Clinical characteristics of melanoma patients with non-V600E/K BRAF mutations.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20036-e20036 ◽  
Author(s):  
Sasan Nowroozi ◽  
Zhuang Zuo ◽  
Keyur Patel ◽  
Sapna Pradyuman Patel ◽  
Rajyalakshmi Luthra ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Primary Melanoma ◽  
Stage Iv ◽  
Distant Metastases ◽  
Unknown Primary ◽  
Sequencing Analysis ◽  
Superficial Spreading ◽  
Braf Mutations ◽  
Number Of Patients ◽  
Melanoma Patients

e20036 Background: BRAF mutations are found in ~50% of melanoma. V600E/K substitutions are the most common and well-characterized. We analyzed the clinical characteristics of patients with non-V600E/K BRAF mutations. Methods: We identified 38 melanoma patients whose tumor contained a non-V600E/K BRAF mutation and reviewed the clinical characteristics. The sequencing analysis was performed with either pyrosequencing or next generation sequencing assay. Results: 38 patients were identified with non-V600E/K BRAF mutations. Mutations detected in more than 1 patient included V600R (n=14, 37%), K601E (5, 13%), G469E (3, 8%); L597S (3, 7%), D594G (2, 5%); 11 other mutations were identified in single patients. Median age was 57 yrs; 82% were men; 95% were white. The common primary subtypes were nodular (26%), superficial spreading (24%), unknown primary (21%); no one were acral, mucosal or uveal melanomas. Ten (26%) of 27 with known ulceration status had ulceration, and 3 (7%) of 22 with known mitosis status had < 1 mitosis /mm2. The sites of primary melanoma were located mostly in the head/neck and the trunk (63%), extremities (16%) and unknown primary (21%). The stage at diagnosis was I /II (29%), III (40%), IV (18%) and unknown (13%). Among 33 (87%) patients who ultimately developed distant metastases, 23(67%) had metastasis in the soft tissue/nodes, 21 (63%) in the lung, 9 (24%) in the brain, 7 (21%) in the liver, 6 (16%) in the bone, and 5 (15%) in the adrenal gland. Among patients (n=25) with initial stage I-III melanoma who later developed distant metastasis, the median duration between the time of initial diagnosis and distant metastases was 36 months. Among the 32 (84%) of the patients who developed stage IV melanoma, the median survival from the time of stage IV diagnosis was 18 months. Five patients received vemurafenib treatment, and 2 patients (K601E; T599_V600ins2) had stable disease and 2 patients (L597Q; G466E) had disease progression and 1 lost to follow up. Conclusions: Unexpectedly higher proportion of the patients with non-V600E/K mutant-melanoma had unknown primary melanoma and higher mitotic rate. In a small number of patients who received vemurafenib, the clinical response appears to be low.

Frequency and outcomes of melanoma subtypes in a diverse population: The Los Angeles County – University of Southern California (LAC-USC) Medical Center experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21063-e21063
Author(s):  
Gino Kim In ◽  
Dongyun Yang ◽  
Jacob Stephen Thomas ◽  
Anthony Pham ◽  
Arnab Basu ◽  
...  
Keyword(s):  
African Americans ◽  
Los Angeles ◽  
Medical Center ◽  
Prior History ◽  
P Value ◽  
Superficial Spreading ◽  
Braf Mutations ◽  
Exact Test ◽  
Number Of Patients ◽  
Melanoma Patients

e21063 Background: Melanoma is a biologically heterogeneous disease that varies by ethnicity and histology. While superficial spreading (SSM) histology is the most common subtype in non-Hispanic whites (NHW), acral lentiginous (ALM) and other subtypes occur more frequently in Hispanics, Asians and African Americans. There are no known risk factors for ALM, and further investigation is warranted. Methods: We retrospectively reviewed a database of melanoma patients diagnosed between 2001-2016 at LAC-USC. Overall survival (OS) was estimated using Kaplan-Meier methodology, and comparisons performed using log-rank testing. Fisher’s exact test was used to evaluate associations between relevant clinicopathological variables. A p-value < 0.05 was considered statistically significant. Results: Among 272 melanoma patients, there were 140 Hispanics (51.5%), 105 NHW (38.6%), 14 Asians, and 4 African Americans. The most frequent histology among Hispanics was ALM (30.7%), while SSM was the most frequent among NHW (33.3%). BRAF V600 mutations were found in 34.5% (10/29) and 58.8% (10/17) of Hispanics and NHW, respectively. A total of 52 patients with ALM were identified, including 43 Hispanics (82.7%). There was a significant association between no prior history of non-melanoma skin cancer (NMSC) and ALM (p < .0001). Median Breslow thickness for ALM was 4.2 mm, and 32.7% were ulcerated. The rate of BRAF V600 mutations among 13 ALM patients tested was 0%. NRAS mutations were found in 3 ALM patients; KIT amplification/mutations were found in 2 ALM patients. Conclusions: We identified a population enriched for Hispanic patients with ALM. We found an association between no prior NMSC and ALM, suggesting that UV exposure is not a causative risk factor. BRAF mutations are less common amongst Hispanics, and nearly absent in ALM. Survival differences were not statistically significant, but cannot be ruled out due to low number of patients in this early study. [Table: see text]

