tbuckley/cabot-search huggingface dataset:
Clinical utility of cfDNA analysis in advanced stage NSCLC and other solid tumors in patients from Colombia.
Authors: Silvia Juliana Maradei, Tatiana Pineda, Ana Maria Zarante, Sandra Ximena Franco, Andres Cardona, Victoria M. Raymond
Journal: Journal of Clinical Oncology (2018)

e21205 Background: Solid tumor molecular testing has advanced our ability to identify an increasing number of targetable genomic alterations (alts). As the number of alts with matched therapies multiplies, tissue biopsy material can be quickly exhausted, resulting in multiple undergenotyped patients (pts). Non-invasive cell-free circulating tumor DNA (cfDNA) assays can detect all National Comprehensive Cancer Network (NCCN) recommended somatic genomic alts, improving treatment and derived costs on health systems. Methods: Adult pts presenting to a Colombian hospital system with stage IV non-small cell lung cancer (NSCLC) or other metastatic solid malignancies (stage III-IV), with tissue unavailable for biopsy or insufficient quantity (QNS) to perform genotype studies in 1st line or progressive disease, documented QNS for genotyping studies by pathology report or negative report, clinical refractoriness to chemotherapy suspected to be related to a genetic alt, or not willing to undergo biopsy or invasive tests were prospectively recruited. Pts underwent clinical cfDNA analysis utilizing a next generation sequencing assay that evaluates single nucleotide variants, and select indels, fusions, and copy number amplifications in up to 73 genes (Guardant360). Clinical outcomes were correlated with cfDNA results. Results: 21 pts met inclusion criteria and underwent cfDNA testing. In 81% (N = 17), at least one genomic alt was found. 29.4% of pts had an alt associated with an FDA approved therapy (N = 5), 88.2% had an alt associated with an off-label therapy or ongoing clinical trial (N = 15), and 29.4% (N = 5) had an alt associated with therapeutic resistance. For all pts with an alt associated with an FDA approved therapy, treatment redirectioning was decided. Given the difficulties in our health system, no off-label therapy has been authorized and no pts who had alts related to clinical trials have been enrolled in one. Conclusions: Almost one-third of pts with cfDNA detected had a genomic alt associated with an FDA approved therapy resulting in a therapy change. In this cohort of pts from Colombia, cfDNA testing provided therapeutically actionable information and avoided repeat invasive biopsies.
An observational, multicenter, retrospective, Italian Sarcoma Group (ISG) study of trabectedin in patients with advanced soft tissue sarcoma (STS).
Authors: Emanuela Palmerini, Piero Picci, Paolo Giovanni Casali, Giovanni Grignani, Virginia Ferraresi, Bruno Vincenzi, Alessandro Comandone, Giuseppe Badalamenti, Antonio Pizzorusso, Elisabetta Setola, Antonella Brunello, Gabriele Luppi, Angela Buonadonna, Tommaso De Pas, Toni Ibrahim, Laura Milesi, Federica Grosso, Emanuela Marchesi, Irene Quattrini, Stefano Ferrari
Journal: Journal of Clinical Oncology (2018)

