tbuckley/cabot-search huggingface dataset:
Analysis of oxaliplatin-induced sensory neurotoxicity (sNT) in patients receiving FIREFOX, alternating regimen of mFOLFOX-6 and FOLFIRI, with metastatic colorectal cancer (MCRC): Results from combined analysis of KSCC0501 and KSCC0701.
Authors: T. Kusumoto, Y. Emi, Y. Kakeji, Y. Akagi, H. Samura, H. Baba, S. Natsugoe, S. Tokunaga, Y. Maehara
Journal: Journal of Clinical Oncology (2011)

492 Background: The Kyushu Study Group of Clinical Cancer (KSCC) conducted two phase II trials (KSCC0501 and KSCC0701, Akagi et al. J Clin Oncol. 28:15s, 2010, UMIN ID: 000001342) to evaluate the efficacy and safety of first-line oxaliplatin-based chemotherapy for MCRC. This combined analysis was performed to compare the incidence of oxaliplatin-induced sNT between the two trials. Methods: Patients (pts) were accrued from 2005 to 2007 in KSCC0501 and from 2007 to 2008 in KSCC0701. Sixty pts received FOLFOX-4 in KSCC0501 and 47 pts received FIREFOX(4 cycles of mFOLFOX-6 alternating with 4 cycles of FOLFIRI) in KSCC0701. All pts were reviewed for efficacy and toxicity (NCI-CTCAEv3.0). Kaplan-Meier analysis was performed to assess the incidence of sNT. Results: The incidence of sNT was 71.4% with FOLFOX-4 and 36.2% with FIREFOX (Table). The ORR was 34.5% (95% CI F22.5-48.1%) for FOLFOX4 and 58.7% (43.9-73.5%) for FIREFOX. Median PFS was 7.0 M (5.1-9.8 M) with FOLFOX-4 and 10.3 M (7.5-11.9 M) with FIREFOX. MST and 2-year survival were respectively 31.5 M (18.1-40.1 M) and 58.0% for FOLFOX4, versus not determined and 57.1% for FIREFOX. The median no. of treatment cycles was 9 for FOLFOX-4 and 12 for FIREFOX. After 4, 8, and 12 cumulative treatment cycles, the incidence of grade 2 + sNT was respectively 24.0%, 30.7%, and 60.5% with FOLFOX-4 versus 6.5%, 6.5%, and 16.0% with FIREFOX. Conclusions: As first-line oxaliplatin-based chemotherapy for MCRC, FIREFOX caused less oxaliplatin-induced sNT and prolonged the duration of treatment. We have now finished enrollment for study KSCC 0801 (KSCC 0701+bevacizumab) and are following the pts. [Table: see text] [Table: see text]
Evidence table development as a novel teaching tool in cancer survivorship education.
Authors: Michelle Shayne, Eva Culakova, Michael T. Milano, Louis S. Constine
Journal: Journal of Clinical Oncology (2016)

3 Background: We established a novel curriculum in Cancer Survivorship Education (CSE), as a collaborative effort between our accredited training programs in Hematology/Oncology and Radiation Oncology. The conceptual framework for all our coursework in cancer survivorship was grounded in the recommendations from the Institute of Medicine report from 2006. As a means of refining our CSE curriculum, we introduced Evidence Table (ET) development. ETs are formatted summaries of methods, data, and outcomes from related studies used to answer specific questions. ETs facilitate the development of recommendations and standards of care. ET development was proposed to enhance the CSE experience allowing trainees to: 1) understand data supporting survivorship recommendations, 2) practice grading the evidence, 3) become more critical in appraisal of published studies, and 4) discover areas where further research is needed to substantiate cancer survivorship care plans. Methods: A total of 19 trainees participated in academic year 2013-2014 and 18 trainees in 2014-2015. Trainees were required to define key questions pertaining to survivorship, probe the literature for available data addressing these questions, and develop ETs in which the evidence was then graded. To ascertain the value of this experience from the trainees’ perspectives, anonymous and voluntary pre- and post-Workshop surveys were administered. The course was modified after the first academic year based on results of a trainee feed-back. Results: Following course modification in 2014-2015, 92% of trainees responded that they used some of the learned course information in their clinics. This represents significant improvement from 45% the previous year (p = 0.02). Significant improvement was observed (from 18% to 67%) in the perception that the course influenced trainees' approach to the medical literature. Ninety-two percent responded that they learned more about survivorship as a result of the CSE Workshop. All trainees reported that, to some extent, CSE has helped to make them better oncologists. Conclusions: ET development is a feasible, meaningful, and novel approach to fostering independent learning in cancer survivorship.
Androgen deprivation therapy educational program: A Canadian true nth initiative.
Authors: Erik Wibowo, Lauren M Walker, Shawn Wilyman, Andrew Matthew, Deborah L McLeod, Richard J Wassersug, John W. Robinson
Journal: Journal of Clinical Oncology (2016)

