tbuckley/cabot-search huggingface dataset:
The American Brachytherapy Society and the American Radium Society Appropriate Use Criteria Genitourinary Committee Endorse the American Society of Clinical Oncology/Cancer Care Ontario Guidelines
Authors: Albert J. Chang, Sean McBride, Mira Keyes, Hans T. Chung, Brian J. Davis, Brett W. Cox, Juanita Crook, David J. Demanes, I. Chow Hsu, Mitchell Kamrava, Daniel J. Krauss, Gerard Morton, Peter F. Orio III, Mack Roach III, Puja S. Venkat, Eric Vigneault, Michael J. Zelefsky
Journal: Journal of Clinical Oncology (2018)
Special considerations of DMCs for oncology studies.
Authors: David Kerr, Kent Koprowicz
Journal: Journal of Clinical Oncology (2017)

e20071 Background: Data Monitoring Committees (DMCs) are an important component of the clinical trial process. They are charged with reviewing interim data and making recommendations to protect the safety of trial participants and ensure the scientific integrity of the study. Oncologists may be involved with the DMC process in a number of ways – as a DMC member, as an investigator, as a sponsor, or in a regulatory role. This presentation will discuss novel aspects of the DMC review process that are particularly relevant for oncology trials. Methods: The authors are leaders of a Contract Research Organization (CRO) that specializes in providing independent DMC services for government and industry sponsored trials. They have worked with hundreds of unique DMCs and facilitated approximately 1,000 DMC meetings. The proposed methodologies for maximizing the efficiency and thoroughness of DMC reviews are based on extensive experience and well-established principles. Results: Topics that will be covered include: Discrepant trends in PFS vs. OS PFS results that are inconsistent between local and central assessment, or are not yet centrally assessed Co-primary endpoints – OS, PFS, ORR, CR Multiple populations of interest – ITT and a biomarker subgroup Interim analyses – overwhelming efficacy and statistical futility Program-wide DMCs – interpreting trends across multiple studies and logistical details Safety assessment in a study with thousands of AEs – novel graphics and tables Laboratory values and vital signs – novel graphics and tables Multiple comparisons and/or multiple p-values Non-standard tables, listings, figures that are particularly useful for DMC review Open-label studies – immediate withdrawals for those randomized to control arm and other potential biases Single-arm studies – how to interpret safety with no control arm Novel therapies – immune-oncology, CAR-T, small sample sizes CIOMS reports or patient narratives Conclusions: DMCs will perform a more thorough and efficient review of accumulating data upon adapting the guidance provided. A more thorough review will enhance the protection of the trial participants while a more efficient review will allow DMCs to focus their efforts appropriately.
Costs of pre-hospice care among metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone + prednisone (ABI) and enzalutamide (ENZ).
Authors: Sophia S Li, Nicole Engel-Nitz, Cori Blauer-Peterson, Ajay S. Behl, Nancy Ann Dawson
Journal: Journal of Clinical Oncology (2017)

e16534 Background: mCRPC patients are likely to receive oral therapies such as ABI or ENZ prior to hospice care. Payers and clinicians perceive hospice care as improving the quality of life for advanced prostate cancer patients dying of cancer, but literature suggests that it may be underutilized. A previous study found a longer time to starting hospice for patients initiated on ABI (vs. ENZ) with no significant difference in time spent in hospice. Understanding the active-treatment period prior to hospice may shed light on the overall burden of treatment without discounting the benefits of hospice. This study examined total pre-hospice per patient per month (PPPM) costs among mCRPC patients who utilized hospice care and treated with ABI or ENZ. Methods: A retrospective study of a large national health claims database identified patients initiated on ABI or ENZ from 09/2012 to 06/2015. Patients included had: ≥1 claim with a prostate cancer diagnosis (ICD-9-CM 185.xx) from 6 mo. pre- to 30 days post-index; ≥6 mo. pre- and ≥3 mo. post-index health plan enrollment. Index was date initiated on first oral therapy (ABI/ENZ). The subset of patients who entered hospice care were identified. Descriptive analyses assessed total PPPM costs (pharmacy, ambulatory, ER, inpatient, other medical costs) for subset of pre-hospice patients and all patients. Generalized linear model (GLM) assessed adjusted pre-hospice costs. Since the GLM used a log-link function with cost as a dependent variable, results are interpreted as a ratio of costs. Results: Among 1,516 mCRPC patients, 213 had utilized hospice care (ABI: 161, ENZ: 52). Total pre-hospice PPPM cost was greater for patients initiated on ENZ (ENZ = $19,485 ABI = $13,252; p = 0.048). Adjusted analysis found a 25.8% greater PPPM cost for those patients (Cost Ratio = 1.26, p = 0.038). Among all 1,516 patients, total all-cause PPPM cost was higher in ENZ but not statistically significant (ENZ = $11,268 ABI = $10,520; p = 0.090). Total prostate cancer related PPPM cost was statistically significant (ENZ = $10,327 ABI = $9,477, p = 0.038). Conclusions: Total pre-hospice PPPM cost is 26% lower for mCRPC patients initiated on ABI vs. ENZ.
MELADIAG: A panel of DNA biomarkers dedicated to melanoma diagnosis.
Authors: Meriem Benfodda, Eduardo Marinho, Rajiv Kumar, Jerome Lamoril, Marion RÃ Â©ocreux, Olivia Beaudoux, Florent Grange, Lydia Dechamps, Armand Bensussan, Yacine Merrouche, Nadem Soufir
Journal: Journal of Clinical Oncology (2016)

