bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ipilimumab in the treatment of uveal melanoma: The Memorial Sloan-Kettering Cancer Center experience.
Authors: Khan Shaheer A. , Callahan Margaret , Postow Michael Andrew , Chapman Paul B. , Schwartz Gary K. , Dickson Mark Andrew , D'Angelo Sandra P. , Luke Jason John , Bluth Mark J. , Roman Ruth Ann , Montefusco Mary , Barker Christopher Andrew , Abramson David H. , Wolchok Jedd D. , Carvajal Richard D. 
Published: March 2020

8549 Background: Ipilimumab (ipi) is an antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4) and improves overall survival in patients (pts) with metastatic melanoma. Uveal melanoma (UM) is a rare and biologically unique disease subtype with no known effective systemic therapy. Ipi has proven efficacy in cutaneous melanoma (CM), but limited data exists regarding its activity in UM. We reviewed our single-institutional experience with ipi in advanced UM. Methods: After IRB approval, the MSKCC melanoma database was queried for patients with metastatic UM treated with ipi between 03/08-01/12. Radiographic response by RECIST and immune-related response criteria (irRC) was assessed by a single radiologist blinded to clinical outcomes. Immune-related adverse events (irAEs), survival and absolute lymphocyte count (ALC) were also evaluated. Results: 20 pts were identified: the median age was 61yrs (range 46-83), 55% were male, 85% had liver metastases, 60% had elevated LDH, and pts reported a median of 1 prior therapies (range 0-5). Pts received a median of 4 doses (range 1-16) of ipi. Response rates (RR) by irRC at 12 and 24 wks are listed below. Among pts with stable disease (SD) at 12 wks, the median time to progression was 30.6 wks (range 19.6-83), with one partial response (PR) occurring after 24 wks (overall RR 10%). Responses were observed in lung, liver and peritoneal metastases. Pts with an ALC ≥ 1.0 at 7 wks had a trend toward a higher clinical benefit (CB= CR + PR + SD) than pts with ALC < 1.0 (5/12 [42%] vs 0/5 [0%]; p= .09), consistent with prior studies in CM. To date, median survival for the group is 8.6 mos (95% CI, 3.5-NR), with two ongoing PRs (3+ yrs and 24+ wks). Reported irAEs include rash/pruritis (10/20), hepatitis (1/20), colitis (1/20), pancreatitis (1/20) and uveitis (1/20). Conclusions: Ipi has potential for benefit in pts with advanced UM; RR and irAE rates are similar to those observed in pts with advanced CM. Further evaluation of ipi in the treatment of UM, including identification of potential biomarkers of CB, is warranted. [Table: see text]
Randomized, double-blind, and multicenter phase II trial of rh-endostatin plus dacarbazine versus dacarbazine alone as first-line therapy for the patients with advanced melanoma.