243 Background: Androgen deprivation therapy (ADT) is commonly prescribed for advanced prostate cancer (PCa) patients, but ADT has many side effects that can impair patients’ quality of life. In various Canadian cities, we are running an educational program to help PCa patients and their partners deal with the side effects of ADT, and maintain a strong relationship with each other while on ADT. Methods: Patients, who are about to start or have been on ADT, and their partners are invited to attend an educational program. Each patient is given a copy of the book Androgen Deprivation Therapy: An essential guide for men with prostate cancer and their partners (Wassersug et al., 2014) and attends a 1.5 hour educational class, where they learn strategies for managing ADT side effects and how to effectively make healthier lifestyle changes using goal-setting exercises. At the end of the class, participants are given the option to attend a monthly follow-up session. To evaluate the effectiveness of the program, participants are asked to complete questionnaire package before attending the class and again 2-3 months later. Results: As of August 2015, 179 patients and 113 partners have attended the ADT Educational Program at Victoria, Vancouver, and Calgary. About 40% of patients returned for the follow-up session. 62 attendees participated in the research evaluation portion of the program. Uniquely designed for this study, the questionnaire package assesses ADT side effect frequency, bother associated with side effects, use of management strategies, and self-efficacy regarding side effect management. An assessment of physical activity and relationship adjustment, and feedback about the class are also included. Conclusions: Patients and partners appreciate being informed about ADT side effects managements and how to make healthier lifestyle changes while on ADT. It remains to be seen how effective the program is in limiting the bother from ADT side effects and helping couples maintain a strong dyadic relationship in the fact of the challenges brought on by ADT. Good enrollment in the in-person program in the 3 cities has propelled the development of the program in Halifax and Toronto starting in fall 2015, and an online version to be available in early 2016.
Prostate cancer (PC) follow-up and treatment by race in an equal access health system: A pilot study.
Authors: Nirupama Devi Mitikiri, Anitha Nallu, C. Daniel Mullins, Ebere Onukwugha, Arif Hussain
Journal: Journal of Clinical Oncology (2013)

177 Background: There are known racial disparities in the incidence and outcomes of PC as well as in receipt of treatment. Although some studies in the Veterans Affairs Health System (VA) suggest that utilization and outcomes are as good, if not better, for African Americans (AA) as for Whites (WH), race appears to have mixed impact on stage-specific PC survival in the VA population. This pilot study aims to identify racial disparities in PC care in an equal access health system such as the VA. Methods: A retrospective cohort study was conducted of 109 consecutive patients with newly diagnosed PC in the year 2010 at the Baltimore VA Medical Center (BVAMC). Baseline characteristics (age, prostate specific antigen (PSA) at diagnosis, Gleason score (GS), stage, race) were extracted from the electronic medical records. Patterns of treatment and follow-up care, including specialist (urologist, medical oncologist, radiation oncologist) visits, time to first treatment, and primary treatment in the first year of diagnosis were examined. Results: Of 109 patients, 32 (30%) were WH, 69 (63%) AA and 8 (7%) other racial groups. AA and WH had similar median age (62, 64), GS (7, 7) and PSA (8.06, 7.46) at diagnosis. More AA were diagnosed with stage IV PC compared to WH (13% vs. 3%). Median time to first follow-up specialist visit since diagnosis was 15 (0-140) and 19.5 (2-169) days for AA and WH, respectively. Median time to initial treatment was 99.5 (1-306) and 146 (6-345) days for AA and WH, respectively. For localized PC, 30% AA received prostatectomy (RP) and 70% external beam radiation therapy (EBRT); in WH it was 19% and 76%, respectively. Conclusions: In an equal access health system such as the BVAMC, there did not appear to be racial differences in PC follow-up with specialists and time to initial treatment. AA had more advanced disease at diagnosis. Interestingly, although both AA and WH received EBRT more often than RP for localized PC, AA underwent RP more frequently than WH. It will be of interest to determine whether these patterns hold for other years and in other equal access health systems.
PARADIGM study: A multicenter, randomized, phase III study of 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus panitumumab or bevacizumab as first-line treatment in patients with <i>RAS</i> (<i>KRAS/NRAS</i>) wild-type metastatic colorectal cancer.
Authors: Takayuki Yoshino, Hiroyuki Uetake, Katsuya Tsuchihara, Kohei Shitara, Kentaro Yamazaki, Eiji Oki, Takeo Sato, Takeshi Naitoh, Yoshito Komatsu, Takeshi Kato, Kouji Iwasaki, Junpei Soeda, Masamitsu Hihara, Takeharu Yamanaka, Atsushi Ochiai, Kei Muro
Journal: Journal of Clinical Oncology (2016)

