tbuckley/cabot-search huggingface dataset:
Morbidity and mortality after laparoscopy-assisted and open distal gastrectomy for stage I gastric cancer: Results from a multicenter randomized controlled trial (KLASS-01).
Authors: Hyuk-Joon Lee, Hyung-Ho Kim, Sang Uk Han, Min-Chan Kim, Woo Jin Hyung, Seung Wan Ryu, Gyu Seok Cho, Chan Young Kim, Han-Kwang Yang, Do Joong Park, Kyo Young Song, Sang Il Lee, Seung Yub Ryu, Joo-Ho Lee, Wook Kim
Journal: Journal of Clinical Oncology (2015)

4 Background: Laparoscopy assisted distal gastrectomy (LADG) is widely performed for gastric cancer in Eastern countries, although large scale prospective data are still lacking. We conducted a phase III, multicenter randomized controlled trial (KLASS-01) to compare the short and long term outcomes of LADG versus open distal gastrectomy (ODG) in patients with clinical stage I gastric cancer in Korea. Methods: The primary end point was 5-year overall survival. The morbidity within 30 postoperative days and the surgical mortality were compared to evaluate the safety of LADG as a secondary end point. A total of 1,416 patients were randomly assigned to the LADG group (n = 705) or the ODG group (n = 711) between Feb 1, 2006 and Aug 31, 2010. Results: 1,256 were eligible for per protocol (PP) analysis (644 and 612, respectively). The overall complication rate was significantly lower in the LADG group (LADG vs. ODG; 13.0% vs. 19.9%, P =.001). In detail, the wound complication rate of the LADG group was significantly lower than that of the ODG group (3.1% vs. 7.7%, P &lt;.001). The major intra-abdominal complication (7.6% vs. 10.3%, P =.095) and mortality rates (0.6% vs. 0.3%, P =.450) were similar between groups. Modified intention-to-treat analysis showed similar results with PP analysis. Conclusions: LADG for patients with clinical stage I gastric cancer is safe and has a benefit of lower occurrence of wound complication compared with conventional ODG. Clinical trial information: NCT00452751.
Prediction of venous thromboembolism in ambulatory patients with cancer receiving chemotherapy: An expanded thromboembolic risk score model.
Authors: R. Labianca, G. Gasparini, S. Barni, M. Verso, E. Bonizzoni, M. Brighenti, M. Mandala, F. Petrelli, C. Bianchini, T. Perrone, G. Agnelli
Journal: Journal of Clinical Oncology (2011)

e19551 Background: Cancer and chemotherapy are well recognized risk factors for thromboembolic events (TEs). Nadroparin has been demonstrated to reduce the incidence of TEs by about 50% in cancer outpatients receiving chemotherapy. Patients receiving regimens containing cisplatin, carboplatin or gemcitabine and their combination have the highest risk of TEs. Khorana and colleagues have validated a score (KS) to identify the risk of TEs in cancer patients, stratifying them according to five variables (site of cancer, platelet count, haemoglobin level, leukocyte count and body mass index). Patients with a score ≥ 3 are at high risk to develop TEs. Methods: In our analysis we have expanded the KS by incorporating the chemotherapy variable: for patients receiving chemotherapy regimens containing cisplatin or carboplatin or gemcitabine 1 point has been added to the score; while regimen containing platinum compound plus gemcitabine 2 points. The aim of this post-hoc analysis was to evaluate the ability of this expanded Khorana risk score (ExKS) to identify high risk patients among the PROTECHT trial (NCT 00951574) population. A receiver operating characteristic (ROC) curve has been used to assess the accuracy of KS and ExKS. Results: Among the 1150 evaluable patients: 381 were allocated in the placebo arm and for 378 of them an evaluation of KS and ExKS has been performed: 11.1% (42/378) and 32.8% (124/378) were at high risk of TEs in the KS and ExKS, respectively. In the study population a total of 15 TEs has been reported. 33.3% (5/15) and 66.7% (10/15) of TEs occurred in the high risk patients according to KS and ExKS, respectively. A ROC curve analysis has been performed to evaluate the predictability of the ExKS respect to KS. The Area under the ROC Curve, which reflects the predictive value of the scores, was larger with ExKS in comparison with KS (0.70 and 0.65 respectively) Conclusions: ExKS could have a higher predictability to identify high risk patients for TEs compared to KS in the PROTECHT study. A prospective study is warranted to validate the score
FDG PET to Diagnose Neurolymphomatosis in a Case of Triple-Hit B-Cell Lymphoma
Authors: Caroline Bund, Céline Heimburger, Philippe Trensz, Cécile Fohrer, Stéphane Kremer, Izzie-Jacques Namer
Journal: Clinical Nuclear Medicine (2017)