Prognostic value of BRAFV600 mutations in melanoma patients after resection of metastatic lymph nodes.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8540-8540
Author(s):  
Philippe Saiag ◽  
Stephanie Moreau ◽  
Philippe Aegerter ◽  
Daphne Bosset ◽  
Christine Longvert ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Prognostic Value ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Primary Melanoma ◽  
Stage Iv ◽  
Cox Proportional Hazards ◽  
Stage Iii ◽  
Rank Test ◽  
Braf Mutations

8540 Background: Prognosis of AJCC stage III melanoma is heterogeneous. BRAFV600 mutations are frequent in melanomas. BRAFV600-targeted therapy has dramatic, but often transitory, efficacy in stage IV patients (pts). We aimed to determine for the first time the prognostic value of BRAFV600 mutations and other known prognostic criteria in stage III pts with sufficient nodal invasion. Methods: We searched all pts with cutaneous melanoma who had radical lymphadenectomy in our institution between 1/1/00 and 15/6/10 and included those with a nodal deposit >2 mm. BRAFV600 mutations were detected by DNA sequencing and pyrosequencing in formalin-fixed nodal samples containing >60% melanoma cells. Samples were considered mutated when >15% of DNA was positive. Endpoints were overall survival (OS) and distant metastasis free survival (DMFS). 92 patients had to be included to demonstrate a doubling of OS in patients without (40 months (m)) and with BRAFV600 mutation (20 m). Log-rank test and multivariate Cox proportional hazards regression model were used. Results: 105 consecutive pts were included, with 72% prospectively followed-up pts. BRAFV600 mutations (E: 83%; K: 14% of pts) were detected in 40% of pts. Median follow-up was 19 m (range: 3-139). Death occurred in 83% and 60% of pts with and without BRAF mutations, respectively, with median OS of 1.4 and 2.8 years. Pts’ age, primary melanoma ulceration, number of invaded nodes, AJCC staging, and BRAF status influenced OS and DMFS in the univariate analysis. The multivariate analysis showed the major prognostic role of BRAF status and of the number of invaded nodes (table). Conclusions: Provided our findings are independently replicated, BRAFV600 status should be used to stage melanoma pts with nodal metastasis. Our results also help to plan adjuvant trials with BRAFV600-targeted therapy in such patients, for whom the low tumor load may induce longer efficacy of BRAF-targeted therapies. [Table: see text]

Clinical and genomic alterations features of patients with advanced colitis associated cancers (CAC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15010-e15010
Author(s):  
David Paul Kelsen ◽  
Vincent A. Miller ◽  
Laura H. Tang ◽  
Marinela Capanu ◽  
Sohail Balasubramanian ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Metastatic Disease ◽  
Stage Iv ◽  
Sporadic Colorectal Cancer ◽  
Sequencing Analysis ◽  
Braf Mutations ◽  
Genomic Alterations ◽  
Agent Based ◽  
Initial Stage ◽  
Next Generation Sequencing Analysis