Authors: Guo Jun , Cui Chuan Liang , GU Kangsheng , Tao Min , Xin Song , Lin Tongyu , Ren Xiu Bao , Qin Shukui 
Published: March 2020

8554 Background: rh-endostatin (Endostar, water-soluble, rES) is an inhibitor of angiogenesis, which is effective as single agent or in combination with chemotherapy for non-small cell lung cancer in phase I/II clinical trials. This study (NCT00813449) was a randomized, double-blind and placebo-controlled phase II trial, aimed to observe the efficacy and safety of rES with dacarbazine (DTIC) as the 1st line therapy for patients (pts) with advanced melanoma. Methods: Untreated pts with ECOG 0/1 and unresectable stage IIIC or IV melanoma (confirmed by histopathology) were enrolled, and randomized (1:1) into Arm A (DTIC 250 mg/m2 d1-5 + placebo d1-14) or Arm B (DTIC 250 mg/m2 d1-5 + rES 7.5 mg/m2 d1-14). Treatment was continued in 21-day cycle until progression or intolerable toxicity occurs. Primary endpoints were progression free survival (PFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR) and safety, evaluated every 2 cycles. Results: From Dec. 2008, 120 pts were enrolled and 110 pts evaluable. 30.9% of them were in M1a, 39.1% in M1b, and 29.1% in M1c. Mean treatment cycles were 3.2 (range: 1-10) in Arm A and 4.0 (range: 1-12) in Arm B. Until the last follow-up in Nov. 2011, 27 pts were still alive. The median PFS was 1.5 months (95% CI: 1.35-1.65) in Arm A and 5.0 months in Arm B (95% CI: 2.45-7.55, P=0.004, log-rank test). The median OS was 7.0 months in Arm A (95% CI: 4.41-9.59) versus 16.0 months in Arm B (95% CI: 10.46-21.54, P=0.003, Breslow test). 1-year survival rate was 22.2% versus 51.0%, and 2-year survival rate 8.9% vs.10.2%. No statistical significance was found for both ORR and toxicities. The most common toxicities were increased transaminase (28.9% in Arm A versus 56.1% in Arm B) and leucopenia (14.4% versus 13.4%). The incidence of grade 3-4 toxicity (increased transaminase and thrombocytopenia) was only 1.7% in Arm B. Conclusions: rES plus DTIC may obviously improve mPFS and mOS versus DTIC alone as the 1st line therapy for advanced melanoma. That combining therapy was well tolerated and could be recommended as a new, safe and effective regimen for untreated pts with advanced melanoma.
Adjuvant sunitinib in high-risk patients with uveal melanoma: A pilot study.
Authors: Valsecchi Matias Emanuel , Shockley Nancy , Summers Deborah , Shields Carol L , Shields Jerry A , Mastrangelo Michael J. , Sato Takami 
Published: March 2020

8560 Background: Uveal melanoma is the most common primary intraocular cancer in adults. Despite the successful treatments for primary tumors, up to 50% of the patients later die of distant metastases. Currently no effective adjuvant treatment is available for these patients. Our group previously reported that sunitinib stabilized systemic metastases in 65% of uveal melanoma patients who failed prior treatments. In this pilot study, we tested sunitinib in an adjuvant setting in high-risk patients with primary uveal melanoma. Methods: Patients with estimated metastatic death rate ≥ 50% based on the following criteria were eligible: (1) monosomy 3 and 8q amplification; (2) large tumor (≥ 15 mm in diameter and ≥7 mm in thickness); (3) monosomy 3 and other risk factors (large tumor, epithelioid dominant cell type, local recurrence, or extra-scleral extension). Sunitinib was given at 25 mg PO daily for at least 6 months. Primary endpoint was disease-free survival (DFS) and overall survival (OS), estimated with Kaplan-Meier analysis (SPSS 17.0). Secondary endpoint was safety. Results: A total of 23 Caucasian patients (median, 54 years; range: 25 – 77) were enrolled. All patients received sunitinib for at least 6 months (range: 6 – 12). Eighteen patients had confirmed monosomy 3, from whom 13 (72%) also showed 8q amplification. The median follow-up was 24 months (range 12 – 54 months). Only one patient died of unknown cause (OS: 30.4 months). A total of seven patients (30%) developed systemic metastases, all of which were liver metastases. The DFS and OS rates at 2 years were 70% (95% CI: 47 – 86%) and 100%, respectively. The OS rate at 2 years was better than historical control with monosomy 3 patients (51%, 95% CI: 31 – 71%) (Invest Ophthalmol Vis Sci 2003; 44:1008). In those patients who relapsed, the median time to progression after finishing sunitinib was 2 months (range: 0 – 8). The most common adverse events were: diarrhea (47%), fatigue (39%), dermatitis (30%), stomatitis (13%), leucopenia (8%), and nausea (4%). Most were grade 1 or 2 (88%) and only one was considered grade 4 (diarrhea). Conclusions: In high-risk uveal melanoma patients with estimated metastatic death rate of ≥ 50%, adjuvant sunitinib showed promising results and deserves further investigation.
