bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation of the DNA damage gene signature to predict for better outcome in malignant melanoma.
Authors: Iddawela Mahesh Y. , Azad Arun , Risbridger Gail 
Published: September 2018

e21036 Background: DNA damage response is a fundamental cellular pathway with an important role in maintaining genomic integrity. As Malignant Melanoma (MM) is associated with high mutation rates, and we postulated that mm is likely to have abnormal DNA repair pathway aberrations that could have prognostic and/or therapeutic significance. Methods: We conducted an unbiased assessment of genes involved in the DNA damage response through a comprehensive survey of established public data repositories and published literature and abstracts in all cancers. This survey was used to generate a 6-gene DNA Damage Signature (DDS). The DDS was then applied to 287 mm samples in The Cancer Genome Atlas. Results: The DDS was altered in 25% (72/287) of patients with mutations being present in all 6 genes including ATM (6%), TP53BP1 (7%), MDC1 (7%), BRCA1 (5%), PRKDC (8%) and RAD50 (1.4%). The DDS was more commonly altered in mm harboring alterations in BRAF (78%, 112/143), NRAS (89%, 73/82) or NF1 (75%, 5/20) than in triple wild type tumors (60%,19/32). The correlation between alteration in BRAF/NRAS/NF1 and DDS (p = 0.02) reached significance, as did the tendency for DDS and NF1 altered subtype to co-occur (p < 0.05). Importantly, alteration in the DDS was associated with significantly longer disease free (88 vs. 44 months, p = 0.02) and overall survival (152 vs. 66 months, P = 0.02). The mutations in ATM and BRCA1, shown to be targets in other cancers for PARP inhibition were seen in these patients as well as other oncogenic or hot-spot mutations. Conclusions: The improved survival associated with alteration of the DDS implicate DNA damage response signaling as favorably modulating the immune system, and propose a possible role for PARP inhibition as a therapeutic strategy in melanoma.
Prognostic relevance of neutrophil to lymphocyte ratio (NLR) before anti-PD1 therapy in metastatic melanoma patients.
Authors: Araujo Daniel Vilarim , de Moraes Rafael Vanin , Ramos Sousa Victor Aurelio , Donadio Mauro Daniel Spina , Fares Aline Fusco , Freitas Helano C. , Lima Vladmir C. , Barros Milton Jose 
Published: September 2018

e21045 Background: Biomarkers to select the patients most likely to benefit from checkpoint inhibitors are urged. NLR is a simple way of measuring systemic inflammation and is an independent predictor of survival before Anti-CTLA4 therapy. We hypothesized if NLR is also a predictor of survival before Anti-PD1 therapy. Methods: We performed a retrospective review of the medical records of all consecutive metastatic melanoma patients who received Nivolumab treatment from January/2014 – February/2017, including 53 patients prospectively collected from an Expanded Access Program. Of 86 patients, 83 patients were included for demographic and efficacy analysis, and 74 had information about baseline pre-treatment NLR. We analyzed NLR as a continuous variable and categorised ≥ 5 vs. < 5. Kaplan-Meier method was used for survival analysis. Long-rank test compared categories and Cox proportional hazards regression model was used to assess the prognostic significance of baseline NLR in univariate and multivariable analysis. Results: Median PFS for the entire population was 6,407 months (3,28 – 9,52) and median OS was not reached (NR) with a median FU of 10,74 months. The median NLR ratio was 3,11 (0,87 – 19). 18 patients (24,3%) had a ≥ 5 NLR vs. 56 (75,7%) < 5. Median PFS for NLR ≥ 5 was: 2,3 (1,75 – 2,84) vs. 12,02 (5,11 – 18,93) for < 5 (HR = 3,11; IC95% 1,52 – 6,27; p = 0,001). Median OS ≥ 5: 3,05 (2,06 – 4,04) vs. NR for < 5 (HR = 5,88; IC95% 2,60 – 13,29; p = 0,001). NLR categorised remained statistically significant in multivariate analysis for PFS and NLR as a continuous variable remained statistically significant for both PFS and OS in multivariate analysis (Table 1). Conclusions: Baseline NLR is a rapid, simple, and cost-free predictor of survival before Anti-PD1 therapy. These results should be validated in a larger cohort of patients. [Table: see text]
Different patterns of non immediate allergic reaction to BRAF inhibitor in two patients with metastatic melanoma.
