tbuckley/cabot-search huggingface dataset:
Intermittent chemotherapy (CT) plus continuous or intermittent cetuximab (C) in the first-line treatment of advanced colorectal cancer (aCRC): Results of the two-arm phase II randomized MRC COIN-B trial.
Authors: Harpreet Wasan, Richard A. Adams, Richard H. Wilson, Cheryl Pugh, David Fisher, Ayman Madi, Bruce Sizer, Rachel Butler, Angela M. Meade, Tim Maughan
Journal: Journal of Clinical Oncology (2012)

536^ Background: COIN-B is a trial of intermittent chemotherapy (ICT) plus intermittent cetuximab (C) vs ICT plus continuous C in the first-line treatment of aCRC. It complements the COIN trial by investigating how C might safely and effectively be added to an ICT strategy. Methods: Patients (pts) had measurable aCRC; no prior CT for metastases; WHO PS 0-2 and good organ function. Randomisation was: Arm D - continuous OxFU + weekly C for 12 wks then a planned break from all therapy; Arm E - OxFU + weekly C for 12 wks then weekly C. Upon RECIST progression on either arm, OxFU (or FU) plus C was restarted and continued until progression on maximal tolerated therapy. Prospective KRAS testing was introduced in May 2008. Primary outcome measure is Failure-Free Survival (FFS) at 10 months (mo) in KRAS-wt pts who had not progressed, died or failed the treatment strategy within 3 mo of randomisation. The trial was powered to differentiate between a desired 10-mo FFS rate of 50% and a minimum of 35%, in 136 pts (168 allowing for drop-outs). Secondary outcome measures included safety, overall survival (OS) and toxicity. Results: 169 KRAS-wt pts were randomised 07/07 to 06/10, 77 arm D / 92 arm E. Median age 64 years (IQR 55-70); 92% PS 0-1. In Arms D and E respectively, 65 (84%) and 67 (73%) pts were eligible for the primary analysis; 10-mo FFS rates were 48% vs 54% (one-sided 95% confidence limit 37% and 43% respectively). Median FFS was 12.0 vs 13.7 mo respectively (IQR 6.1-20.3 and 8.6-23.2). Median OS was 20.1 vs 18.4 mo. First CFI length was 3.7 mo vs 5.1 mo (IQR 2.5-6.2 and 2.5-8.9). In pre-planned exploratory analysis, median time to progression/death after chemo break was 3.1 mo (IQR 2.1-8.1) in Arm D and 6.0 mo (IQR 2.9-10.9) in Arm E. Toxicity was similar and only 1 arm D pt had G 3 hypersensitivity following C reintroduction. Analyses by BRAF &amp; NRAS (tested retrospectively) will be presented. Conclusions: C was safely incorporated in 2 ICT strategies. Continuous C as maintenance was associated with a longer CFI and longer time to progression/death. This encouraging strategy of incorporating biological maintenance therapy needs validation in phase III trials.
Somatic Point Mutations in RUNX1/CBFA2/AML1 Are Common in High-Risk Myelodysplastic Syndrome, but Not in Myelofibrosis with Myeloid Metaplasia.
Authors: David P. Steensma, Richard J. Gibbons, Ruben A. Mesa, Ayalew Tefferi, Douglas R. Higgs
Journal: Blood (2004)
Retrospective study to evaluate prostate cancer screening in a resident practice at a major teaching hospital.
Authors: V. Sahai, A. Sharma, A. Skandhan, K. Lochinski, C. Reese
Journal: Journal of Clinical Oncology (2010)

