tbuckley/cabot-search huggingface dataset:
Radiation and Androgen Deprivation Therapy With or Without Docetaxel in the Management of Nonmetastatic Unfavorable-Risk Prostate Cancer: A Prospective Randomized Trial
Authors: Anthony V. D'Amico, Wanling Xie, Elizabeth McMahon, Marian Loffredo, Shana Medeiros, David Joseph, Jim Denham, Parvesh Kumar, Glenn Bubley, Molly Sullivan, Richard Hellwig, Juan Carlos Vera, Rolf Freter, W. Jeffrey Baker, Jeffrey Y. Wong, Andrew A. Renshaw, Philip W. Kantoff
Journal: Journal of Clinical Oncology (2021)

Although docetaxel is not recommended when managing men with unfavorable-risk prostate cancer (PC) given negative or inconclusive results from previous randomized trials, unstudied benefits may exist.Between September 21, 2005, and January 13, 2015, we randomly assigned 350 men 1:1 with T1c-4N0M0 unfavorable-risk PC to receive radiation therapy (RT) and androgen deprivation therapy (ADT) plus docetaxel (60 mg/m2 once every 3 weeks for three cycles before RT and 20 mg/m2 once weekly during RT) versus ADT + RT. We evaluated the treatment effect of adding docetaxel to ADT + RT on the primary end point of overall survival (OS) and the incidence of RT-induced cancers and explored whether the impact of the treatment effect on OS differed within prostate-specific antigen (PSA) subgroups (< 4, > 20 v 4-20 ng/mL) using the interaction test for heterogeneity adjusted for age and PC prognostic factors.After a median follow-up of 10.2 years, 89 men died (25.43%); of these, 42 from PC (47.19%). Although OS was not significantly increased in the docetaxel arm (the restricted mean survival time over 10 years was 9.11 v 8.82 years; P = .22), significantly fewer RT-induced cancers were observed (10-year estimates: 0.61% v 4.90%; age-adjusted hazard ratio of 0.13; 95% CI, 0.02 to 0.97; P = .046). The treatment effect of adding docetaxel to ADT + RT on OS significantly differed in men with a PSA < 4 ng/mL versus 4-20 ng/mL (adjusted hazard ratio: 0.27 and 1.51, respectively) because of less PC-specific mortality on the docetaxel arm (0.00% v 28.57%) among men with PSA < 4 ng/mL.Adding docetaxel to ADT + RT did not prolong OS in men with unfavorable-risk PC, but decreased RT-induced cancer incidence, and may prolong OS in the subgroup of men with a PSA < 4 ng/mL by reducing PC-specific mortality.
Analysis of DNA damage response gene signature for prognosis prediction of esophageal squamous cell carcinoma.
Authors: Weitao Zhuang, Xiao-song Ben, Dan Tian, Zihao Zhou, Gang Chen, Cheng Deng, Yuchen Liao, Jing Zhao, Guoqiang Wang, Shangli Cai, Jiming Tang, Ruiqing Shi, Liang Xie, Dongkun Zhang, Haiyu Zhou, Gui-Bin Qiao
Journal: Journal of Clinical Oncology (2021)

e16073 Background: Esophageal squamous cell cancer (ESCC) is a malignant tumor with a poor 5-year relative survival. A prognosis prediction signature associated with DNA Damage Response (DDR) genes in ESCC was explored in this study. Methods: The clinical and gene expression profiles of ESCC patients were downloaded from the GEO and TCGA database. Univariate Cox regression and 1000 iterations of 10-fold cross-validation of LASSO Cox regression with binomial deviance minimization criteria were used to identify DDR genes as potential object and a prognostic signature for ESCC survival prediction, followed by validation of the signature via TCGA cohort and identification of independent prognostic predictors. A nomogram for prognosis prediction was built and Gene Set Enrichment Analysis (GSEA) was performed to further understand the underlying molecular mechanisms. Results: A signature of 8 DDR genes were constructed as being significantly associated with overall survival (OS) among patients with esophageal squamous cell carcinoma. The pronostic signature stratified ESCC patients into low- vs high-risk groups in terms of OS in the training set, testing set and the validation cohorts, and remained as an independent