for ruxolitinib were expanded to include treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.
Dr. Zwald’s patient had a 10-year history of polycythemia vera. He was initially well controlled on the standard hydroxyurea treatment. In the meantime, he began working as a caddy at a major U.S. golf club. He developed many facial squamous cell carcinomas that were treated with excision and radiation. A year before he presented to Dr. Zwald, he stopped responding to hydroxyurea and was placed on ruxolitinib.
The patient presented with a 4-cm ulcerated lesion over part of his right temple and to the right helical crus; the lesion had developed over 3 months. Dr. Zwald consulted with the patient’s medical oncologist; treatment with ruxolitinib continued, albeit at a reduced dosage in light of recent events.
She performed Mohs surgery on the patient. It was a challenging case, she said, not the least because adequate anesthesia could not be achieved with local anesthetic. Preoperative staging showed no nodal spread.
“He did, unfortunately demonstrate a large, indurated mass located over one branch of the superficial temporal artery. At the helical crus there was an area of bound-down, fixed tumor. Knowing that I would not be able to fully resect this, I passed him on to the operating room,” Dr. Zwald said. “This tumor was found to extend down to the parotid capsule, but margins were clear.” The surgical defect was successfully repaired with a split-thickness skin graft.
The tumor recurred about 3 months later, and the patient underwent another surgery.
“This time we could not get clear surgical margins, and the tumor was approaching the external auditory meatus. Surgery was abandoned due to fears of complications to that area,” she said.
She presented the case at tumor board, during which she and her colleagues discussed adjuvant radiation. They initially abandoned this idea because he had already had so much radiation to his face. After the second surgery, they decide to proceed with radiation. “The next conversation we have will be whether to add another adjuvant therapy to treatment.”
She sent out the case and requests for feedback to the International Transplant Skin Cancer Collaborative, an 800-member consortium of dermatologists and Mohs surgeons who take care of transplant patients. She received information on three additional cases of aggressive squamous cell carcinoma (SCC) associated with ruxolitinib treatment:
• A patient with myelodysplastic syndrome with aggressive scalp SCC with cutaneous metastases.
• A patient with undifferentiated pleomorphic sarcoma of the scalp, several cutaneous SCCs.
• A patient with a myelodysplastic syndrome with in-transit metastases and explosive cutaneous SCCs. The patient has had the ruxolitinib dose reduced and may be switched to capecitabine.
Dr. Zwald noted that her patient was at risk for aggressive skin cancers for reasons in addition to ruxolitinib treatment.
“He was already immunosuppressed from his malignancy. He was on hydroxyurea, a drug that’s a cumulative phototoxin, and he’s out in the sun playing golf every day, and then was put on ruxolitinib. But the question we face now is how to try and stop this medication so we can get better treatment for him which will, of course, be very difficult.”
To contribute to Dr. Zwald’s case series, please email her at Fiona.Zwald@gmail.com.
She had no relevant financial disclosures.
On Twitter @Alz_Gal
ORLANDO – The hematologic cancer drug ruxolitinib seems to be associated with cases of aggressive nonmelanoma skin cancer.
After treating a very aggressive squamous cell carcinoma in a 55-year-old man treated with ruxolitinib for polycythemia vera, and hearing firsthand of three other similar cases, Dr. Fiona Zwald is collecting additional data on the association. She intends to publish these cases in a monograph as a warning to dermatologists, hematologists, oncologists, and other physicians who manage patients with hematologic malignancies, she said at the annual meeting of the American College of Mohs Surgery.
The prescribing information for ruxolitinib (Jakafi, Incyte Pharmaceuticals; Jakavi, Novartis) was updated in 2014 to warn that patients taking the drug face an increased risk of nonmelanoma skin cancers. The label also recommends that physicians inspect the skin regularly and urge patients to be alert for and report any new or changing lesions.
Despite the warnings and recommendations, cases are occurring – and some are quite serious, said Dr. Zwald, a Mohs surgeon in Atlanta.
“People should know this is actually happening. If you have experience with this medication, please let us know so we can compile this report. We are trying to assess the number of skin cancers before and after initiating this medication,” she said.