e15008 Background: The American Cancer Society recommends against routine prostate cancer screening but encourages discussion of potential benefits and limitations of screening. All primary care physicians are required to discuss and document that they adequately informed as well as involved their patients in shared decision making (SDM). This is a retrospective study to investigate resident physician behavior with screening and SDM as well as the impact of training year or gender on screening practices. Methods: A total of 318 male patients between ages 50 and 74 were seen on 3 or more visits between 2007 and 2008 at the residents' continuity practice which serves an economically disadvantaged urban population. Mean age (+SD) of the population was 58.21(+6.48) with 42.45% Caucasian, 54.71% African-American and 2.83% other. Patients were seen on an average (+SD) 6.76(+2.98) visits between the study period January 2007 and December 2008. Statistical analysis was done using Microsoft Excel 2007 and SAS v9.1. Results: Out of total patients seen, the resident physicians screened (prostate-specific antigen [PSA] or digital rectal examination [DRE]) 27.35%, and had SDM discussion with 1.21%, while 8.36% were evaluated by Urology. Screening with both PSA and DRE, or SDM was done in 11.5% patients. DRE was offered to 12.71% with refusal by 25% of patients. Third year residents screened 19.86%, while second and first year residents screened 10.62% and 5.57% patients respectively; Chi-square 9.012 (dF=2) and p-value significant at 0.01. Male and female residents did not screen 44.75% and 19.23% patients respectively; Chi-square 8.85 (dF=1) and p-value significant at <0.01. DRE was done by 53.42% and 46.58% male and female residents respectively; Chi-square 3.03 (dF=1) with p-value 0.08. Conclusions: This is the first study to analyze resident behavior for prostate cancer screening and SDM. Our study suggests that there is considerable opportunity to address SDM counseling in the residents' practice. As with other ambulatory quality research initiatives in our practice, this information will be shared with the residency with plans to track improvement in this area. No significant financial relationships to disclose.
Frequency of fertility discussions among young patients diagnosed with colorectal cancer.
Authors: A. Kumar, A. Merali, G. R. Pond, K. M. Zbuk
Journal: Journal of Clinical Oncology (2011)

e19735 Background: Colorectal cancer (CRC) is the 3rd most common malignancy with 6% of cases diagnosed in the first four decades of life. Chemotherapy and radiation may lead to infertility in patients with cancer. In younger patients, fertility risks and options should be discussed when developing a treatment plan. In 2006, ASCO established guidelines on fertility preservation in cancer patients, but recent data suggests these are not widely followed. A retrospective chart review was performed at our institution amongst patients under age 40 with newly diagnosed CRC to identify the frequency of fertility discussions and what characteristics influenced the rate of discussion. Methods: Charts of patients aged 18-40 years with newly diagnosed CRC presenting to the Juravinski Cancer Center from 2000-2009 were reviewed for documentation of discussion regarding the fertility risks with treatment and reproductive options available. The influence of gender, age, year of diagnosis, stage of cancer and treatment (radiation and type of chemotherapy) on the frequency of discussion were assessed. Results: 59 patients (35 male, 24 female, mean age = 35) were included. Documented fertility discussion occurred in 20 patients (34%; 12 male, 8 female). Frequency of fertility discussion decreased with increasing age (p=0.013) and increased for patients receiving radiation (p<0.001). Multivariately, the odds of fertility being addressed was increased for patients receiving radiation (OR=9.31, 95% CI: 2.49-34.77, p<0.001), and decreased by age (OR=0.86, 95% CI:0.74-0.99, p=0.040). 85% of patients <35 years undergoing radiation treatment had a documented fertility discussion. No significant difference in frequency of discussion occurred after 2006, corresponding to the ASCO guidelines publication (p=0.63, 31.4% [2000-06] vs. 37.5% [2007-09]). Conclusions: Discussions regarding fertility risks associated with CRC treatment occur infrequently among young adults with newly diagnosed CRC. However, discussions occur more frequently in younger patients and those undergoing radiation. Further investigations assessing barriers and physician attitudes to fertility risk discussion and reproductive options are planned.
Allogeneic stem cell transplantation from HLA identical donor in high-risk sarcoma.
Authors: F. Fagioli
Journal: Journal of Clinical Oncology (2010)

