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402 Systematic review of treatments for keratinocyte carcinoma
Clinical Research: Patient Outcomes Research | ABSTRACTS 400
The balance between the malignant clone and reactive T-cells in skin reliably predicts progression in CTCL T Kupper BWH, Boston, MA Most patients with cutaneous T-cell lymphomas (CTCL) present with indolent early-stage disease. A small but significant subset will develop aggressive and fatal disease, unless successfully treated with hematopoietic stem cell transplant. Currently we have limited ability to predict which patients are destined to progress to advanced disease. We analyzed the prognostic value of gene expression signatures, malignant T cell burden and benign T cell diversity in lesional skin of CTCL patients. We sequenced the T-cell receptor beta gene in the skin of 208 CTCL patients. The expression of 78 genes previously identified as potential biomarkers was studied concomitantly. The findings were validated on an independent cohort of 102 patients. Unsupervised analysis of gene expression in the first cohort revealed 3 clusters of patients with different progression-free survival (PFS). Patients with a poor prognosis displayed a higher malignant clone %, corresponding to fewer benign reactive T cells. The frequency of the malignant clone in skin was significantly associated with PFS and overall survival (OS) (p25% (HR, 4.9 (95% CI, 2.5-10), pwith a tumor clone were alive and progression-free 5 years later, vs only 18% of patients with a tumor clone >25% (HR, 10.2 (95% CI, 3.5-30), p < 0.001). Thus, the malignant T cell clone frequency in skin is a robust predictor of progression and survival in CTCL patients.
401
Cancer risk in clinically amyopathic dermatomyositis: A retrospective cohort study at four tertiary care centers J Pinard1, M Roman2, D Kurtzman1, A Ho1, A Femia2 and R Vleugels1 1 Brigham and Women’s Hospital and Harvard Medical School, Boston, MA and 2 New York University School of Medicine, New York, NY Clinically amyopathic dermatomyositis (CADM), characterized by pathognomonic cutaneous findings without muscle weakness, is an important subset and accounts for 20% of patients with dermatomyositis (DM). In patients with CADM, limited literature exists regarding the associated risk of malignancy as most studies have focused on classic DM or polymyositis. Therefore, we investigated the association between CADM and cancer at 4 tertiary care centers. Using the Partners Healthcare and New York University medical record systems, we reviewed the medical records of all patients with CADM treated between 2000 and 2016. A total of 117 patients with CADM diagnosed by a board-certified dermatologist or rheumatologist were identified. The mean age of diagnosis was 49.8 years, and the vast majority of patients were women (90.6%). Patients diagnosed with a solid or hematologic cancer in the 2 years preceding or the 5 years following CADM diagnosis were considered as having malignancy-associated CADM, and these represent 13.7% (16/117) of the entire cohort. Breast cancer was the most frequently diagnosed malignancy (43.8%), and only one patient developed a hematologic malignancy. 68.6% (11/16) of cancer diagnoses were made in the period including the year prior and the 2 years following CADM diagnosis, and the risk was highest in the first year following diagnosis (8/16, 50.0%). In this cohort of CADM patients, which is the largest reported to date, the risk of associated malignancy is somewhat lower than that traditionally reported for classic DM. As there is significant heterogeneity among studies on the association between DM and malignancy, this study focusing on CADM helps to clarify the risk of cancer in this population.
402
Systematic review of treatments for keratinocyte carcinoma F Moustafa1, G Adam2, V Langberg2, B Smith2, A Gazula2, MA Weinstock3, A Drucker4 and T Trikalinos2 1 Brown Dermatology, Providence, RI, 2 Brown University School of Public Health, Providence, RI, 3 Brown University, Providence Veterans Affairs Medical Center, Providence, RI and 4 Brown Unversity, Providence, RI Basal Cell Carcinomas (BCCs) and Squamous Cell Carcinomas (SCCs) can be treated with many interventions, whose comparative efficacy and safety is not clear. We systematically identified 57 RCTs and 45 NRCS comparing 21 interventions in 9 categories and we summarize comparisons of important outcomes across the network of compared treatments. For BCC and lack of clinical clearance, surgical excision was statistically significantly better than Imiquimod (odds ratio [OR] 0.07, 95% CI 0.02, 0.29), but not than PDT (excision vs. MAL-PDT: OR 3.44 [0.06, 199]; excision vs. ALA-PDT: OR 0.43 [0.11, 1.78]. There was no difference between cryotherapy and external beam radiation, MAL-PDT, and ALA-PDT. MALPDT combined with laser treatment was better than MAL-PDT alone, but not significantly so (OR 0.18 [0.01, 3.97]). External beam radiation was non-significantly worse than Imiquimod (OR 1.24 [0.02, 67.0]). Imiquimod, Interferon, and Ingenol mebutate were all significantly better than no treatment (OR 0.02 [0.01, 0.05]; OR 0.07 [0.03, 0.16], and OR 1.4 [0.07, 28], respectively). With regards to lack of clinical clearance of SCC in situ, MAL-PDT was less likely to have lack of clinical clearance compared to laser and MAL-PDT as well as other types of PDT (OR 0.18 [0.03, 0.96]; OR 0.1 [0.03, 0.32], respectively). Cryotherapy was nonsignificantly inferior to ALA-PDT (OR 3.1 [0.8,11.5]). ALA-PDT was superior to topical 5FU (OR 0.29 [0.1, 0.8]). Surgical excision with topical imiquimod was favored over surgical excision alone, but not significantly (OR 0.19 [0.01, 4.08]). This systematic review summarizes currently available evidence and points to gaps in the current literature.