A 46-year-old man with stage IV triple-hit B-cell lymphoma diagnosed in February 2016 was treated with chemotherapy. He was followed classically with FDG PET/CT, which assessed the complete metabolic response in June 2016. In July 2016, he had autologous stem cell transplantation. Two months later, he underwent an FDG PET/CT for revaluation. It showed intense FDG uptake in the medullary canal from cervical 4 to thoracic 4, bilateral cervical 7 to thoracic 8, and right thoracic 9 to 12 nerve roots, leading to the diagnosis of neurolymphomatosis. A clinical cervical radiculopathy and spinal MRI results reinforced this diagnosis.
Relevance of peritoneal lavage cytology before and after gastrectomy in CY1 and R1 surgery for primary advanced gastric cancer
Authors: O. Kobayashi, A. Tsuburaya, T. Yoshikawa, T. Osaragi, H. Murakami, T. Yoshida, M. Sairenji
Journal: Journal of Clinical Oncology (2005)

4198 [Background] Peritoneal lavage cytology (CY) has been integrated in the Japanese classification of gastric cancer (JCGC) due to similar prognostic impact of CY and peritoneal metastases. CY is diagnosed from either ascites or peritoneal lavage in T2-T4 cases before gastrectomy and is classified as CY1 (positive) and CY0 (negative). CY1 is defined as a decisive factor of Stage IV and non-curative resection, even after macroscopically complete tumor resection. However, the role of residual cells after gastrectomy and thorough peritoneal wash is unknown. We conducted the CY before and after gastrctomy (ACY) in order to elucidate an additional prognostic factor. [Patients & Methods] Between 02/1988 and 11/2004, 23 patients underwent R1 gastrectomy only by CY1, ACY was done after gastrectomy and lavage with 3000ml saline from the Douglas pouch. [Results] Incidence of ACY1 was 26% (6/23) and overall 2-year survival rate was 39%. Median survival time (MST) was 573 days and 392 days in patients with ACY0 and ACY1, respectively. Median peritoneal metastasis-free survival was 355 days and 238 days in patients with ACY0 and ACY1, respectively. Among 20 patients followed up for more than a year, 12 patients (4 of 5 with ACY1 and 8 of 15 with ACY0) developed peritoneal metastases within a year. 14 patients (4 with ACY1 and 8 with ACY0) died, in whom 13 patients developed overt peritoneal metastases in the course. Cause of death from ACY1 was peritoneal dissemination, however, 4 patients with ACY0 died of multiple distant organ metastases. No patient with ACY1 lived longer than 3 years, whereas 3 patients with ACY0 did without evidence of relapse. [Conclusion] ACY may predict high risk of peritoneal metastases and short term prognosis after R1 gastrectomy only by CY1. No significant financial relationships to disclose.
Use of combined FDG-PET and laboratory data for predicting relapse in multiple myeloma.
Authors: B. M. Elliott, S. Peti, D. Lee, K. Osman, L. M. Isola, E. Scigliano, L. Kostakoglu
Journal: Journal of Clinical Oncology (2010)