9561 Background: To evaluate the feasibility of an allogeneic stem cell transplantation (ASCT) from HLA identical donor in patients (pts) affected by resistant or relapsed rabdhomyosarcoma (RMS) or Ewing sarcoma (ES) in which the 1 year probability of survival is lesser than 5%. Methods: 21 pts, median age 16 (6-22) years, affected by resistant (3) or relapsed (8) RMS and resistant (6) or relapsed (4) ES, were enrolled and submitted to an ASCT after a conditioning regimen consisting of thiotepa + melphalan ± fludarabine or cyclophosphamide. The donor was an identical sibling in 14 cases or an unrelated donor (UD) in 7. At time of transplant 19 pts were in PR and 2 (1 RMS and 1 ES) in progressive disease. Graft versus host disease (GVHD) prophylaxis consisting of cyclosporin A ± anti-lymphocytic serum and short term methotrexate in UD setting. SC sources were bone marrow in 13 cases and peripheral blood in 8. Results: The reconstitution of bone marrow function was obtained in all the 21 pts. Acute GVHD of grade II-IV occurred in 6 pts and a complete marrow donor chimerism was observed after 40 and 60 days in sibling and UD setting respectively. After a median follow-up of 28 (1-58) months for ES and 4 (1-18) months for RMS, 8 pts (5 RMS and 3 ES) relapsed, 14 dead (7 for progressive disease and 7 for TRM) and 6 pts are alive and well. The 1 years probability of OS (SE) and EFS (SE) were 0.43 (0.19) and 0.29 (0.17) for ES and 0.37 (0.16) and 0.14 (0.12) for RMS. The 100 days probability of TRM was 0.00 for ES and 0.29 (0.14) for RMS. Conclusions: Despite an high TRM in RMS pts, our experience shows the feasibility of an allogeneic ASCT in relapsed or resistant sarcomas even in heavily pre treated pts. On the basis of these observations a prospective national study is now open on behalf of Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP), Gruppo Italiano Trapianto Midollo Osseo (GITMO) and Italian Sarcoma Group (ISG), to evaluate the efficacy of a reduced intensity conditioning regimen followed by ASCT from related or unrelated HLA identical donor for poor prognosis at diagnosis SE and RMS in paediatric and adult pts. No significant financial relationships to disclose.
Use of EGF A61G polymorphism to predict overall survival in a phase III study of gemcitabine plus cetuximab versus gemcitabine in patients with locally advanced or metastatic pancreatic adenocarcinoma (SWOG 0205).
Authors: Melissa Janae Labonte, Bryan H. Goldman, Wu Zhang, C. D. Blanke, Philip Agop Philip, Ralph Wong, Eileen Mary O'Reilly, Jacqueline K. Benedetti, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2012)

203 Background: The SWOG 0205 phase III study failed to demonstrate an advantage from the addition of cetuximab to gemcitabine for overall survival (OS), progression-free survival (PFS) or objective response in advanced pancreatic cancer. Molecular markers may identify subgroups of pts who benefit from this regimen. This report summarizes the results of a pilot project aimed at screening germline single nucleotide polymorphisms (SNPs) in genes involved in gemcitabine metabolism pathway (CDA and RRM1) and EGFR signaling pathway (EGF, EGFR, IGF1, FCGR2A/3A, KRAS, IL8, COX-2, CCND1) to identify pts that may benefit from this treatment. Methods: Genomic DNA was extracted from 88 available serum samples for this molecular correlates pilot study. Sixteen SNPs were evaluated using PCR-based protocols. There were no differences in baseline characteristics or outcome between pts included in the analysis and the entire study population. Associations between genotype and OS were assessed using stratified Cox regression, with adjustment for treatment arm. Genotypes were parameterized as the number of dominant alleles. No p value adjustments were made for multiple comparisons. Results: Median age was 63.3 years (range: 29.6-85.0), and median OS (95% CI) was 5.7 months (mos) (range: 4.4-6.8) in this subset. There was a statistically significant association between EGF A61G SNP (rs4444903) genotype and OS (p=0.04). Among pts carrying the AA genotype, median OS was 8.4 mos (95% CI 4.9-15.0), as compared to 5.6 mos (95% CI 3.0-9.0) among those with the AG genotype and 5.3 mos. (95% CI 2.2-7.1) for the GG genotype. Evidence was weak for interaction between treatment arm and rs4444903 genotype (p=0.13). No significant associations between other SNPs and OS were observed. Conclusions: This exploratory study suggests that the EGF A61G polymorphism may be a useful molecular marker for predicting clinical outcomes in metastatic pancreatic adenocarcinoma pts treated with gemcitabine-based chemotherapy.
The impact of early tumor shrinkage on survival in WJOG4407G trial, a randomized phase III trial of mFOLFOX6 plus bevacizumab versus FOLFIRI plus bevacizumab in first-line treatment for metastatic colorectal cancer.
Authors: Michitaka Nagase, Kentaro Yamazaki, Hiroshi Tamagawa, Shinya Ueda, Takao Tamura, Kohei Murata, Takashi Tsuda, Eishi Baba, Masahiro Tsuda, Toshikazu Moriwaki, Taito Esaki, Yasushi Tsuji, Kei Muro, Koichi Taira, Tadamichi Denda, Masahiko Ando, Satoshi Morita, Narikazu Boku, Ichinosuke Hyodo
Journal: Journal of Clinical Oncology (2015)

