tbuckley/cabot-search huggingface dataset:
Assessment of safety of bevacizumab (bev) use for metastatic colorectal cancer (mCRC) in elderly patients treated at the Centre Hospitalier de l’Université de Montréal (CHUM): A retrospective study.
Authors: Francois-Xavier Bicharh Otte, Francine Aubin, Mustapha Ali Tehfe, Richard Letourneau, Rasmy Lougnarath, Carole S. Richard, Denis Soulieres, Danielle Charpentier, Guy Biron, Jean-Pierre M. Ayoub
Journal: Journal of Clinical Oncology (2012)

677 Background: A 2004 randomized study showed a meaningful improvement in survival with bev added to chemotherapy (CT) for patients with mCRC. This combination is now widely used and generally well tolerated although adverse events (AEs) are described associated with the use of bev, some of which may be increased in incidence in an elderly population. In this study, we assessed these AEs in a population of elderly patients treated with bev in a major center in Montréal. Methods: Patients with mCRC who received bev at our institution outside a clinical trial were retrieved from the pharmacy registry. Medical records were sought from patients who qualified for the inclusion criteria: ≥ 65 years, bev therapy at 5mg/kg every two weeks, combination with CT, period 2007-2011. A retrospective analysis of specific AEs was done and grade according to NCI-CTC (version 4.0) was assessed: febrile neutropenia, hypertension, proteinuria, diarrhea, venous thromboembolic event (VTE), arterial thromboembolic event (ATE), bleeding and gastrointestinal perforation. Results: 47 patients received a total of 486 cycles of bev. Out of these cycles, 210 were given with FOLFOX, 199 with FOLFIRI and 77 with other combinations. Median age of the patients was 69 years. 3 episodes of febrile neutropenia were noted. Grade 3 or 4 arterial hypertension occurred in 4 patients of which 2 had to definitively stop bev. Grade 3 proteinuria was reported with definitive cessation of bev in 2 patients. Grade 3 or 4 diarrhea was observed in 2 cases. We reported 1 cerebral ATE leading to discontinuation of bev and grade 2 VTE in two patients. One grade 5 gastrointestinal perforation was reported. No major bleeding was noted. Conclusions: The number of adverse events observed in this population of elderly patients is comparable to other studies. Thus, age should not be an exclusion criteria for treatment with bev and CT.
Whole Exome Sequencing Reveals Clonal Evolution of Myeloproliferative Neoplasms to Acute Myeloid Leukemia
Authors: Jelena D Milosevic Feenstra, Elisa Rumi, Daniela Pietra, Andreas Schönegger, Christoph Bock, Mario Cazzola, Robert Kralovics
Journal: Blood (2015)
Clinical characteristics of multiple myeloma (MM) in Vietnam-era (V) and non–Vietnam-era veterans (Non V).
Authors: S. Srinivas, R. Paulin, C. Abanonu, K. Kim, L. Soriano, M. Tufail, B. Kasimis, V. T. Chang, L. Duque, B. Crump, M. McPherson
Journal: Journal of Clinical Oncology (2011)

