tbuckley/cabot-search huggingface dataset:
Effect of different chemotherapy regimens on pathological response in the preoperative combined chemo radiotherapy of rectal adenocarcinomas: A retrospective analysis.
Authors: Rebecca Buecker, Ulrich Schafer, Frank Hartmann
Journal: Journal of Clinical Oncology (2018)

e15564 Background: To investigate the influence of different neoadjuvant chemotherapy modalities on Tumor Regression Grading Methods: We analyzed a total of 80 patients (pts) with locally advanced stage rectal adenocarcinoma, treated from Jan 2013 to Jan 2017. Treatment consisted of preoperative radio chemotherapy. Radiotherapy was delivered to a total dose of 50.4 Gy. Three different regimens were used: 5-Fluorouracil 1000mg/m² week 1 and 5 (5-FU W1+W5), 5-Fluorouracil 225mg/m² as a continuous infusion (5-FU cont.) or Capecitabine 825 mg/m2 twice daily. After surgery Tumor Regression Grading (TRG) according to the Dworak system (grade 0-1 versus grade 2 versus grade 3-4) was assessed in all cases and compared with the different chemotherapy regimens. To exclude bias of other variables, preoperative histological grading (G1 versus G2 versus G3-G4), preoperative T-stage (T1 versus T2 versus T3), preoperative N-stage (N0 versus N+), and treatment interruption (no versus yes) were also included in this analysis. To determine whether there is a significant difference between the expected frequencies and the observed frequencies, a chi-squared test was used. Results: In 35/80 (44%) pts, chemotherapy consisted of 5-FU W1+W5, in 20/80 (25%) pts of Capecitabine, and in 25/80 (31%) pts of 5-FU cont. Of all patients, 13/80 (16%) pts achieved TRG grade 0-1, 40/80 (50%) pts TRG grade 2 and 27/80 (34%) pts TRG grade 3-4. In comparison with the different chemotherapy regimens, TRG grade 0-1, 2 and 3-4 was achieved in 4/35 (11%) pts, 24/35 (69% ) pts and 7/35 (20%) pts with 5-FU W1+W1, in 6/20 (30%) pts, 7/20 (35%) pts and 7/20 (35%) pts with Capecitabine and in 3/25 (12%) pts, 9/25 (36%) pts and 13/25 (52%) pts with 5-FU cont. These differences were significant with a p-value of 0.02. The other included variables did not affect TRG significantly. Conclusions: In this small patient cohort, the kind of chemotherapy regimen appears to have a significant influence on pathologic tumor regression after preoperative combined chemo radiotherapy of rectal cancer, with the best results of 5-Fluorouracil 225mg/m² as a continuous infusion. Further investigations seem to be useful.
Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update
Authors: Randy A. Taplitz, Erin B. Kennedy, Eric J. Bow, Jennie Crews, Charise Gleason, Douglas K. Hawley, Amelia A. Langston, Loretta J. Nastoupil, Michelle Rajotte, Kenneth V. Rolston, Lynne Strasfeld, Christopher R. Flowers
Journal: Journal of Clinical Oncology (2018)

To provide an updated joint ASCO/Infectious Diseases Society of America (IDSA) guideline on antimicrobial prophylaxis for adult patients with immunosuppression associated with cancer and its treatment.ASCO and IDSA convened an update Expert Panel and conducted a systematic review of relevant studies from May 2011 to November 2016. The guideline recommendations were based on the review of evidence by the Expert Panel.Six new or updated meta-analyses and six new primary studies were added to the updated systematic review.Antibacterial and antifungal prophylaxis is recommended for patients who are at high risk of infection, including patients who are expected to have profound, protracted neutropenia, which is defined as < 100 neutrophils/µL for > 7 days or other risk factors. Herpes simplex virus-seropositive patients undergoing allogeneic hematopoietic stem-cell transplantation or leukemia induction therapy should receive nucleoside analog-based antiviral prophylaxis, such as acyclovir. Pneumocystis jirovecii prophylaxis is recommended for patients receiving chemotherapy regimens that are associated with a > 3.5% risk for pneumonia as a result of this organism (eg, those with ≥ 20 mg prednisone equivalents daily for ≥ 1 month or on the basis of purine analog usage). Treatment with a nucleoside reverse transcription inhibitor (eg, entecavir or tenofovir) is recommended for patients at high risk of hepatitis B virus reactivation. Recommendations for vaccination and avoidance of prolonged contact with environments that have high concentrations of airborne fungal spores are also provided within the updated guideline. Additional information is available at www.asco.org/supportive-care-guidelines .
Can machine learning predict resecability of a peritoneal carcinomatosis.
Authors: Alexandre Maubert, Loic Birtwisle, Nicolas Mounier, jean-Louis Bernard, Anne-Claire Frin, Jean-Marc Bereder
Journal: Journal of Clinical Oncology (2018)

