bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of BRAF and NRAS mutation status with tumor characteristics and treatment outcomes in melanoma patients with brain metastasis.
Authors: Koay Eugene Jon , Bucheit Amanda Dawn , Jakob John Andrew , Hyun Eric D. , Settle Stephen H , Brown Paul D. , Davies Michael A. , Sulman Erik P. 
Published: March 2020

8584 Background: The management of melanoma has evolved rapidly with the identification of activating mutations in the majority of patients (pts). We reviewed characteristics and outcomes of molecularly characterized melanoma pts with brain metastasis (BM) to help design and interpret future clinical trials. Methods: We reviewed clinical and pathologic features of melanoma pts with known BRAF and NRAS mutation status and BM. Pt demographics, intra- (IC) and extra-cranial (EC) tumor characteristics, and IC/EC disease treatments were correlated to BM treatment outcomes (local and distant brain control [LC, DC]) and overall survival (OS). Univariate and multivariate analyses were performed to identify significant associations between mutation status and outcome. Results: We identified 296 pts with melanoma BM and known BRAF/NRAS mutation status diagnosed from 2005 to 2011. Mutation prevalence was BRAF 57%, NRAS 17%, and wild-type for both genes (WT) 26%. The initial treatments given for BM were surgery/radiosurgery (SRS) 60%, surgery/SRS + whole brain radiation (WBRT) 7%, WBRT alone 19%, systemic therapy alone 9%, and no treatment 5%. Mutation status was not significantly associated with sex, performance status, EC disease status, number of brain lesions, or BM treatment. Pts with mutations were younger (p<0.0001) and more likely to have symptomatic BM (p=0.0003) than WT pts. In univariate analysis, BM treatment strategy (p<0.001) and mutation status predicted for poor LC, with 6 month LC rates of 70% for any mutation and 88% for WT (HR=1.86, p=0.048). Compared to systemic agents alone, use of radiation (SRS or WBRT) improved LC for pts with a mutation (HR 0.23, p=0.0006). Subsequent multivariate analysis identified mutation status and radiation treatment as independent predictors of LC (HR 2.5 and 0.25, respectively). Mutation status did not predict for DC or OS. Conclusions: The presence of BRAF and NRAS mutations predicts worse LC following conventional treatments for melanoma BM. Radiation may improve LC in pts with a mutation. This data suggest a role for combining radiation with targeted therapies in melanoma pts with activating BRAF or NRAS mutations in the treatment of BM.
KIT, NRAS, BRAF, and PTEN alterations in acral lentiginous melanomas.
Authors: Zebary Abdlsattar , Omholt Katarina , Hoiom Veronica , Johansson Carolina , Linden Diana , Vassilaki Ismini , Hansson Johan 
Published: March 2020

8588 Background: Acral lentiginous melanoma (ALM) accounts for ~5% of all melanomas. ALMs are often located on palms, soles and under nails. Patients with ALM are significantly older at diagnosis and have a poorer prognosis than patients with other types of cutaneous melanoma. We analyzed a large series of ALMs from Swedish patients to better define the frequency of KIT, BRAF, NRAS, and PTEN mutations in ALM. The effect of mutation status on tumor and patients characteristics was also studied. Methods: A total of 77 primary ALMs and 8 paired metastases were analyzed. Laser capture microdissection was used to dissect tumor cells from formalin-fixed paraffin-embedded tissue. Tumors were screened for mutations in the KIT (exons 11, 13, 17 and 18), NRAS (exons 1 and 2), BRAF (exons 11 and 15) and PTEN (exons 1, 3-6, 10, 11 and 12) genes by direct sequencing. Results: There were 42 females and 35 males with a median age at diagnosis of 71 years. The most common location was the feet (60.5%), followed by subungual sites (34.2%). Overall, mutations in KIT, NRAS and BRAF were detected in 11.8%, 14.5% and 16.0% of the ALMs, respectively. In no case were KIT, NRAS and BRAF mutations detected in the same tumor. For 8 primary ALMs the corresponding metastases were available for analysis. In five metastases the same KIT (n=3) or BRAF (n=2) mutation was detected as in the primary ALMs, suggesting that the KIT and BRAF mutations had occurred before metastasis. BRAF and NRAS mutations were significantly more common in females (P=0.044). ALMs with NRAS and BRAF mutations were more commonly located on the feet compared with KIT mutated ALMs which were more frequent on subungual sites (P=0.041). Other clinicopathological features such as age at diagnosis, thickness, ulceration, histological subtype and Clark’s level showed no significant correlation with the mutation status. A subset of 25 tumors was evaluated for mutations in the PTEN tumor suppressor gene. One tumor was found to carry a nonsense mutation (W111X). To our knowledge, this is the first description of a PTEN mutation in ALM. Conclusions: Our results confirm the presence of KIT, NRAS and BRAF mutations in ALM. KIT, NRAS and BRAF mutation status associated significantly with anatomical site. PTEN mutations seem to be rare in ALMs.
TILs in metastatic melanoma tumors: A biomarker for immunotherapy?
Authors: Chandra Sunandana , Ding Yi , Ma Michelle W. , Bannan Michael , Darvishian Farbod , Berman Russell S. , Shapiro Richard , Krogsgaard Michelle , Osman Iman , Pavlick Anna C. 
Published: March 2020

