tbuckley/cabot-search huggingface dataset:
Correlation of MET complete status and outcome in patients with metastatic clear cell renal cell carcinoma (m-ccRCC) treated by sunitinib.
Authors: Solene-Florence Kammerer-Jacquet, Sarah Medane, Angelique Brunot, Benoit Peyronnet, Romain Mathieu, Gregory Verhoest, Karim Bensalah, Brigitte Laguerre, Pierre Kerbrat, Frantz Dupuis, Jean-Christophe Bernard, Mokrane Yacoub, Alain Ravaud, Frederic Dugay, Marc-Antoine Belaud-Rotureau, Nathalie Rioux-Leclercq
Journal: Journal of Clinical Oncology (2016)

e16079 Background: Clear cell renal cell carcinoma (ccRCC) are highly metastatic tumors. Anti-vascular growth epithelial factor (VEGF) therapies are currently used in first line of metastatic ccRCC but most patients develop resistance to these treatments. Cabozantinib, an inhibitor of tyrosine kinases including VEGFR, MET and AXL recently shows interesting results in second line treatment. Moreover, the HGF/MET signaling pathway implicated in angiogenesis may be responsible for resistance to anti-VEGF therapy. To better understand MET role in metastatic ccRCC and potential resistance, we assessed MET complete status in a well-characterized population of 90 patients with metastatic ccRCC treated by first line sunitinib therapy. Methods: For this purpose, we studied MET expression by immunohistochemistry (IHC), MET amplification by fluorescence in situ hybridization (FISH) on formalin-fixed paraffin-embeded (FFPE) samples and MET mutation by next generation sequencing (NGS) on frozen samples in their 90 primary tumors. MET status was then correlated to pathological criteria using Chi-squared test and clinical outcome using Kaplan Meier curves compared by log rank test. Results: 31.1% of ccRCCs had low expression of MET (absent to weak intensity by IHC) versus 68.9% with high expression (moderate to strong intensity). High expression of MET was associated with gain in FISH analyses (p = 0.0284) without amplification. No mutation was detected by NGS. High expression of MET was associated with lymph node invasion and sarcomatoid component (p = 0.004 and p = 0.029). No statistical differences were observed between the two groups of patients in terms of progression free survival and overall survival after sunitinib introduction (p = 0.72 and p = 0.93). Conclusions: This study is the first to analyze complete MET status in metastatic ccRCC treated by sunitinib. High expression of MET, although not associated with sunitinib resistance, may suggest a benefit from MET inhibitors.
Selective induction of PD-L1 expression in plasma-derived exosomes by gem-nab-paclitaxel vs. folfirinox in pancreas cancer.
Authors: Marzia Del Re, Caterina Vivaldi, Eleonora Rofi, Stefania Crucitta, Elena Arrigoni, Giulia Pasquini, Silvia Catanese, Irene Pecora, Gianna Musettini, Enrico Vasile, Alfredo Falcone, Romano Danesi
Journal: Journal of Clinical Oncology (2018)