e23502 Background: Trabectedin (T) is approved for patients (pts) with STS after failure of anthracyclines (A) and ifosfamide (I), or pts unsuited to receive AI. ISG performed a retrospective study to assess T in real-life clinical practice. Methods: Pts enrolled in clinical trials were excluded. T was given as 24-h infusion every 3 weeks. According to National Health Service reimbursement rules, tumor response evaluation was performed after two cycles. Results: From 1/2010-12/2015 a total of 420 pts (55% female) with a median age of 57 years (range: 21-87) were included. Performance status was 0 in 254 (63%), 1 in 131 (32%) and >1 in 20 (5%) pts. Leiomyosarcoma (36%; uterine: 12% and non-uterine: 24%) and liposarcoma (32%) were the most prevalent histological types. Pts received a median of 3 T cycles (range: 1-10) either at a recommended dose of 1.5 mg/m2 (n=153, 36%) or at a lower dose of 1.3 mg/m2 (n=267, 64%) as a 2nd (n=197, 55%), 3rd (n=107, 30%) or ≥4th (n=55, 15%) treatment line. The objective response rate (ORR) was 11.9% (3 CR, 47 PR), with 35% (147 pts) achieving stable disease (SD). Higher responses were documented in leiomyosarcoma (ORR: 15%, SD: 36%) and liposarcoma (ORR: 15%, SD: 44%), and when T was delivered as 2nd line treatment (ORR: 15%, SD: 37%). No difference in outcome according to T dose was observed (1.3 mg: ORR: 13%, SD: 35% vs. 1.5 mg: ORR: 12.5%, SD: 38%) The 4- and 6-month PFS rates were 45% and 36%, respectively, with better results for leiomyosarcoma (53%/44%) and liposarcoma (57%/49%), and no differences according to T dose (1.3 mg: 47%/38% vs. 1.5 mg: 45%/35%). The 1-year survival rate was 67% (89% for pts with response, 82% for SD, 50% for PD, p=0.001). Grade 3-4 adverse events were recorded in 21% of pts (1.3 mg: 15% vs. 1.5 mg: 34%; p<0.001). Dose reduction occurred in 26% of pts (1.3 mg: 21% vs. 1.5 mg: 40%; p< 0.01). Toxic death occurred in 2 pts (2 febrile neutropenia). Conclusions: In clinical practice, T shows results comparable to those achieved in pts enrolled in phase II/III trials. In pts treated with a lower dose (1.3 mg/m2), toxicity was less pronounced, with similar activity compared to the recommended dose (1.5 mg/m2). Clinical trial information: NCT02793050.
Treatment decision-making priorities and satisfaction among melanoma survivors.
Authors: Joanne S. Buzaglo, Melissa F Miller, Shauna McManus, Niraj K. Gupta, Alexandra Katherine Zaleta
Journal: Journal of Clinical Oncology (2018)

e21618 Background: Understanding priorities in making treatment decisions is essential for shared decision-making. This study examined patient priorities in making melanoma treatment decisions and satisfaction with health care team (HCT) communication.Methods: Of 114 melanoma survivors enrolled in the Cancer Experience Registry, 72 completed questions about treatment decision-making (TDM). Respondents rated (0 =Not at all; 4 =Very much) the importance of cost of care (CoC), length of life (LoL), quality of life (QoL), and family impact when making a treatment decision and rated satisfaction with the TDM process and treatment outcomes. Associations between treatment-related variables and socio-demographic and clinical variables were examined via Spearman correlations. Results: Participants were 93% White, 72% female; mean (SD) age 54 (13) years, 4.8 (8.0) years since diagnosis; 35% received chemotherapy; 35% radiation; 25% targeted therapy; 25% biological and 59% immunotherapy. The most important factor for TDM was QoL (96% quite a bit or very much), followed by LoL (86%), family impact (84%), and CoC (29%). 64% were quite a bit or very much involved in TDM; 43% felt knowledgeable about options; 35% were prepared to discuss options with their HCT. 27% received decision support prior to TDM; 39% wanted more support. Fewer participants were satisfied with HCT discussion of CoC (43%) than with how a decision was made (68%), level of TDM participation (65%), and HCT explanation of treatment risks and side effects (62%; ps < .001). Satisfaction with TDM process was associated with knowledge before TDM (ρ= .46, p< .001), level of involvement (ρ= .58, p< .001), feeling prepared to discuss options (ρ= .59, p< .001), and metastatic disease (ρ= .25, p= .04). Satisfaction with treatment outcome was associated with knowledge (ρ= .24, p= .04), involvement (ρ = .43, p= < .001), and preparation (ρ= .41, p< .001). Conclusions: Many melanoma survivors do not feel fully knowledgeable about nor prepared to discuss treatment options with their HCT, and were not satisfied with cost of care discussions. These results support enhanced HCT communication around treatment options, especially regarding the impact of treatment on symptom burden and finances.
Treatment patterns, effectiveness, and safety of Trastuzumab in Chinese patients with metastatic gastric cancer: Interim analysis of the EVIDENCE registry study.
Authors: Shukui Qin, Shen Lin, Ruihua Xu, Wuyun Su, Yong Tang, Xin Wang, Jian-ming Xu, Weiping Zhou, Tongjian Cui, Suxia Luo, Xiaohui Wu, Jiafu Ji
Journal: Journal of Clinical Oncology (2017)