Authors: Berciano-Guerrero Miguel-Angel , Lavado Rocío , Montesa Álvaro , Alvarez Martina , Santonja Angela , de Luque Vanessa , Robles Cynthia , Gómez Marta , Alonso-Carrión Lorenzo , Salas María 
Published: September 2018

e21052 Background: Non immediate allergic reactions (niAR) related with oncology drugs are a rare entity. Usually, it is called Drug Reaction with eosinophilia and sistemic symptoms (“DRESS”), occurring at first ten days of treatment.Recently, the treatment of metastatic melanoma (MM) has included new drugs in patients wtih BRAF V600E mutation. Despite skin reactions are usual, niAR to these drugs have not been reported. We present 2 clinical cases with mm treated with BRAFi, developing such niAR. Methods: Patient 1: 47yo female with lymph node relapse and multiple subcutaneous skin metastases (previously pT1N0M0 melanoma) that received nivolumab in adjuvant setting. BRAF-mutated. She starts with Vemurafenib-Cobimetinib (V-C). At 8 days, niAR (maculo-papular exantema G4, fever G2). After discontinuation of this treatment (3 weeks), it is changed to Dabrafenib(50%)-Trametinib (D-T). With only 1 dose, skin niAR (G3) is newly developed. Biopsy are taken at the beginning (T0), during (T1) and after desentizitation (T2). Patient 2: 60 yo female, lung and lymph node relapse of melanoma (previously pT2bN0M0) after IFN-alpha adjuvant 2 years before. BRAF-mutated. Start with V-C. At 9 days, skin niAR (G4), with fever (G1). Discontinuation of treatment. Biopsys and blood test are taken (T0, T1 and T2). Gene expression was performed with PanCancer Immune Profiling Panel Nanostring™ in this points. Results: Different lymphocytic subpopulations in blood and biopsy at acute phase are showed in table 1. Immune gene expression profiling found decreased expression of 5 genes: UBC, IL8, IL32, NFKB1A and FOS, increasing IFNGR1 (pt 1). In both of pts, desensitizitation protocol by Allergologists was made succesfully, with incremental oncology drugs and steroid reduction protocol. Both of pts had a maior partial response (RECIST), even the scarce of the drug received. Conclusions: D and V develop important “of class” skin niAR. Different immunologic patterns are related with this niAR. Previous exposition to IFN or anti-PD1 therapy might modulate such response. Immune gene expression profiling could be used as a method to identify biomarkers. Desensitization with BRAFi has enough efficacy and tolerance.
Natural killer cells as a predictive biomarker for response to anti-PD-1 therapy in patients with advanced solid tumors.