prognostic factor in multivariate analyses (hazard ratio (HR) in training set, 0.17 [95% CI, 0.09-0.35; P &lt; 0 .001], HR in testing set, 0.38 [95% CI, 0.16-0.93; P = 0.029], HR in discovery cohort, 0.171 [95% CI, 0.03-0.48; P &lt; 0 .001]) after adjusting for clinicopathological factors. The 8-DDR gene signature achieved a higher accuracy (C-index, 0.69; AUCs for 1-, 3- and 5-year OS, 0.74, 0.77 and 0.76, respectively) than 7 previously reported multigene signatures (C-index range, 0.53 to 0.60; AUCs range, 0.55to 0.66, 0.54 to 0.64 and 0.62 to 0.66, respectively) for estimation of survival in comparable cohorts. A nomogram incorporating tumor location, grade, adjuvant therapy and signature-based risk group showed better predictive performance for 1- and 3- year survival than for 5 year survival. Moreover, GSEA revealed that the DNA repair was more prominently enriched in the high-risk group while the low-risk group had not enrichment of any process (P &gt; 0.05 for all). Conclusions: Taken together, our study identified 8 DDR genes related to the prognosis of ESCC patients, and constructed a robust prognostic signature to effectively stratify ESCC patients with different survival rates, which may help recognize high-risk patients potentially benefiting from more aggressive treatment.
Real-world Indian scenario of CDK4/6 inhibitors (palbociclib and ribociclib) with endocrine therapy in upfront hormone positive metastatic breast cancer.
Authors: Ajay Gogia, Shalabh Arora, Priyanshu Choudhary, Rakesh Kumar, Sanjay Thulkar, S. V. S. Deo, Dayanand Sharma, Sushma Bhatnagar
Journal: Journal of Clinical Oncology (2021)

e13028 Background: CDK4/6 inhibitors (CDKi), in combination with endocrine therapy (ET), has become the standard of care in the treatment of hormone positive (HR+)/ HER2 neu negative metastatic breast cancer (MBC) patients. We evaluated clinical outcomes and toxicity in MBC patients, who have received ET with two CDKi, namely palbociclib and ribociclib. Methods: This is an ambispective, single institutional analysis of de-novo HR+ MBC patients treated with CDKi (palbociclib 125 mg and ribociclib 600 mg once a day for 21 days /28 days cycle) from November 2016- October 2020 at AIIMS, New Delhi, India. The primary endpoint was progression-free survival (PFS) and the secondary endpoint was response rate and toxicity. A total of 157 female patients were recruited in this study however the response and toxicity data were available in 120 cases. All premenopausal women received ovarian suppression or ovarian ablation. Results: A total of 120 patients were included in this study with a median age of 57 years (35-75) and 93 (77.5%) cases were postmenopausal. Twenty-three (19.1%) patients had a bone-only disease, 49 (40.9%) had bone and visceral disease and 48 (40%) had only visceral disease. In this study 91 (75.9%) patients received palbociclib and 29 (24.2%) received ribociclib. The median PFS was 18 months (4-36). Twenty four (20%) patients achieved a complete response, 69 (57.5%) patients attained partial response, 18(15%) patients had stable disease and 9 (7.5%) had disease progression. Grade 3–4 neutropenia, thrombocytopenia, and anaemia were observed in 18(15%), 8 (6.7%), and 4 (3.3%) cases respectively. None of the patients developed febrile neutropenia. Cutaneous, renal, hepatic, and gastrointestinal toxicity was observed in 1,1,3,4 cases respectively. Prolonged QTc was observed in one case. Grade 3 fatigue was observed in 7 cases. Dose interruption/delay (mean dose delay of 7 days), dose modification, and drug discontinuation were observed in 24 (20%), 12 (10%), and 10 (8.3%) of cases respectively. Conclusions: This is one of the largest real-world Indian data on CDK4/6 inhibitors on upfront HR+ MBC. Side effects are less than published literature with similar efficacy. Neutropenia was the most common side effect which was managed by brief dose interruption.