e23258 Background: Genetics of melanoma (MM) has greatly progressed in the last decades by the discovery of mutations in BRAF, NRAS and KIT. However, there is a large genetic variability not only of a tumor to another but also depending on the stage of the disease. In order to deepen our knowledge about this and for a purpose referred to therapeutic and prognosis we studied 118 MM tumors and 73 nevi by target next generation sequencing. Methods: After extraction, tumor DNA of 118 tumors (44 metastatic tumors, 46 SSM, 11 ALM, 5 nodular, 2 Dubreuilh and 3 spitzoid) and 73 nevi (50 benign nevi, 18 dysplastic nevi and 5 spitzoid nevi) were sequenced using a panel of 15 genes (ALK, BRAF, CDKN2A, CTNNB1, GNA11, GNAQ, KIT, NOTCH1, NOTCH2, NRAS, RAC1, RAF1, SF3B1, TERT and TP53) on a new generation sequencer (PGM Ion Torrent) using chips 318 with a depth > 51000x . The analysis of the variants was made by dedicated software (Ion Reporter, wAnnovar) and we selected only those which had a sufficient quality score. Results: The results of the sequencing showed the presence of very large number of mutations. In the begnin nevi, excepting BRAF mutations (V600E and V600K, present in 86%) there were no other mutations. At the opposite, the percentage of mutations in many other genes (ALK, KIT,CDKN2A,TP53...) in MM tumors range from 55% (Breslow < 1mm) to 90% in metastatic tumors. More than 80% of mutations were transitions C > T reflecting the UV-induced mutagenesis. Interestingly, in 33% of atypical and Spitz nevi, we also found at least one mutation in one of these genes (40% of these mutations were reported in Cosmic databases). Comparison of the proportion of somatic mutations between the different types of nevi, tumors with low thickness and metastatic tumors clearly showed an accumulation of somatic mutations during tumor development. Conclusions: This chip dedicated to MM is interesting: high sensitivity, allowing a better tumor classification and rapid identification of therapeutic targets. In addition, it could help for MM diagnosis in case of pigmented lesions with atypical component or uncertain diagnosis. In a second step, this panel of markers will be used to detect circulating tumor DNA in plasma of patients and to correlate their presence with melanoma prognosis.
Outcomes of metastatic adrenocortical carcinoma (ACC): A 16-year single institutional experience.
Authors: Dwight Hall Owen, Sandipkumar Patel, John E Phay, Lawrence Andrew Shirley, Lawrence S Kirschner, Carl Richard Schmidt, Sherif Abdel-Misih, Pamela Brock, Lai Wei, Manisha H. Shah, Bhavana Konda
Journal: Journal of Clinical Oncology (2017)