Ruxolitinib is an inhibitor of Janus kinase with a special affinity for the JAK1 and JAK2 subtypes. Like other cytokine-signaling molecules, their function depends on cell context; it may inhibit cell growth in one setting, and, in another, stimulate it. Ruxolitinib was initially approved in 2011 for the treatment of intermediate- and high-risk myelofibrosis, including primary myelofibrosis, post–polycythemia vera myelofibrosis, and post–essential thrombocythemia myelofibrosis.
In 2014, indications for ruxolitinib were expanded to include treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.
Dr. Zwald’s patient had a 10-year history of polycythemia vera. He was initially well controlled on the standard hydroxyurea treatment. In the meantime, he began working as a caddy at a major U.S. golf club. He developed many facial squamous cell carcinomas that were treated with excision and radiation. A year before he presented to Dr. Zwald, he stopped responding to hydroxyurea and was placed on ruxolitinib.
The patient presented with a 4-cm ulcerated lesion over part of his right temple and to the right helical crus; the lesion had developed over 3 months. Dr. Zwald consulted with the patient’s medical oncologist; treatment with ruxolitinib continued, albeit at a reduced dosage in light of recent events.
She performed Mohs surgery on the patient. It was a challenging case, she said, not the least because adequate anesthesia could not be achieved with local anesthetic. Preoperative staging showed no nodal spread.
“He did, unfortunately demonstrate a large, indurated mass located over one branch of the superficial temporal artery. At the helical crus there was an area of bound-down, fixed tumor. Knowing that I would not be able to fully resect this, I passed him on to the operating room,” Dr. Zwald said. “This tumor was found to extend down to the parotid capsule, but margins were clear.” The surgical defect was successfully repaired with a split-thickness skin graft.
The tumor recurred about 3 months later, and the patient underwent another surgery.
“This time we could not get clear surgical margins, and the tumor was approaching the external auditory meatus. Surgery was abandoned due to fears of complications to that area,” she said.
She presented the case at tumor board, during which she and her colleagues discussed adjuvant radiation. They initially abandoned this idea because he had already had so much radiation to his face. After the second surgery, they decide to proceed with radiation. “The next conversation we have will be whether to add another adjuvant therapy to treatment.”
She sent out the case and requests for feedback to the International Transplant Skin Cancer Collaborative, an 800-member consortium of dermatologists and Mohs surgeons who take care of transplant patients. She received information on three additional cases of aggressive squamous cell carcinoma (SCC) associated with ruxolitinib treatment:
• A patient with myelodysplastic syndrome with aggressive scalp SCC with cutaneous metastases.
• A patient with undifferentiated pleomorphic sarcoma of the scalp, several cutaneous SCCs.
• A patient with a myelodysplastic syndrome with in-transit metastases and explosive cutaneous SCCs. The patient has had the ruxolitinib dose reduced and may be switched to capecitabine.
Dr. Zwald noted that her patient was at risk for aggressive skin cancers for reasons in addition to ruxolitinib treatment.
“He was already immunosuppressed from his malignancy. He was on hydroxyurea, a drug that’s a cumulative phototoxin, and he’s out in the sun playing golf every day, and then was put on ruxolitinib. But the question we face now is how to try and stop this medication so we can get better treatment for him which will, of course, be very difficult.”
To contribute to Dr. Zwald’s case series, please email her at Fiona.Zwald@gmail.com.
She had no relevant financial disclosures.
On Twitter @Alz_Gal
ORLANDO – The hematologic cancer drug ruxolitinib seems to be associated with cases of aggressive nonmelanoma skin cancer.
After treating a very aggressive squamous cell carcinoma in a 55-year-old man treated with ruxolitinib for polycythemia vera, and hearing firsthand of three other similar cases, Dr. Fiona Zwald is collecting additional data on the association. She intends to publish these cases in a monograph as a warning to dermatologists, hematologists, oncologists, and other physicians who manage patients with hematologic malignancies, she said at the annual meeting of the American College of Mohs Surgery.
The prescribing information for ruxolitinib (Jakafi, Incyte Pharmaceuticals; Jakavi, Novartis) was updated in 2014 to warn that patients taking the drug face an increased risk of nonmelanoma skin cancers. The label also recommends that physicians inspect the skin regularly and urge patients to be alert for and report any new or changing lesions.
Despite the warnings and recommendations, cases are occurring – and some are quite serious, said Dr. Zwald, a Mohs surgeon in Atlanta.