8148 Background: With growing alternatives in multiple myeloma (MM) therapy, the ability to predict treatment response is increasingly essential. Current guidelines are based on International Myeloma Working Group (IMWG) consensus. However, studies indicate that these criteria may not accurately forecast outcomes. Despite encouraging results in lymphoma, the potential of FDG-PET/CT (PET) for predicting relapse/progression in MM is yet to be explored. Methods: PET and laboratory data (labs: serum chemistry, β2-microglobulin, immunofixation, bone marrow biopsy, free light chain) were reviewed for 37 previously-treated MM patients (median age 61 yr) and date of relapse/progression determined by IMWG criteria. Sensitivity, specificity, and predictive values of the PET/labs combination with respect to 12-mo progression-free survival (PFS) were then calculated and compared with those of each test alone. PFS was estimated by the Kaplan-Meier method. Results: The median time from chemotherapy or transplant to PET was 11.5 mo (0.75-60), median follow-up 22.6 mo, and median PFS 12.4 mo (0.5-39+). Overall survival and PFS at last follow-up were 84% and 49%, respectively. Sensitivity of PET for predicting relapse/progression was lower than that of labs (0.67 vs. 0.89, ns), but PET was more specific (0.89 vs. 0.79, ns). PPV and NPV for PET were 0.86 and 0.74, respectively, versus 0.80 and 0.88 for labs. For the PET/labs combination, a positive result for either test predicted 12-mo PFS with a sensitivity of 0.89, and a positive result for both tests was 100% specific. 12-mo PFS was significantly greater for those with a negative versus positive PET (p = 0.0005, 95% CI 0.054-0.44, HR 0.15), negative versus positive labs (p<0.0001, 95% CI 0.048-0.400, HR 0.13), and for both tests negative versus both tests positive (p<0.0001, 95% CI 0.015- 0.175, HR 0.05). Median PFS both for the 14 patients with positive PET and the 20 patients with positive labs was 7.9 mo. Conclusions: Combining PET with lab data improves prediction of 12-mo PFS. Thus, integration of PET in the current algorithm of MM follow-up may impact management. No significant financial relationships to disclose.
Phase II trial of chemotherapy with high-dose FOLFIRI plus bevacizumab in the front-line treatment of patients with metastatic colorectal cancer (mCRC) and genotype UGT1A1*1/ UGT1A1*1 or UGT1A1*1/ UGT1A1*28 (FFCD 0504 trial): Final results.
Authors: E. Mitry, O. Bouche, J. Seitz, P. Etienne, J. Legoux, T. Aparicio, G. Breysacher, C. Lecaille, T. Lecomte, J. Jouve
Journal: Journal of Clinical Oncology (2011)

3578 Background: The combination of high-dose irinotecan (260mg/m2) with LV5FU2 (FOLFIRI HD regimen) is feasible with an acceptable safety profile and promising efficacy data (Ducreux et al. Oncology 2008;74:17-24). The aim of this phase II study was to evaluate the combination of FOLFIRI HD plus bevacizumab (B) in patients (pts) selected on the UGT1A1 polymorphism, which could be predictive of the irinotecan toxicity and efficacy. Methods: Pts with UGT1A1 *1/*1 (group 1) or *1/*28 (group 2) genotypes and previously untreated mCRC were treated with bevacizumab 5 mg/kg D1, irinotecan 260 mg/m² D1, LV 400 mg/m² D1, 5FU 400 mg/m² IV bolus D1 and 5FU 2400 mg/m² 46h infusion D1-2 every 2 weeks. Using Bryant & Day design with objective response rate (ORR) (independent review, H0 ≤ 40%; H1 ≥ 60%) and toxicity (gr 4 neutropenia or febrile neutropenia or gr 3-4 diarrhea; H0 ≥ 20%; H1≤ 5%) as primary endpoints; a total of 108 pts, 54 in each group, was required (alpha 5% and power 80%) with a planned interim analysis after the inclusion of 17 pts by group. The trial will be stopped at interim analysis if ≤ 7 pts had an OR and/or ≥ 3 pts had a severe toxicity. All analyses were performed in ITT. Results: At the time of interim analysis, done when the 17th pt of group 1 had a 6-months follow-up, 86 pts were included (group 1: 40 pts, group 2: 46 pts). Results of primary endpoints at the interim analysis are presented in the table. According to interim analysis rules, the trial was closed to inclusion for unacceptable toxicity. Conclusions: The trial was stopped after interim analysis because of unacceptable toxicity according to trial's criteria, even if toxicity was manageable and most of the patients continued the treatment after dose adaptation. Defined toxicity criteria to stop the trial at interim analysis may have been too strict and not clinically adapted. There is however no clear benefit of the FOLFIRI HD - B combination in terms of efficacy. Group 1 Group 2 N 17 17 ORR (%) 52.9 58.8 Toxicity (%) 41.2 18.8
Quality assurance metrics in clinical trial conduct.
Authors: Jennifer Li, Susanna Sellmann, Lindsay Philip, Cristina Guglielmi, Pamela Degendorfer, Amit M. Oza
Journal: Journal of Clinical Oncology (2016)