Treatment patterns among patients with advanced/recurrent endometrial cancer in the United States.
Authors: Jinan Liu, Eric M Maiese, Bruno Émond, Marie-Hélène Lafeuille, Patrick Lefebvre, Isabelle Ghelerter, Caterina Wu, Jean Hurteau, Premal H. Thaker
Journal: Journal of Clinical Oncology (2021)

291 Background: Among patients (pts) with endometrial cancer (EC), response rates for platinum-based regimens in the first-line (1L) setting range from 40% to 62% in clinical trials. This study describes patient characteristics, treatment patterns, time to next treatment (TTNT), and overall survival (OS) among pts with advanced/recurrent EC treated with a platinum-based regimen in a real-world setting in the US. Methods: This retrospective study used Optum Clinformatics Extended Data Mart de-identified databases from January 1, 2007, to December 31, 2019. Adult pts with advanced/recurrent EC who initiated a 1L platinum-based regimen and subsequently initiated second-line (2L) antineoplastic therapy were identified. Prior to initiation of 1L, a 12-month washout period of continuous enrollment without use of antineoplastic agents (except hormonal agents) was imposed. Kaplan-Meier (KM) rates were used to report TTNT and OS from 2L, third line (3L), and fourth line (4L), separately. Results: A total of 1878 pts with advanced/recurrent EC initiated 2L therapy following a platinum-based regimen in 1L. Among them, 739 (39.4%) pts initiated 3L and 330 (17.6%) initiated 4L or later (4L + ) therapy. Median pt age was 68.0 years. More pts received platinum-based regimens (56.4%) in 2L than other options (Table). Few pts (3.3%) received immunotherapy. Among pts receiving 3L, a similar percentage of pts were treated with platinum-based (33.2%) and other chemotherapy regimens (33.8%); few pts received immunotherapy (3.0%). Among pts receiving 4L + , the most frequent treatment option was other chemotherapy (46.1%). Median TTNT was 17.7, 10.6, and 8.4 months for 2L, 3L, and 4L pts, respectively. KM rates of OS following initiation of 2L therapy at 1, 2, 3, and 4 years were 68.4%, 49.6%, 41.3%, and 33.6%, respectively, with a median OS of 23.5 months. Conclusions: Among pts with advanced/recurrent EC treated with platinum-based therapy in 1L, platinum-based regimens remain prevalent treatment choices in later lines of therapy. In this study, immunotherapy was used infrequently in 2L, 3L, and 4L+. The median TTNT decreased in later lines of therapy. This study highlights a critical need for novel, more effective treatment options in later lines of therapy to optimize outcomes among pts with advanced/recurrent EC.[Table: see text]
Outcomes with preemptive donor lymphocyte infusions after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes: A systematic review and meta-analysis.