Authors: Tang Bixia , Chi Zhihong , Sheng Xinan , Si Lu , Cui Chuanliang , Kong Yan , Li Si Ming , Yan Xieqiao , Mao Li Li , Lian Bin , Bai Xue , Wang Xuan , Zhou Li , Li Dan , Yu Jiayi , Guo Jun 
Published: September 2018

e21055 Background: Assessment of PD-L1 expression in tumor biopsy has been widely used for predicting anti-PD-1 therapy. Several factors, including tumor heterogeneity, false negative staining and unavailability of biopsy samples limit the application. Natural killer (NK) cells exert cytotoxicity against cancer cells. Therefore, we explored using NK cells percentage in peripheral blood (PB) as a biomarker to identify pts who are more likely to benefit from anti-PD-1 therapy. Methods: Pts treated with anti-PD-1 antibody (JS001) 1 mg/kg, 3mg/kg or 10mg/kg every 2 weeks in a Phase I clinical trial (ClinicalTrials.gov Identifier: NCT02836795) had PB collected at baseline and at time of radiographic evaluation performed every 8 wks. Disease status (shrinking stable disease, growing stable disease, partial response, complete response, or progressive disease) was characterized using RECIST v1.1 and immune-related response criteria. Frequencies of NK cells (CD3-CD16+CD56+) were measured by flow cytometry. Results: Thirty-six patients were enrolled in this trial, including 22 melanoma, 9 urothelial carcinoma and 5 renal cell carcinoma. As of 1/27/2017, median treatment duration: 3.92 months. Radiographic tumor evaluation has been performed in 32 pts: 1/32 CR, 6/32 PR, 6/ 32 shrinking SD, 4/32 growing SD and 15/32 PD. Pts with high NK cells at baseline observed 60% (6/10) Clinical Benefit Rate (CR/PR/ shrinking SD) versus 40% (13/32) in overall pts. Patients with clinical benefit had higher frequency of NK cells at baseline compared to pts with radiographic growing SD and PD (mean 24.3% vs. 17.9%, P = 0.076). Furthermore, pts with NK cell level consistently above UN or increasing above UN during treatment are more likely to get clinical benefit than those under UN (7/10 vs 3/22, P = 0.013). Conclusions: Baseline high NK cells frequency may predict a favorable response to anti-PD-1 therapy, which provides a non-invasive way to monitor response to PD-1 blockade. These results are being validated in a phase II trial. Clinical trial information: NCT02836795.
Immune checkpoint inhibition-related colitis: Correlation between ulcers and need for infliximab.
Authors: Geukes Foppen Marnix Heimen , Rozeman Elisa A. , van Wilpe Sandra , Postma Cindy , Snaebjornsson Petur , Van Thienen Johannes V. , van Leerdam Monique Esther , van den Heuvel Michel M , Blank Christian U. , van Dieren Jolanda , Haanen John B. A. G. 
Published: September 2018

e21062 Background: Immune checkpoint inhibition has improved survival of patients with several types of advanced cancer. With these new treatments previously unseen adverse events (AE) have become relevant. Considering the fact that most of these immune related AEs can be reversed when identified early and treated adequately, the need for updated algorithms is crucial. Colitis is one of the most severe AEs upon anti-CTLA-4 (e.g. ipilimumab) monotherapy or combination therapies. Severe colitis with deep ulcerations is associated with life-threatening complications such as perforation. Therefore, early recognition and treatment is warranted. Anti-TNF therapy (infliximab) can resolve colitis fast. We sought to identify endoscopic features that indicate the need for early treatment with infliximab. Methods: We retrospectively analyzed all patients who developed diarrhea upon checkpoint inhibition. Only patients undergoing endoscopy were included. All patients were treated at the NKI between August 2010 and March 2016 for either metastatic melanoma or non-small cell lung cancer. Results: A total of 89 patients underwent an endoscopy due to immune related diarrhea (irDiarrhea). Patients were treated with either monotherapy anti-CTLA-4, anti-PD-(L)1, a combination of both, or the combination of anti-CTLA-4 and radiofrequency ablation. Median age was 58 years (range 30-88) and 54% of patients were female. A colonoscopy was performed in 64 (72%) patients and a sigmoidoscopy in 25 (28%) patients. Ulcers were seen during 29 endoscopies (32%). In 18 endoscopies (20%) there were ≤ 10 ulcers and in 11 endoscopies (12%) > 10. Of all patients that had ulcers at endoscopy 23 (79%) required additional infliximab treatment for corticosteroid refractory colitis, while only 25 (42%) of patients without ulcers required additional infliximab ( p= 0.001). Conclusions: Patients with ulcerative irColitis require twice as often infliximab in addition to corticosteroids. Early treatment with infliximab may be indicated in ulcerative irColitis. Treatment based on endoscopic features makes colonoscopy an important diagnostic tool in irDiarrhea. Prospective analysis of endoscopy-driven management of irColitis is warranted.