e24128 Background: Pancreatic ductal adenocarcinoma (PDAC) is considered a poorly immunogenic tumor and treatment with immune checkpoint inhibitors lacks efficacy in this disease. Recently, the use of immune checkpoint inhibitors with radiation therapy in PDAC has demonstrated synergistic activity (1). The aim of this study was to evaluate the effect of FOLFIRINOX and GEMnPAC on PD-L1 expression in plasma-derived exosomes of PDAC patients. Methods: Four ml of plasma were obtained at baseline (before initiation of chemotherapy) and at the time of first radiological evaluation (3 months) from patients undergoing first-line FOLFIRINOX or GEMnPAC chemotherapy. Exosomes and RNA extraction from plasma were performed using the exoRNeasy kit (Qiagen, Valencia, CA, USA); PD-L1 expression was evaluated by digital droplet PCR (Bio-Rad, Hercules, CA, USA). Results: A total of 22 pancreatic cancer patients were enrolled in this study; 15 (68.2%) were treated with GEMnPAC and 7 (31.9%) with FOLFIRINOX. In the GEMnPAC group one patient had a partial response (RP), 11 patients had stabilization of disease (SD) and 3 progressed (PD). In the FOLFIRINOX group there were 1 RP, 5 SD and 1 PD. Eleven patients treated with GEMnPAC had a significant increase of PD-L1 expression at 3 months vs. baseline. Indeed, the mean PD-L1 copies/ml was 90 at baseline and 170 at 3 months (p = 0.02). On the contrary, in the FOLFIRINOX group, PD-L1 levels were increased in 3 patients and remained stable/decreased in 4 subjects; the mean baseline copies/ml were 70 vs. 80 at 3 months (p = 0.4). The selective induction of PD-L1 expression was independent from tumor response. Conclusions: These pilot data suggest that, due to its ability to increase PD-L1 expression, GEMnPAC regimen may be used as induction-treatment for immunotherapy in pancreatic cancer, either sequentially or concomitantly. References 1. Azad A, Yin Lim S, D'Costa Z, Jones K, Diana A, Sansom OJ, Kruger P, Liu S, McKenna WG, Dushek O, Muschel RJ, Fokas E. PD-L1 blockade enhances response of pancreatic ductal adenocarcinoma to radiotherapy. EMBO Mol Med 2017;9(2):167-180
Bridging the financial assistance gap: A pilot study of a patient-facing app to identify drug financial assistance programs.
Authors: Yousuf Zafar, Ian Manners, Jonathan Nicolla, Fred Friedman, Ben Gagosian, Kathryn I. Pollak
Journal: Journal of Clinical Oncology (2017)

e18296 Background: Many cancer patients face high treatment-related costs and are often unaware of available financial resources. We designed “Bridge” as a stand-alone, smartphone app to reduce out-of-pocket treatment costs by connecting patients to tailored financial assistance programs. The goal of this pilot study was to evaluate the usability and preliminary effectiveness of Bridge. Methods: Eligible cancer patients were receiving anti-cancer treatment, owned a smartphone, and reported out-of-pocket treatment-related costs. Patients interacted with Bridge, inputted personal and financial data, and reviewed personalized financial resource results. Usability was assessed via the validated System Usability Scale (SUS). To be usable, patients would have to score at least 68 on the SUS. Effectiveness was assessed by two measures: “Bridge improved my knowledge about financial aspects of cancer care and what can be done about it” (1 = strongly disagree to 5 = strongly agree) and “Using this tool was helpful with my financial concerns” (1 = strongly disagree to 5 = strongly agree). Results: We enrolled 30 patients. 63% were female, 23% were non-white, 66% had greater than high school education, 97% were insured (48% Medicare), and 23% were employed. Median annual household income was $60,796. All patients completed a full interaction with the app, with median time to results of 116 seconds. 72% of patients matched to at least one currently open program, with patients matching to a median of 4 financial assistance programs. 90% of patients reported an SUS score of usable (i.e., &gt; 68 out of 100). The median SUS score was 85. 83% of patients agreed or strongly agreed that “Bridge improved my knowledge about financial aspects of cancer care and what can be done about it.” 53% of patients agreed or strongly agreed that “Using this website was helpful with my financial concerns.” Conclusions: We found that patients rated Bridge as usable and acceptable. We also found that Bridge helped match most patients to relevant assistance programs and improved knowledge about financial aspects of cancer care. The next phase of this NCI-funded study will test the effectiveness of Bridge in a large, randomized, controlled trial.
Correction to: White paper: statement on conflicts of interest
Authors: Julian Bion, Massimo Antonelli, LLuis Blanch, J. Randall Curtis, Christiane Druml, Bin Du, Flavia R. Machado, Charles Gomersall, Christiane Hartog, Mitchell Levy, John Myburgh, Gordon Rubenfeld, Charles Sprung
Journal: Intensive Care Medicine (2018)
Prevalence and clinical correlates of vulnerable status using the Vulnerable Elders Survey 13 (VES-13) in newly diagnosed adult non-Hodgkin lymphoma (NHL) patients: A LEO cross-sectional analysis.
Authors: Angelo Fama, Peter Martin, Carla Casulo, Loretta J. Nastoupil, Carrie A. Thompson, Brian K. Link, Izidore S. Lossos, Brad Kahl, Matthew Maurer, Cristine Allmer, David L. Jaye, Andew L. Feldman, Susan L. Slager, Jonathan W. Friedberg, Thomas Matthew Habermann, Christopher Flowers, James Robert Cerhan
Journal: Journal of Clinical Oncology (2018)