e15010 Background: CAC are a catastrophic complication of inflammatory bowel disease. The spectrum of genomic alterations (GA) in CAC is different than that of sporadic colorectal cancer (CRC) (Yaeger et al PMID 27063727). While the prognosis for CAC patients (pts) may be worse than that of sporadic CRC pts, there is little data regarding outcome for metastatic CAC pts treated with standard chemotherapy regimens. We reviewed demographic features and clinical outcome for pts with metastatic CAC in the context of somatic tumor GA. Methods: We identified small and large bowel CAC cases seen at Memorial Sloan Kettering between 2003 and 2015 with tissue available for study. Hybrid capture based next-generation sequencing analysis of over 300 cancer-related genes was used to comprehensively characterize GA. The electronic medical record of each patient was reviewed. Demographic and clinical data was extracted and outcome reviewed in the context of somatic tumor GA. Results: Clinical features for 17 pts with metastatic CAC are shown below. All pts with initial stage III CAC received FOLFOX adjuvant therapy. First-line treatment for metastatic disease included FOLFOX/FOLFIRINOX/FU-LV in 10 previously untreated pts and FOLFIRI after adjuvant therapy. Median duration of survival from time of metastatic disease was 14.8 months, (95% CI 5.7-24.3;range 2-68+ months), substantially less than that expected for pts with Stage IV CRC. Only 4 patients survived for > 24 months. GA were identified in TP53 (87%) and KRAS (33%); potentially targetable alterations were found in 8 pts ( IDH1 (1), EML4-ALK(1), ERBB2 (1); FGFR1/2 (3); BRAF (1); PIK3CA(1). 2 pts received a targeted agent based on GA; 1 partial response to a FGFR inhibitor is ongoing. No patient had a hyper-mutated tumor. Conclusions: Metastatic CAC pts have an exceedingly poor prognosis, with survival well below that expected for sporadic CRC. BRAF mutations associated with poor outcome in sporadic CRC are rare in CAC. 47% of CAC pts had potentially targetable GA. [Table: see text]

First Recurrence Analysis of 840 Cutaneous Melanomas: A Proposal for a Follow-Up Schedule

1994 ◽  
Vol 80 (3) ◽  
pp. 188-197 ◽  
Author(s):  
Laura Martini ◽  
Paola Brandani ◽  
Cristina Chiarugi ◽  
Umberto M. Reali
Keyword(s):  
Cutaneous Melanoma ◽  
Primary Melanoma ◽  
Neck Region ◽  
Stage I ◽  
Lower Limbs ◽  
Depth Of Invasion ◽  
Number Of Patients ◽  
Melanoma Patients ◽  
First Recurrence

Aims and background A correct follow-up schedule for patients who underwent an excision for stage I cutaneous melanoma might allow the early detection of local and distant metastases. At present, there is no general agreement on follow-up protocols. In order to work out a follow-up guide, we have retrospectively evaluated the records of 840 stage I cutaneous melanoma patients surgically treated and followed during the postoperative period in the Division of Plastic Surgery of the University of Florence from 1975 to 1992. Methods We evaluated the patients’ records by analyzing time, pathway and site of any first recurrence in relation to the main prognostic factors such as patient sex, site, histological type and depth of invasion of each primary melanoma. A statistical analysis was performed. Results To summarize, the salient results were the following: 80% of relapses occurred in the first 3 years and they occurred significantly earlier when the primary melanoma was localized in the trunk and significantly later when the melanoma was localized in the lower limbs and for < 1.5 mm lesions. The first recurrence occurred earlier by the lymphatic than by the hematic pathway regarding the overall number of patients. The hematic pathway was the most frequent (with respect to the overall percentage of hematic metastases) for the melanomas localized in the head and neck region and for lentigo malignant melanomas, whereas the lymphatic pathway was most frequent for melanomas of the lower limbs and > 3 mm in thickness. Conclusions We suggest a follow-up schedule taking into consideration the postoperative behavior of stage I cutaneous melanoma patients (in terms of time and pathway of the first recurrence) in relation to the site and depth of invasion of the tumor.

Shedding of distinct cryptic epitope (HU177) in sera of melanoma patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8550-8550
Author(s):  
J. Zakrzewski ◽  
B. Ng ◽  
M. Warycha ◽  
P. Christos ◽  
R. Shapiro ◽  
...  
Keyword(s):  
Primary Melanoma ◽  
Tumor Thickness ◽  
Collagen Type Iv ◽  
Tumor Cell Adhesion ◽  
Superficial Spreading ◽  
Normal Volunteers ◽  
Type Iv ◽  
Cryptic Epitope ◽  
Melanoma Patients