Article Tools Gastrointestinal (Colorectal) Cancer Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2018.36.15_suppl.e15543 Journal of Clinical Oncology - published online before print June 1, 2018 Can machine learning predict resecability of a peritoneal carcinomatosis. Alexandre MaubertxAlexandre MaubertSearch for articles by this author, Loic BirtwislexLoic BirtwisleSearch for articles by this author, Nicolas MounierxNicolas MounierSearch for articles by this author, jean-Louis Bernardxjean-Louis BernardSearch for articles by this author, Anne-Claire FrinxAnne-Claire FrinSearch for articles by this author, Jean-Marc BerederxJean-Marc BerederSearch for articles by this author Show More University Hospital Sophia Antipolis, Nice, France; Department of Hematology, CHU l'Archet, Nice, France; Hopital Archet 2, Nice, FranceAbstract Disclosures https://doi.org/10.1200/JCO.2018.36.15_suppl.e15543 Abstract Abstracte15543Background: about 20% of initially eligible patients in a HIPEC procedure, eventually underwent simple surgical exploration. These procedures are named "Open & Close", represent up to 48 %. The objective of this study was to predict the resecability of the peritoneal carcinomatosis by using a model of machine learning for decision-making support, at eligible patients in a procedure of HIPEC. Methods: The study was conducted as an intention to treat, based on three databases including a prospective, between January 2000 and December 2015. A propensity score allowed to obtain two groups of comparable and matched patients. Then, several algorithms models of classification were studied (simple classification, conditional tree, SVM, Random Forest) to determine the model having the best performance and accuracy. Results: Two groups of 155 patients were obtained, one group without resection and one group with. Nine criteria of non-resecability have been retained, reflecting the organ involvement . They were coded according to their importance. Five classification algorithms were tested. Training data included 218 patients and test data 92. The Random Forest model was the best performance with an accuracy close to 98 %. Only two errors of prediction were observed Conclusions: A largest number of patients will allow improving the precision prediction. Gathering more data such biologic, radiologic even coelioscopic features, should improve the knowledge of disease and decrease the number of "Open & Close" procedures.© 2018 by American Society of Clinical Oncology
Phase 2 study of veliparib plus FOLFIRI ± bevacizumab versus placebo plus FOLFIRI ± bevacizumab in metastatic colorectal cancer.
Authors: Vera Gorbunova, Thaddeus Beck, Ralf Hofheinz, Pilar Garcia-Alfonso, Marina Nechaeva, Antonio Cubillo Gracian, Laszlo Mangel, Elena Elez, Dustin A. Deming, Ramesh K. Ramanathan, Alison Torres, Danielle Marie Sullivan, Philip B. Komarnitsky, Jordan Berlin
Journal: Journal of Clinical Oncology (2018)

3543 Background: Survival rates for patients with metastatic colorectal cancer (mCRC) are low. Current front-line therapy includes a combination of irinotecan/5-fluorouracil/leucovorin (FOLFIRI) ± bevacizumab. Veliparib (Vel) is a potent, competitive poly (ADP-ribose) polymerase (PARP)-1/2 inhibitor that enhances the activity of irinotecan in pre-clinical models. This study assessed if addition of oral Vel concurrent to FOLFIRI, with the goal to potentiate irinotecan activity, improves survival in patients with previously untreated mCRC. Methods: This is a randomized, blinded, phase 2 study (NCT02305758) comparing Vel (200 mg BID administered for 7 days of each 14-day cycle) to placebo (PBO), each in combination with FOLFIRI. Bevacizumab was allowed in both arms. Endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR) by RECIST 1.1, duration of overall response (DOR), safety and tolerability. Results: As of October 31, 2017, 130 patients were randomized to receive either Vel (n= 65) or PBO (n= 65). Median PFS was 12 vs 11 months (Vel vs PBO) [HR = 0.94 (95% CI: 0.60, 1.48)]. Median OS was 25 vs 27 months (Vel vs PBO) [HR = 1.26 (95% CI: 0.74, 2.16)]. There were 27 OS events each in the Vel and PBO arms. ORR was 56.9% (Vel) and 61.5% (PBO). Median DOR was 11.1 vs 9.4 months (Vel vs PBO) [HR = 0.73 (95% CI: 0.38, 1.40)]. Common adverse events (AE) (in ≥20% patients) assessed as related to Vel that did not differ from Vel to PBO arm were nausea, fatigue, and vomiting. Grade 3/4 AE (in ≥5% patients) assessed as related to Vel (for Vel vs PBO) include neutropenia (22% vs 11%), diarrhea (5% vs 9%), nausea (8% vs 2%), and asthenia (6% vs 0%). SAE assessed as related to Vel (for Vel vs PBO) include febrile neutropenia (3% vs 3%) and diarrhea (2% vs 3%). All grade hematopoietic cytopenias were more common with Vel than PBO (79% vs 52%, p= 0.003). Two treatment-emergent AE deaths occurred in each Vel and PBO arm. 14% of patients in Vel arm and 15% in PBO arm prematurely discontinued treatment due to AEs. Conclusions: Vel added on to FOLFIRI ± bevacizumab demonstrated similar efficacy as FOLFIRI ± bevacizumab in frontline mCRC patients. Overall, there were no unexpected safety concerns. Clinical trial information: NCT02305758.
Adherence to oral anticancer medications after implementation of an ambulatory adherence program at a large urban academic hospital.
Authors: Marjorie Adams Curry, Tyler Redelico, Constance Terrell, Iloabueke Gabriel Chineke, Jennifer Ann LaFollette, Winifred Bell, Darica Flood, Pooja Mishra, Steve Power, Leon Bernal-Mizrachi
Journal: Journal of Clinical Oncology (2018)