10042 Background: The VES-13 is a self-reported tool designed to identify people at risk of functional decline and death. We evaluated the prevalence of vulnerable (VUL) status in newly diagnosed NHL patients, overall, and by age, gender and clinical features. Methods: We used pre-treatment data from 1194 NHL patients consented 7/2015 to 7/2017 into the Lymphoma Epidemiology of Outcomes (LEO) cohort study (NCT02736357). Patients with a VES-13 score ≥3 were classified as VUL. χ2 tests and unconditional logistic regression were used to identify correlates of VUL. Results: The median age was 62 years (range 18-94), 44% were ≥65 years, and 61% were male. Overall, 22% (268/1194) of the patients were classified as VUL, with a prevalence of 18% (117/666) for age < 65 years and 29% (151/528) for age ≥65 years. The prevalence of VUL status was higher in women vs men (26% vs 20%, p = 0.009), performance status ≥2 vs 0-1 (74% vs 19%, p < 0.0001), any B-symptoms (36% vs 19%, p < 0.0001), stage III-IV vs I-II (24% vs 20%, p = 0.11), ≥2 vs 0-1 comorbidities (41% vs 19%, p < 0.0001) and subtype (p = 0.0003, DLBCL 30%). All of these patterns were similar in analyses stratified on age 65 years. In a multivariable model, age (OR = 1.02 per year, 95% CI 1.01-1.04), female gender (OR = 1.6, 95% CI 1.2-2.2), PS ≥2 (OR = 8.1, 95% CI 4.5-14), B-symptoms (OR = 2.2, 95% CI 1.5-3.1), ≥2 comorbidities (OR = 2.5, 95% CI 1.7-3.8) and DLBCL subtype (OR = 2.0, 95% CI 1.3-3.1) were all predictors of VUL status. As physicians were unaware of the VES-13 score, we next evaluated VUL status by anthracycline (ATC) use as initial therapy (not accounting for dosing) in DLBCL cases. 89% of VUL patients (83/93) received an ATC compared to 90% of patients not classified as VUL (198/221; p = 0.93). Conclusions: Over 20% of newly diagnosed NHL patients were classified as VUL, including 18% < 65 years, highlighting the need for functional assessment of patients across a wider age spectrum. VUL status correlated with more adverse prognostic factors. The initial use of ATC not accounting for dosing/dose reduction in the treatment of DLBCL did not differ by VUL status. Future work will evaluate VES-13 with patient outcomes.
Enhanced bioreduction-responsive diselenide-based dimeric prodrug nanoparticles for triple negative breast cancer therapy
Authors: Xi He, Jinxiao Zhang, Chao Li, Yu Zhang, Yifei Lu, Yujie Zhang, Lisha Liu, Chunhui Ruan, Qinjun Chen, Xinli Chen, Qin Guo, Tao Sun, Jianjun Cheng, Chen Jiang
Journal: Theranostics (2018)