A single-arm, open-label, U.S. expanded access study of vemurafenib in patients with metastatic melanoma.
Authors: Schuchter Lynn Mara , Flaherty Lawrence E. , Hamid Omid , Linette Gerald P. , Hallmeyer Sigrun , Gonzalez Rene , Cowey Charles Lance , Pavlick Anna C. , Kudrik Fred J. , Lawson David H. , Margolin Kim Allyson , Ribas Antoni , McDermott David F. , Khatcheressian James L. , Flaherty Keith T. , Day Bann-Mo , Linke Rolf Gerhard , Hainsworth John D. 
Published: March 2020

8567 Background: Vemurafenib (vem) has been FDA approved for the treatment of unresectable or metastatic BRAFV600E mutated melanoma since August 2011 based on results of a randomized phase III study (treatment-naive) and a single arm phase II study (previously treated). We report results of an expanded access study that allowed appropriate patients (pts) to receive vem until the drug was approved. Methods: Eligible pts had metastatic melanoma with a BRAFV600E mutation as detected by the cobas 4800 BRAFV600 Mutation Test. Enrolled pts received oral vem 960 mg b.i.d. Adverse events (AEs) were evaluated for vem-related toxicities; tumor responses were assessed using RECIST 1.1. Results: 29 US sites screened 745 pts and enrolled 374 from December 2010 until October 2011. The following results are based on a median follow up time and treatment duration of 2 months. At baseline, mean age of pts was 54 y with 22% of pts ≥65 y; 75% had stage M1c disease; 29% had received radiotherapy for brain metastases. 19% of pts were ECOG PS 2 or 3; 71% of pts had prior systemic therapy for metastatic melanoma (21% 1 regimen; 50% ≥2 regimens). 50 pts had prior adjuvant treatment. At data cut-off, 243 pts had sufficient follow-up time for tumor assessment. In this group, the unconfirmed overall response rate was 52% (95% CI, 46 to 59). The median time to response was 1.8 months. Based on 240 pts with available ECOG PS status at time of analysis, response rate was 53% for pts with ECOG PS 0 or 1 (n=209), and 45% for pts with ECOG PS 2 or 3 (n=31). 370 pts were evaluable for safety analysis. The most common vem-related AEs were rash (36%), arthralgia (33%) and fatigue (21%) with the majority (~90%) of grade 1 or 2. 25 vem-related serious AEs were reported in 5.4% of pts with a slightly higher rate of pts with ECOG PS 2 or 3 (8.7%) compared to ECOG PS 0 or 1 (4.7%). 18% of pts missed at least one dose and 11% of pts required dose reduction of at least one level due to AEs. Conclusions: This expanded access study, with its limited follow-up time, confirms the established rapid and high tumor response rate with vem. No new safety signals were detected. Compared to the overall population, pts with an ECOG PS 2 or 3 demonstrated a similar benefit.
Development of a melanoma risk prediction model incorporating MC1R genotype and indoor tanning exposure.