e15595 Background: Trastuzumab (TRA) was approved for HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma (mGC) in China in August 2012. However, real-world data on the treatment patterns, effectiveness, and safety of TRA in Chinese patients (pts) with mGC are limited. Methods: EVIDENCE is a prospective, multicenter, non-interventional, registry study of 5 cohorts (NCT01839500). Cohort I enrolled pts with HER2-positive mGC (IHC3+ or IHC2+/ISH+) diagnosed up to 6 months previously. This interim analysis evaluated the effectiveness and safety of TRA in the first 95 pts of cohort I who were treated at 33 hospitals in China between April 2013 and August 15, 2016. Results: 71 of the 95 pts (74.7%) were male and the median age at diagnosis was 61 years (range 21-87 years). At the data cut-off date, the preliminary median PFS was 9.5 months (95% CI 7.6-11.8 months), and the preliminary median overall survival (OS) was 30.0 months (95% CI 18.6-38.7 months). 90 pts were treated with TRA + chemotherapy; XELOX (capecitabine + oxaliplatin) (28 pts, 31.1%) and capecitabine (20 pts, 22.2%) were the mostly commonly used regimens with TRA for first-line therapy, while paclitaxel was most commonly used with TRA for second-line (7.8%) and third-line (2.2%) therapy. TRA was also used in neoadjuvant (7 pts) and adjuvant (8 pts) settings prior to recurrence. During follow-up, 48 pts had progressive disease, and 21 (43.8%) received TRA beyond progression; 7 pts (14.6%) continued TRA after their 2nd disease progression. TRA-related adverse events (AEs) were observed in 26 pts (27.4%), including neutropenia in 10 pts (10.5%), thrombocytopenia in 9 (9.5%), and a decreased white blood cell count in 7 (7.4%). Only 6 pts (6.3%) experienced grade &gt; = 3 TRA-related AEs (which included neutropenia and thrombocytopenia). Conclusions: In routine clinical practice in China, TRA combined with various chemotherapy regimens proved effective and well tolerated for treating mGC HER2+ pts. In addition to its use in palliative settings, TRA was also used as neoadjuvant/adjuvant treatment. Clinical trial information: NCT01839500.
NCCN Guidelines Insights: Head and Neck Cancers, Version 1.2018
Authors: A. Dimitrios Colevas, Sue S. Yom, David G. Pfister, Sharon Spencer, David Adelstein, Douglas Adkins, David M. Brizel, Barbara Burtness, Paul M. Busse, Jimmy J. Caudell, Anthony J. Cmelak, David W. Eisele, Moon Fenton, Robert L. Foote, Jill Gilbert, Maura L. Gillison, Robert I. Haddad, Wesley L. Hicks, Ying J. Hitchcock, Antonio Jimeno, Debra Leizman, Ellie Maghami, Loren K. Mell, Bharat B. Mittal, Harlan A. Pinto, John A. Ridge, James Rocco, Cristina P. Rodriguez, Jatin P. Shah, Randal S. Weber, Matthew Witek, Frank Worden, Weining Zhen, Jennifer L. Burns, Susan D. Darlow
Journal: Journal of the National Comprehensive Cancer Network (2018)

<section class="abstract"><p id="P1">The NCCN Guidelines for Head and Neck (H&amp;N) Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the H&amp;N, and separate algorithms have been developed by the panel for very advanced H&amp;N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding evaluation and treatment of nasopharyngeal carcinoma. </section>
Using deep learning algorithms on histopathology images for the prediction of <i>BRAF</i> and <i>NRAS</i> mutations in invasive melanoma.
Authors: Randie H Kim, Sofia Nomikou, Zarmeena Dawood, Nicolas Coudray, Jeffrey S. Weber, Richard L. Shapiro, Russell S. Berman, Iman Osman, Aristotelis Tsirigos
Journal: Journal of Clinical Oncology (2018)