Efficient drug accumulation in tumor is essential for chemotherapy. We developed redox-responsive diselenide-based high-loading prodrug nanoparticles (NPs) for targeted triple negative breast cancer (TNBC) treatment.
TCT-272 Outcomes of Drug-Eluting versus Bare-Metal Stents in Saphenous Vein Graft Lesions: A Meta-Analysis of Randomized Controlled Trials
Authors: Toufik Mahfood Haddad, Aravdeep Jhand, Jai Parekh, Luay Sarsam, Abdul Saadi, Aiman Smer, Himanshu Agarwal, Michael Delcore, Venkata M. Alla
Journal: Journal of the American College of Cardiology (2018)
Correlation of tumor mutational burden and predicted functional impact of mutations across cancer types.
Authors: Jun Jia, Peng Zhang, Wenjin Liu, Shuo Mu, Gung-wei Chirn, Weifeng Wang, Kai Wang, Yu-An Dong
Journal: Journal of Clinical Oncology (2018)

e24296 Background: Tumor mutational burden (TMB) has emerged as a potent biomarker for cancer immunotherapy. A reflection of many competing on- and off- molecular switches, TMB has a clear rationale but complex mechanisms. In terms of protein structure and function, many mutations are harmless and tolerated, while others will disrupt protein folding altogether or severely impact its intended function. In this work, we seek to establish the link between the quantity (TMB) and quality (functional impact) of mutations across different cancer types. Methods: We downloaded publicly available TCGA datasets and computed TMB for all samples. For each cancer type, the median sample TMB was taken as the representative. Neo-antigen load (NAL) was also computed when applicable. For the assessment of functional impact of mutations, we used the prediction tool SIFT with recommended cutoff value of 0.03 (where mutations with scores of < = 0.03 are considered functional). For each cancer type, we considered all mutations within all tumor samples and computed the fraction of functional mutations (FFM). Results: There is strong correlation between TMB and NAL (on 12 cancer types where both data are available, r = 0.86, p < 0.01), validating the rationale behind TMB. However, there actually exists significant negative correlation between TMB and FFM (on 21 cancer types, r = -0.47, p = 0.03). In other words, as the number of mutations increase, relatively fewer have functional impact. In terms of cancer types, SKCM and DLBC exhibit high TMB but low FFM; while on the end of the spectrum, THCA, THYM, PRAD, and MESO have low TMB but high FFM. For cancers with similar TMB, there can be significant variation in FFM (e.g. TGCT vs MESO); conversely, cancers with large difference in TMB can have very similar FFM (e.g. BRCA and LUSC). Conclusions: All mutations are not the same. We established the link between the quantity and quality of tumor mutations for the first time. Surprisingly, cancer types with higher TMB tend to have lower FFM, which would mitigate the currently known TMB variability across cancer types. It remains to be seen whether TMB, adjusted by functional prediction, can better associate with other biomarkers and reveal new mechanistic insights.
Image Gallery: Hairy‐cell leukaemia presenting with Sweet syndrome
Authors: P.R. Shah, G. Scott, L.A. Beck
Journal: British Journal of Dermatology (2018)

Dear Editor, A 57-year-old man presented with a 1-month history of fevers, dermatitis and pancytopenia in the setting of a 14-lb weight loss, fatigue, night sweats and arthralgia. Skin examination revealed multiple erythematous papules on the (a) trunk and (b) extremities. Erythrocyte sedimentation rate and C-reactive protein were elevated (104 mm h−1 and 14·8 mg L−1, respectively). Work-up was negative for infection or autoimmune conditions. (c, d) Skin biopsy was notable for dense neutrophilia and dermal oedema, consistent with Sweet syndrome. Bone marrow biopsy and flow cytometry were consistent with hairy-cell leukaemia, which constitutes only 2% of all leukaemias.1 Treatment with cladribine and prednisone resulted in improved cell counts and resolution of the rarely observed hairy-cell leukaemia-associated Sweet syndrome.1, 2
Expression and clinical correlations of PRAME in sarcoma subtypes.
Authors: Jason Roszik, Wei-Lien Wang, Vinod Ravi, Patrick Hwu, Cassian Yee, Andrew Futreal, Alexander Lazar, Anthony Paul Conley
Journal: Journal of Clinical Oncology (2016)