“People should know this is actually happening. If you have experience with this medication, please let us know so we can compile this report. We are trying to assess the number of skin cancers before and after initiating this medication,” she said.
Ruxolitinib is an inhibitor of Janus kinase with a special affinity for the JAK1 and JAK2 subtypes. Like other cytokine-signaling molecules, their function depends on cell context; it may inhibit cell growth in one setting, and, in another, stimulate it. Ruxolitinib was initially approved in 2011 for the treatment of intermediate- and high-risk myelofibrosis, including primary myelofibrosis, post–polycythemia vera myelofibrosis, and post–essential thrombocythemia myelofibrosis.
In 2014, indications for ruxolitinib were expanded to include treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.
Dr. Zwald’s patient had a 10-year history of polycythemia vera. He was initially well controlled on the standard hydroxyurea treatment. In the meantime, he began working as a caddy at a major U.S. golf club. He developed many facial squamous cell carcinomas that were treated with excision and radiation. A year before he presented to Dr. Zwald, he stopped responding to hydroxyurea and was placed on ruxolitinib.
The patient presented with a 4-cm ulcerated lesion over part of his right temple and to the right helical crus; the lesion had developed over 3 months. Dr. Zwald consulted with the patient’s medical oncologist; treatment with ruxolitinib continued, albeit at a reduced dosage in light of recent events.
She performed Mohs surgery on the patient. It was a challenging case, she said, not the least because adequate anesthesia could not be achieved with local anesthetic. Preoperative staging showed no nodal spread.
“He did, unfortunately demonstrate a large, indurated mass located over one branch of the superficial temporal artery. At the helical crus there was an area of bound-down, fixed tumor. Knowing that I would not be able to fully resect this, I passed him on to the operating room,” Dr. Zwald said. “This tumor was found to extend down to the parotid capsule, but margins were clear.” The surgical defect was successfully repaired with a split-thickness skin graft.
The tumor recurred about 3 months later, and the patient underwent another surgery.
“This time we could not get clear surgical margins, and the tumor was approaching the external auditory meatus. Surgery was abandoned due to fears of complications to that area,” she said.
She presented the case at tumor board, during which she and her colleagues discussed adjuvant radiation. They initially abandoned this idea because he had already had so much radiation to his face. After the second surgery, they decide to proceed with radiation. “The next conversation we have will be whether to add another adjuvant therapy to treatment.”
She sent out the case and requests for feedback to the International Transplant Skin Cancer Collaborative, an 800-member consortium of dermatologists and Mohs surgeons who take care of transplant patients. She received information on three additional cases of aggressive squamous cell carcinoma (SCC) associated with ruxolitinib treatment:
• A patient with myelodysplastic syndrome with aggressive scalp SCC with cutaneous metastases.
• A patient with undifferentiated pleomorphic sarcoma of the scalp, several cutaneous SCCs.
• A patient with a myelodysplastic syndrome with in-transit metastases and explosive cutaneous SCCs. The patient has had the ruxolitinib dose reduced and may be switched to capecitabine.
Dr. Zwald noted that her patient was at risk for aggressive skin cancers for reasons in addition to ruxolitinib treatment.
“He was already immunosuppressed from his malignancy. He was on hydroxyurea, a drug that’s a cumulative phototoxin, and he’s out in the sun playing golf every day, and then was put on ruxolitinib. But the question we face now is how to try and stop this medication so we can get better treatment for him which will, of course, be very difficult.”
To contribute to Dr. Zwald’s case series, please email her at Fiona.Zwald@gmail.com.
She had no relevant financial disclosures.
On Twitter @Alz_Gal
AT THE ACMS ANNUAL MEETING
Mohs with CK-7 staining: 98% 5-year cure rate for extramammary Paget disease
ORLANDO – Mohs surgery with cytokeratin-7 immunohistochemistry staining effected complete removal of extramammary Paget disease and resulted in a 5-year, 95% recurrence-free cure rate.
The results are significantly better than the often-cited 77% cure rate seen with Mohs surgery alone, Dr. Ali Alexander Damavandy said at the annual meeting of the American College of Mohs Surgery.