Authors: Smith Lauren A , Qian Meng , Ng Elise , Shao Yongzhao , Berwick Marianne , Lazovich DeAnn , Polsky David 
Published: March 2020

8574 Background: Invasive melanoma is the second most common cancer in young adults, yet they exhibit poor skin-protective behavior. We previously demonstrated a significant association between melanoma risk, melanocortin receptor (MC1R) polymorphisms, and indoor ultraviolet light (UV) exposure. As existing melanoma risk models do not take these factors into account, we investigated whether these variables would improve the predictive ability of a clinical risk model, especially in a younger population. Methods: We determined MC1R genotype and collected self-reported phenotypic and UV (indoor and outdoor) exposure variables from 923 melanoma cases and 813 healthy controls between ages 25 – 59 from the Minnesota Skin Health Study. These data were initially used to develop a clinical melanoma risk model (Model A) with conventional risk factors (i.e. age; gender; hair, skin, and eye color; mole count, freckling, and family melanoma history). We then developed a second model (Model B) combining outdoor UV, indoor UV, and MC1R genotype variables with those in Model A to determine if the model’s predictive ability improved. Finally, we assessed the predictive ability of both models when confined to younger subjects (ages 25-35). Results: The clinical model, combining conventional melanoma risk factors (Model A), yielded an area under the receiver operating characteristic curve (AUC) of 0.72 (95% CI 0.70 – 0.75). Incorporating outdoor UV, indoor UV, and MC1R genotype variables (Model B) increased the AUC to 0.75 (p=0.001, 0.72 – 0.77). Confining the analyses to younger subjects substantially increased the AUC of Model A to 0.78 (0.72 – 0.84) and Model B to 0.83 (p=0.007, 0.78-0.88). Conclusions: This preliminary risk model is the first in melanoma to demonstrate that the addition of genotypic data and indoor UV exposure results in a measurable increase in predictive ability when compared to models comprised only of clinical and outdoor UV exposure variables. The enhanced predictive ability of the model (AUC>0.80) when limited to younger individuals suggests the potential for developing tools to facilitate targeted screening and prevention strategies in melanoma.
Diagnosis of melanoma: Importance of comparative analysis and “ugly duckling” sign.
Authors: Grob Jean Jacques , Wazaefi Yanal , Bruneu Yvane , Gaudy-Marqueste Caroline , Monestier Sandrine , Thomas Luc , Avril Marie-Françoise , Triller Raoul , Pellacani Giovanni , Malvehy Joseph , Fertil Bernard 
Published: March 2020

8578 Background: “Ugly duckling” (UD) sign is widely admitted as a major sign for melanoma (MM) detection. UD is based on the concept of intra-individual comparative analysis, which has never been validated. It is assumed that, in a given individual, variability of nevi is limited and represented by a few similarity clusters (SC) grouping all nevi sharing the same pattern, and that a nevus is suspicious when it does not fit with the SCs of this individual (UD). Objective: To validate the concept of UD and SC. Methods: 9 international experts (dermatologists) and 9 novices (untrained individuals) were blindly tested, using digital images of the nevi at clinical and dermoscospic scale successively in 80 patients, (2,089 nevi and 7 MM). Concordance was assessed by kappa statistics for UDs, and B-cubed metrics for SCs. Results: At clinical scale, experts had a better concordance for UDs (kappa= 0.53, [0.33 - 0.87]) and SCs (B-cubed = 0.65, [0.55, 0.73]), than novices (0.31, [0.03, 0.51] and 0.56 [0.49, 0.64], respectively). Experts identified a mean number of 1 UD and 2.7 SCs per patient, and agreed on consensual UD and SCs, whatever their natural propensity to see a high or a low number of UDs and SCs: among the 254 nevi considered as UDs by at least 1 expert, 54 were considered as such by at least 5, and from them, 20 by all 9 experts. The 20 consensual UDs included all the MMs (7/7) (sensitivity for MM: 100%). At dermoscopic scale, concordance tended to be lower for SCs than at clinical scale. Conclusions: We demonstrated the limited variability of nevi patterns in each patient, the consistency in the recognition of UD, and its clinical relevance, supporting evidence that it is useful for experts and to a lesser degree to general population to spot the skin lesions with the highest probability of being MM.
Molecular profiling and comparative genomic hybridization analysis in human melanoma cell lines and identification of BRAF amplification in a PLX4032 acquired resistance cell line.
Authors: Von Euw Erika Maria , Dering Judy , Anderson Lee , Ginther Charles , Cheng Hsiao-Wang , Gong Ke-Wei , Konkankit Veerauo V , Finn Richard S. , Slamon Dennis J. 