11067 Background: PRAME (Preferentially Expressed Antigen In Melanoma), a member of the cancer-testis antigen family, has been shown to have increased expression in solid tumors, including sarcoma. PRAME-specific therapies are currently in development for other cancers.Methods: To map the landscape of PRAME expression in sarcoma, we used publicly available data from the Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE) and determined which sarcoma subtypes have increased PRAME expression. We also analyzed how PRAME expression correlates with survival and other clinical variables. Furthermore, tumor and normal tissue expression comparisons were performed using data from the Genotype-Tissue Expression (GTEx) project (n = 8,555). Results: PRAME mRNA expression was available for 110 leiomyosarcoma (LMS), 76 undifferentiated pleomorphic sarcoma / myxofibrosarcoma (UPS/MFS), 58 dedifferentiated liposarcoma (DDLPS), 10 synovial sarcoma, 12 malignant peripheral nerve sheath tumor (MPNST), and 57 carcinosarcoma patients in the TCGA and 46 various sarcoma cell lines in the CCLE. We found that PRAME was highly expressed in all synovial sarcomas: the expression in these samples was significantly higher than in LMS, UPS/MFS, and DDLPS (p < 0.001). Furthermore, PRAME also had a significantly higher expression in multifocal LMS compared to non-multifocal LMS (p < 0.05). We did not find any significant difference in survival or in other clinical parameters in these sarcoma subtypes. In uterine carcinosarcoma, PRAME expression was significantly higher than in normal uterus (p < 0.001). In the CCLE cell line data we found that sarcoma subtypes show diverse PRAME expressions, however, all four chondrosarcoma lines have a low expression, which is significantly lower than in Ewing's sarcoma (p < 0.01), and it shows a similarly lower trend than osteosarcoma (p = 0.0535).Conclusions: To our knowledge this is the first comprehensive analysis of PRAME in multiple sarcoma subtypes. We report statistically significant associations to help guide PRAME specific therapies of sarcoma.
Prognostic impact of genetic variation in steroidogenic enzymes in advanced stage prostate cancer.
Authors: Moritz Binder, Ben Yiming Zhang, Brian Addis Costello, Fernando Quevedo, Manish Kohli
Journal: Journal of Clinical Oncology (2016)

e16605 Background: Extragonadal androgen biosynthesis controls tumor growth and impacts survival in men with metastatic castration-resistant prostate cancer (mCRPC). We investigated the associations between single nucleotide polymorphisms (SNPs) in CYP17A1 and HSD3β2, genes that code for key enzymesinvolved in sex steroid pathways with survival in men with advanced prostate cancer. Methods: Germline DNA was extracted from peripheral blood mononuclear cells of mCRPC patients. Six SNPs in the two genes (CYP17A1 and HSD3β2 ) with minor allele frequency (MAF) ≥ 0.05 were identified using a haplotype-based tagging algorithm, providing 100% coverage of the common genetic variations. Genotyping was carried out on the MassARRAY iPLEX platform. The adjusted α-level after correcting for multiple testing was 0.010. The outcome measure of interest was overall survival, defined as time from initial diagnosis to death or the date of last follow-up. Multivariable Cox regression models were used to assess the association between genetic variation and overall survival. Effect measures were expressed as hazard ratios per minor allele. Results: We successfully genotyped 328 men with prostate cancer. The median age at diagnosis was 64 years (Range 43-89). After a median follow-up time of 8 years (0 - 38), 184/328 men (56%) had died. The genetic variant rs4919685 in CYP17A1 (MAF = 0.29) was associated with increased mortality (HR 1.39, 95% CI 1.10-1.75, p = 0.005), after adjusting for age, stage, grade, and prostate-specific antigen at the time of diagnosis. No SNP in HSD3β2 was associated with the outcome of interest. Conclusions: Genetic variation in CYP17A1, a gene that encodes key sex steroidogenic enzymes has demonstrated prognostic significance in prostate cancer. These promising results warrant validation in a larger independent cohort.
Use of heart rate variability (HRV) biofeedback for symptom management among cancer survivors.
Authors: Mark Allen O'Rourke, Regina A. Franco, Jameson Sofge, Jay Ginsberg, Kerri Susko, Elizabeth Crowley, Annie Anderson, Alex Christ, John Hanna, William Hendry, James Burch
Journal: Journal of Clinical Oncology (2017)