“These are statistically significant and clinically substantial results,” said Dr. Damavandy, a procedural dermatology fellow at the University of Pennsylvania, Philadelphia. “With this method you can tell a patient that in 5 years, he has a 95% chance of still not having the tumor. The high recurrence-free rate we have seen supports the view that Mohs surgery with cytokeratin-7 [CK-7] immunohistochemistry should be considered the curative treatment of choice for both primary and recurrent extramammary Paget disease of the skin.”
Dr. Damavandy’s retrospective review of 49 cases may seem small, he said, but it is “far and away the biggest cohort that exists, and the only substantial cohort with immunohistochemistry staining of CK-7.” The 5-year follow-up is also a strength of the study, he added.
Extramammary Paget disease (EMPD) remains an “extraordinarily hard tumor to treat. It typically presents with widespread intraepithelial islands of disease that are not clinically apparent. Local recurrence rates range from 33% to 60%, “leaving a lot of room for improvement,” Dr. Damavandy said.
“The explanations for recurrence are twofold,” he added. “First there is difficulty visualizing tumor cells in frozen sections. Second, it is a multifocal tumor that grows in a discontinuous fashion.”
Although one simply has to deal with the tumor spread, improvements can be made in reading the histopathology. Immunohistochemistry staining with CK-7 allows highly accurate visualization of individual Paget tumor cells, which express a very high level of the protein.
“Our hypothesis was that combining this improved tumor cell visualization with Mohs total excision would really make a dent in the recurrence rates of this disease,” Dr. Damavandy said.
He conducted a review of patients who were treated at four practices from 2004 to 2012. The cohort comprised 49 patients with 62 tumors; 43 were primary and the rest were recurrences. The majority (90%) occurred in the urogenital and anogenital region; the rest were axial or facial. All were treated with Mohs microsurgery enhanced by CK-7 staining of frozen sections. Recurrences were biopsy proven.
The typical Mohs technique for EMPD is to delineate a tumor-free area peripherally, and then excise the central tumor and tumor-bearing islands. The procedure can be long and arduous. Many cases are multiday efforts with large areas of excision.
“These can be very difficult wounds to manage even in a hospital. It’s resource-intense surgery,” Dr. Damavandy said.
The mean margin necessary to clear the lesions in this cohort was 2.6 cm. A 4-cm margin cleared almost 80%; 10% required a 7-cm margin.
“If we were going to make a recommendation to a nonMohs surgeon, it would be that 7 cm are needed to clear 98% of the tumors. That seems to me not reasonable for these anatomically complex and delicate regions. At the same time, the most commonly reported margin in the literature is 2 cm. In this cohort that would only have cleared 40% of the tumors.”
A mean of 3.4 Mohs stages were needed to obtain clear margins, although the range was wide (1-14 stages). Surgery took a mean of 1.5 days (range 1-5 days). Four patients could not be cleared and needed multidisciplinary care. These included two with vaginal invasion and two with invasion of the anal canal.
By 5 years, the overall tumor-free survival rate was 97%; the tumor-free survival rate was slightly better for primary than recurrent tumors (98% vs. 95%). When these rates were compared with Mohs without CK-7 staining, “primary Mohs doesn’t compare very well,” Dr. Damavandy said. At 5 years, the literature-reported recurrence rate for primary tumors treated with Mohs alone was 16% vs. Dr. Damavandy’s report of 2.3% for Mohs plus CK-7 staining. For recurrent tumors, the recurrence rates were 50% vs. 5.3%.
Two tumors recurred; the mean time to recurrence was 31 months. One recurrence was of a primary tumor treated by peripheral Mohs surgery, which was an uncommon approach in this cohort. This patient had a deep recurrence at 16 months.
The other case was a recurrence of a vulvar tumor that extended into the vaginal epithelium and across the cervix. Despite a vaginectomy and vaginal hysterectomy with clear margins, the patient had a recurrence at 46 months.
The patients were retreated and at last follow-up were free of disease.
Dr. Damavandy had no financial disclosures.
ORLANDO – Mohs surgery with cytokeratin-7 immunohistochemistry staining effected complete removal of extramammary Paget disease and resulted in a 5-year, 95% recurrence-free cure rate.
The results are significantly better than the often-cited 77% cure rate seen with Mohs surgery alone, Dr. Ali Alexander Damavandy said at the annual meeting of the American College of Mohs Surgery.