e18579 Background: There has been increased interest in V veterans with lymphoid malignancies. We compared the survival and severity of MM in veterans from V and non-V at a VA medical center. Methods: In an IRB -approved protocol, we reviewed the records of veterans diagnosed with MM from January 2002 to October 2010 at the VANJHCS. Records were reviewed for demographic, clinical, pathological data, Vietnam status, treatments, and survival. We tabulated the performance status (PS), International Staging System (ISS), Durie-Salmon stage, Charlson Co morbidity Index (CCI), the Kaplan-Feinstein Comorbidity Index (KFI), the Cumulative Illness Rating Scale (CIRS), and Vietnam status. We then performed Cox regression analyses and tests of proportions to determine predictors of survival. Results: There were 72 veterans who met the eligibility criteria and their data were analyzed. There were 21 V and 51 non-V. The groups did not differ in the following characteristics PS, stage, laboratory parameters and comorbidity indice. Differences in their clinical features are summarized in the table. Survival predictors for the non V veterans were the BMI (p 0.046), hemoglobin (p 0.01), alb (p 0.001), beta 2-microglobulin (p 0.003) and ISS (p 0.004) but these were not predictors of survival for V veterans. Median survival for V veterans was 840 days (91-4654) and Non V was 766 days (464-1995) (p<0.0001). Conclusions: The V veterans were younger than the Non V veterans and their survival was better. This difference could be due to evolution of newer treatments. Further research is needed in a bigger sample to explain these differences. Parameters V Non V Age (years) Median 63 (54-86) 77 (40-90) P <0.0001 Race (AA) 13/21 22/51 P 0.07 Survival (days) 840 (91-4654) 766 (26-3284) P <0.0001
Impact of Disseminated Neuroblastoma Cells on the Identification of the Relapse-Seeding Clone
Authors: M. Reza Abbasi, Fikret Rifatbegovic, Clemens Brunner, Georg Mann, Andrea Ziegler, Ulrike Pötschger, Roman Crazzolara, Marek Ussowicz, Martin Benesch, Georg Ebetsberger-Dachs, Godfrey C.F. Chan, Neil Jones, Ruth Ladenstein, Inge M. Ambros, Peter F. Ambros
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Tumor relapse is the most frequent cause of death in stage 4 neuroblastomas. Since genomic information on the relapse precursor cells could guide targeted therapy, our aim was to find the most appropriate tissue for identifying relapse-seeding clones. Experimental design: We analyzed 10 geographically and temporally separated samples of a single patient by SNP array and validated the data in 154 stage 4 patients. Results: In the case study, aberrations unique to certain tissues and time points were evident besides concordant aberrations shared by all samples. Diagnostic bone marrow–derived disseminated tumor cells (DTCs) as well as the metastatic tumor and DTCs at relapse displayed a 1q deletion, not detected in any of the seven primary tumor samples. In the validation cohort, the frequency of 1q deletion was 17.8%, 10%, and 27.5% in the diagnostic DTCs, diagnostic tumors, and DTCs at relapse, respectively. This aberration was significantly associated with 19q and ATRX deletions. We observed a significant increased likelihood of an adverse event in the presence of 19q deletion in the diagnostic DTCs. Conclusions: Different frequencies of 1q and 19q deletions in the primary tumors as compared with DTCs, their relatively high frequency at relapse, and their effect on event-free survival (19q deletion) indicate the relevance of analyzing diagnostic DTCs. Our data support the hypothesis of a branched clonal evolution and a parallel progression of primary and metastatic tumor cells. Therefore, searching for biomarkers to identify the relapse-seeding clone should involve diagnostic DTCs alongside the tumor tissue. Clin Cancer Res; 23(15); 4224–32. ©2017 AACR.
Paradigm shift in the management of high-intermediate risk stage I endometrial cancer.