In-hospital cardiac arrest among patients with malignancy.
Authors: Rosen Sheri , Eng Kevin , Yang Jenny , Tyagi Sanjeev , Odish Mazen , Sell Rebecca , Beitler Jeremy 
Published: September 2018

e21583 Background: Malignancy is generally considered a poor prognosticator for in-hospital cardiopulmonary arrest. Recent studies have shown that overall survival in those with localized disease and fewer than two comorbidities approximates the general population, likely reflective of advances in cancer treatment and more selective use of cardiopulmonary resuscitation. The present study was conducted to evaluate whether malignancy is an independent risk factor for death before discharge following in-hospital cardiopulmonary arrest. Methods: This single-center retrospective study included consecutive in-hospital cardiac arrests for whom cardiopulmonary resuscitation was attempted between 2011-2015. Patients were identified from an inpatient cardiac arrest registry and excluded if the arrest occurred in the operating room or emergency department prior to admission. Data related to each patient’s oncologic history was obtained via manual chart review by physician investigators. The primary outcome was survival to discharge among patients according to malignancy status. Results: Over the five-year study, 532 patients experienced in-hospital arrest and met inclusion criteria. Fifteen percent (n = 81) had a known cancer diagnosis at the time of arrest; 9% of arrests (n = 46) had a cancer that was considered active (not in remission). One-fourth of all cancer diagnoses at time of arrest were hematologic malignancies. Overall post-arrest survival to discharge was 34%. Survival did not differ significantly for patients with versus without current or prior malignancy (OR 0.69, 95% CI 0.41-1.18; p = 0.17), nor with active malignancy at time of arrest (OR 0.52; 95% CI 0.25-1.07; p = 0.08). The subgroup of patients with hematologic malignancy had significantly lower survival (OR 0.21, 95% CI 0.05-0.91; p = 0.04). Conclusions: Malignancy was not associated with decreased survival to hospital discharge among patients experiencing in-hospital arrest for whom resuscitation was attempted.
Phase II feasibility study of rekindle: An online psychosexual intervention for cancer survivors and/or their partners.
Authors: Lawsin Catalina Rosario , McGeechan Kevin , Williams Douglas O , Butow Phyllis , Juraskova Ilona , Hobbs Kim , Boyle Frances M. , Kay Judy , Miller Annie , Dhillon Haryana M. 
Published: September 2018

e21597 Background: Changes to sexual wellbeing can negatively impact long-term quality of life for cancer patients and their partners. Rekindle is an online intervention aimed to provide accessible and tailored psychosexual support to cancer survivors. This study aimed to assessed the feasibility of delivering psychosexual support via Rekindleto cancer survivors and partners who self-report unmet sexual concerns. Methods: This phase II feasibility study, recruited Australian adult cancer survivors who had completed primary therapy > 6 months earlier and/or their partners. Participants were randomized 1:2:1 ratio to either: i) wait list control (WC); ii) Rekindle (10-week online intervention addressing psychoeducational sexual communication and function) (Int); iii) Rekindle Plus ( Rekindleintervention plus three support telephone calls) (Int+). Intervention ran for 10 weeks, after which WC group had access to Int. Participants completed assessments at baseline (T1), intervention end/10 weeks (T2), and six months (T3). The primary feasibility endpoint was the proportion of participants completing prescribed intervention modules. Results: Nov 2015-Dec 2016, 100 participants were randomized: WC: 19, Int: 54, Int+: 27. Baseline characteristics were matched across groups. 57% were male and 91% cancer survivors; 46% had prostate and 23% breast cancer. Participants were prescribed a mean of 6.5 out of 7 modules based on self-reported unmet sexual needs. They completed mean of 1.9 (Int) and 2.5 (Int+) modules with 30% (Int) and 38% (Int+) completed within 10 weeks. A high proportion of users (94%, 100%) commenced Module 1 (Foundations). The largest drop-out between occurred between Modules 1 and 2. Once started, the majority of participants completed each module (76-100%). The mean number of days taken to complete each module varied (4-14 days). Factors impacting engagement with the intervention will also be reported. Conclusions: This phase II study has demonstrated: a need for psychosexual support amongst cancer survivors, that it is feasible to recruit them into an online sexual support study, and to deliver online psychoeducational content for sexual concerns. Clinical trial information: ACTRN12614001245684.