“These are statistically significant and clinically substantial results,” said Dr. Damavandy, a procedural dermatology fellow at the University of Pennsylvania, Philadelphia. “With this method you can tell a patient that in 5 years, he has a 95% chance of still not having the tumor. The high recurrence-free rate we have seen supports the view that Mohs surgery with cytokeratin-7 [CK-7] immunohistochemistry should be considered the curative treatment of choice for both primary and recurrent extramammary Paget disease of the skin.”
Dr. Damavandy’s retrospective review of 49 cases may seem small, he said, but it is “far and away the biggest cohort that exists, and the only substantial cohort with immunohistochemistry staining of CK-7.” The 5-year follow-up is also a strength of the study, he added.
Extramammary Paget disease (EMPD) remains an “extraordinarily hard tumor to treat. It typically presents with widespread intraepithelial islands of disease that are not clinically apparent. Local recurrence rates range from 33% to 60%, “leaving a lot of room for improvement,” Dr. Damavandy said.
“The explanations for recurrence are twofold,” he added. “First there is difficulty visualizing tumor cells in frozen sections. Second, it is a multifocal tumor that grows in a discontinuous fashion.”
Although one simply has to deal with the tumor spread, improvements can be made in reading the histopathology. Immunohistochemistry staining with CK-7 allows highly accurate visualization of individual Paget tumor cells, which express a very high level of the protein.
“Our hypothesis was that combining this improved tumor cell visualization with Mohs total excision would really make a dent in the recurrence rates of this disease,” Dr. Damavandy said.
He conducted a review of patients who were treated at four practices from 2004 to 2012. The cohort comprised 49 patients with 62 tumors; 43 were primary and the rest were recurrences. The majority (90%) occurred in the urogenital and anogenital region; the rest were axial or facial. All were treated with Mohs microsurgery enhanced by CK-7 staining of frozen sections. Recurrences were biopsy proven.
The typical Mohs technique for EMPD is to delineate a tumor-free area peripherally, and then excise the central tumor and tumor-bearing islands. The procedure can be long and arduous. Many cases are multiday efforts with large areas of excision.
“These can be very difficult wounds to manage even in a hospital. It’s resource-intense surgery,” Dr. Damavandy said.
The mean margin necessary to clear the lesions in this cohort was 2.6 cm. A 4-cm margin cleared almost 80%; 10% required a 7-cm margin.
“If we were going to make a recommendation to a nonMohs surgeon, it would be that 7 cm are needed to clear 98% of the tumors. That seems to me not reasonable for these anatomically complex and delicate regions. At the same time, the most commonly reported margin in the literature is 2 cm. In this cohort that would only have cleared 40% of the tumors.”
A mean of 3.4 Mohs stages were needed to obtain clear margins, although the range was wide (1-14 stages). Surgery took a mean of 1.5 days (range 1-5 days). Four patients could not be cleared and needed multidisciplinary care. These included two with vaginal invasion and two with invasion of the anal canal.
By 5 years, the overall tumor-free survival rate was 97%; the tumor-free survival rate was slightly better for primary than recurrent tumors (98% vs. 95%). When these rates were compared with Mohs without CK-7 staining, “primary Mohs doesn’t compare very well,” Dr. Damavandy said. At 5 years, the literature-reported recurrence rate for primary tumors treated with Mohs alone was 16% vs. Dr. Damavandy’s report of 2.3% for Mohs plus CK-7 staining. For recurrent tumors, the recurrence rates were 50% vs. 5.3%.
Two tumors recurred; the mean time to recurrence was 31 months. One recurrence was of a primary tumor treated by peripheral Mohs surgery, which was an uncommon approach in this cohort. This patient had a deep recurrence at 16 months.
The other case was a recurrence of a vulvar tumor that extended into the vaginal epithelium and across the cervix. Despite a vaginectomy and vaginal hysterectomy with clear margins, the patient had a recurrence at 46 months.
The patients were retreated and at last follow-up were free of disease.
Dr. Damavandy had no financial disclosures.
ORLANDO – Mohs surgery with cytokeratin-7 immunohistochemistry staining effected complete removal of extramammary Paget disease and resulted in a 5-year, 95% recurrence-free cure rate.
The results are significantly better than the often-cited 77% cure rate seen with Mohs surgery alone, Dr. Ali Alexander Damavandy said at the annual meeting of the American College of Mohs Surgery.