Authors: J. O. Schorge, A. H. Russell, L. A. Garrett, A. Goodman, M. G. del Carmen, W. B. Growdon, D. M. Boruta
Journal: Journal of Clinical Oncology (2011)

5103 Background: Recent randomized trials have suggested that high-intermediate risk endometrial cancer patients may safely be treated with adjuvant vaginal brachytherapy (VBT) rather than external beam radiotherapy (EBRT). The purpose of this study was to determine how this paradigm shift might impact clinical outcomes. Methods: All women with stage IA grade 3, stage IA with endocervical gland extension and grade 1-2, or stage IB grade 1-2 endometrioid carcinoma (FIGO 2009 system) treated from 2005 to 2010 at our institution were retrospectively identified. Data was extracted from computerized medical records. Group A consisted of 49 patients in the 1st half of the study and Group B 40 pts in the 2nd half. Results: 89 pts underwent abdominal (65%) or minimally invasive (35%) hysterectomy. Group A was more likely to not be surgically staged (28% v 8%; P = 0.02) or have pelvic lymphadenectomy (PLN) only (55% v 33%; P = 0.05). Group B had a much higher rate of both PLN and para-aortic lymphadenectomy (PAALN; 59% v 18%; P < 0.001). Postoperatively, Group A was more likely to receive either EBRT (23% v 0%; P < 0.001) or no radiotherapy (33% v 8%; P = 0.01). Group B more frequently received only VBT (92% v 44%; P < 0.001). 2 of 4 patients with positive/equivocal cytology were the only ones to receive postoperative cytotoxic chemotherapy (6 cycles of paclitaxel and carboplatin). 5 of 89 (6%) patients (3 Group A, 2 Group B) relapsed during the follow-up interval (median 2 years): 2 having positive cytology that did not receive chemotherapy relapsed in the lung and the peritoneum, respectively; 1 staged with PLN only who received postoperative pelvic EBRT relapsed in the para-aortic nodes; 2 relapsed at the vaginal apex, neither of whom had received postoperative radiation. Conclusions: The paradigm shift favoring postoperative VBT cancer is effective at preventing local relapse while avoiding long-term toxicity in women with high-intermediate risk stage I endometrial cancer. Comprehensive PLN and PAALN is integral to this approach by excluding nodal disease. Peritoneal washings, although no longer part of the formal staging system, should be collected and may suggest the need for cytotoxic chemotherapy when positive.
Influence of renal dysfunction on the pharmacokinetic of intravenous vinflunine: Results of a phase I trial in patients with cancer.
Authors: J. Delord, N. Isambert, P. Fumoleau, A. Ravaud, T. Nguyen, P. Ferre, S. Favrel, M. Pinel, J. Tourani
Journal: Journal of Clinical Oncology (2011)

2570 Background: Vinflunine (VFL) (Javlor) is a novel microtubule inhibitor indicated in monotherapy for the treatment of advanced or metastatic urothelial transitional cell after platinum failure at 320 mg/m² every 3 weeks in patients (pts) with performance status (PS) 0 or 280 mg/m² in pts with PS 1 or prior pelvic irradiation. This trial was designed to investigate the pharmacokinetics of VFL in pts with renal impairment and to propose dose-adjustments. Methods: 2 groups of pts were open to recruitment based on centralized creatinine clearance (Clcreat) calculated using Cockcroft & Gault formula: pts with a Clcreat between [40 to 60 mL/min [ (Group 1), or [20 to 40 mL/min[ (Group 2) received i.v. VFL at 280 mg/m² and 250 mg/m² on cycle 1, respectively. VFL PK parameters (AUC, Cltot) were estimated using a non-compartmental analysis and compared to reference values from pts with normal renal function (Clcreat > 60mL/min) (control group). 90% confidence intervals (CI) were built for the ratio of test/reference PK parameters. Results: 13 pts in Group 1, and 20 pts in Group 2; males 10 / 9, females 3 / 11, median age 68 / 70, WHO PS 0: 4 / 3; PS 1: 7 / 14; PS 2: 2 / 3, median Clcreat 45 / 33 mL/min, were treated, respectively.When compared to control group, VFL Cltot was 12 % (90% CI: [0.78 - 0.98]) and 28% (90% CI: [0.65 - 0.79]) reduced in groups 1 and 2, respectively. Given the reduction of administered doses, homogeneous blood exposure were achieved between control and tested groups. Regarding safety, in this heavily pre-treated population with a medically significant moderate or severe renal impairment there were: no toxic death, no unexpected adverse event, neutropenia 92% (G 3 / 4 69 %) and 85% (G 3 / 4 75%) of pts in Groups 1 and 2, respectively, 2 episodes of febrile neutropenia, 1 neutropenic infection; fatigue and constipation in 75% and 66% of pts, respectively. Conclusions: based on these results, VFL dose should be reduced in renal impaired pts : 280 mg/m² in patients with Clcreat between 40 and 60 mL/min, and 250 mg/m² for pts with Clcreat between 20 and 40 mL/min.
