tbuckley/cabot-search huggingface dataset:
Reconstruction of continuous isoperistaltic jejunum interposition after proximal gastrectomy preserving gastric antrum.
Authors: Xinbao Wang, Ling Huang, Qiming Yu, Chao Hu
Journal: Journal of Clinical Oncology (2018)

e16046 Background: To investigate the clinical application of reconstruction of continuous isoperistaltic jejunum interposition(CIPJIP) after proximal gastrectomy preserving gastric antrum and search for a better operative mode of proximal stomach tumor. Methods: 31 cases of proximal gastric tumor patients who were applyed proximal subtotal gastrectomy and preserved gastric antrum were performed. The reconstruction of CIPJIP were applied (jejunum interposition about 20cm between esophagus and gastric antrum), as well as the safety of operation and the quality of life after operation of these patients were analysed. Results: Among 31 cases, 2 cases were gastric cardia stomal tumor, 2 cases were leiomyoma, and 27 cases were proximal gastric cancer. 31 patients had no postoperative complications such as bleeding, fistulas et al. All of them stayed in hospital for 7-9 days after operation. One patient with III stage was discovered metastasis in pelves 6 monthes after operation, another case of stromal tumor had severe regurgitation after 3 months because of proximal ligation line off. All of 31 patients, except 2 cases of affresaid special patients, regained their weight to the preoperative level, and the quality of life shows well. All patients, except 1 case of proximal ligation line off appeared heartburn, have no severe acid reflux symptoms. Conclusions: Compared with the data shows aboved, reconstruction of CIPJIP after proximal gastrectomy preserving gastric antrum is safe, and quality of postoperative life is significantly better than that of gastroesophageal anastomosis and total gastrectomy patients. Therefore, it deserves further research or application.
Utility of comprehensive genomic profiling (CGP) at an NCI-designated cancer center for identifying clinically relevant genomic alterations (CRGA) and implementing genomically directed therapy (GDT).
Authors: Talal Hilal, Mary Nakazawa, Jacob Hodskins, Susanne M. Arnold, Philip A. DeSimone, Lars M. Wagner, Lowell Brian Anthony, Mara D. Chambers, John L. Villano, Aju Mathew, Sherry L. Bayliff, Gaurav Goel, Edward H. Romond, Ravneet Thind, Peng Wang, Tom C. Badgett, John A. D'Orazio, Fredrick R. Ueland, John VanNagell, Peter Joel Hosein
Journal: Journal of Clinical Oncology (2016)

e18018 Background: GDT produces higher response rates and improved survival compared to empiric therapy in some series of patients (pts) with refractory cancers. Limited data exists on the utility of CGP in a real-world setting. Herein we describe our experience with CGP using the Foundation One (F1) panel. Methods: The F1 methodology, which has been well described and validated, was used for CGP. Data were collected on demographics, CGP results and treatment outcomes. The decision to perform CGP was solely at the physician’s discretion. Results: Between 11/2012 and 9/2015, 90 pts had F1 testing. There were 17 pediatric and 73 adult pts. The pediatric cases included 8 brain tumors, 6 sarcomas, 2 neuroblastomas, and 1 melanoma. The adult cases included 18 GI cancers, 17 sarcomas, 11 lung cancers, 8 breast cancers, and 19 other tumors. CRGA were identified in 77 (86%) pts – 14 (18%) had FDA-approved options, 59 (77%) had off-label options and all 77 (100%) had clinical trial options identified. Fourteen (16%) received GDT; 8 had no benefit, 4 are ongoing on therapy on clinical trials and 2 achieved stable disease, including 1 child with anaplastic astrocytoma and a BRAF mutation treated with vemurafenib and 1 adult with NSCLC and a KRAS mutation treated with trametinib. Among the 76 pts who did not receive GDT, the most common reasons were ongoing standard-of-care therapy in 31 pts (41%), poor performance status in 17 (23%), no evidence of disease or stable disease in 12 (16%), and lack of access to a relevant clinical trial in 11 (15%). Apart from the therapeutic implications, 2 pts with sarcoma had their diagnosis modified based on the result of the EWSR1 rearrangement in their tumors. Conclusions: CGP identified potential treatment options in the majority of pts profiled and helped to clarify the diagnosis in some cases. Many pts had testing performed too late in their disease course to act upon. Another barrier was lack of access to clinical trial options. Earlier integration of CGP in patient care and ongoing trials such as LUNG-MAP and NCI-MATCH may overcome some of these limitations.
Safety and preliminary efficacy data from a phase I study of an implantable low intensity pulsed ultrasound (LIPU) device for disrupting the blood-brain barrier (BBB) in patients treated by chemotherapy for recurrent glioblastoma (GBM).
Authors: Ahmed Idbaih, Michael Canney, Carole Desseaux, Alexandre Vignot, Bruno Law-Ye, Delphine Leclercq, Lisa Belin, Anne Bissery, Yann De Ricke, Marc Sanson, Khe Hoang-Xuan, Caroline Dehais, Caroline Houillier, Florence Laigle-Donadey, Jean-Yves Delattre, Alexandre Carpentier
Journal: Journal of Clinical Oncology (2018)