Published: March 2020

8592 Background: Melanoma is the most aggressive form of skin cancer. Its management is evolving rapidly due to an improved understanding of the molecular heterogeneity and the development of effective, personalized targeted therapies. PLX4032 is a BRAF inhibitor that induces tumor response in patients with BRAF mutation whose response is limited due to acquired resistance. We used comprehensive microarray and genomic analysis to molecularly characterize a panel of melanoma cell lines with the goal of identifying new molecular subgroups. To better understand the mechanisms of acquired resistance to PLX4032, we included two cell lines that were conditioned in vitro to acquire resistance. Methods: Using microarray, we studied 52 melanoma cell lines for mRNA expression and performed array CGH using genome microarrays. Data analysis was done using Rosetta Resolver and Agilent Analytics 4.0 software. Results: Microarray analysis suggests melanoma is comprised of at least two distinct molecular groups. One group has a differentiated melanocyte phenotype and the other has an expression signature characteristic of progenitor-like cells. The progenitor-like group expresses SOX9, WNT5A and WNT5B and also has the lowest relative expression of MITF. The most differentiated group had the highest MITF and SOX5 levels, while the progenitor-like cell lines have decreased expression. MITF appears to be a strong candidate marker for this group. Positive correlation exists between MITF expression levels and gene copy number, as almost all of the MITF samples amplified by CHG analysis are also overexpressed. A third group shows strong expression of SOX5, SOX10 and Nestin. One of the most important findings is M14-R cell line, conditioned to acquire PLX4032 resistance, has a focal, high level amplification of BRAF (Log2 ratio = 3, 8-fold amplification) when compared with the parental cell line, which is extremely sensitive to PLX4032. Conclusions: These results afford new insight into the potential pathogenesis and classification and provide a greater understanding of melanoma. BRAF amplification could be a novel mechanism of resistance to PLX4032.
Parenteral hydration (PH) in advanced cancer patients: A multi-center, double-blind, placebo-controlled randomized trial.
Authors: Dalal Shalini , Hui David , Torres-Vigil Isabel , Palmer J. Lynn , Allo Julio , Frisbee-Hume Susan , Tarleton Kenneth , Bruera Eduardo 
Published: March 2020

9025 Background: The vast majority of cancer patients at the end of life receive PH in hospitals and no PH in hospice. There is limited evidence supporting either practice. Our preliminary study suggested that PH (1L/day) improved dehydration symptoms (Bruera et al. JCO 2005). In this randomized controlled trial, we determined the effect of PH on symptoms associated with dehydration, quality of life and survival for patients with advanced cancer. Methods: We randomly assigned 129 cancer patients from 6 hospices to receive subcutaneous PH (normal saline 1 L/day) or placebo (normal saline 100 mL/day) daily over 4 hours. The primary outcome was change in the sum of 4 dehydration symptoms (fatigue, myoclonus, sedation and hallucinations, 0=best and 40=worst possible) between day 4 and baseline. Secondary outcomes included Edmonton Symptom Assessment Scale (ESAS), Memorial delirium assessment scale [MDAS], Nursing delirium screening scale [NuDESC], unified myoclonus rating scale [UMRS], FACIT-F, creatinine, urea, and overall survival. Intention-to-treat analysis was conducted to examine the change in each variable between baseline and day 4 or day 7. Log rank test was used for survival analysis. Results: Mean age was 67 (range 43-92), female 61%, Caucasians 60%, gastrointestinal, genitourinary and lung cancers 70%, performance status 3-4 113 (88%), with no baseline differences between the hydration (N=63) and placebo (N=66) groups. No significant differences were found between the hydration and placebo groups for the sum of 4 dehydration symptoms (-3.3 v. -2.8, p=0.77), ESAS (all non-significant), MDAS (1 vs. 3.5, p=0.084), NuDESC (0 v. 0, p=0.13) and UMRS (0 vs. 0, p=0.54). We also did not identify any group differences for day 7, except for a decrease in urea level in the hydration group (-2 vs. 2, P=0.02). Median overall survival was 21 days for PH and 15 days for placebo (p=0.83). Conclusions: PH at 1 L/day did not improve symptoms, quality of life or survival compared to placebo. Further studies are required to determine if any subgroups would benefit from PH.