e16088 Background: ACC is a rare malignancy with limited data to guide management of metastatic disease. Prior research regarding survival has focused on pts with locoregional disease, but has not offered insight into the management and outcomes of pts with metastatic disease. Methods: We retrospectively reviewed patients (pts) with metastatic ACC who were treated with systemic therapy between January 2000 and October 2016 at The Ohio State University Comprehensive Cancer Center. Kaplan-Meier and Cox proportional hazards regression models were used for survival analysis. Results: A total of 18 pts received systemic therapy for distant metastatic disease. Median age at diagnosis was 51 (range 31 – 72). Median overall survival (OS) from time of diagnosis of ACC was 15.5 months (95% CI 4.8 – 28.2), and from time of systemic treatment (ST) was 7.1 months (95% CI 3.3 – 26). A germline variant of uncertain significance in MSH2 (c.138C &gt; G) was identified in one patient. Baseline FDG-PET scans were obtained in 11/18 pts, and demonstrated avidity in all patients. Maximum SUV ranged from 4.1 to 47.6, with a median of 15. First line therapy was etoposide, doxorubicin, cisplatin, and mitotane (EDPM) in 13/18 pts and clinical trial with IMC-A12 (IGF-1 receptor antibody) in four pts. Median duration of first line therapy was 1.8 months (95% CI 0.9 – 2.8). Survival was not statistically different for patients receiving EDPM as first or second line therapy (median OS 23.3 vs 12.0 months, p = 0.96). Additional lines of therapy included EDPM, IMC-A12, AT-101, mifepristone, OSI-906 (IGF-1R inhibitor), and nivolumab. Median lines of therapy given were 2. The presence of bone metastases (p = 0.69) or lung metastases (p = 0.21) at the time of initiation of ST was not associated with OS from ST. Conclusions: In our experience, the prognosis of pts with metastatic ACC receiving systemic therapy is poor with most pts receiving ≤ 2 lines of therapy. Patients receiving first or second line EDPM seemed to have worse outcomes than noted in previously published trials, possibly due to our patients being sicker at baseline. Metastasis to the lung or bone at initiation of ST did not impact OS.
Clinical and pathological analysis of eleven adult patients with inflammatory myofibroblastic tumor.
Authors: Xin Liu, Xiaowei Zhang, Huijie Wang, Chunmeng Wang, Yong Chen, Jian WANG, Zhiguo Luo
Journal: Journal of Clinical Oncology (2018)

11545 Background: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal malignancy which occurs primarily in children and adolescents. Complete surgical resection is the major treatment, and conventional chemotherapy and radiotherapy are usually invalid. In this study, we retrospectively analyzed the clinical and pathological features of eleven patients with adult IMT. Methods: A total of eleven patients with adult IMT were enrolled into this study between February 2013 and November 2017. The clinical, pathological data, treatment and prognosis were analyzed. Results: Among the eleven patients with adult IMT, five patients were male (45%), six patients were female (55%), and the median age was 39 (24-74 years). The primary tumor was located in two patients (18%) in the lung and two cases (18%) in the retroperitoneum, and seven cases (64%) in the abdominopelvic region. Four cases were abdominal epithelioid inflammatory myofibroblastic sarcoma. The positive rate of anaplastic lymphoma kinase (ALK) immunohistochemical expression was 82% (9/11), and the positive rate of ALK translocation was 86% (6/7). Seven patients with ALK-positive advanced disease received the treatment of ALK inhibitor crizotinib, the response rate was 86%, and the median progression free survival (PFS) was 20.8 months (95% confidence interval: 7.6 months-34.0 months). Two patients were treated with the more potent ALK inhibitor ceritinib after progression of disease on crizotinib and both of them showed significant and durable partial responses. Conclusions: The treatment of crizotinib in adult patients with ALK-positive advanced IMT resulted in a very high response rate and a long-term PFS, and the patients still responded to the next generation of ALK inhibitor after the failure of crizotinib in our study, which suggested that ALK signaling pathway may play an important role in the development of adult IMT. Further studies are warranted to clarify the effects of ALK signaling pathway and the mechanism of ALK inhibitor resistance in adult patients with IMT.
P04.80 Diagnostic potential of the IgM igOme (IgM repertoire) biomarkers for brain tumors
Authors: V Kostov, D Ferdinandov, V Shivarov, T Vassilev, E Hovig, A Pashov
Journal: Neuro-Oncology (2018)