2016 Background: The BBB limits the efficacy of many chemotherapies in GBM patients by blocking the passage of drugs to the brain. Two to four minutes of LIPU in combination with injection of micron-sized microbubbles can transiently disrupt the BBB to increase the passage of drugs such as carboplatin. Methods: This first-in-man, single arm, monocentric trial was performed at Hôpital Universitaire Pitié-Salpêtrière, Paris, France from 2014-2018. Recurrent GBM patients were implanted with (1) or (3) 1 MHz, 10-mm diameter cranial devices in burr holes during debulking surgery or during a dedicated procedure under local anesthesia. Ultrasound dose was escalated using a Simon titration design. The device was activated monthly to transiently disrupt the BBB before IV administration of carboplatin (AUC4-6). BBB disruption was visualized using MRI and patients were monitored clinically. Results: Twenty-seven patients were implanted with LIPU devices and 25 per-protocol were sonicated: 19 patients with (1) US emitter and six patients with (3) US emitters. In 85 ultrasound sessions, BBB disruption was visible on post-sonication T1w MRI for 72 sonications and was ultrasound dose dependent. Few transient and manageable severe related adverse events were observed: a partial seizure, two cases of transient edema (H1 and D15) and one transient facial palsy. No carboplatin-related neurotoxicity was observed. All patients treated with (1) emitter had tumor progression and 3/19 patients were alive. In this cohort, patients with no or poor BBB disruption (n = 8) had a median PFS of 13 weeks, and a median OS of 8.9 months. Patients with clear BBB disruption (n = 11) had a median PFS of 15 weeks, and a median OS of 13 months. Conclusions: LIPU was well tolerated and may increase the effectiveness of drug therapies in the brain. The sonication of larger volumes of brain in recurrent GBM will be investigated in a future trial and may further enhance the observed effectiveness of this treatment modality. Clinical trial information: NCT02253212. Clinical trial information: NCT02253212.
Efficacy of adjuvant vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (VEGFRi) in renal cell carcinoma (RCC): A systematic review and meta-analysis.
Authors: Tobias Engel Ayer Botrel, Otávio Clark, Francisco Flávio Horta Bretas, Marcus V. Sadi, Ubirajara Ferreira, Luciano Paladini, Wagner Matheus, Ronilson Oliveira Duraes, Antônio Carlos Lima Pompeu
Journal: Journal of Clinical Oncology (2020)