6591 Background: Oral anticancer medications (OAMs) offer convenient administration, reducing the burden of cancer treatment, but create new challenges including adherence to treatment and toxicity management. Using the Quality Oncology Practice Initiative, we identified a baseline 30% OAM adherence in the cancer center at Grady Health System, the largest public hospital in Atlanta, Georgia. To improve patient adherence, we conducted a quality improvement initiative in our ambulatory hematology and medical oncology clinics. Methods: The aim of this initiative was to increase OAM patient adherence by 30 percentage points. Through cause and effect analysis, significant barriers to adherence were identified including a lack of reminders and increased toxicities. This led to the development of two strategies: low cost adherence aids and a pharmacist-led OAM adherence program. Patients initiating new OAM regimens were consulted by a pharmacist for education and assistance with drug procurement. Patient education consisted of one-on-one education, drug information handouts, a treatment calendar, and a pillbox filled by the pharmacist. Patients were scheduled for mid-cycle adherence and toxicity assessments with the pharmacist. The adherence endpoint was satisfied if the patient had the drug available ≥80% to < 120% of the days evaluated for four treatment cycles. To define the impact of this QI initiative, we collected prescription refill data prior to and after the intervention using prescription fill data and specialty pharmacy records. Results: Data was collected from 50 patients prior and 52 patients after implementation of the QI initiative. Five hundred and ninety-one interventions were documented including drug acquisition support, pillbox preparation, treatment calendar creation, supportive care adjustments and toxicity management. The program increased adherence from 30% to 85% in 2 years. Furthermore, the variability in adherence among patients was reduced (CI -3.24 – 156.7 vs. 52 – 140). Conclusions: A pharmacist-led adherence program combined with low cost adherence aids exceeded the goal for the adherence initiative at Grady Health System.
Abstract 10331: Aspirin Responsiveness Testing Predicts Bleeding During Coronary Artery Bypass Grafting: The Verify Pre-Op - TIMI 45 Study
Authors: Grant W Reed, Jianping Guo, Elaine B Hoffman, Andrew O Maree, Prem Shekar, Sary Aranki, Kenneth Rosenfield, Christopher P Cannon
Journal: Circulation (2013)

Introduction: Many patients receive aspirin prior to coronary artery bypass grafting (CABG), despite its association with perioperative bleeding and variable effectiveness among individuals. Hypoth...
Multicenter randomized controlled trial for advanced cancer patients receiving parenteral nutrition (PN) versus oral feeding (OF): Results of AlimK study.
Authors: Carole Bouleuc, Amelie Anota, Cécile Cornet, Ghislain Grodard, Antoine Thiery Vuillemin, Lionel Pazart, Regis Aubry
Journal: Journal of Clinical Oncology (2018)