Prospective non-randomized study of concurrent radiation and platinum plus 5-FU based chemotherapy with or without paclitaxel with consecutive surgery in esophageal cancer patients
Authors: M. Zemanova, A. Pazdro, F. Novak, G. Pazdrova, M. Smejkal, M. Haluzik, J. Krizova, L. Petruzelka
Journal: Journal of Clinical Oncology (2005)

4081 Background: Combined modality treatment in esophageal cancer is suggested to improve survival. Results of study with new chemoradiotherapy regimen and special interest on nutritional status are presented. Methods: 80 patients (pts), 67men, median age of 58 (range 44–76 years), with operable esophageal cancer were enrolled. They received the following neoadjuvant therapy: carboplatin, AUC 6, IV on days 1 and 22, fluorouracil, 300mg/day, CI on days 1 to 42, radiation therapy 45Gy/25fr/5 weeks beginning on day 1. 41pts (51%) were non-randomly assigned to paclitaxel 200 mg/m2/3hours IV on days 1 and 22. Nutritional supports since the beginning of the study was offered to all pts. Surgery was done within 4–8 weeks after completion of CRT if feasible. Results: All pts were evaluated for toxicity with G3+4 leukopenia 30%, neutropenia 32%, anemia 7%, trombocytopenia 27%, febrile neutropenia 8%, esophagitis 22%, vomiting 10%, pneumotoxicity 12%. 55 pts (69%) had surgery, 43 (54%) were completely resected with 20 (25%) achieving pathologic complete remission (pCR) and additional 8 (10%) having microscopic residual disease. There were 9 surgery-related deaths, mostly due to pulmonary insufficiency. 25 pts were not resected, 15 for early progression, 10 for medical reasons. After a median follow-up of 24 months 31/80 (39%) pts are still alive with median survival (MS) 17,5 months. Mean weight loss before treatment start was 8 kg and during CRT 2,25 kg. Patients with above-average weight loss had non-significantly shorter MS (p=0.128). Paclitaxel didn’t influence treatment results in terms of MS or pCR. 12/20 patients having pCR are alive, median survival was not reached. Conclusions: This combined-modality approach for the treatment of localized esophageal cancer is feasible and the efficacy is encouraging, with 46% of completely resected patients having pCR as positive predictive factor for survival. Relatively increased postoperative mortality was observed in this group. Worse prognosis of patients with substantial weight loss is reason for intensive nutritional support during treatment. Supported by grant IGA MZ CR 7530–3. No significant financial relationships to disclose.
Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature
Authors: G. Des Guetz, B. Uzzan, P. Nicolas, M. Cucherat, J.-F. Morere, J.-L. Breau, G. Perret
Journal: Journal of Clinical Oncology (2005)

9641 Background Tumor-induced angiogenesis is a central pathogenic step in the process of tumor growth and metastasis. The aim of this study was to determine whether angiogenesis, quantified with VEGF expression or Micro Vessel densities (MVD) in colorectal cancer would be considered as a prognostic factor. Methods We performed a meta-analysis of all published studies relating intratumoral MVD (40 studies) or VEGF expression (27 studies). Four studies did not mention survival data or fit inclusion criteria, 4 were multiple publications of same series, leaving 32 independent studies for MVD (3496 patients). Eighteen studies were analysed for VEGF (2050 patients). Analysis was performed for RFS and OS. MVD was assessed by immunohistochemistry, using antibodies against factor VIII (16 studies), CD31 (10 studies) or CD34 (7 studies). Results: High MVD significantly (p < 0.001) predicted poor RFS (RR = 2.43 ; 95% CI: 1.55–3.81) and was of borderline significance (p = 0.06) for OS (RR = 1.32 ; 95% CI: 0.99–1.77). Using CD31 or CD34, MVD was correlated with survival, whereas it was not using factor VIII. VEGF expression significantly predicted poor RFS (8 studies ; RR = 2.94 ; 95% CI: 1.93–4.47) and OS (10 studies ; RR = 1.65 ; 95% CI: 1.27–2.14). Conclusion Between-study variations could result from patient selection criteria, techniques to stain and count microvessels, and cut off selection. The benefit of postoperative adjuvant chemotherapy in patients with stage II colorectal cancer is still uncertain. So prognostic biomarkers may be useful for identifying high-risk patients. Their assessement should be better standardized in future studies. No significant financial relationships to disclose.