e21561 Background: Precision treatments for melanomas require mutational profiling for BRAF and NRAS oncogenes. Therefore, rapid and accurate screening assays are a critical adjunct to diagnostic molecular tests. We examined whether deep machine learning computer algorithms can predict BRAF and/or NRAS mutations of digitized hematoxylin-and-eosin (H&E) slides of tumors with known mutation status. Methods: We first trained the network on H&E stained images from The Cancer Genome Atlas (TCGA) of 95 melanomas (BRAF, n = 50; NRAS, n = 13; WT/WT, n = 32). We also tested an additional cohort of 164 invasive melanomas (BRAF, n = 60; NRAS, n = 52; WT/WT, n = 52) from New York University (NYU) Melanoma database. Tumors were annotated using Aperio ImageScope software. 299x299 pixel “tiles” partitioned at 20X magnification were used to train a Convolutional Neural Network (CNN) model (Inception v3). CNNs were trained for: (1) binary classification (BRAF mutant vs. BRAF WT) on the TCGA dataset, and (2) three-way classification (BRAF mutant vs. NRAS mutant vs. WT/WT) on the NYU cohort. In each classification, 75% of the images were used for training, 15% for validation, and 15% for testing. Results: Model performance was measured by Area Under the Curve (AUC) on the held-out independent test set (Table 1). Prediction of mutated BRAF from the TCGA dataset resulted in AUC 0.852 with a sensitivity (SENS) of 0.75 and a specificity (SPEC) of 0.78. Predictive accuracy of the NYU cohort achieved AUC 0.764 for mutated BRAF (SENS 0.89 and SPEC 0.75) and AUC 0.76 for mutated NRAS (SENS 0.79 and SPEC 0.73). Conclusions: Distinct morphological changes by BRAF and NRAS mutations in melanoma can be detected on histopathological images by deep learning algorithms with robust accuracy rates among different cohorts. Additional training with larger sample size can potentially improve predictive performance. Table 1. AUC achieved by different classifiers Classification AUC [CI], aggregated per slide BRAF vs. non-BRAF (TCGA) 0.85 [0.65-1.0] BRAF vs. NRAS vs. WT/WT (NYU) BRAF 0.76 [0.53-0.95] NRAS 0.76 [0.54-0.96]
Prognostic value of mitoses in thick primary melanoma.
Authors: Eric Michael Robinson, Brooke E Rosenbaum, Robert Rogers, Sung Won Han, Jeremy Tchack, Una Moran, Judy Zhong, Russell S. Berman, Farbod Darvishian, Iman Osman, David Polsky, Richard L. Shapiro
Journal: Journal of Clinical Oncology (2016)

e21046 Background: Patients with thick primary melanomas ( ≥ 4mm) have variable outcomes. With the availability of promising adjuvant therapies, new tools are needed to identify subsets of patients at high risk of relapse. The prognostic value of mitotic index in thick tumors is inconclusive, and it is currently only used for staging thin tumors ( < 1mm). Additionally, the clinical value of sentinel lymph node biopsy (SLNB) in patients with thick primary tumors is controversial. Methods: We identified patients with thick primary melanoma without evidence of distant metastases who were prospectively enrolled into a melanoma database at NYUMC. We tested associations between clinicopathological factors and survival outcomes using univariate and multivariate analyses. Results: We studied 170 patients; 106 (62.4%) were male; the median age was 69 years and the median follow up was 3.0 years. The median tumor thickness was 6 mm, 119 (70.0%) patients had ulcerated tumors, and 118 (69.4%) patients had nodular melanomas. After staging work up, 70 patients were determined to have lymphatic disease and were treated according to the standard of care. Under univariate analysis ulceration (HR = 3.11, p < 0.01), mitoses (present/absent) (HR = 3.34, p = 0.04), lymph node disease (present/absent) (HR = 4.18, p < 0.01), and satellitosis (HR = 2.65, p < 0.01), were significantly associated with worse recurrence-free survival (RFS). Tumor thickness was not significantly associated with worse RFS in this cohort of patients with thick primary melanomas (p = 0.20). In multivariate analysis only mitoses (HR = 4.16, p = 0.05), satellitosis (HR = 2.04, p = 0.04), and lymph node disease (HR = 4.03, p < 0.01) remained significant predictors of poor RFS. In multivariate analysis for overall survival only satellitosis (HR = 2.26, p = 0.02) and lymph node disease (HR = 3.5, p < 0.01) were independent predictors of poor outcomes. Conclusions: Our data suggest that in patients with thick primary melanomas, measures of cell proliferation, such as mitotic index, may identify patients at high risk for disease recurrence. Our data also support the value of lymph node sampling in patients with thick melanomas for improved prognostication and disease management.
A phase II study of regorafenib in patients with thymic epithelial tumours previously treated with chemotherapy.
Authors: Matteo Perrino, Silvia Bozzarelli, Paolo Andrea Zucali, Tommaso Martino De Pas, Matteo Simonelli, Fabio De Vincenzo, Fabio Conforti, Pasquale Persico, Chiara Miggiano, Nadia Cordua, Angela Cioffi, Simona Sala, Federica Mrakic Sposta, Laura Giordano, Armando Santoro
Journal: Journal of Clinical Oncology (2018)