10029 Background: The decision to use PN in patients with advanced cancer is controversial. There is lack of high evidence level demonstrating its interest and safety in this population. In case of refractory cachexia, PN interest would be to improve health-related quality of life (HRQoL) and to reduce certain symptoms caused by food intake without significant toxicity. AlimK (NCT02151214) study was performed to address this gap. Methods: We planned a prospective multicenter randomized controlled parallel-group phase IV trial, with a Zelen single-consent design for randomization. Intervention arm received PN whereas control arm were pursuing OF alone. Primary objective assessed PN influence on HRQoL deterioration free survival (HRQFS) of one of the 3 targeted scores of the EORTC QLQ-C15-PAL: global HRQoL, physical functioning and fatigue. HRQFS was defined as a definitive deterioration of 10 points at least compared to the baseline score, or death. A p-value < 0.0166 was considered statistically significant (Bonferroni adjustment) to ensure an overall bilateral alpha risk of 5%. Key secondary endpoints included overall survival (OS) and safety. Results: Between 07/2012 and 03/2017, 148 cancer patients were enrolled in 13 French cancer centers. Informed consent was obtained for 111 patients: 48 (43%) in PN arm and 63 (57%) in OF arm. PN was refused by 8/48 (18%) patients. Among all patients, 98% were metastatic with life expectancy less than one year and 97 % were still on anticancer treatment. Patients were malnourished with median weight loss over 6 months of -8.20 (range -26.5; 10). There was a trend favoring HRQFS in the OF group for global HRQoL (HR = 1.31 95%CI, 0.88-1.94, p = 0.18), physical functioning (HR = 1.58, 95%CI, 1.06-2.35 p = 0,024) and fatigue (HR = 1.19, 95%CI, 0.80-1.77 p = 0.34). Median OS was 3.12 (95%CI 2.27-4.14) months in OF arm vs 1.97 (1.18-3.06) in PF arm. There was a higher total adverse events in PN arm (52%) than in OF arm (41%). Conclusions: In this study PN did not provide clinical benefit for advanced cancer patients with numerically reduced OS and increased toxicity. More data will be shown about tolerance of PN and influencing factors on HRQoL scores. Clinical trial information: NCT02151214.
Patient reported outcomes following palliative gastric RadiOtherapy for symptomatic advanced gastric cancer (PROG): Results from a phase 2 trial.
Authors: Jeremy Chee Seong Tey, Huili Zheng, Yu Yang Soon, Wee Yao Koh, Cheng Nang Leong, Keith Hsiu Chin Lim, Ivan Weng Keong Tham, Jiade J. Lu
Journal: Journal of Clinical Oncology (2017)

e21667 Background: To determine the effect of gastric radiotherapy (RT) on patient reported outcomes (PROs; secondary endpoint) in the PROG trial. Methods: Patients with symptomatic locally advanced or metastatic gastric carcinoma with at least one index symptom of bleeding, pain or obstruction were treated with palliative gastric radiotherapy to a dose of 36Gy in 12 fractions (at 3Gy daily fractions). PROs were assessed using the European Organisation for Research and Treatment of Cancer Qualify of Life Questionanaire-C30 and stomach module STO22. The primary PRO hypothesis was that at least 30% of patients will achieve a &gt; 10 point absolute improvement (considered significant) in the fatigue, nausea/vomiting and pain subscales in the C30, and dysphagia and pain subscales in the STO22 at 12 fractions and one month after radiotherapy. Assessments were performed at baseline, 12 fractions and one month post radiotherapy. Paired T test was used to compare the mean scores from baseline, and at 12 fractions and one month post completion of RT Results: Questionnaires were available from 49 of 50 patients (98%) at baseline, 36 of 45 patients (80%) at 12 fractions and 16 of 38 patients (42%) at one-month post RT. At 12 fractions, 50%, 28% and 44% of patients achieved a significant improvement in fatigue, nausea/vomiting and pain subscales in the C30 respectively. 42% and 28% of patients achieved a significant improvement in dysphagia and pain subscale in the STO22. The observed mean difference was 11 points and 4 points for pain subscale in the C30 and STO22 (P &lt; 0.02). At one-month post RT, 63%, 31% and 50% of patients achieved a significant improvement in fatigue, nausea/vomiting and pain subscales in the C30 respectively. 44% and 19% of patients achieved a significant improvement in dysphagia and pain subscale in the STO22. There were no significant differences in the mean scores in the subscales of interest. Conclusions: Palliative gastric radiotherapy resulted in improvements in fatigue, dysphagia and pain at 12 fractions and at 1-month post radiotherapy in a significant proportion of patients. A phase III trial comparing the effects of different fractionation regimens on PROs is warranted. Clinical trial information: NCT01341756.
Validation of a combined residual risk score for healthy unaffected women presenting to breast cancer (BC) screening centers.
Authors: Kathryn Dalton, Elisha Hughes, Wade Hedegard, Carol A. Adami, Alison Sibley, Mike Piz, John Holman, Alexander Gutin, Jerry S Lanchbury, Danna F. Grear
Journal: Journal of Clinical Oncology (2018)