8589 Background: Increased tumor infiltrating lymphocytes (TILs) in primary (P) and locoregional melanoma tissue correlate with improved clinical outcome. Our recent data have suggested that matrix metalloproteinase 23 (MMP 23) expression (exp) in P result in lower prevalence of TILs and correlate with poor clinical outcome. On this basis, we examined P and metastatic (M) melanoma tissues to assess for concordance between the presence of TILs, MMP 23 protein levels and clinical response(resp) to anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) therapy (tx). Methods: 21 melanoma patients (pts) with M specimens were analyzed. 17 matched P specimens were also evaluated. Immunohistochemical (IHC) staining for TILs of the pre-anti-CTLA4 specimens were conducted and confirmed by 2 pathologists. IHC TILs were graded- 2+: >10% TILs present in multiple foci in both peri- and through the tumor; 1+: 1-10% TILs present in one or more foci in the tumor and predominantly peri-tumor; 0: no TILs were present or if the lymphocytes did not infiltrate the tumor. TILs in P and M were analyzed for concordance and potential for predictability of resp to anti-CTLA4 tx. Staining to identify lymphocyte subtypes and MMP 23 exp in M is being completed. Results: 20 pts received anti-CTLA4 tx. M analysis- 6 pts with 0 TILs in M (5 no response [NR], 1 partial response[PR]); 8 pts with 1-2+ TILs in M (1 complete response [CR], 5 PR, 2 progressive disease [PD]); 6 pts with 2+ TILs in M ( 3 CR, 2 PR, 1PD). 1 pt with 2+ TILs in M resected, no tx and 4 years disease free. TILs present in 13 P, absent in 4 P and not evaluable in 4 pts with unknown P melanoma. MMP 23 protein scores in P (range 2-4) correlated with melanoma recurrence. MMP 23 exp in M will be reported. Conclusions: TILs in P do not appear to correlate with TILs in M or predict for resp to anti-CTLA4 tx. TILs in M may be an indicator of responsiveness to anti-CTLA4 tx. Identification of the type of M TIL subsets may further refine tx recommendations.
Patterns of care in adjuvant systemic therapy of patients with stage III melanoma: A U.S. population-based study.
Authors: Hu Boyu , Koon Henry B. , Kim Julian 
Published: March 2020