Measuring concordance with head and neck cancer survivorship algorithms.
Authors: Rodriguez Maria Alma , Palos Guadalupe R. , Gilmore Katherine Ramsey , Chapman Patricia , Lewis-Patterson Paula A. 
Published: September 2018

e21602 Background: We developed institutional algorithms for cancer survivors that are site specific. However, little data exists regarding concordance with these clinical management tools. Our aim was to evaluate concordance rates with our Head and Neck (H/N) survivorship algorithms. Methods: We reviewed electronic health records (EHR) of patients seen in the H/N Survivorship Clinic between 9/01/2011 and 8/31/2014. Eligibility included: diagnosis of primary head and neck cancer, ≥ 18 years of age, no active disease, and alive at time of abstraction. Data were collected at baseline (V1) and visits 9-15 months after prior visits (V2 and V3). Data were obtained from tumor registry, a departmental database and the EHR. Twelve data elements were grouped as: 1) lab/diagnostic tests, 2) physical and psychological late effects, and 3) history and physical exams. Concordance rate (%) for each element was defined as a clinical action or recommendation aligned to the standards outlined in the H/N algorithms. Descriptive statistics were used to summarize clinical, demographic, and concordance rates. Results: Included in this analysis were patients with primary H/N malignancies of oropharynx, oral cavity, larynx, and hypopharynx, and who had completed 3 visits (V1-3). 53 patients were evaluable for concordance analyses. Compliance ranged from 55% to 100%, with lowest rates for: CT scans (55.6%), distress screening (75.5%), T4/TSH level (78.4%) and laryngoscopy (79.2%). Highest rates were noted for full physical exam (100%), chest x-ray (97.5%), dental exam (95.9%), and dysphagia evaluation (95.1%). Assessments for lymphedema and xerostomia were similar (91.8%). Conclusions: High compliance ( > 90%) occurred when elements of the algorithm relied on the clinician’s assessment, whereas lower levels of compliance were seen with elements that required orders (CTs and labs), or reliance on others’ actions (i.e. distress screening by nursing). Concordance can be improved using best practice advisories in the EHR to remind providers of orders, and by fostering strong inter-professional communication on the elements of care.
Examination of factors that influence use of extended adjuvant endocrine therapy (ET).