TPS776 Background: Optimal combination of monoclonal antibody (anti-VEGF vs. anti-EGFR antibody) with standard chemotherapy as first-line treatment in patients (pts) with RAS (KRAS/NRAS) wild-type metastatic colorectal cancer (mCRC) remains controversial. FIRE-3 study demonstrated a significant improvement in overall survival (OS) with anti-EGFR over bevacizumab in pts with KRAS exon 2 wild type mCRC, while CALGB 80405 study did not. PARADIGM study is designed to compare panitumumab vs. bevacizumab combined with mFOLFOX6 in pts with RAS wild-type chemotherapy-naive mCRC. Methods: Eligible pts are aged 20-79 years with ECOG performance status (PS) 0-1 and histologically/cytologically confirmed RAS wild-type mCRC. 800 pts will be randomly assigned in a 1:1 ratio to mFOLFOX6 plus panitumumab or bevacizumab, and stratified according to institution, age (20-64 vs. 65-79 years), and liver metastases (present vs. absent). Each treatment regimen includes oxaliplatin 85 mg/m 2 , l-leucovorin 200 mg/m 2 , 5-fluorouracil (5-FU) iv 400 mg/m 2 at day 1, 5-FU civ 2400 mg/m 2 at day 1-3, and either panitumumab 6 mg/kg or bevacizumab 5 mg/kg at day 1 every two weeks. The primary endpoint is the OS; the study was designed to detect the OS hazard ratio of 0.76, with a one-sided type I error of 0.025 and 80% power. Secondary efficacy endpoints include progression-free survival, response rate, duration of response, and curative resection rate. One interim analysis is planned for the OS when approximately 70% of the targeted 570 events has been observed. Exploratory endpoint is to investigate possible biomarkers including oncogenic mutations using tumor tissue and circulating tumor DNA (Study ID: NCT02394834). As of August 2015, 21 pts have been randomized and recruitment is ongoing. Clinical trial information: NCT02394795.
Use of elevated insulin-like growth factor binding protein-1 (IGFBP-1) to predict outcomes in men with metastatic prostate cancer treated with androgen-deprivation therapy (ADT).
Authors: Jaya Sharma, Kathryn P. Gray, Mari Nakabayashi, Gillian Petrozziello, Carolyn Evan, Raina Fichorova, Philip W. Kantoff, Christopher Sweeney
Journal: Journal of Clinical Oncology (2012)

191 Background: IGF-1 has been shown to promote cancer growth by activation of PI3 kinase and downregulation of AMPK. IGFBP-1 shuttles IGF-1 across blood vessel membranes. Elevated IGFBP-1 blood levels may be indicative of tissue IGF-1 levels and has been associated with prostate cancer risk. We hypothesized that IGF-1 and IGFBP-1 blood levels might effect ADT efficacy. Methods: A retrospective analysis of IGF-1 and IGFBP-1 was undertaken in men commencing ADT for metastatic prostate cancer. Blood was drawn within one month of initiating ADT and stored. Proteins were measured using multiplex electrochemiluminescence assays. A cohort of 122 patients was compiled from a prospective trial (50 patients) and chart review (72 patients). A multivariate analysis (MVA) using a COX model was performed to identify associations between blood levels of the markers and time to the development of castration resistant prostate cancer (CRPC) and overall survival (OS). The covariates analyzed were age at time of ADT, ECOG score, race, baseline PSA, and extent of disease. Results: At time of initiating ADT the cohort had a median age of 67 years, PSA of 27.4 and 82% had ECOG 0. 91% were Caucasian. 62% had extensive metastatic disease. Median OS was 42.2 months. The median (med) baseline levels for IGF-1 was 75.6 ng/ml and for IGFBP-1 was 1844 pg/ml. As detailed in the table, patients with IGFBP-1 levels above the median had significantly shorter time to development of CRPC and OS on MVA. There was no association between IGF-1 levels and time to CRPC development or OS. Conclusions: Elevated levels of IGFBP-1 are associated with shorter duration of ADT efficacy in men with metastatic prostate cancer. This correlative data supports the ongoing SWOG trial assessing whether IGF signaling blockade improves ADT efficacy, as has been seen in preclinical models. [Table: see text]
Identification of germline genetic mutations in patients with pancreatic adenocarcinoma.
Authors: Erin E Salo-Mullen, Eileen Mary O'Reilly, David Paul Kelsen, Maeve Aine Lowery, Kenneth H. Yu, Rohini Rau-Murthy, Beth Siegel, Leonard Saltz, Robert C Kurtz, Kenneth Offit, Mark E. Robson, Zsofia Kinga Stadler
Journal: Journal of Clinical Oncology (2013)