8595 Background: Use of adjuvant systemic therapy in patients with stage III melanoma is widely known to be variable based upon multiple factors such as patient age and comorbidities as well as the preference and even geographic location of the oncologist and patient. The purpose of this study was to compare the use of adjuvant therapy among patients treated in teaching hospitals and community hospitals. Methods: The study population consisted of patients with stage III melanoma enrolled into the National Cancer Database (NCDB) between 2000-2008. Patients were selected based upon surgery as the first course of therapy which resulted in a total of 27,353 eligible for analysis. The study population was then categorized into those who were treated at Teaching Hospitals (TH) including National Cancer Institute-designated cancer centers or Community Hospitals (CH). Multiple variables including age, median household income, insurance status, race and overall survival were compared between patients in the two hospital groups. Results: The overall proportion of stage III patients who received adjuvant systemic therapy was approximately 30%. There was no difference in the proportion of patients receiving adjuvant systemic therapy between patients treated in TH as compared to CH, and there was no obvious trend towards increased use over time. Of interest was that the cohort of patients designated as being treated at TH had a higher proportion of patients less than 70 years old as compared to CH. Median household income was found to be higher in patients treated at TH. Finally, despite the observation that the proportion of patients who received adjuvant therapy was not different, there a significantly higher 5-year overall survival in patients treated at TH as compared to CH. Conclusions: Although the proportion of patients who received adjuvant systemic therapy was comparable in TH and CH, there was a significant increase in 5-year overall survival within TH. Additional factors such as age, lesser comorbidities, more favorable socioeconomic factors or other unmeasured factors such as type of adjuvant therapy or whether adjuvant therapy was completed may have contributed to the improved survival in patients treated at TH.
Comparison of sun protection modalities in parents and children.
Authors: Mortier Laurent , Saiag Philippe , Robert Caroline , Sassolas Bruno , Lhomel Christine , Lebbe Celeste , Grange Florent 
Published: March 2020

8601 Background: Routine sun protection is recommended to prevent skin cancer. Our aims were to examine and compare, in an observational survey, modalities of sun protection in parents and their children. Methods: This French nationwide observational survey, EDIFICE melanoma, was conducted through phone interviews among a representative sample of 1502 subjects aged ≥ 18 years old, using the quota method. The survey took place shortly after summer, from 28 Sep 2011 to 20 Oct 2011. Results: 1502 subjects were interviewed. Among them 1067 reported that they were sun-exposed (SE) at least ten days per year, 748 were parents, and 319 had no children. Sun protection measures seemed well done both in “parents” and “nonparents” groups: 74% used clothing; 43% used sunscreen, which was regularly renewed in 57% of cases. Sun protection measures used by SE parents for SE children were superior, both qualitatively and quantitatively to those used for themselves, ie 50% of parents reported using clothing, sunglasses and hat for their children vs 23% for themselves. In 87% of cases, parents reported regular re-application of sunscreen for their children vs 44% for themselves. The sunscreen SPF (Sun Protection Factor) was significantly lower for parents than for their children. Such data are in accordance with Buller et al. (Oncol Nurs Forum 1995), but contrast with the findings of Riordan et al. (J Pediatr 2003) with children being significantly less likely to wear sunglasses and to adopt sun avoidance habits than their parents. Conclusions: Sun protection awareness seems globally satisfying in the French population, with no difference between adult parents and nonparents, and is similar to that reported in Germany (Gambicher JEADV 2010), but seems better than in the US (Buller et al. JAAD 2011). Furthermore, French parents use sun protective measures qualitatively and quantitatively more efficiently for their children than for themselves.
EXCAP exercise to improve fatigue, cardiopulmonary function, and strength: A phase II RCT among older prostate cancer patients receiving radiation and androgen deprivation therapy.
Authors: Mustian Karen Michelle , Sprod Lisa , Janelsins Michelle Christine , Peppone Luke Joseph , Mohile Supriya Gupta , Trevino Lara Anne , Gewandter Jennifer S. , Chandwani Kavita Dayal , Heckler Charles E , Morrow Gary R. 
Published: March 2020

