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Association between TERT promoter mutations and BRAF/NRAS mutations in patients with primary and metastatic melanoma tumors [Meeting Abstract]
Chang, Gregory A; Tadepalli, Jyothirmayee S; Fleming, Nathaniel H; Lui, Kevin; Shao, Yongzhao; Darvishian, Farbod; Pavlick, Anna; Berman, Russell; Shapiro, Richard; Osman, Iman; Polsky, David
ISI:000370972700021
ISSN: 1538-7445
CID: 2029702
Integration of melanoma genotyping in clinical care [Meeting Abstract]
Salhi, Amel; Da Silva, Ines Pires; Lui, Kevin P; Ismaili, Naima; Wu, Chaowei; de Miera, Eleazar CVega-Saenz; Shapiro, Richard L; Berman, Russell S; Pavlick, Anna C; Zhong, Judy; Heguy, Adriana; Osman, Iman
ISI:000370972700025
ISSN: 1538-7445
CID: 2029792
Analysis of recurrence patterns in acral versus nonacral melanoma: should histologic subtype influence treatment guidelines?
Gumaste, Priyanka V; Fleming, Nathaniel H; Silva, Ines; Shapiro, Richard L; Berman, Russell S; Zhong, Judy; Osman, Iman; Stein, Jennifer A
Current surgical treatment of primary melanoma is uniform for all histosubtypes, although certain types of melanoma, such as acral lentiginous melanoma (ALM), have a worse prognosis. No study has explored the effectiveness of standard melanoma treatment guidelines for managing ALM compared with nonacral melanoma (NAM). Study subjects were identified from a prospectively enrolled database of patients with primary melanoma at New York University. Patients with ALM were matched to those with NAM (1:3) by gender and melanoma stage, including substage (ALM, 61; NAM, 183). All patients received standard-of-care treatment. Recurrence and survival outcomes in both cohorts were compared. ALM histologic subtype was an independent negative predictor of recurrence-free survival (hazard ratio [HR], 2.24; P=.001) and melanoma-specific survival (HR, 2.58; P=.001) compared with NAM. Recurrence was significantly more common in patients with ALM than in those with NAM (49% vs 30%; P=.007). For tumors less than 2 mm in thickness, a significantly higher recurrence rate was seen with ALM versus NAM (P=.048). No significant difference was seen in recurrence for tumors greater than 2 mm (P=.12). Notably, the rate of locoregional recurrence was nearly double for ALM compared with NAM (P=.001). The data presented herein reveal a high rate of locoregional failure in ALM compared with NAM when controlling for AJCC stage. These results raise the question of whether ALM may require more aggressive surgical treatment than nonacral cutaneous melanomas of equal thickness, particularly in tumors less than 2 mm thick. Larger multicenter trials are necessary for further conclusions.
PMCID:4469335
PMID: 25505211
ISSN: 1540-1405
CID: 1424152
Training and certification of the surgical oncologist
Berman, Russell S; Weigel, Ronald J
Surgical Oncology has evolved as a distinct subspecialty of General Surgery with a well-defined curriculum focused on surgical care of the cancer patient, specific areas of clinical and basic science research focus and specialty journals dedicated to the discipline. The Society of Surgical Oncology (SSO), originally formed as the James Ewing Society, has provided leadership in developing training programs in Surgical Oncology and for three decades has been involved in the approval and oversight of Surgical Oncology training programs. Over this time, Surgical Oncology Fellowship training has expanded and in 2013 there were 103 applicants for 56 fellowship positions in 21 programs. The basic tenants of Surgical Oncology training has remained devoted to the core principles of multidisciplinary care, surgical management of cancer patients and a focus on education in research, clinical trials, community outreach, patient advocacy and leadership in oncology. With the maturation of Surgical Oncology as a separate specialty, Surgical Oncology training programs are now accredited by the Accreditation Council on Graduate Medical Education (ACGME) and graduates of the programs will soon be offered subspecialty certification in Complex General Surgical Oncology (CGSO) by the American Board of Surgery, which has created a component Surgical Oncology Board (SOB). Similar expansion has occurred in other specialty areas including an expansion of Breast Fellowships, which are still being approved by the SSO. In the 2013 SSO Breast Oncology Match, there were 67 applicants for 54 positions in 39 Breast Fellowship programs. Continued advances in cancer biology and technology will challenge us to evolve training programs in Surgical Oncology to produce surgeons capable of advancing the multidisciplinary care of cancer patients.