8550 Background: Our preclinical data suggest that a newly identified cryptic epitope HU177 within collagen regulates endothelial and tumor cell adhesion in-vitro and angiogenesis and tumor growth in-vivo. We investigated whether 1) HU177 shedding can be measured in melanoma patients’ sera, and 2) if HU177 concentration correlates with clinicopathological features, recurrence and survival. Methods: Sera from 291 melanoma patients (primary Stage I, n=140; II n=41; III n=29; recurrent/metastatic n=81) and 30 normal volunteers prospectively enrolled at the NYU School of Medicine were analyzed for HU177 epitope concentration (ng/ml) by ELISA. Microtiter plates were incubated overnight with monoclonal antibody (anti-HU177 epitope). Patients’ sera and standards (denatured type-IV collagen) were added in duplicate followed by dilutions of biotinylated anti-collagen type IV polyclonal and HRP-labeled anti-biotin antibodies with multiple washes after each incubation. Absorbance was monitored at 400 nm. Results: The mean concentration of anti-HU177 epitope was 5.8 ng/ml (range 0.1 to 139.8). Normal volunteers were 1.6±0.3 (mean ± SEM). A significant correlation was observed between HU177 concentration and tumor thickness in patients who presented with primary melanoma (=1.00 mm, n=113, 3.8±0.4; 1.01–3.99 mm, n=72, 8.9 ±2.1; =4.00 mm, n=22, 10.3±2.2; P=0.003 by ANOVA test) and nodular melanoma histological subtype (nodular, n=47, 10.5±3.1; superficial spreading, n=95, 4.4±0.5; others, n=68, 6.0±2.1; P=0.02, ANOVA). Multivariate analysis confirmed the independent correlation between higher HU177 concentration and nodular subtype after controlling for tumor thickness (P=0.04). Primary patients with ulcerated melanomas and those who developed recurrences both showed higher HU177 epitope levels, however, the difference was not significant (P>0.05). Conclusions: This is the first study on HU177 epitope shedding in melanoma patients. Data demonstrate the clinical feasibility of HU177 testing in melanoma patients’ sera and suggest that HU177 epitope shedding correlates with thicker primary melanomas. Longer follow-up is required to better define the prognostic value of HU177 epitope shedding in melanoma patients. [Table: see text]

The spectrum of genomic alterations in young adult non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8077-8077
Author(s):  
Geoffrey R. Oxnard ◽  
Jennifer C. Heng ◽  
Stacy L. Mach ◽  
Peter C. Lo ◽  
Mohit Butaney ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Characteristics ◽  
Stage Iv ◽  
Egfr Mutations ◽  
Insertion Mutation ◽  
Braf Mutations ◽  
Genomic Alterations ◽  
Kras Mutations ◽  
Targeted Next Generation Sequencing ◽  
Undifferentiated Histology

8077 Background: Identification of targetable genomic alterations in patients (pts) with NSCLC can have a profound impact on treatment and clinical outcomes. Given the complexity and cost of comprehensive genomic testing, clinical characteristics enriching for targetable genomic alterations are of interest. We hypothesized that young adults with NSCLC would have a higher prevalence of targetable genomics alterations compared to the general NSCLC population. Methods: An institutional database of pts with NSCLC was reviewed in an IRB-approved fashion to identify subjects with age < 40 at diagnosis. Clinical characteristics and risk factors were reviewed. Tumor genotyping for alterations in EGFR, KRAS, ALK, BRAF, HER2, and ROS1was pursued as part of an institution-wide genomics protocol. Targeted next-generation sequencing (NGS) of wild-type cases is underway. Results: From 2032 subjects with NSCLC, we identified 70 diagnosed at an age < 40 (3.4%). Pt characteristics: median age 35 (range 20-39); 63% never-smokers, 33% with ≥10 pack-years; 74% adeno, 9% squam, 14% undifferentiated, 3% neuroendocrine; 19% had a family history of lung cancer; 61% stage IV at diagnosis. Median survival from date of advanced disease was 15.8 months. Genotyping was performed on 51 pts with adeno or undifferentiated histology: 14 with EGFR mutations (27%), 5 with KRAS mutations (10%), 8 with ALK rearrangements (16%), 0 with BRAF mutations, 1 with a HER2 insertion (2%), 1 with a ROS1 rearrangement (2%). Compared to a reference prevalence from the Lung Cancer Mutation Consortium (Kris et al, ASCO, 2011), KRAS mutations were less common (p=0.01) and ALK rearrangements were more common (p<0.01). NGS of 2 cases to date has identified one pt with a novel 21 base-pair insertion mutation in FGFR2, not present in germline tissue. Conclusions: 47% (CI: 33%-60%) of pts diagnosed with NSCLC under age 40 harbor a targetable alteration in EGFR, ALK, HER2, or ROS1. These patients may be enriched for targetable genotypes and deserving of a unique treatment approach, and additionally represent an attractive population for genomic discovery.Supported in part by the Bonnie J. Addario Lung Cancer Foundation and the Conquer Cancer Foundation of ASCO.

A multifactorial analysis of melanoma. IV. Prognostic factors in 200 melanoma patients with distant metastases (stage III).