159 Background: The emergence of PARP-inhibitors for potential treatment of BRCA-associated cancers highlights the importance of identifying germline mutations in individuals with pancreatic adenocarcinoma (PAC) (NCT 01585805 for PARP-i in PAC). Optimal selection of PAC patients for genetic testing remains to be determined. Our objective was to investigate prevalence of germline mutations in our PAC patients. Methods: MSKCC Clinical Genetics database was reviewed for PAC patients offered germline testing from 1/1/2011 to present. Clinical data was extracted from records. Pedigrees were reviewed to verify NCCN (PAC at any age with ≥2 close relatives with breast/ovarian/PAC at any age) and/or other testing criteria. Results: 70 PAC patients (33 males, 40 Ashkenazi Jewish (AJ)) were seen; 36 met NCCN criteria and 16 were AJ with 1 close relative with breast/ovarian/PAC. Of 18 not meeting these criteria, 7 were AJ, 3 were early-onset, and 7 were non-AJ with at least 1 additional BRCA-associated cancer in either themselves or a close relative. 63 patients accepted BRCA testing: 6 (9.5%) had a BRCA1 (n=2) or BRCA2 (n=4) mutation. Only 2 of these met NCCN criteria; 3 were AJ with 1 close relative with a BRCA-associated cancer; and 1 was non-AJ descent with 1 close relative with early-onset breast cancer. 36 AJ patients pursued BRCA testing: 4 (11.1%) had a BRCA1 (n=1) or BRCA2 (n=3) mutation; all were founder mutations. Additional genetic testing, based on family history, identified 1 MSH2 mutation, 1 MSH6 mutation, and 1 p16 mutation. Overall mutation detection rates were 13.6% (9/66) in total cohort who pursued any genetic testing and 15.8% (6/38) in tested AJ group. 6 patients with PAC before age 50 were tested: 1 non-AJ patient had a BRCA1 mutation and 1 (with history of melanoma) had a p16 mutation. Conclusions: With mutation detection rates of nearly 14% in total tested population &amp; 16% in AJ cohort, germline genetic testing is important for PAC patients with potential implications for treatment and for relatives. By limiting BRCA testing to patients who meet current NCCN testing criteria, 66.7% (4/6) of our patients with BRCA mutations would not have been identified. Reassessment of testing criteria is needed for optimal care of PAC patients.
Expanded criteria in men on active surveillance monitored by MRI-TRUS fusion biopsy.
Authors: Thomas P Frye, Steven F. Abboud, Richard Ho, Michele Fascelli, Raju Chelluri, Arvin Koruthu George, Peter L. Choyke, Baris Turkbey, Bradford J. Wood, Peter A. Pinto
Journal: Journal of Clinical Oncology (2016)

115 Background: Active surveillance (AS) is an established option for men with prostate cancer. Studies have shown that multiparametric-MRI along with MRI-TRUS fusion-guided biopsy (FB) may better assess risk in patients eligible for AS, compared to 12-core biopsy, due to improved detection of clinically significant cancers. The objective is to evaluate the performance of expanded criteria eligibility in men on AS being monitored with MRI-TRUS guided biopsy. Methods: Men on AS were included if they had mp-MRI and pathology data for 2 or more FB sessions. FB procedures consisted of targeted biopsies and random 12 core biopsies. Men participated in AS with low and intermediate risk prostate cancer, Gleason score ≤ 3+4=7 with no restriction on percent core involvement or number of cores positive. Progression was defined by patients with initial Gleason 3+3=6 to any Gleason 4, and Gleason 3+4=7 disease progressing to a primary Gleason 4 or higher. Results: 124 men on AS met study criteria. Low risk men had a mean age of 61.3 years versus intermediate risk men with a mean age of 65.5 years (p=0.0062). Mean PSA levels of the low and intermediate risk groups were 5.8 and 5.76 ng/ml (p=0.95), respectively. The mean length of follow-up was 22.56 months (range: 3.6 – 74.4 mo). Rates of pathologic progression in the intermediate and low risk patients were, 38.5% vs. 28.5% (p=0.33). Intermediate risk men had a mean progression-free survival (PFS) of 2.8 years compared to low risk men of 3.9 years (p=0.27). Patients were stratified according to established AS criteria (Epstein, Toronto, PRIAS) and rates of progression are summarized in the Table. 69% of patients met Epstein criteria for AS of which 29.4% (20/68) progressed compared to 28.5% for the low risk cohort overall. Conclusions: Men in our cohort who met strict criteria for AS had the same rate of progression as the entire expaned criteria low risk cohort, 29.4% vs 28.5%, respectively. Our data suggests that with accurate initial Gleason classification other AS criteria such as percent core or number of cores positive have no added benefit in predicting which men may have reclassification or progression of disease. [Table: see text]
Epigenetic inactivation of HOXA5 and MSH2 gene in clear cell renal cell carcinoma.
Authors: Seung-Kwon Choi, Joong Geun Lee, Koo Han Yoo
Journal: Journal of Clinical Oncology (2012)