10099 Background: Late effects of cancer and its treatment include pain, fatigue, stress, and depression all mediated by autonomic dysfunction. Heart Rate Variability (HRV) coherence is an established measure of autonomic dysfunction. Cancer survivors have lower HRV coherence than normal controls. HRV biofeedback (HRV-B) training improves HRV coherence, restores autonomic health, and reduces the above symptoms. This report describes a feasibility study of HRV-B in symptomatic cancer survivors. Methods: In a randomized, waitlist controlled, clinical trial, 179 were screened, 34 enrolled and 31 completed the protocol. Participants in the intervention arm received weekly HRV-B training up to six weeks. Outcome measures assessed at baseline (pre) and after week six (post) included HRV coherence plus Insomnia Symptom Questionnaire (ISQ), Suscro Distress Inventory (SDI), Brief Pain Inventory (BPI), Multi-Dimensional Fatigue Inventory (MFI), Perceived Stress Scale (PSS) and Beck Depression Inventory II (BDI-II). Results: See table below. Conclusions: Delivering HRV Biofeedback training to cancer survivors is feasible at our Cancer Institute. This pilot study provides preliminary evidence that HRV-B for cancer survivors improves HRV coherence and reduces insomnia, pain, fatigue, depression, and stress. The intervention has great potential and further research is indicated. [Table: see text]
The role of platinum rechallenge as second line chemotherapy for metastatic endometrial carcinoma.
Authors: Ronaldo Pereira Souza, Gregorio Pinheiro Soares, Liana Valente Lage, Marcello Ferretti Fanelli, Solange Moraes Sanches, Andrea Paiva G. Guimaraes, Adriana Regina G. Ribeiro, Augusto Saito, Alexandre Andre Balieiro Anastacio da Costa, Maria Del Pilar Estevez-Diz
Journal: Journal of Clinical Oncology (2016)

e17108 Background: Combination chemotherapy with taxane and platinum, with or without anthracycline, has been the standard first-line chemotherapy regime for metastatic endometrial cancer (EC) and there is no standard second-line. The purpose of this study was to evaluate the efficacy of second-line platinum-based chemotherapy in this setting. Methods: We analyzed retrospectively a cohort of patients treated with second line chemotherapy for metastatic EC, from Jan/2005 to Dec/2015, at 2 Brazilian cancer centers. Primary endpoint was the analysis of overall survival between patients treated with platinum rechallenge (PR) compared to other second-line treatments. Overall survival (OS) and progression free survival (PFS) were calculated from the beginning of second line chemotherapy. Platinum free interval (PFI) was defined as the time from last platinum infusion in the first line to the beginning of second line chemotherapy. We used Kaplan-Meier method for survival analysis, log-rank test to compare survival curves, Cox regression to multivariable analysis and Chi-square or Fisher’s exact test were used to compare proportions among groups. Results: A total of 83 patients were evaluated. Median age was 66.2 years, most of them ECOG performance status 1-2 (78%), endometrioid histology (70%) and grade 2 tumors (44%). All patients, but one, received platinum based chemotherapy at first-line. At second-line 44% (36/82) were PR and of them 66.6% had PFI > 6 months. Median follow-up was 27.6m (20.7–34.5m). Re-exposure carboplatin plus paclitaxel achieved higher overall response rate (ORR) compared to other regimens (42.9% vs 13.3%; p = 0.01). Median OS was 9.7 m (7-12.3m) and PFS, 4.1 m (3.4-4.8m). PR was associated with a higher median PFS, 5.2 (2.9-7.5) vs 3.2m (1.7-4.6) for non re-exposed (p = 0.004), and OS, 13.9 (9.48-18.25m) vs 7.9 m (5.32-10.45m) (p = 0.005). PR remain the only factor independently related to OS in multivariate analysis (HR 0.5; 0.25-0.98 CI95%; p = 0.044). Conclusions: Re-exposure to platinum based chemotherapy in second-line for metastatic endometrial cancer is associated with higher response rates, PFS and OS.