9010 Background: Radiation therapy (RT) and androgen deprivation therapy (ADT) result in cancer-related fatigue (CRF), decreased cardiopulmonary function (CPF) and decreased strength. Research suggests exercise can improve CRF during RT and ADT, through physical conditioning responses that improve CPF and strength. We explored the influence of an individually-tailored, home-based exercise intervention (EXCAP), including progressive resistance and aerobic training, on CRF, CPF and strength. Methods: Older prostate cancer patients (N=58; mean age=67), receiving RT (47%) or ADT (53%), were randomized to 6 wks of EXCAP (7 days/wk) or standard care (RT or ADT with no exercise). CPF (VO2 max) was assessed via graded exercise testing (GXT) or a 6-minute walk test when GXT was contraindicated. Muscular strength was assessed using multiple repetition maximum testing (chest press and leg extension). CRF was assessed via valid self-report questionnaires (BFI, POMS-FI, MFSI). All assessments were pre- and post-intervention. Results: ANCOVAs, controlling for baseline, revealed significant differences between groups in mean levels of CRF on the BFI and POMS-FI (all p<0.05), and a trend toward differences on the MFSI (p<0.10) with significant baseline interactions (all p<0.05) post-intervention: exercisers decreased CRF while controls increased. ANCOVAs revealed a trend toward differences between groups in mean levels of CPF (VO2 max) and strength (all p<0.10): exercisers improved while controls declined in performance. Pearson correlations revealed significant inverse associations between changes in CRF (BFI) and CPF (p<0.05;r=-0.0.36), and CRF and strength (p<0.05;r=-0.0.31). MANOVA revealed that changes in CPF and strength significantly predicted changes in CRF (p<0.05, r=0.67) and accounted for 45% of the variance. Conclusions: Exercise improves CRF and these improvements may be mediated, in part, by improvements in CPF and strength. Future phase III RCTs with prostate cancer patients receiving RT and ADT are needed to confirm these relationships. Funding: DOD W81XWH-07-1-0341, NCI K07CA120025, NCI 1R25CA102618.
Prognostic factors of the loss of autonomy (LoA) in older patients with cancer receiving first-line chemotherapy.
Authors: Soubeyran Pierre-Louis , Fonck Marianne , Hoppenreys Laurent , Hoppe Stephanie , Bellera Carine , Blanc-Bisson Christele , Blanc Jean-Frédéric , Ceccaldi Joel , Mertens Cecile , Imbert Yves , Cany Laurent , Vogt Luc , Dauba Jérôme , Houede Nadine , Floquet Anne , Chomy François , Brouste Veronique , Ravaud Alain , Mathoulin-Pelissier Simone , Rainfray Muriel 
Published: March 2020

9012 Background: Actual data on prognostic geriatric factors of health outcomes are lacking. We aimed to examine whether a decrease in autonomy for activities of daily living (ADL) after a first cycle of chemotherapy influences elderly cancer pts prognosis, and to determine prognostic factors of this LoA from a range of biological and geriatric evaluation factors. Methods: Pts> 70 years receiving 1st-line chemotherapy for a range of cancers were included in this multicentre prospective study. A LoA was defined as a decrease of 0.5 or more points on the ADL scale between the beginning of treatment and the 2nd cycle (ADL scored 6 to 0). The association between a LoA and OS was examined and prognostic factors were sought from the pre-treatment Geriatric Assessment data (CIRS-G, IADL, MNA, MMSE, GDS et Get up and Go) and from baseline biological and clinical information (age, sex, tumor extension and localization, performance status, BMI, weight loss, albumin, CRP, haemoglobin levels, leucocyte and platelet count, creatinine clearance). Pts completely dependent at baseline (ADL score 0) were excluded as a LoA was not possible. Results: Among 364 pts included, 299 pts were evaluable and 50 experienced a LoA. A LoA was significantly associated with an increased risk of death (RR 1.518, 95%CI[1.079-2.135]). Biological and clinical factors were not associated with LoA but pre-treatment low GDS15, dependencies on the IADL, low MMS, slow Get Up and Go, low ECOG-PS and poor MNA were found to be prognostic of a LoA in univariate analyses. In the multivariate model, low GDS (OR 2.4, p=0.01, 95%CI [1.23-4.66]) and dependencies on the IADL (OR 3.0, p= 0.027, 95%CI = [1.13-9.09]) were independently associated with an increased risk of LoA. Conclusions: Our study underlines the close link between LoA during treatment and poorer prognosis of elderly pts with cancer. Pts with a pre-treatment low GDS15 and IADL-dependent were the most likely to experience LoA after the 1st chemotherapy cycle. This research suggests that the GDS15 and IADL should be included as part of any screening for elderly pts before treatment.
Rates and risks of suicidality in young adults (YAs) with advanced cancer.
Authors: Trevino Kelly Marie , Fasciano Karen , Prigerson Holly Gwen 
Published: March 2020