1507 Background: Recent studies have identified single-nucleotide polymorphisms (SNPs) that individually confer modest risk but together explain genetic BC predisposition in many women testing negative for monogenic mutations. We have previously developed and validated an 86-SNP residual risk score (RRS) and a combined residual risk score (cRRS) that incorporates version 7.02 of the Tyrer-Cuzick (TC) model in large consecutive cohorts of women who tested negative for mutations in known BC predisposition genes during hereditary cancer testing. Here, we describe validation of the cRRS in a consecutive cohort of women enrolled from BC screening centers. Methods: This was a prospective, IRB-approved study conducted according to a case-control design. The primary objective was to demonstrate that cRRS offers significantly improved discriminatory accuracy compared to TC alone. A consecutive series of unaffected controls and recently diagnosed BC-affected cases of European ancestry who presented to screening centers were enrolled. Consented patients provided blood or saliva samples for SNP and multi-gene panel testing, and clinical information for the TC model. Discriminatory accuracy of cRRS and TC were evaluated with age-adjusted weighted logistic regression models. P-values were based on likelihood ratio chi-squared test-statistics, and reported as two-sided. Results: 518 patients (256 BC cases; 262 unaffected controls) who met study eligibility criteria were enrolled from 4 screening centers: Elizabeth Wende Breast Care (123); The Breast Center of NWA (145); Bethesda Health (113); CUDA/CCHC (137). Patients with mutations in BC genes were excluded from analysis. Both cRRS and TC significantly discriminated BC cases from unaffected controls in terms of remaining lifetime (cRRS p < 10-11; TC p < 10-5) and 5-year (cRRS p < 10-10; TC p < 10-4) risk estimates. The cRRS showed significantly improved discriminatory accuracy compared to TC alone (lifetime p < 10-7; 5-year p < 10-7). Conclusions: The cRRS offers superior risk stratification compared to TC alone, and may improve prevention and screening strategies for unaffected women testing negative for monogenic BC mutations. Clinical trial information: NCT03067389.
Early determination of benefit or futility in treating NSCLC using the LCSS 3-Item Global Index (3-IGI).
Authors: Richard J. Gralla, Patricia J Hollen, Richard Delmar Hall, Ryan D. Gentzler, Haiying Cheng, Balazs Halmos, Jeffrey Crawford, Martin Lesser
Journal: Journal of Clinical Oncology (2018)

9086 Background: Early assessment of the effect of treatment for advanced NSCLC can prevent unnecessary exposure to toxic and costly therapy while aiding in decision making to change treatment if necessary. Analysis in mesothelioma (Symanowski JCO 2014) suggested that a 20% decline from baseline after 2 cycles of chemotherapy in the 3-Item Global Index of the LCSS identified patients unlikely to benefit. The 3-IGI (global distress, activities, QL) takes < 2 minutes to assess. Methods: 164 patients with NSCLC receiving chemotherapy or check point inhibitors were prospectively evaluated with the LCSS at baseline and every 3 weeks using electronic media. Patients were also randomized 1:1 so that their physicians knew the results of the LCSS immediately in half of the patients. Results: Patients: Stage IV 92%; first line 73%; female 43%; median PS 1; mean age 63. The LCSS was completed after 2 cycles of treatment and prior to planning for the next cycle (generally 6 weeks after baseline; representing 91% of the 148 patients living). Patients with a 20% decline in the 3-IGI compared with baseline had a median survival of 7.6 months, contrasted to 15.8 months for those without this degree of 3-IGI decline (p = 0.01); 1 year survivals = 26% versus 62%. Even with the marked PRO decline after 2 treatment cycles, patients in the 20% decline group received a median of 2.3 more cycles of the same chemotherapy (median cost = $10,712 / patient). In the 50% of patients for which their physicians knew the ongoing LCSS results, fewer chemotherapy cycles and imaging studies were performed, but the differences were not significant (p = 0.8). Conclusions: Assessing change from baseline with the 3-IGI of the LCSS identifies after only 2 cycles of treatment those patients who have poor response and survival outcomes if continued on the same therapy. This PRO assessment is rapid, easy and inexpensive. Physicians need to consider the impact of change on decision options given that even when physicians were aware of the worsening PRO they often did not act on the findings. Responding to 3-IGI changes can result in better decisions concerning continuing or changing treatment, lessening toxicity, and savings in cost of unhelpful treatment. Support: NIH/NCI R01 CA157409 Clinical trial information: NCT01924416.