Authors: Syed Ather Hussain, Atif N khan, VENKATA S THAMMINENI, Muhammad Nauman Riaz, Moazzam Shahzad, Priyanjali Pulipati, Fatima Khalid, Zahoor Ahmed, Iqra Anwar, Sibgha Gull Chaudhary, Ramesh Balusu, Nausheen Ahmed, Sharad Khurana, Faiz Anwer, Muhammad Umair Mushtaq
Journal: Journal of Clinical Oncology (2021)

e19014 Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) but relapse and graft versus host disease (GVHD) remain the most common challenges. Donor lymphocyte infusion (DLI) is the infusion in which lymphocytes from the original stem cell donor are infused, after the transplant, to augment an anti-tumor response or to ensure that the donor stem cells remain engrafted. In this systematic review and meta-analysis, we focused at outcomes of preemptive DLI in AML and MDS. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA) PubMed, CINAHL, Cochrane, and Clinical trials.gov were searched. We included 8 out of 214 articles, excluding duplicates and non-relevant articles. The quality of the included studies was evaluated using NIH quality assessment tool. Proportions along with 95% Confidence Interval (CI) were extracted to compute pooled analysis using the ‘meta’ package by Schwarzer et al. in the R programming language (version 4.16-2) to report the efficacy of preemptive DLI. We pooled the experimental arms results of the included trials using the inverse variance method and logit transformation. Between studies, the variance was calculated using Der Simonian-Laird Estimator. Results: We identified 222 patients who received preemptive DLI. Median age, time since transplant and DLI dose were 48 (32-58) years, 82 (7-160) days and 1.4 million cells/kg respectively. CR and PR were 43% (95%CI 0.14-0.78, I 2 93%, n= 127) and 61% (95%CI 0.40-0.78, I 2 62%, n= 81) respectively. After median follow up of 46 months, non-relapsed mortality (NRM) was 52% (95%CI 0.38-0.65, I 2 49%, n = 121). OS was reported 72% (95%CI 0.62-0.80, I 2 0%, n= 100). Acute and chronic GVHD incidence after DLI was 20% (95% CI 0.13-0.29, I 2 4%, n= 105) and 25% (95% CI 0.08-0.56, I 2 =79%, n=101) respectively (Table). Conclusions: Preemptive DLI significantly improves OS with a low incidence of acute and chronic GVHD. However, NRM was seen in more than half of all the patients and prospective studies are needed to evaluate safety of preemptive DLI. Outcomes with preemptive DLI (n= 222).[Table: see text]
Clinical, pathologic, and demographic characteristics of colorectal cancer in patients under age 50 in a third level Mexican cancer center.
Authors: Omar Serrano Villamayor, Benigno Rodriguez, Diana Alejandra Villegas Osorno, Geovani Amador, Raul Alejandro Andrade Moreno, Lorena López Zepeda, Ervin Saúl Enciso López, Daniela Shveid Gerson, Efrain Isaias Camarin Sanchez, José Fabián Martínez-Herrera, Alberto Villalobos, Gabriela Olivia Regalado Porras, Guillermo Olivares, Raquel Gerson Cwilich
Journal: Journal of Clinical Oncology (2021)

e15592 Background: Colorectal cancer (CRC) is the most common gastrointestinal neoplasia, with 1.36 million cases worldwide, representing the third cause of death due to cancer. Commonly affects people after the 6th decade of life, but recently the diagnosis in patients below 50 years is increasing. Methods: We conducted an observational, retrospective, longitudinal analysis based on medical records of patients diagnosed with colorectal cancer treated in the ABC Medical Center. Information was collected between January 2016 and January 2021. Descriptive statistics were utilized regarding data analysis. Results: We identified 289 patients with CRC, of which 23 (8.2%) patients were less than 50 years of age at diagnosis. Gender distribution reflected slightly more feminine patients (56%). The median age at diagnosis was 43 years, oncologic family history in first- or second-degree family members was documented in 31.4% of patients. At diagnosis, 22% of patients presented with an early-stage neoplasm, 31% had locoregional disease and 50% had advanced disease. Left sided disease was present in 78% of patients, 8% on the right colon and 13% were in rectum. Adenocarcinoma was found in 95% of patients. Mucinous pattern was present in 39% of patients studied, intestinal tumors in 21%, singlet ring cells in 4.3%. Histologic grade was G2: 69%. Molecular analysis was conducted in 86% of tissue biopsies. Regarding RAS mutations, 15% were positive (Gly12asp, K117N and Gly13Asp), but none in NRAS. BRAF mutation was studied in 43% of patients, no mutations were found. The search for microsatellite instability was conducted in all tumors, finding it present in only one patient (5%). At median follow up of 31.8 months, 91.4% remainded alive. Patients with early stage cancer were given adjuvant therapy in 69%. mean RFS was 40 months. All patients diagnosed in stage IV disease received systemic therapy, with a medium PFS of 10 months. First line treatment was FOLFOX in 58% of patients. Target therapy with anti-EGFR and anti-VEGF was prescribed in 83.3% and 8.3% of patients in the first line respectively. Conclusions: We found that patients under 50 years with dignosis of colorectal cancer, have a family history of cancer in up to a third of patients, the most frecuent histology reported was adenocarcinoma with mucinous pattern. We observed a low frecuency of KRAS mutations compared with literature reports. A longer follow-up is requiered to asses overall survival.