274 Background: Quality assurance (QA) in clinical trials is a safeguard against non-compliance, which impacts patient safety and data integrity. On an institutional level, compiling quality findings provides insight to gaps within existing processes, protocol compliance, and educational content. A QA metrics methodology has been implemented, which is streamlined with the ICH-GCP, and institutional Standard Operating Procedures (SOPs) and policies. Methods: Individual findings are assigned an alphanumerical code, based on severity and category, and a reference for each Quality Assurance Review (QAR). Annual data is tracked for all QAR findings. Different data sets are created to allow for analysis of quality gaps and quality changes over time. Results are used in the creation or revision of educational content, SOPs, and to drive process improvement. Results: To date, a total of 1608 QAR observations between 2014 and mid-2015 have been coded and tracked across 22 studies. Areas of quality gaps, such as most-cited categories (e.g. 27% in Source Documentation and 13% in Regulatory) and references (e.g. 30% on SOPs and 14% on guidelines), are communicated to the Quality and Education team regularly and incorporated into training content. This has also prompted the development of new SOPs, processes, and research tools, after which QA metrics continues to be used to monitor program wide quality improvement. For example, following the implementation of Electronic Source Documentation, the proportion of findings on delays in Adverse Event sign off has seen a decline. For individual QARs, a personalized trends summary is provided to the study team with an overview of the quality of the study conduct. The report displays the distribution of findings across different categories and severity levels. Lastly, quality metrics has increased the efficiency of tracking and reporting program wide QA activity. Conclusions: The regular analysis of quality metrics has proven to be a pivotal step in the Quality Management Cycle. It presents a quick snap shot of the quality of individual research studies under review. When implemented on an institutional scale, it offers valuable feedback on the current SOPs, processes, and training content.
Outcomes, complications, and costs of care of Bosniak IIF, III, and IV cystic renal lesions/malignancies: Data from the largest multi-institutional study to date.
Authors: Andrew D. Smith, Brian Allen, Rupan Sanyal, Haowei Zhang, Daniel Carson, Xu Zhang
Journal: Journal of Clinical Oncology (2013)

344 Background: To evaluate outcomes, complications and costs associated with management of Bosniak IIF, III, and IV cystic renal lesions/malignancies. Methods: An IRB-approved HIPAA-compliant multi-institutional retrospective data registry of prospectively classified Bosniak IIF (N=143), III (N=114), and IV (N=29) cystic renal lesions diagnosed in adults between January 2000 and October 2011 at UMMC, UAB, or WFUBMC was performed. Included patients were managed by surgical excision (N=86), ablation (N=19), or imaging-surveillance &gt;1yr (N=181). De-identified coded data was entered into a web-based REDCap database containing 168 fields/patient. Complication severity was assessed using the Clavien classification system. Inpatient/outpatient technical/professional charges from 6 months prior to 6 months after surgery or ablation were gathered. Results: Patient level malignancy on surgical pathology was 38% (3/8) for BIIF, 40% (26/65) for BIII, and 89% (17/19) for BIV lesions. No metastatic BIIF lesions (0/143). One metastatic BIII lesion (1/114) developed after thermal ablation in a patient with a prior history of papillary RCC. One metastatic BIV (1/29) at the time of initial diagnosis (necrotic papillary RCC). Moderate/severe complications in 19%(16/86) of surgical and 5%(1/19) of ablative patients (p = 0.299). 0%(0/181) complications in patients managed by imaging surveillance &gt;1yr. 0%(0/286) deaths for any management strategy. Median charges of $51,902 for partial nephrectomy (N=50), $42,411 for complete nephrectomy (N=36), and $22,442 for ablation (N=19) were significantly different (p &lt; 0.001). Median charges in surgical patients with moderate/severe complications was $80,393 (N=16), significantly higher than $45,024 (N=70) for no/mild complications (p = 0.002). Conclusions: No deaths from Bosniak IIF or III lesions, irrespective of management approach. Imaging surveillance appears to be a safe primary management strategy for Bosniak III lesions. Moderate/severe complications occurred in 19% of surgery and 5% of ablation patients and nearly doubled the charges for surgery.
Pilot study of vemurafenib and panitumumab combination therapy in patients with BRAF V600E mutated metastatic colorectal cancer.
Authors: Rona D. Yaeger, Andrea Cercek, Eileen Mary O'Reilly, Diane Lauren Reidy, Nancy E. Kemeny, Tamar Wolinsky, Marc J. Gollub, Mario E. Lacouture, Neal Rosen, Efsevia Vakiani, Leonard Saltz
Journal: Journal of Clinical Oncology (2015)