424 Background: The high-throughput method using microarray is easy and fast way to analyze the methylation status of hundreds of preselected genes and to screen them for signatures in methylation. The aim of our study is to detect hypermethylated genes and to analyze the association between methylation status and clinicopathological parameters of clear cell renal cell carcinoma. Methods: The genetic substrate included 62 cancer tissues and 62 matched adjacent normal kidney tissues. We adapted the GoldenGate genotyping assay to determine the methylation state of 1505 specific CpG sites in 807 genes. Results: We identified two genes (HOXA5 and MSH2) with β-value differences of more than 0.3 between cancer and normal tissues. High methylation group in HOXA5 had high Fuhrman’s nuclear grade (P=0.041). Other data in HOXA5 and MSH2 were not significant with methylation status (P&gt;0.05). Survival curve of high methylation group in HOXA5 was slightly lower than that of low methylation group. However, the statistical significances of overall survival in HOXA5 and MSH2 were low (P&gt;0.05). Conclusions: We report the hypermethylation of two genes in clear cell renal cell carcinoma. The data we obtained could provide the basis for a diagnostic test pathological assessment, or prognosis in clear cell renal cell carcinoma.
<i>KRAS</i> mutation as a prognostic factor in patients undergoing hepatic resection for metastatic colorectal cancer.
Authors: Justin John Baker, Rachel Aufforth, James Todd Auman, Robert Eil, Howard L. McLeod, Hong Jin Kim, Michael O. Meyers, Benjamin F. Calvo, Jen Jen Yeh
Journal: Journal of Clinical Oncology (2012)

444 Background: It is well known that KRAS mutations limit the efficacy of anti-EGFR therapy in patients with metastatic colorectal cancer (mCRC). However the role of KRAS mutations in patients who undergo a curative liver resection for mCRC is less clear. The purpose of our study was to evaluate the relationship between KRAS mutation status and survival in this patient population. Methods: We examined an IRB approved tissue repository and retrospective database of 129 patients from 1998-2010 who underwent curative liver resection for mCRC. Tumors were sequenced for KRAS codons 12, 13, and 61 mutations using pyrosequencing. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression method. Results: The median follow-up for our cohort was 20.4mo (0.4-112). Mean age was 61.4±12.3. Prior to surgical resection 55 (43%) patients received chemotherapy. 35 (27%) tumors were KRAS mutant (mt), 83 (64%) were wild-type (wt), and 11 (9%) were not characterized. Median OS for KRAS wt patients was 40.3mo vs. 27.1mo for KRAS mt patients (p=0.046). Median DFS for KRAS wt was 13.6mo vs. 7.7mo for KRAS mt patients (p=0.037). 8 patients received cetuximab post–operatively. Cetuximab status was unknown in 50 patients. When we excluded those treated with cetuximab, the median OS was 40mo for KRAS wt vs. 25mo for KRAS mt patients (p=0.007). There were no differences in OS or DFS in patients who received cetuximab (p=0.7). In a multivariable model with pre-operative chemotherapy (p=0.2), extent of resection (p=0.053), and cetuximab therapy (p=0.7), the presence of KRAS mutation was independently associated with poor prognosis (HR=2.7 [1.3-5.5]). Conclusions: In patients undergoing curative liver resection for mCRC, KRAS mutation status is independently predictive of a worse outcome regardless of cetuximab therapy. KRAS status may be associated with more aggressive tumor biology. Our data supports the critical need to define KRAS mutation status and to develop therapies against KRAS and its downstream effectors.