Molecular profiling and targeted agents in recurrent, metastatic salivary gland tumor (R/M SGT) patients (pts) treated at two academic centers.
Authors: Alberto Hernando-Calvo, Alejandra Rezqallah, Eoghan Ruadh Malone, Omar Saavedra Santa Gadea, Anna Spreafico, Maria Vieito, Ilan Weinreb, Susana Aguilar, Anneli Eliason, Juan David Assaf, Angela Rodriguez, Coro Bescos, Katherine Lajkosz, Juan Lorente, Sarah Jennings, Enriqueta Felip, Elena Garralda, Lillian L. Siu, Aaron Richard Hansen, Irene Brana
Journal: Journal of Clinical Oncology (2021)

6081 Background: Treatment selection based on actionable alterations (AAs) is an appealing strategy for pts with R/M SGT. The GEMS-001 study (NCT02069730) at Princess Margaret Cancer Centre (PM) and the Vall D´Hebron Institute of Oncology (VHIO) pre-screening program facilitate the identification of AAs for R/M SGT pts and treatment selection. Methods: We analyzed R/M SGT treated at PM and VHIO from 2015 to 2020. Clinicopathological features, molecular alterations and treatment modalities were correlated with outcomes. The primary endpoint was overall response rate (ORR) by RECIST 1.1. Clinical benefit rate (CBR) was defined by pts with partial response or stable disease ≥4 months. Clinical actionability of multigene panel testing (NGS) and immunohistochemistry (IHC) were assessed as per institutional molecular tumor boards or investigators. Pts were opportunistically matched to available therapies from each center. Results: In total 206 pts were enrolled. On IHC, HER2 overexpression was present in 9%, Androgen Receptor (AR) 33%, Estrogen/Progesterone Receptor (ER/PR) 11% and ALK overexpression 0%. On NGS, PIK3CA mutation (mut) was in 9%, NTRK fusion 6%, NOTCH1-3 mut 5%, HRAS mut 6%, ERBB2/3 alterations (alt) 4% and FGFR1-4 alt 3%. Up to 92 pts (45%) displayed at least 1 AA and 36 pts (18%) had ≥2 AAs. A total of 60 pts (29%) were matched to AAs. Of those matched, median age was 60 years (range 33-84), M:F 21:39, 95% ECOG≤1 with a median number of prior treatment lines 0 (range 0-3), and their AAs included 26 AR, 9 HER2 or ERBB2 overexpression, 9 PIK3CA mut, 3 NTRK fusion, 3 FGFR1-3 alt and 10 other AAs (2 ER/PR overexpression, 2 EGFR mut, 1 c-kit mut, 1 BAP1 mut, 1 Non-V600 BRAF mut, 1 CDKN2A mut, 1 CHEK2 mut and 1 PTCH1 mut). Overall, ORR was 27% for the matched population. See table for outcomes. Conclusions: In our cohort, almost one third of the population received therapies matched to AAs. Our results suggest that targeted therapies have promising activity in pts with R/M SGT supporting comprehensive molecular and IHC profiling in treatment determination.[Table: see text]
An EBMT Analysis of Matched Sibling, Mismatched Family or Matched Unrelated Donors for Allogeneic Stem Cell Transplants in MDS
Authors: Kavita Raj, Diderik-Jan Eikema, Gerhard Ehninger, Christine Wolschke, Linda Koster, Gérard Socié, Jürgen Finke, Maria Teresa Van Lint, Mauricette Michallet, Arnold Ganser, Liisa Volin, Koc Yener, Didier Blaise, Dietrich W Beelen, Henrik Sengeloev, Johanna Tischer, Mutlu Arat, Pavel Jindra, Zafer Gülbas, Maria-Jesús Pascual, Fabio Ciceri, José Luis Díez-Martín, Marie Robin, Kroger Nicolaus
Journal: Blood (2017)
LIQA: long-read isoform quantification and analysis
Authors: Yu Hu, Li Fang, Xuelian Chen, Jiang F. Zhong, Mingyao Li, Kai Wang