611 Background: BRAF mutant metastatic colorectal cancer (mCRC) is an aggressive subset of colorectal cancer that exhibits minimal response to selective RAF inhibitors. Preclinical data suggest that epidermal growth factor receptor (EGFR) reactivation with RAF inhibition attenuates the efficacy of RAF inhibitors in mCRC and that combined EGFR and RAF inhibition may be a promising therapeutic strategy. Methods: We undertook a pilot trial to assess the response rate and safety of the combination of the selective RAF inhibitior vemurafenib and anti-EGFR antibody panitumumab in patients with BRAF mutant mCRC. Patients received panitumumab 6 mg/kg IV every 14 days starting on day 1 and vemurafenib 960 mg orally twice daily continuously starting on day 8, with treatment staggered for planned correlative studies. Results: Fifteen patients received treatment. Median age was 62 years (range 22-83 years), seven patients (47%) were male, and 11 patients (73%) had a right-sided primary tumor. Performance status was ECOG 0 in four patients (27%) and ECOG 1 in 11 patients (73%). All patients had progressed through at least one standard treatment regimen, and eight patients (53%) had received previous fluoropyrimidine, oxaliplatin, and irinotecan chemotherapy. Acneiform rash (all grade 1 or 2) (53%), fatigue (53%), and arthralgias (40%) were the most frequently observed treatment-related adverse events. Treatment response was assessed in 12 patients because two patients died from disease progression before the first scan and one patient withdrew consent soon after starting treatment. Two patients (13%) had confirmed partial responses (100% and 64% regression) lasting 40 and 24 weeks, respectively. Eight patients (53%) had stable disease (SD) with tumor regression of &gt;15% by RECIST measurement in six of these patients, including two of whom achieved stable disease lasting over six months. Conclusions: Combined RAF and EGFR inhibition is well tolerated and leads to tumor regression in a subset of patients with BRAF mutant mCRC. Planned correlative studies will evaluate degree of pathway inhibition and reactivation of other upsteam pathways with vemurafenib and panitumumab treatment. Clinical trial information: NCT01791309.
FOLFOX4 plus cetuximab administered weekly or every two weeks in first-line treatment of patients with <i>KRAS </i>and<i> NRAS</i> wild-type (wt) metastatic colorectal cancer (mCRC).
Authors: Thomas Brodowicz, Damir Vrbanec, Klaus Kaczirek, Tudor-Eliade Ciuleanu, Regina Knittelfelder, Elisabeth Lindner, Diethelm Messinger, Christoph Zielinski, Berthold Streubel
Journal: Journal of Clinical Oncology (2014)

LBA391^ Background: Efficacy and safety of first-line FOLFOX4 plus either cetuximab (weekly or every two weeks) have been reported to be similar in 152 patients with KRAS exon 2 wt mCRC within the randomized phase II CECOG/CORE2 study. Recent analyses have shown that also mutations in KRAS exons 3/4 and NRAS (exons 2, 3, and 4) are associated with an inferior PFS and OS with EGFR-targeted monoclonal antibody containing therapy. The impact of these additional mutations on the reported findings in the CECOG/CORE2 study were investigated. Methods: Tumor samples of 148 randomized KRAS exon 2 wild-type metastatic colorectal cancer patients were available for testing of additional mutations by conventional Sanger sequencing. Objective response rate (ORR), PFS and OS were compared in patients with KRAS (exons 2, 3, and 4) and NRAS (exons 2, 3, and 4) wild-type tumors [RAS wt] versus patients with mutations in KRAS (exons 3 and 4) or NRAS (exons 2, 3 and 4) [RAS mt]. Patients with BRAF mutations were excluded from this comparison. The Cochran-Mantel-Haenszel procedure was used to compare the ORR. Kaplan-Meier methods, log-rank test and Cox proportional hazard methods were used to analyze PFS and OS. Results: Of the 148 KRAS exon 2 wt patients 124 patients had RAS and BRAF wt tumors, 10 patients had RAS mutations only and 14 had only BRAF mutations. In the RAS wt and the RAS mt groups ORR was 61.3% (95% CI 52.1-69.9) and 40% (95%CI 12.2-73.8), (Odds ratio 0.43, p=0.1966). Median PFS was 9.7 months (95% CI 8.9-11.2) versus 7.2 months (95% CI 6.7-10.8) (hazard ratio HR=0.56, p=0.1135). Median OS was 28.5 months (95% CI 24.0-31.3) versus 16.3 months (95% CI 15.9-20.7), (HR=0.43, p=0.0199). The difference in OS remained statistically significant in the Cox model, if adjusted for significant confounding factors. ORR, PFS, and OS in BRAF mt and RAS mt patients were similar. Conclusions: RAS wt patients treated with cetuximab and FOLFOX4 experience a significant prolongation of OS as compared to RAS mt patients. This analysis supports the findings of other trials that RAS mutational analyses in metastatic CRC disease is recommended prior to initiation of an EGFR-targeted monoclonal antibody therapy. Clinical trial information: NCT00479752.