8579 Background: Angiogenesis has an important role in thymic epithelial tumours (TETs); VEGF, PDGF and PDGFRα are overexpressed in TETs, and VEGF expression and microvessel density are associated with invasiveness and stage. Regorafenib potently inhibits VEGFR1, 2, and 3, TIE2, FGFR and PDGFR-β. The aim of this study is to determine the activity of Regorafenib as monotherapy in patients (pts) with advanced/metatstatic Thymoma (type B2 – B3) (T) and Thymic Carcinoma (TC) previously treated with cisplatin-based chemotherapy. Methods: Pts with progressive disease were prospectively enrolled in single arm, phase II trial to receive oral Regorafenib 160 mg once daily 3 weeks on/1 week off until documented disease progression, unacceptable toxicity, or pt refusal. Tumour assessment and safety were asessed every six and three weeks, respectively. This Fleming phase II trial was designed to reject the null hypothesis of a progression free survival (PFS) rate ≤25% with a type I error of 0.10 and a statistical power of 80% at the alternative hypothesis of a PFS rate of ≥50%. The drug should be recommended for further study if 8 or more of the 19 total evaluable pts would be progression free at 2 months. Clinical trial information: NCT02307500. Results: Results of the 19 enrolled pts are presented. Pt characteristics are as follow: median age 54 years (range 40;75), male/female 11/8 (58%/42%); T/TC 7/12 (37%/63%), and number of previous lines (1line/≥2lines) of chemotherapy 9/10 (47%/53%). Two pts were not evaluable for response (10.6%). According to RECIST criteria, we observed partial response (PR) in 1 pt (T) (5.3%), stable disease (SD) in 14 pts (9T/5TC) (73.5%), and progressive disease (PD) in 2 pts (1T/1TC) (10.6%), with a disease control rate of 78.8%. Response evaluation with Choi criteria is planned. With a median follow up of 6.4 months (0.9-39.3 months), median PFS was 8.9 months, while median OS was not reached. Thirteen patients were progression free at 2 months. The 1-year PFS rate and 1-year OS rate were 17.9% and 94.4%, respectively. Conclusions: The primary end-point of this study was reached. On the basis of PFS and OS results, the efficacy of Regorafenib should be better evaluated in subsequent larger trials. Clinical trial information: NCT02307500.
Monitoring and Treatment of Patients Undergoing Immunotherapy With Anti-CD20 Who are Exposed to HBV
Authors: Wai-Kay Seto, Thomas Sau-Yan Chan, Yu-Yan Hwang, Lung-Yi Mak, Danny Ka-Ho Wong, James Fung, Kevin Sze-Hang Liu, Ka-Shing Cheung, Ching-Lung Lai, Yok-Lam Kwong, Man-Fung Yuen
Journal: Clinical Gastroenterology and Hepatology (2018)
P01.064 Correlation with MGMT pyrosequencing-based methylation levels and overall survival in glioblastoma patients with gross total resection and concomitant chemio and radiotherapy
Authors: A Parlangeli, E Pirola, M Caroli, C Pesenti, S Buonamassa, M Miozzo, P Rampini
Journal: Neuro-Oncology (2018)

MGMT methylation may enhance the response to temozolomide and has been associated with improved survival in glioblastoma (GBM). Literature data do no clarify which is the clinical role of different grades of methylation in GBM patients with gross total resection (GTR) and concomitant chemio e radiotherapy. The aim of our study is to analyze the relationship between MGMT methylation levels in tumors of patients diagnosed with GBM IDH wild type undergoing “gold standard therapy”, and the overall survival (OS). We collected data from 69 patients with GBM (WHO grade IV, IDH wild type, age 21–75 years old median 61, Karnoski >70) admitted in the Neurosurgical Unit, Ospedale Maggiore Policlinico, Milan, Italy and underwent GTR, from January 2005 to December 2016.MGMT promoter methylation status was analyzed by pyrosequencing technology.Patients were divided into 5 groups according to cut-off levels of MGMT methylation status: group 1 MGMT 5%, group 2 MGMT 10%, group 3 MGMT 15%, groups 4 MGMT 20%, group 5 MGMT 25%. Kaplan-Meier survival curves were obtained and compared between MGMT methylation status, through Log-rank test. A positive correlation between OS and increased level of MGMT methylation status was observed in all groups. Median OS was 16 month in patients with MGMT levels greater than 10% and 13 months in MGMT inferior to 10% (p=0,003). Our study confirmed that MGMT methylation status has a prognostic value in patients undergoing “gold standard therapy” and with positive prognostic factors (KPS >70, Age > 70; GTR, concomitant chemio e radiotherapy and adjuvant cycles of temozolomide). A cut-off of 10% in the MGMT methylation could be used to stratify cases with MGMT methylation into two subclasses with different prognosis. Further studies are needed to establish further clinical role and cut-off values of MGMT levels in patients with primary GBM.