A proportion of the human IgM repertoire (IgM igome) antibodies is partially autoreactive and by interacting with intrinsic structures, this part can reflect changes in the internal environment. Thus, it can be a potential source of biomarkers for various pathological processes. The aim of the current study is to create an optimal library of probes (IgM mimotopes) to test the applicability and the diagnostic potential of IgM igome biomarkers for patients with brain tumors using a method that is clinically suitable and convenient. Sera from 34 patients with glioblastoma (GBM), cerebral metastases of breast cancer (MB) and from non-tumor-bearing patients (C) (e.g. trauma, etc.) were tested using custom PEPperPRINT™ microarray chips containing a set of 594 7-mer peptides selected from 220 000 IgM mimotopes. The chips were scanned using a GenePix 4000 Microarray Scanner and the data was normalized and analyzed using cluster analysis based feature selection. An optimal feature set was used to build a proof of principle model separating glioblastoma from other brain tumors using kernel based support vector machine. An IgM mimotope library containing 220 000 7-mer sequences was used to select an optimal set of 594 mimotopes designed as a multipurpose diagnostic tool. In a proof of principle predictor it differentiated between the three groups of brain tumor patients based on the mimotope reactivities of the individual patients’ sera. Four cases of GBM and two cases of breast cancer metastases set aside as a testing set were diagnosed correctly using a GBM-targeted feature set based on 8 controls, 11 GBM and 9 lung cancer metastasis patients. IgM repertoire monitoring can be used as a diagnostic tool to provide clinically relevant information regarding neoplasms, including tumors of the central nervous system, and has the potential to be used as a predictor in the future.
Trajectory of recurrent falls in postmenopausal breast cancer survivors and matched cancer-free controls.
Authors: Kathy Pan, Arti Hurria, Roberta M. Ray, Jane A. Cauley, Aladdin H. Shadyab, Rowan T. Chlebowski
Journal: Journal of Clinical Oncology (2018)

e22100 Background: Cross-sectional studies suggest that falls are more prevalent among older cancer survivors than those without cancer. While nearly half of breast cancer survivors are > 70 years old, fall risk in this population has not been comprehensively examined. Therefore, we compared recurrent fall risk in older breast cancer survivors to risk pre-cancer diagnosis and to risk in cancer-free women. Methods: In the Women’s Health Initiative (WHI), 161,808 postmenopausal women aged 50-79 were recruited at 40 U.S. clinical centers from 1993-1998 and queried semiannually or annually about number of falls over the previous reporting period. We identified women with stage I-II breast cancer diagnosed at age ≥60 who were assessed for falls during the three years before and three years after cancer diagnosis. Cases were matched 1:1 to controls by age, calendar year of WHI entry, and baseline fall frequency in the three-year pre-diagnosis interval or corresponding interval for controls. The primary outcome, proportion of each group reporting recurrent falls (defined as ≥2 falls in any 12 month period), was compared between groups using McNemar’s test. Adjusted odds ratios were calculated using conditional logistic regression models. Results: 2058 women with breast cancer were matched with 2058 cancer-free controls. Mean age at diagnosis was 70 years (SD 6.53). Over the three-year pre-diagnosis interval, 18.6% of breast cancer survivors reported recurrent falls. Over the three-year post-diagnosis interval, 22% of survivors reported recurrent falls compared to 20.1% of cancer-free controls over the same period (P = 0.13). Odds of recurrent falls in women with breast cancer did not differ from that in controls over the corresponding interval (OR 1.13, 95% CI 0.97-1.33), even after adjustment for race/ethnicity, BMI, physical function, alcohol use, vision problems, and chronic conditions. Conclusions: In contrast to prior reports, older breast cancer survivors in this study were no more likely to have recurrent falls than age-matched counterparts. These findings underscore the need for incorporation of cancer-free control populations in survivorship studies to distinguish cancer sequelae from normal aging.
A multicenter, randomized, double-blind, placebo-controlled phase III study of apatinib or placebo plus gefitinib as first-line treatment in patients with <i>EGFR-</i>mutant advanced non-small cell lung cancer (NSCLC).
Authors: Hongyun Zhao, Zhonghan Zhang, Fan Luo, Yuxiang Ma, Wenfeng Fang, Yunpeng Yang, Yang Zhang, Yan Huang, Li Zhang
Journal: Journal of Clinical Oncology (2018)