Journal: Genome biology (2021)

Long-read RNA sequencing (RNA-seq) technologies can sequence full-length transcripts, facilitating the exploration of isoform-specific gene expression over short-read RNA-seq. We present LIQA to quantify isoform expression and detect differential alternative splicing (DAS) events using long-read direct mRNA sequencing or cDNA sequencing data. LIQA incorporates base pair quality score and isoform-specific read length information in a survival model to assign different weights across reads, and uses an expectation-maximization algorithm for parameter estimation. We apply LIQA to long-read RNA-seq data from the Universal Human Reference, acute myeloid leukemia, and esophageal squamous epithelial cells and demonstrate its high accuracy in profiling alternative splicing events.
Postoperative PET-CT in patients (pts) with pathological stage III colon cancer (CC): Interim results from the first prospective validation study.
Authors: Roi Tschernichovsky, Gali Perl, Inbar Finkel, Idit Peretz, Oded Jacobi, Michal Sternschuss, Olga Ulitsky, Yulia Kundel, Aaron Sulkes, Hanna Bernstine, David Groshar, Baruch Brenner
Journal: Journal of Clinical Oncology (2021)

e15599 Background: A substantial number of pts with pathological stage III CC recur despite the absence of metastatic disease on pre-operative CT. In a previous large retrospective study from our institution on 348 pts, we reported that early postoperative PET-CT modified the staging and management of 13.4% of assumed stage III CC pts. The aim of the current study was to prospectively validate these results. Methods: A prospective, single-center study of pts with pathological stage III CC who underwent early postoperative PET-CT between the years 2013-2021. Results: 83 pts were accrued and 81 (48.1% males, median age 66y) were evaluable for the primary endpoint i.e. PET-CT results. Pathological stage was IIIA, IIIB and IIIC in 7 (8.6%), 56 (69.1%) and 17 (21%) of pts, respectively. Median number of lymph nodes examined and of positive nodes were 17 (range, 9-134) and 2 (range, 0-15), respectively. Post-operative PET-CT findings were significant in 7 pts (8.6%): 4 pts (4.9%) were upstaged to stage IV, 2 (2.5%) were diagnosed with a second primary malignancy, and 1 (1.2%) was both upstaged and diagnosed with another cancer. Three additional pts (3.7%) are currently undergoing evaluation for suspicious PET-CT findings. At a median follow-up of 30.6 months (range, 6.2-92), 13 of the 71 pts with true stage III CC recurred; the estimated 3y disease-free survival rate was 81%. The estimated 5y overall survival rates for the entire cohort and for true stage III pts were 82% and 90%, respectively. Of the 5 pts found to have metastatic disease based on PET-CT findings, one is scheduled to undergo potentially curative surgical removal of a solitary liver metastasis. Conclusions: Interim results from the first prospective study to evaluate the impact of early postoperative PET-CT in pts with pathological stage III CC seem to support earlier retrospective data: the use of PET-CT in this setting changed the staging and management of 8.6% of pts, including the possibility for early detection of potentially curable metastatic disease. Additional data, with more pts and longer follow-up, will be presented at the meeting.