1983 ◽  
Vol 1 (2) ◽  
pp. 126-134 ◽  
Author(s):  
C M Balch ◽  
S J Soong ◽  
T M Murad ◽  
J W Smith ◽  
W A Maddox ◽  
...  
Keyword(s):  
Survival Rate ◽  
Cox Regression ◽  
Primary Melanoma ◽  
Distant Metastases ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Cox Regression Analysis ◽  
Multifactorial Analysis ◽  
Melanoma Patients

A multifactorial analysis of 200 cutaneous melanoma patients with distant metastasis (stage III) was performed on 13 clinical and pathological factors using the Cox regression analysis. There were only three dominant prognostic variables that independently predicted the patient's clinical course: (1) number of metastatic sites (1 vs. 2 vs. greater than or equal to 3, p less than 0.00001), (2) remission duration (less than 12 mo vs. greater than or equal to 12 mo, p = 0.0186), and (3) the location of the metastases (visceral vs. nonvisceral vs. combined, p = 0.0192). Factors that were not significant in the multifactorial analysis included the patients' age and sex, the site of the primary melanoma, the sequence of metastases, and all histopathological features of the primary melanoma (thickness, level of invasion, ulceration, growth pattern, pigmentation, and lymphocyte infiltration). For a single metastatic site, the 1-yr survival rate was 36%, while it was only 13% for 2 sites, and 0% for greater than or equal to 3 sites (p less than 0.00001). The 1-yr survival for patients was 40% for nonvisceral sites (skin, subcutaneous, distant lymph nodes) compared to only 11% for visceral metastases and 8% for combined sites (p less than 0.00001). Pulmonary metastases were associated with a significantly higher survival rate than metastatic melanoma in any other visceral site. The most common first site of distant metastases (either alone or in combination) was skin (38%), lung (36%), liver (20%), and brain (20%). The skin, subcutaneous and distant lymph node group was the first site of metastases in 59% of patients. This finding emphasizes the importance of careful physical exams in routine metastatic evaluations. Only a minority (25%) of stage I patients progressed to stage III disease after a median interval of 2.8 years. In contrast, the majority (75%) of melanoma patients with nodal metastases (stage II) progressed to stage III disease after a median duration of only 11 mo. Of the patients who eventually developed stage III disease, 95% of those who initially presented with stage II disease progressed within 3 yr, while stage I patients who progressed to stage III did not reach a 95% cumulative incidence until 8 yr.

Epidemiological study of unknown primary melanoma patients from the French national melanoma database RIC-Mel.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e21571-e21571
Author(s):  
Emilie Varey ◽  
Stéphane Dalle ◽  
Jean-Michel NGuyen ◽  
Alain Dupuy ◽  
Jean-Philippe Lacour ◽  
...  
Keyword(s):  
Epidemiological Study ◽  
Primary Melanoma ◽  
Unknown Primary ◽  
Melanoma Patients

scholarly journals BRAF mutation status in primary, recurrent, and metastatic malignant melanoma and its relation to histopathological parameters

2019 ◽  
Author(s):  
Aris Spathis ◽  
Alexander Katoulis ◽  
V Damaskou ◽  
Aikaterini Liakou ◽  
Christine Kottaridi ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Braf Mutation ◽  
Histopathological Examination ◽  
Direct Sequencing ◽  
Statistical Significance ◽  
Common Finding ◽  
Unknown Primary ◽  
Superficial Spreading ◽  
Braf Mutations ◽  
Mutation Status

Background: BRAF mutations are a common finding in malignant melanoma (MM). Nevertheless, apart from their significance as a therapeutic target in advanced melanoma, their prognostic value is still debated. Objective: To assess BRAF mutation status in primary, recurrent, or metastatic MM and its correlations with histopathological findings. Methods: We analyzed 203 samples from 178 consecutive patients: 129 primary cutaneous MM, 49 metastatic and recurrent MM of unknown primary site, and 25 cases of recurrences or metastases of primary MM. BRAF mutations in exon 15 were identified with real-time polymerase chain reaction and/or direct sequencing or pyrosequencing. Histopathological examination was performed according to standard procedures. Results: We observed a 42.1% prevalence of BRAF mutations at codon 600 among our patients, 84% of whom harbored the V600E mutation. Mutations showed a statistically significant increase in younger patients (P = 0.011), in ulcerated tumors (P = 0.020), and in tumors lacking solar elastosis in adjacent dermis (P = 0.008). Mutations were also more common in male patients, as well as in primary MMs of the torso, and in nonvisceral metastases, however without reaching statistical significance. Logistic regression analysis identified type and ulceration as the only significant predictors of BRAF mutation. The highest frequencies of mutated BRAF were identified in superficial spreading and nodular types, and the lowest in acral lentiginous and lentigo maligna types. In situ MM and primary dermal melanoma displayed intermediate frequencies. Conclusion: Frequency of mutated BRAF is type-related and correlated with ulceration, a known adverse prognostic factor.

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