PMID: 25841526
ISSN: 2304-3873
CID: 1544152
Enhanced immunohistochemical detection of neural infiltration in primary melanoma: is there a clinical value?
Scanlon, Patrick; Tian, Jaiying; Zhong, Judy; Silva, Ines; Shapiro, Richard; Pavlick, Anna; Berman, Russell; Osman, Iman; Darvishian, Farbod
Neural infiltration in primary melanoma is a histopathologic feature that has been associated with desmoplastic histopathologic subtype and local recurrence in the literature. We tested the hypothesis that improved detection and characterization of neural infiltration into peritumoral or intratumoral location and perineural or intraneural involvement could have a prognostic relevance. We studied 128 primary melanoma cases prospectively accrued and followed at New York University using immunohistochemical detection with antihuman neurofilament protein and routine histology with hematoxylin and eosin. Neural infiltration, defined as the presence of tumor cells involving or immediately surrounding nerve foci, was identified and characterized using both detection methods. Neural infiltration rate of detection was enhanced by immunohistochemistry for neurofilament in matched-pair design (47% by immunohistochemistry versus 25% by routine histology). Immunohistochemical detection of neural infiltration was significantly associated with ulceration (P = .021), desmoplastic and acral lentiginous histologic subtype (P = .008), and head/neck/hands/feet tumor location (P = .037). Routinely detected neural infiltration was significantly associated with local recurrence (P = .010). Immunohistochemistry detected more intratumoral neural infiltration cases compared with routine histology (30% versus 3%, respectively). Peritumoral and intratumoral nerve location had no impact on clinical outcomes. Using a multivariate model controlling for stage, neither routinely detected neural infiltration nor enhanced immunohistochemical characterization of neural infiltration was significantly associated with disease-free or overall survival. Our data demonstrate that routinely detected neural infiltration is associated with local recurrence in all histologic subtypes but that improved detection and characterization of neural infiltration with immunohistochemistry in primary melanoma does not add to prognostic relevance.
PMCID:4691539
PMID: 24890944
ISSN: 0046-8177
CID: 1030852
When surgeons decide to become surgeons: new opportunities for surgical education
Hochberg, Mark S; Billig, Jessica; Berman, Russell S; Kalet, Adina L; Zabar, Sondra R; Fox, Jaclyn R; Pachter, H Leon
BACKGROUND: When surgeons decide to become surgeons has important implications. If the decision is made prior to or early in medical school, surgical education can be more focused on surgical diseases and resident skills. METHODS: To determine when surgeons - compared with their nonsurgical colleagues - decide on their medical path, residents in surgery, internal medicine, obstetrics and gynecology, pediatrics, psychiatry, and emergency medicine were surveyed. Timing of residency choice, demographic data, personal goals, and reason for residency choice were queried. RESULTS: A total of 234 residents responded (53 surgical residents). Sixty-two percent of surgeons reported that they were "fairly certain" of surgery before medical school, 13% decided during their preclinical years, and 25% decided during their clerkship years. This compares with an aggregate 40%, 7%, and 54%, respectively, for the other 5 residency specialties. These differences were statistically significant (P = .001). When the 234 residents were asked about their primary motivation for choosing their field, 51% pointed to expected job satisfaction and 44% to intellectual curiosity, and only 3% mentioned lifestyle, prestige, or income. CONCLUSIONS: General surgery residents decide on surgery earlier than residents in other programs. This may be advantageous, resulting in fast-tracking of these medical students in acquiring surgical knowledge, undertaking surgical research, and early identification for surgical residency programs. Surgical training in the era of the 80-hour work week could be enhanced if medical students bring much deeper knowledge of surgery to their first day of residency.