Authors: Kadakia Kunal C. , Kidwell Kelley M. , Barton Debra L. , Griggs Jennifer J. , Henry Norah Lynn 
Published: September 2018

e21618 Background: Extending adjuvant ET from 5 to 10 years has been shown to improve outcomes; however, limited data are known about if and why women pursue extended ET. The primary objective was to estimate the proportion of women who were willing to receive extended ET and secondarily, to determine what factors were associated with this decision. Methods: 133 women on ET for 3-5 years who had not made a decision on extended ET completed a survey about willingness to continue ET, quality-of-life (Functional Assessment of Cancer Therapy-Endocrine Subscale [FACT-ES]), and beliefs about medicines (Beliefs about Medicines Questionnaire Specific [BMQ-S]). BMQ-S assesses patients need for a treatment (necessity beliefs) and concerns about its adverse effects (AEs). The primary outcome, responses to "If in meeting with your doctor, he or she recommends continuing hormonal therapy for longer than 5 years (up to 10 years), how willing ("Not at all" to "Extremely") would you be to continue taking your current hormonal therapy?" was analyzed descriptively. Logistic regression tested for associations between clinical factors (age, stage, chemotherapy), FACT-ES, BMQ-S, and the primary outcome. Results: Most women (112, 85%, 95% confidence interval, CI, 78-91%) were "Moderately" to "Extremely" likely to pursue extended ET. On univariate analysis, younger age (<49 vs ≥50), lower total and social well-being on FACT-ES, and lower necessity and higher concerns on BMQ-S were associated with less willingness to pursue extended ET. Neither stage nor prior chemotherapy was associated with this decision. On multivariable analysis, age and FACT-ES were not associated with this decision (odds ratio, OR 1.03, 95% CI 0.96-1.09, p=0.41; OR 1.01, 95% CI 0.98-1.05, p=0.49). Greater patient perception of necessity of ET compared to concern for AEs was the only independent factor associated with willingness to pursue extended ET (BMQ-S OR 1.34, 95% CI 1.15-1.57, p=0.0005). Conclusions: Most women are likely to purse extended ET if recommended by their physician. Patient decision-making appears to be largely influenced by beliefs of medicines rather than breast cancer-specific clinical factors and should be considered when counseling patients on extended ET.
Phase II study of efficacy of bevacizumab plus chemotherapy in management of malignant pleural effusion (MPE) in non-squamous non-small cell lung cancer (NSCLC) patients with MPE unsuccessfully controlled by tube drainage or pleurodesis (North East Japan Study Group Trial NEJ-013B-2).
Authors: Noro Rintaro , Kobayashi Kunihiko , Usuki Jiro , Hosomi Yukio , Nishitsuji Masaru , Okamoto Hiroaki , Hino Mitsunori , Hagiwara Koichi , Miyanaga Akihiko , Seike Masahiro , Kubota Kaoru , Gemma Akihiko 
Published: September 2018

e21660 Background: Prospective and retrospective studies on intrapleural therapy of malignant pleural effusion (MPE) have reported that the success rate for controlling pleural effusion was 50–70% at 2.5 months, and that the median post-pleurodesis survival time was 6-9 months. When pleurodesis is unsuccessful, and the lung is not fully expanded after drainage, the patients cannot receive effective chemotherapy. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of MPE. Here, a multicenter phase II trial was conducted to evaluate bevacizumab therapy in non-squamous non-small cell lung carcinoma patients with unsuccessful management of MPE. Methods: Non-squamous NSCLC patients with MPE who had received unsuccessful tube drainage or pleurodesis received chemotherapy with bevacizumab (15 mg/kg) every 3 weeks. The primary endpoint was Pleural effusion control rate (PECR), defined as the percentage of patients without reaccumulation of MPE for 8 weeks. The secondary endpoint was pleural Progression-free survival (PPFS), defined as PFS without reaccumulation of MPE. Results: Fifteen of 20 patients entered received a median of 4 cycles of carboplatin plus paclitaxel or pemetrexed including maintenance therapy with bevacizumab. The PECR was 80% of treated patients (95% CI: 78-82%). PPFS was 16.6 months (95% CI: 11.46-21.80 months). The response rate (RR) and disease control rate (DCR) were 45% (95% CI: 39.6-50.4%), and 80% (95% CI: 78.0-82.0 %), respectively, and the median PFS and overall survival (OS) were 9.8 months (95% CI: 4.38-15.28 months) and 19.6 months (95% CI: 4.38-15.28 months), respectively. Toxicities of grade ≥3 included neutropenia (50.0%), thrombocytopenia (10.0%), proteinuria (10.0%), hypertension (2.0%), pulmonary embolism (5%). Conclusions: The combination of bevacizumab with chemotherapy demonstrated efficacy with acceptable toxicities in controlling MPE in patients with non-squamous NSCLC whose MPE was unsuccessfully controlled by tube drainage or pleurodesis.