www.jidonline.org S69
The balance between the malignant clone and reactive T-cells in skin reliably predicts progression in CTCL T Kupper BWH, Boston, MA Most patients with cutaneous T-cell lymphomas (CTCL) present with indolent early-stage disease. A small but significant subset will develop aggressive and fatal disease, unless successfully treated with hematopoietic stem cell transplant. Currently we have limited ability to predict which patients are destined to progress to advanced disease. We analyzed the prognostic value of gene expression signatures, malignant T cell burden and benign T cell diversity in lesional skin of CTCL patients. We sequenced the T-cell receptor beta gene in the skin of 208 CTCL patients. The expression of 78 genes previously identified as potential biomarkers was studied concomitantly. The findings were validated on an independent cohort of 102 patients. Unsupervised analysis of gene expression in the first cohort revealed 3 clusters of patients with different progression-free survival (PFS). Patients with a poor prognosis displayed a higher malignant clone %, corresponding to fewer benign reactive T cells. The frequency of the malignant clone in skin was significantly associated with PFS and overall survival (OS) (p25% (HR, 4.9 (95% CI, 2.5-10), pwith a tumor clone were alive and progression-free 5 years later, vs only 18% of patients with a tumor clone >25% (HR, 10.2 (95% CI, 3.5-30), p < 0.001). Thus, the malignant T cell clone frequency in skin is a robust predictor of progression and survival in CTCL patients.
401
Cancer risk in clinically amyopathic dermatomyositis: A retrospective cohort study at four tertiary care centers J Pinard1, M Roman2, D Kurtzman1, A Ho1, A Femia2 and R Vleugels1 1 Brigham and Women’s Hospital and Harvard Medical School, Boston, MA and 2 New York University School of Medicine, New York, NY Clinically amyopathic dermatomyositis (CADM), characterized by pathognomonic cutaneous findings without muscle weakness, is an important subset and accounts for 20% of patients with dermatomyositis (DM). In patients with CADM, limited literature exists regarding the associated risk of malignancy as most studies have focused on classic DM or polymyositis. Therefore, we investigated the association between CADM and cancer at 4 tertiary care centers. Using the Partners Healthcare and New York University medical record systems, we reviewed the medical records of all patients with CADM treated between 2000 and 2016. A total of 117 patients with CADM diagnosed by a board-certified dermatologist or rheumatologist were identified. The mean age of diagnosis was 49.8 years, and the vast majority of patients were women (90.6%). Patients diagnosed with a solid or hematologic cancer in the 2 years preceding or the 5 years following CADM diagnosis were considered as having malignancy-associated CADM, and these represent 13.7% (16/117) of the entire cohort. Breast cancer was the most frequently diagnosed malignancy (43.8%), and only one patient developed a hematologic malignancy. 68.6% (11/16) of cancer diagnoses were made in the period including the year prior and the 2 years following CADM diagnosis, and the risk was highest in the first year following diagnosis (8/16, 50.0%). In this cohort of CADM patients, which is the largest reported to date, the risk of associated malignancy is somewhat lower than that traditionally reported for classic DM. As there is significant heterogeneity among studies on the association between DM and malignancy, this study focusing on CADM helps to clarify the risk of cancer in this population.
402
Systematic review of treatments for keratinocyte carcinoma F Moustafa1, G Adam2, V Langberg2, B Smith2, A Gazula2, MA Weinstock3, A Drucker4 and T Trikalinos2 1 Brown Dermatology, Providence, RI, 2 Brown University School of Public Health, Providence, RI, 3 Brown University, Providence Veterans Affairs Medical Center, Providence, RI and 4 Brown Unversity, Providence, RI Basal Cell Carcinomas (BCCs) and Squamous Cell Carcinomas (SCCs) can be treated with many interventions, whose comparative efficacy and safety is not clear. We systematically identified 57 RCTs and 45 NRCS comparing 21 interventions in 9 categories and we summarize comparisons of important outcomes across the network of compared treatments. For BCC and lack of clinical clearance, surgical excision was statistically significantly better than Imiquimod (odds ratio [OR] 0.07, 95% CI 0.02, 0.29), but not than PDT (excision vs. MAL-PDT: OR 3.44 [0.06, 199]; excision vs. ALA-PDT: OR 0.43 [0.11, 1.78]. There was no difference between cryotherapy and external beam radiation, MAL-PDT, and ALA-PDT. MALPDT combined with laser treatment was better than MAL-PDT alone, but not significantly so (OR 0.18 [0.01, 3.97]). External beam radiation was non-significantly worse than Imiquimod (OR 1.24 [0.02, 67.0]). Imiquimod, Interferon, and Ingenol mebutate were all significantly better than no treatment (OR 0.02 [0.01, 0.05]; OR 0.07 [0.03, 0.16], and OR 1.4 [0.07, 28], respectively). With regards to lack of clinical clearance of SCC in situ, MAL-PDT was less likely to have lack of clinical clearance compared to laser and MAL-PDT as well as other types of PDT (OR 0.18 [0.03, 0.96]; OR 0.1 [0.03, 0.32], respectively). Cryotherapy was nonsignificantly inferior to ALA-PDT (OR 3.1 [0.8,11.5]). ALA-PDT was superior to topical 5FU (OR 0.29 [0.1, 0.8]). Surgical excision with topical imiquimod was favored over surgical excision alone, but not significantly (OR 0.19 [0.01, 4.08]). This systematic review summarizes currently available evidence and points to gaps in the current literature.
www.jidonline.org S69