TPS9116 Background: Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathway is becoming an encouraging strategy in the treatment of advanced NSCLC. Apatinib is a tyrosine kinase inhibitor that selectively inhibits the VEGF receptor-2. Our phase I study of Apatinib plus Gefitinib has shown a manageable tolerability profile and promising antitumor activity with an anticipated progressive-free survival (PFS) > 14 mos. This phase III study aims to evaluate the efficacy and safety of Apatinib or placebo plus Gefitinib as first-line treatment in patients (pts) with stage IIIB-IV NSCLC harboring an activating EGFR mutation. Methods: Treatment-naïve stage IIIB or IV NSCLC pts with EGFR 19 Del or 21 L858R mutation are enrolled. Other inclusion criteria include ECOG PS of 0 or 1, ≥1 measurable lesion according to RECIST v1.1 and adequate organ function. Eligible pts will be randomized in a 1:1 ratio to receive either Apatinib or Placebo 500 mg QD plus Gefitinib 250 mg QD until progressive disease or unacceptable toxicity. Stratified randomization is based on EGFR mutation status, gender and ECOG PS. The primary endpoint is PFS. Secondary endpoints include overall survival, objective response rate, disease control rate, time to progression, duration of response, quality of life and the safety profile. Independent Data Monitoring Committee and Independent Review Committee will be used in this study. According to previous report (erlotinib plus bevacizumab vs. erlotinib alone: 16.0 vs. 9.7 mos, HR 0.54, Lancet Oncol, 15(11):1236-1244), it was assumed that the estimated median PFS would be 15 mos in the Apatinib + Gefitinib group and 10 mos in the Placebo + Gefitinib group. To detect a 5-mos improvement of PFS in Apatinib + Gefitinib group at a two-sided significant level of 0.05 and a power of 0.8, allowing for a dropout rate of 20%, the sample size should be 155 patients per group. In total, 310 patients will be enrolled in this trial at 30 sites in China. From August 2017, 100 patients have been enrolled. Clinical trial information: NCT02824458.
Transcriptomic activity of apoptosis regulatory genes during uterine tissues malignization.
Authors: Dmitry I. Vodolazhsky, Oleg Ivanovich Kit, Denis S. Kutilin, Ivan Nikitin, Tatiana Moiseenko, Elena Mikhaylovna Frantsiyants, Natalia V. Chernikova
Journal: Journal of Clinical Oncology (2016)

e17125 Background: Changes in apoptosis signaling pathways are now considered to play a significant role in uterine tissue malignization process. Therefore, the purpose of our study was the screening of expression of genes responsible for the regulation of pro- (BAX, CASP7, CASP3, CASP8, CASP9, p53) and anti-apoptotic signaling pathways (MDM2, BCL2, CFLAR) during malignization of uterus in order to create a panel of specific tumor markers. Methods: This study used biopsies of conditionally healthy and tumor tissues of 27 patients aged 33-75 years with histologically confirmed diagnosis of uterine cancer. Relative expression of genes was determined by RT-qPCR (ACTB gene – reference). Total RNA was isolated from tissue by Chomczynski&Sacchi method. Reverta-L reagent kit (Russia, InterLabService) was used to synthesize cDNA library. Primers were designed using the NCBI GenBank database. RT-qPCR amplification was performed on Thermal Cycler Bio-Rad CFX96 (Bio-Rad, USA). Results: All patients were divided into two groups - up to 55 years and older than 55 years. Patients older than 55 years showed significant increase in expression of pro-apoptotic gene BAX by 80% (p < 0.0005) in tumor compared with healthy tissue, and patients under 55 years did not show significant changes in gene expression. Patients with G1 uterine adenocarcinoma (median age 63 years) showed significant (p < 0.05) increase in the expression of genes MDM2, CASP3, CASP9, BCL2 and p53 by 85%, 222%, 131%, 100% and 98 %; patients with G2 uterine adenocarcinoma (median age 59 years) - increase in expression of gene BAX by 79% (p < 0.005); patients with G3 uterine adenocarcinoma (median age 58 years) - significant (p < 0.005) increase in expression of genes CASP7, CASP8 and CASP3 71%, 90% and 53% respectively in the tumor tissue compared with healthy uterine tissue. Conclusions: Gene expression has characteristics associated with age and stage of tumor cell differentiation during uterine tissue malignization. Thus, a simultaneous increase in expression of both pro-apoptotic and anti-apoptotic genes was observed in patients with G1 grade of tumor cell differentiation, while in patients with G2 and G3 only pro-apoptotic genes expression increased.