9015 Background: Suicide rates in YA cancer patients are higher than in the general population. Although cancer is associated with a four-fold increase in the likelihood of a suicide attempt, little is known about suicidality in YAs with cancer. This study examined rates and clinical risk factors associated with suicidality in a sample of YAs with advanced cancer. Methods: Structured interviews were conducted between 4/2010 and 9/2011 with 70 YA advanced cancer patients (range 20-40 yrs, M=33.97, SD=5.61) receiving care at the Dana-Farber Cancer Institute. Validated measures assessed suicidality (i.e., Yale Evaluation of Suicidality), quality of life, major depressive disorder, grief over cancer-related losses, and social support. Scores on the suicidality measure were dichotomized into positive screen = 1 and negative screen = 0. Chi-square, t-test, and logistic regression analyses evaluated the relationship between suicidality and participant characteristics and psychosocial variables, controlling for confounding variables. Results: Over one-fifth (21.4%) of the sample screened positive for suicidality. Female gender χ2(1, N = 70) = 4.95, p = .026), breast compared with other cancer diagnosis χ2(1, N = 70) = 5.66, p = .017), and better performance status (t(68) = 3.13, p < .01) were associated with lower rates of suicidality. Participants who met criteria for current (OR [95% CI] 8.67 [1.78, 42.22]) or lifetime major depressive disorder (5.38 [1.60, 18.12]) endorsed higher rates of suicidality. Better overall (.97 [.94, .99]), psychological (.93 [.87, .94]), and existential quality of life (.91 [.85, .98]) were associated with reduced suicidality risk. More severe grief was associated with greater risk (1.15 [1.04, 1.28]) whereas greater social support was associated with lower suicidality risk (.85 [.74, .97]). Conclusions: YAs with advanced cancer reported higher rates of suicidality than observed in other age groups. Developmentally targeted interventions that promote physical function, effectively treat depression, improve quality of life and reduce grief, and provide opportunities for social support may reduce rates of and risk for suicidality in this population.
Patterns of antidepressant use in cancer patients (pts): An analysis from SOAPP (ECOG E2Z02: Symptom Outcomes and Practice Patterns).
Authors: Manola Judith , Zhao Fengmin , Miller Andrew H. , Pirl William F. , Wagner Lynne I. , Fisch Michael 
Published: March 2020

9016 Background: Antidepressant (AD) use is common in outpatient oncology, but the pattern and determinants of prescribing for commonly used AD are unknown. Methods: 3106 pts with cancer of the breast, prostate, colon/rectum, or lung were enrolled from multiple sites in a study of symptoms. Five depression case-finding methods were explored : 3 based on MDASI items reported by patients (1) sadness/ depression>=4, (2) distress>=4, (3) interference with mood>=7 or enjoyment>=7; 2 based on clinician’s report (4) presence of psychological distress, (5) depression being listed as one of top 3 symptoms. AD use (excluding tricyclic antidepressants and psychostimulants) was examined by depression status. Logistic regression models were used to examine the effect of demographic and clinical characteristics on AD use. Results: Rates of depressive symptoms varied by casefinding method (1=29%, 2=28%, 3=14%, 4=24%, 5=11%); 47% (1457) pts were defined as having depressive symptoms by at least one method. AD were prescribed in 25% of depressed pts compared to 14% of non-depressed pts. After adjusting for other covariates, factors associated with greater use of AD included depression (OR=1.7, P<0.01), family history of depression (OR=2.2, P<0.01), female sex (OR=1.8, P<0.01), younger age (OR=1.2, P=0.04), non-Hispanic White race (OR=2.0, P<0.01), prior chemo/immune/ hormonal treatment (OR=1.5, P<0.01), more concurrent medication use (OR=3.3, P<0.01), anxiolytics use (OR=2.0, P<0.01), sedative use (OR=2.1, P<0.01), receiving counseling (OR=1.6, P=0.04), patient’s perception of poor QOL (OR=1.3, P=0.02), duration of current treatment >1 year (OR=1.6, P<0.01), and being enrolled by a CCOP (OR=1.8, P=0.01). These significant associations remained regardless of the case-finding method used for depression, with only slight changes in the magnitude of ORs. Conclusions: Depressive symptoms are common in outpatients with cancer. One-fourth of solid tumor pts with depressive symptoms are taking an AD. Antidepressant prescribing varies by type of institution, race/ethnicity, age, concomitant medication exposure and several other clinical factors.