679 Background: Early tumor shrinkage (ETS) has been reported as an important predictor of favorable outcomes in patients with metastatic colorectal cancer (mCRC) receiving first-line chemotherapy. We investigated the impact of ETS on survival in a randomized phase III study (WJOG4407G), which directly compared mFOLFOX6+bevacizumab (Bev) with FOLFIRI+Bev as first-line treatment. Methods: The subjects of this study were patients with measurable lesions whose tumor responses at 8 weeks were evaluated. ETS was defined as 20% or more decrease in the sum of the longest diameters of target lesions (RECIST ver.1.0) at 8 weeks. Progression-free survival (PFS) and overall survival (OS) were compared between patients with ETS and without ETS in each treatment. Results: Of 402 patients enrolled in the WJOG4407G trial, 354 (mFOLFOX6+Bev/FOLFIRI+Bev 175/179) patients were evaluated for this analysis. In this population, response rate, median PFS, and median OS of mFOLFOX+Bev/FOLFIRI+Bev were 65.7/68.2%, 10.7/12.1 months (HR 0.916, 95%CI 0.725-1.157, p=0.281), and 28.9/31.9 months (HR 0.870, 95%CI 0.653-1.159, p=0.272), respectively. One hundred (57.1%)/113 (63.1%) patients in the FOLFOX+Bev/FOLFIRI+Bev groups achieved ETS. No significant difference of the ratio of the patients with ETS between both groups was observed (p=0.099). In the FOLFIRI+Bev group, both PFS and OS were significantly longer in patients with ETS than those without ETS while there were no remarkable differences in the mFOLFOX6+Bev group (see Table). Conclusions: There were substantial differences in PFS and OS between the patients with and without ETS in the FOLFIRI+Bev group, but not in the FOLFOX+Bev group. The impact of ETS on survival is suggested to be different according to chemotherapy regimens. Clinical trial information: UMIN000001396. [Table: see text]
A population pharmacokinetic (PK) model for erlotinib (E), a small molecule inhibitor of the epidermal growth factor receptor (EGFR)
Authors: J. Lu, S. M. Eppler, B. L. Lum, M. Halmilton, A. Rakhit, J. Gaudreault
Journal: Journal of Clinical Oncology (2005)

2032 Background: E as a single agent produced a survival benefit in patients with advanced NSCLC after failure of at least one prior chemotherapy regimen. The objective of this analysis was to: 1) describe the PK of E and its active metabolite (OSI-420) using a population approach and 2) identify covariates that impact E PK. Methods: A population PK model was developed using 2670 E concentrations from 708 patients enrolled in 4 Phase II single-agent trials and 2 Phase III trials in combination with chemotherapy. A subsequent analysis was performed using 2576 concentrations in 591 patients from 4 phase II single agent study plus a single-agent Phase III NSCLC trial once its data became available. Results: A one-compartment model described the concentration data well. The covariate effects were similar between the two analyses, where total bilirubin, α-1-glycoprotein, and smoking status were the most important factors affecting clearance (CL/F). The overall contribution of these covariates was modest and may not be clinically relevant considering the large inter-patient variability observed for CL/F (∼50%). Other factors such as chemotherapy, sex, alkaline phosphatase, albumin, and creatinine clearance were also statistically significant effects (p < 0.005), but their overall influence on E PK was small and their estimated coefficient of variation (CV) was large. From single-agent data, the CL/F and volume of distribution (Vc/F) for a typical patient were 3.95 L/hr and 233 L, respectively. Based on the individual PK parameters from 591 patients, the predicted means (± SD) for the steady-state AUCSS, and Cmin,SS were 41.3 ± 22.0 μg/mL · hr, and 1240 ± 826 ng/mL, respectively. Median t1/2 was 36.2 hours in these patients. Conclusions: The long half-life and the modest effects of covariates on CL/F of erlotinib support the current recommended dosing regimen. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-La Roche, Genentech, OSI Hoffmann-La Roche, Genentech, OSI
Randomized phase II trial of prophylactic use of celecoxib for the prevention of oxaliplatin-related peripheral vascular pain in CapeOX for stage II/III colon cancer patients (YCOG1205).
Authors: Jun Watanabe, Mitsuyoshi Ota, Kazuteru Watanabe, Shuuji Saito, Koutaro Nagamine, Yusuke Suwa, Hirokazu Suwa, Masashi Momiyama, Atsushi Ishibe, Yasushi Ichikawa, Mari Saito Oba, Itaru Endo
Journal: Journal of Clinical Oncology (2016)