PMID: 24468025
ISSN: 0002-9610
CID: 778232
GENETIC DETERMINANTS OF IPILIMUMAB OUTCOMES FOR ADVANCED MELANOMA [Meeting Abstract]
Kirchhoff, T; Adaniel, C; Rendleman, J; Kern, E; Fleming, N; Polsky, D; Berman, R; Shapiro, R; Shao, Y; Heguy, A; Osman, I; Pavlick, A
ORIGINAL:0013163
ISSN: 1569-8041
CID: 3589082
IL10 LOCUS AS A BIOMARKER OF MELANOMA SURVIVAL [Meeting Abstract]
Rendleman, J; Adaniel, C; Kern, E; Fleming, N; Krogsgaard, M; Polsky, D; Berman, R; Shapiro, R; Pavlick, A; Shao, Y; Osman, I; Kirchhoff, T
ORIGINAL:0013165
ISSN: 1569-8041
CID: 3589112
Melanoma risk loci as determinants of melanoma recurrence and survival
Rendleman, Justin; Shang, Shulian; Dominianni, Christine; Shields, Jerry F; Scanlon, Patrick; Adaniel, Christina; Desrichard, Alexis; Ma, Michelle; Shapiro, Richard; Berman, Russell; Pavlick, Anna; Polsky, David; Shao, Yongzhao; Osman, Iman; Kirchhoff, Tomas
BACKGROUND: Steadily high melanoma mortality rates urge for the availability of novel biomarkers with a more personalized ability to predict melanoma clinical outcomes. Germline risk variants are promising candidates for this purpose; however, their prognostic potential in melanoma has never been systematically tested. METHODS: We examined the effect of 108 melanoma susceptibility single nucleotide polymorphisms (SNPs), associated in recent GWAS with melanoma and melanoma-related phenotypes, on recurrence-free survival (RFS) and overall survival (OS), in 891 prospectively accrued melanoma patients. Cox proportional hazards models (Cox PH) were used to test the associations between 108 melanoma risk SNPs and RFS and OS adjusted by age at diagnosis, gender, tumor stage, histological subtype and other primary tumor characteristics. RESULTS: We identified significant associations for rs7538876 (RCC2) with RFS (HR = 1.48, 95% CI = 1.20-1.83, p = 0.0005) and rs9960018 (DLGAP1) with both RFS and OS (HR = 1.43, 95% CI = 1.07-1.91, p = 0.01, HR = 1.52, 95% CI = 1.09-2.12, p = 0.01, respectively) using multivariable Cox PH models. In addition, we developed a logistic regression model that incorporates rs7538876, rs9960018, primary tumor histological type and stage at diagnosis that has an improved discriminatory ability to classify 3-year recurrence (AUC = 82%) compared to histological type and stage alone (AUC = 78%). CONCLUSIONS: We identified associations between melanoma risk variants and melanoma outcomes. The significant associations observed for rs7538876 and rs9960018 suggest a biological implication of these loci in melanoma progression. The observed predictive patterns of associated variants with clinical end-points suggest for the first time the potential for utilization of genetic risk markers in melanoma prognostication.
PMCID:4228352
PMID: 24188633
ISSN: 1479-5876
CID: 617512
Mitotic Rate in Melanoma: Prognostic Value of Immunostaining and Computer-assisted Image Analysis
Hale, Christopher S; Qian, Meng; Ma, Michelle W; Scanlon, Patrick; Berman, Russell S; Shapiro, Richard L; Pavlick, Anna C; Shao, Yongzhao; Polsky, David; Osman, Iman; Darvishian, Farbod
The prognostic value of mitotic rate in melanoma is increasingly recognized, particularly in thin melanoma in which the presence or absence of a single mitosis/mm can change staging from T1a to T1b. Still, accurate mitotic rate calculation (mitoses/mm) on hematoxylin and eosin (H&E)-stained sections can be challenging. Antimonoclonal mitotic protein-2 (MPM-2) and antiphosphohistone-H3 (PHH3) are 2 antibodies reported to be more mitosis-specific than other markers of proliferation such as Ki-67. We used light microscopy and computer-assisted image analysis software to quantify MPM-2 and PHH3 staining in melanoma. We then compared mitotic rates by each method with conventional H&E-based mitotic rate for correlation with clinical outcomes. Our study included primary tissues from 190 nonconsecutive cutaneous melanoma patients who were prospectively enrolled at New York University Langone Medical Center with information on age, gender, and primary tumor characteristics. The mitotic rate was quantified manually by light microscopy of corresponding H&E-stained, MPM-2-stained, and PHH3-stained sections. Computer-assisted image analysis was then used to quantify immunolabeled mitoses on the previously examined PHH3 and MPM-2 slides. We then analyzed the association between mitotic rate and both progression-free and melanoma-specific survival. Univariate analysis of PHH3 found significant correlation between increased PHH3 mitotic rate and decreased progression-free survival (P=0.04). Computer-assisted image analysis enhanced the correlation of PHH3 mitotic rate with progression-free survival (P=0.02). Regardless of the detection method, neither MPM-2 nor PHH3 offered significant advantage over conventional H&E determination of mitotic rate.
PMCID:3654084
PMID: 23629443
ISSN: 0147-5185
CID: 346512