“These are statistically significant and clinically substantial results,” said Dr. Damavandy, a procedural dermatology fellow at the University of Pennsylvania, Philadelphia. “With this method you can tell a patient that in 5 years, he has a 95% chance of still not having the tumor. The high recurrence-free rate we have seen supports the view that Mohs surgery with cytokeratin-7 [CK-7] immunohistochemistry should be considered the curative treatment of choice for both primary and recurrent extramammary Paget disease of the skin.”
Dr. Damavandy’s retrospective review of 49 cases may seem small, he said, but it is “far and away the biggest cohort that exists, and the only substantial cohort with immunohistochemistry staining of CK-7.” The 5-year follow-up is also a strength of the study, he added.
Extramammary Paget disease (EMPD) remains an “extraordinarily hard tumor to treat. It typically presents with widespread intraepithelial islands of disease that are not clinically apparent. Local recurrence rates range from 33% to 60%, “leaving a lot of room for improvement,” Dr. Damavandy said.
“The explanations for recurrence are twofold,” he added. “First there is difficulty visualizing tumor cells in frozen sections. Second, it is a multifocal tumor that grows in a discontinuous fashion.”
Although one simply has to deal with the tumor spread, improvements can be made in reading the histopathology. Immunohistochemistry staining with CK-7 allows highly accurate visualization of individual Paget tumor cells, which express a very high level of the protein.
“Our hypothesis was that combining this improved tumor cell visualization with Mohs total excision would really make a dent in the recurrence rates of this disease,” Dr. Damavandy said.
He conducted a review of patients who were treated at four practices from 2004 to 2012. The cohort comprised 49 patients with 62 tumors; 43 were primary and the rest were recurrences. The majority (90%) occurred in the urogenital and anogenital region; the rest were axial or facial. All were treated with Mohs microsurgery enhanced by CK-7 staining of frozen sections. Recurrences were biopsy proven.
The typical Mohs technique for EMPD is to delineate a tumor-free area peripherally, and then excise the central tumor and tumor-bearing islands. The procedure can be long and arduous. Many cases are multiday efforts with large areas of excision.
“These can be very difficult wounds to manage even in a hospital. It’s resource-intense surgery,” Dr. Damavandy said.
The mean margin necessary to clear the lesions in this cohort was 2.6 cm. A 4-cm margin cleared almost 80%; 10% required a 7-cm margin.
“If we were going to make a recommendation to a nonMohs surgeon, it would be that 7 cm are needed to clear 98% of the tumors. That seems to me not reasonable for these anatomically complex and delicate regions. At the same time, the most commonly reported margin in the literature is 2 cm. In this cohort that would only have cleared 40% of the tumors.”
A mean of 3.4 Mohs stages were needed to obtain clear margins, although the range was wide (1-14 stages). Surgery took a mean of 1.5 days (range 1-5 days). Four patients could not be cleared and needed multidisciplinary care. These included two with vaginal invasion and two with invasion of the anal canal.
By 5 years, the overall tumor-free survival rate was 97%; the tumor-free survival rate was slightly better for primary than recurrent tumors (98% vs. 95%). When these rates were compared with Mohs without CK-7 staining, “primary Mohs doesn’t compare very well,” Dr. Damavandy said. At 5 years, the literature-reported recurrence rate for primary tumors treated with Mohs alone was 16% vs. Dr. Damavandy’s report of 2.3% for Mohs plus CK-7 staining. For recurrent tumors, the recurrence rates were 50% vs. 5.3%.
Two tumors recurred; the mean time to recurrence was 31 months. One recurrence was of a primary tumor treated by peripheral Mohs surgery, which was an uncommon approach in this cohort. This patient had a deep recurrence at 16 months.
The other case was a recurrence of a vulvar tumor that extended into the vaginal epithelium and across the cervix. Despite a vaginectomy and vaginal hysterectomy with clear margins, the patient had a recurrence at 46 months.
The patients were retreated and at last follow-up were free of disease.
Dr. Damavandy had no financial disclosures.
AT THE ACMS ANNUAL MEETING
Key clinical point: Mohs surgery enhanced with cytokeratin-7 immunohistochemistry appears to be very effective for extamammaory Paget disease.
Major finding: The 5-year recurrence rate was less than 5%.
Data source: The case review comprised 49 patients with 62 tumors.
Disclosures: Dr. Damavandy had no financial disclosures