A misperceived threat: Understanding the increasing mastectomy rates.
Authors: Andrea Marie Covelli, Nancy N. Baxter, Margaret Fitch, Frances Catriona Wright
Journal: Journal of Clinical Oncology (2015)

75 Background: Rates of unilateral (UM) and contralateral prophylactic mastectomy (CPM) for early-stage breast cancer (ESBC) have been increasing. Both surgeons’ preference and patients’ choice have been suggested to play a role. Methods: A qualitative study was conducted examining surgeon’s practices and patient’s decision-making during treatment for ESBC. The Health-Belief Model was applied identifying factors influential in the choice for UM+/-CPM. Purposive sampling identified non-high-risk women across Toronto, Canada who were candidates for breast conserving therapy (BCT) but underwent UM+/-CPM. Academic and community breast surgeons from across Ontario, Canada and the United States were also recruited. Data were collected through semi-structured interviews. Constant comparative analysis identified key ideas. Results: 29 patients and 45 surgeons were interviewed. The dominant theme was the ‘misperceived threat of ESBC: an overestimated risk’. Surgeons described the high survivability of ESBC, yet patients greatly overestimated the threat of death from their cancer and strived to eliminate this threat by choosing UM+/-CPM. Surgeons described BCT and UM as equivalent treatment options for ESBC, and recommended BCT. In this average-risk population CPM was discouraged by the surgeons describing no survival advantage; despite this, women requested UM+CPM. Personal cancer experiences with family and friends were extremely influential in women’s request for UM+/-CPM. Previous negative experiences translated into an overestimated risk of recurrence, contralateral cancer, metastasisand subsequent death. Patients’ misperceived the severity of ESBC, and believed that by choosing UM+/-CPM they would live longer. Most women did not perceive any risks of undergoing mastectomy, yet many had ongoing issues with skin sensation, cosmesis and body image. Conclusions: Despite surgeons counseling otherwise, women greatly overestimated the risk of ESBC and misperceived the benefits of mastectomy. As undergoing UM+/-CPM is not without risks, improved discussion of patient sources of information and fears around survival may benefit surgical consultations, facilitating informed decision-making.
Reducing patient wait time on an inpatient hematology and transplant unit.
Authors: Ryan J. Mattison, Rory Joseph Makielski, Kurt Osterby, Mike Fallon, Nicole Domask, Vicki Hubbard, Eva Allen, Blythe Gage, Gail Hettrick, Jessica Fischer, Andrew Brown, Brianna Grahn, Brett Welhouse, Hannah Draayers, Mark Juckett, Jean Ligocki, Ruth O'Regan, Laurie Kaufman
Journal: Journal of Clinical Oncology (2016)

87 Background: The University of Wisconsin Hematology and Bone Marrow Transplant services admit 250 patients per year for scheduled treatment. Time from patient arrival to chemotherapy initiation averages 7 hours. This long time leads to patient dissatisfaction and prolonged length of stay. Chemotherapy often begins in the evening when physicians and pharmacists are not on site to clarify treatment questions. Methods: A multidisciplinary team was formed in April 2015 as part of the ASCO Quality Training Program. The team developed the aim to reduce time from 7 hours to 5 hours to allow for more daytime nursing shift chemotherapy starts. The group created a process map and an Ishikawa diagram to identify causes of treatment delays. The team observed that treatment orders were often written and signed after hospital admission, though the plan of care was available prior to admission. Using a prioritized list, the initial process change was to have physicians write and sign chemotherapy treatment plans prior to admission. The process measure was the percentage of orders signed before admission. The outcome measure was time from arrival to chemotherapy start. Balance measures included narrative comments from physician and nursing staff about the process change. Data were obtained from EHR time stamps. Physicians were asked to begin making signed treatment plans available after August 1, 2015. Results: Data from 55 patients prior to the change (May 1-July 31) and 52 patients post-change (August 1-October 16) were analyzed. The number of treatment plans signed prior to admission increased from 27% to 58% (p = 0.0018). Mean time from admission to treatment pre-process change was 404 minutes and 383 minutes post-change. When plotted on a control chart, a sustained shift in the process was not apparent. Feedback from physician and nursing staff did not identify efficiency or safety concerns with the new process. Conclusions: Though the percentage of orders signed prior to admission increased, there was no improvement in the time from patient admission to treatment initiation with this change. Future PDSA cycles will include increasing the percentage of orders signed prior to admission as well as address other sources of delay identified in the process map.