703 Background: CapeOX is widely used as a six month adjuvant chemotherapy regimen of colorectal cancer which does not need central vein catheter insertion. However, oxaliplatin-related vascular pain interferes with peripheral administration. We assessed the prophylactic effect of COX-2 inhibitors on oxaliplatin-related vascular pain. Methods: A multicenter of Yokohama Clinical Oncology Group in Japan, open label, randomized non-comparative phase II study with 400mg of celecoxib with CapeOX group (C+ group) and CapeOX group (C- group) was conducted. Stratification factors were performance status 0/I, usage of low dose aspirin and institution. Primary endpoint is the appearance frequency of grade 2 or more vascular pain assessed using the Verbal Rating Scale (VRS) by a medical therapist who has no information about celecoxib administration. C- group patients who developed grade 2 or more vascular pain received celecoxib and were estimated with VRS. Results: Between October 2012 and February 2014, 81 patients were recruited from nine institutions in this study and randomly divided into two groups: 42 patients in C+ group and 39 patients in C- group. Grade II or more vascular pain rate was 55.3% in C+ group and 56.8% in C- group (p = 1.000). Fourteen patients in C- group who developed grade II or more vascular pain were given celecoxib and 50% of patients showed downgrading of vascular pain. Rate of grade II or more peripheral neuropathy was 36.6% in C+ group and 39.5% in C- group (p = 0.7916). Conclusions: Celecoxib has no prophylactic impact on either vascular pain or peripheral neuropathy. However, celecoxib effectively diminished vascular pain in patients with onset of grade II or more vascular pain. Clinical trial information: 000008814.
The Adhesion Molecule “G-Protein Coupled Receptor 56” (Gpr56) Cooperates with the Homeobox Gene Hoxa9 to Induce Acute Myeloid Leukemia in Mice
Authors: Deidre Daria, Andrew L Muranyi, Susann Ihme, Konstanze Döhner, Hartmut Döhner, Michaela Feuring-Buske, Christian Buske
Journal: Blood (2014)
Outcomes after post-operative radiation therapy.
Authors: Hao Nguyen, Clint Cary, Ayesha Appa, Janet E. Cowan, Christopher J Welty, Mack Roach, Katsuto Shinohara, Peter Carroll
Journal: Journal of Clinical Oncology (2014)

138 Background: Adjuvant radiotherapy following radical prostatectomy has been shown to improve prostate-specific antigen (PSA) recurrence free survival for patients with high-risk pathologic features. However, an alternative strategy is careful follow-up after surgery and selective salvage radiation therapy. We aim to investigate voiding and sexual function, and oncological outcomes of patients who underwent adjuvant radiotherapy (ARD) or salvage radiotherapy (SRT) after radical prostatectomy (RP). Methods: We conducted a retrospective analysis of patients with localized prostate cancer treated with open or robotic assisted laparoscopic RP at the University of California, San Francisco (UCSF) from 2002 to 2013. Primary outcomes were voiding and sexual function, PSA recurrence-free survival (PRFS), combined bone metastasis free-survival/cancer-specific survival (BMFS/CSS), and overall survival (OS). Survival outcomes were analyzed using the Kaplan-Meier method. Results: Among 2,908 men in the study, mean age was 60, median PSA was 5.9 ng/ml, and median PSA density was 0.19 at diagnosis. Median follow-up was 28 months (IQR 8-61). Of those with high risk pathologic features, 1,086 patients did not undergo post-RP radiation (NRT), 109 had ART, and 156 had SRT. All patients had comparable pre-treatment sexual and voiding function. However, patients treated with ART or SRT had worse sexual function (SHIM scores) at 4 years post-RP compared to patients without radiation (5.2 (ART/SRT) versus 11.1 (NRT), p=0.01). There were no differences in voiding function at 4 years between the three groups. PRFS at 4 years was 92% for NRT, 82% for ART, and 55% for SRT cohort, log-rank p&lt;0.01. Four-year BMFS/CSS and OS both were 98% and were similar for all groups. In a sub-analysis of men with stage pT2/3a, positive margins, and negative lymph nodes, PRFS were 86% (NRT) and 90% (ART). The PRFS following SRT was 63%. Conclusions: This study provides novel information on both oncological and functional outcomes for men managed with surgery and post-operative radiation therapy at UCSF. Such information allows for better pre- and post-operative counseling of men. Further analyses are required to better determine which men benefit from immediate adjuvant radiation as compared to a strategy of surveillance followed by selective salvage radiation.