Association of screening for psychosocial distress in patients with newly diagnosed stage IV NSCLC and survival.
Authors: Pirl William F. , Greer Joseph A. , Gallagher Emily R. , Temel Jennifer S. , Traeger Lara , Lennes Inga Tolin 
Published: March 2020

9030 Background: While screening for psychosocial distress has become an ASCO QOPI indicator of quality cancer care, data has yet to show an association with improved cancer outcomes. We examined the relationship between adherence to the QOPI measure for assessment of emotional well-being and survival in a sample of patients with newly diagnosed stage IV NSCLC. Methods: From 8/07 to 9/10, we recruited consecutive new patients in a multidisciplinary thoracic oncology clinic to participate in a research database for which patients completed self-report instruments for depression (PHQ-9) and anxiety (GAD-7) at their first oncology visit. We then performed a QOPI chart audit for patients with stage IV NSCLC who received care at our institution. To adhere to the QOPI measure, oncologists were required to document their own assessment of patient emotional well-being (without access to patient self-report data) within one month of the first office visit. Survival was calculated from first oncology visit to death. Cox proportional hazards models were used to test associations with survival. Results: 243 patients completed baseline assessments and had follow up. Emotional well-being was assessed in 90 (37%). Median survival of those with an emotional assessment was 12 months vs. 10 months for those without (p=.03). Yet, emotional assessment was associated with younger age (p=.01) and higher depression (p=.05) and anxiety scores (p=.03). Controlling for age, sex, performance status, smoking, primary oncology provider, PHQ-9, and GAD-7, having an assessment of emotional well-being was associated with improved survival (HR .68, 95% CI .49-.93, p=.02). Although higher PHQ-9 scores were independently associated with worse survival (HR 1.05, 95% CI 1.02-1.08, p=.004), neither depression nor anxiety moderated the relationship between clinician screening and survival. Conclusions: In this large prospective study of patients with newly diagnosed stage IV NSCLC, adherence to the QOPI measure for assessment of emotional well-being was associated with a survival benefit. This benefit appears to extend to all patients, not just those with depression and anxiety. Randomized trials are needed to confirm these findings.
Difficult conversations with terminal patients: Palliative care and death at home.
Authors: Morgenfeld Eduardo L. , Martin Reinas Gaston , Gercovich Daniela , Gil Deza Ernesto , Rivarola Edgardo G. J. , Gercovich Felipe G. 
Published: March 2020

9038 Background: More than half the total number of oncological patients may die due to the disease’s progression, and at some point in time the oncologist must communicate that the disease is terminal. This is the hardest conversation (HC) of a clinical oncologist. The following paper’s objective is to determine whether or not the treatments applied to patients, and their evolution, are affected by having had the HC. Methods: All patients who died due to progression of the disease in 2011 were selected for this study. Both medical histories and applied treatments were evaluated. All doctors were interviewed to establish when the HC had taken place. The distribution of variables was analyzed and both populations compared. Results: Between January 2011 and December 2011, 110 patients who met the previous criteria were studied. Population characteristics: Sex (Female: 52 pts; Male: 58 pts). Median age at the time of death: 61 years (Range: 27-88). Patients were divided in two groups: A (terminal status of the disease had been discussed; 70 pts) and B (terminal status of the disease had not been discussed; 40 pts). Both groups were similar in diagnosis, age and previous treatments. During the post HC evolution, three elements were categorized according to the table below. Conclusions: 1 – The conviction, ethical sense and strength of will of the doctor are determining factors when related to his or her capacity to talk with the patient about the terminal aspect of the disease. 2 – The chemotherapy treatments applied during the last two months of life are similar in both groups. 3 – The percentage of patients that died at their homes under palliative care was remarkably higher amongst those who had been informed than those who had not been informed. [Table: see text]