Analysis of <i>KRAS/NRAS, PI3CA</i>, and<i> BRAF </i>mutations in the phase II KSCC0901 study of cetuximab plus S-1 as third-line treatment for metastatic colorectal cancer in Japanese patients.
Authors: Yasunori Emi, Eiji Oki, Hiroshi Saeki, Hiroyuki Kitao, Hironori Samura, Takao Takahashi, Terumitsu Sawai, Yoshito Akagi, Akihito Tsuji, Susumu Eguchi, Kazuhiro Yoshida, Hideo Baba, Yutaka Ogata, Shoji Natsugoe, Mototugu Shimokawa, Yoshihiko Maehara
Journal: Journal of Clinical Oncology (2014)

587 Background: Exploratory biomarker studies in the randomized phase III PRIME study suggested that patients with mCRC tumors harboring a mutation (MT) in KRAS or NRAS (beyond KRAS exon 2) do not respond to panitumumab-FOLFOX4 (2013 ASCO, JCO 31, #3511). We reported the efficacy and safety of S-1+. Cetuximab (Cmab) in wild-type (WT)-KRAS (exon 2) mCRC patients (pts) as third-line therapy (KSCC0901) (2012 ASCO, JCO 30, s3558). The full spectrum of characterized RAS (KRAS and NRAS), PI3CA, and BRAFMTs may affect efficacy in S-1+Cmab therapy in Japanese patients. Methods: An analysis was conducted to assess the treatment effect of S-1+Cmab, according to RAS (KRAS and NRAS), PI3CA, and BRAF MTs. The treatment protocol of KSCC0901 was as follows: weekly intravenous Cmab administration of 400 mg/m 2 (day 1), 250 mg/m 2 /week (following day 1) and oral administration of 80 mg/m 2 /day S-1 on days 1–28 of each 42-day cycle. MTs in KRAS codons 12 and 13 (exon 2) were detected using direct sequencing according to the manufacturer’s instructions. MTs in KRAS codons 61 and 146, NRAS codons 12, 13 and 61, BRAF codon 600 and PIK3CA codons 542, 545, 546, and 1047 were detected using the multiplex PCR-Luminex method-based MEBGEN MT Kit (Medical and Biological Laboratories, Nagoya, Japan). Results: 35 pts were eligible for the analysis. Number of MT cases of KRAS, NRAS, BRAF, and PIK3CA were 4, 2, 2, and 5, respectively. One case had MTs of NRAS and PIK3CA. In 37 cases with WT KRASexon2 pts, median progression-free survival (mPFS) was 5.6 [95% CI: 4.4 – 5.7] months; median overall survival (mOS), 13.5 [8.5-16.5] months; and best overall response (ORR), 37.8%. In the all-WT subgroup 23 cases, mPFS was 5.6 [5.1-7.1] months; mOS, 13.5 [9.3-21.2] months; and best ORR, 47.8%. In 12 patients with any MT, mPFS was 4.0 [2.7-7.5] months; mOS, 5.5[2.9- ] months; and best ORR, 16.7%. Conclusions: These results suggest that also in Japanese patients receiving a Cmab containing regimen, RAS, BRAF and PIK3CA MT status beyond KRAS exon2 might predict non-responders to treatment. Clinical trial information: UMIN000002475.