680 Background: To perform a systematic review and meta-analysis of all randomized controlled trials (RCTs) comparing the efficacy of adjuvant VEGFRi in locally advanced, non-metastatic clear renal-cell carcinoma (RCC). Methods:Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. We included studies that compared the addition of VEGFRi versus placebo, after nephrectomy. Analyzed endpoints were overall survival (OS) and disease-free survival (DFS). The data extracted from the studies were combined by using Hazard Ratio (HR) or Risk Ratio (RR) with their corresponding Confidence Intervals of 95% (CI95%). Results: Overall, 121 references were identified and screened. The final analysis included 5 trials (S-TRAC, ATLAS, ASSURE, PROTECT and SORCE) comprising 6,128 patients that underwent previous nephrectomy for RCC. The DFS was similar in patients who received VEGFRi (fixed effect: HR=0.94, CI95%=0.87 to 1.03; p=0.19), with no heterogeneity (Chi 2 = 4.33, df = 5 (P=0.50); I 2 = 0%). Overall survival also was not statistically better in patients who received VEGFR inhibitors (HR=1.01, CI95%=0.90 to 1.15; p=0.84), with no heterogeneity (Chi 2 = 3.57, df = 5 (P=0.61); I 2 = 0%). In the final combined analysis of the higher-risk disease group (pT3, pT4, or N+ disease), patients who received VEGFRi had a longer DFS (fixed effect: HR=0.85, CI95%=0.74 to 0.97; p=0.02), with no heterogeneity (Chi 2 = 2.46, df = 3 (P=0.48); I 2 = 0%). Overall survival was not statistically different for these higher-risk disease patients (fixed effect: HR=0.93, CI95%=0.74 to 1.16; p=0.5). Conclusions: This is the first meta-analysis including the five available RCTs in the literature (the previous meta-analysis reviewed only four), comparing adjuvant VEGFRi versus placebo in patients submitted to nephrectomy with a locally advanced, non-metastatic RCC. Adjuvant VEGFRi did not increase the OS in this group of patients. Amodest benefit of DFS with the use of adjuvant VEGFR inhibitors was restricted to patients with the highest risk of relapse.
The effect of neutropenic diets on infection and mortality rates in cancer patients: An updated systematic review and meta- analysis.
Authors: Mohamad B. Sonbol, Belal Firwana, Thomas DeLeon, Tania Jain
Journal: Journal of Clinical Oncology (2018)

e22087 Background: Neutropenic diet (ND) has been prescribed to cancer patients with the assumption that it provides a theoretical benefit of decreasing infections during the neutropenic phase. We previously reported the insufficient evidence supporting this dietary approach. In this meta-analysis, we sought to determine the efficacy of ND in reducing infection rates when compared to regular diet (RD) based on an updated search strategy. Methods: We searched databases, including PubMed, Embase, and Cochrane Central Register of Controlled Trials to identify studies comparing ND to RD. Both comparative retrospective and prospective trials were allowed. Outcomes of interest were major infections (pneumonia, bacteremia/fungemia, or pneumonia accompanied with bacteremia or fungemia), and the composite outcome of neutropenic fever or infection (major infections as defined above, minor infections, or fever).The overall effect was pooled using the DerSimonian and Laird random effects models. Results: Overall, five studies (4 prospective and 1 retrospective) encompassing 1068 patients were identified. 726 (67.9%) patients had hematopoietic stem cell transplantation (HCT). There was no difference between the ND and RD groups in terms of the rates of major infections (RR 1.13; 95% CI 0.84 to 1.51), bacteremia/fungemia (RR 0.92; 95% CI 0.49 to 1.71), or mortality (RR = 1.08, 95% CI 0.78 to 1. 50). These results did not change significantly when performing a sensitivity analysis including only the prospective studies. On the other hand, when analyzing the overall composite outcome of any infection or fever, ND was found to be detrimental compared to RD (RR 1.18; CI 1.04 to 1.32). Conclusions: There continues to be insufficient evidence to support the use of neutropenic diet over regular diet in cancer patients, including those undergoing HCT. Safe food-handling methods should, however, be encouraged to decrease the rate of infections, rather than further restriction on dietary habits.
TCT-33 Mortality After Repeat Revascularization Following PCI or CABG for Left Main Coronary Artery Disease: The EXCEL Trial
Authors: Gennaro Giustino, Patrick Serruys, Roxana Mehran, Joseph Sabik, David Kandzari, David Taggart, Anthony Gershlick, Yangbo Liu, Thomas McAndrew, Ovidiu Dressler, Stuart Pocock, A. Pieter Kappetein, Ori Ben-Yehuda, Gregg Stone
Journal: Journal of the American College of Cardiology (2018)
Pre-injection wheel running preserves mobility in a rodent model of paclitaxel neurotoxicity.
Authors: Elizabeth Hile, Nataliya Kostereva, Kacey Marra
Journal: Journal of Clinical Oncology (2017)

e21640 Background: Peripheral neurotoxicity (PN), a common side-effect of paclitaxel (Ptx) chemotherapy, can reduce quality of life through persistent balance/gait dysfunction, and even shorten survival by limiting therapy. Exercise before chemo, or ‘prehabilitation’ (prehab), seems to protect cardiac and cognitive function, but few have studied mobility, or identified gait parameters most sensitive to PN, to inform larger neuroprotection work. Aims of this preclinical, proof of concept pilot were to identify 1) if pre-Ptx wheel running preserves mobility, 2) key gait parameters for the Ptx-PN phenotype, 3) potential mechanisms for prehab neuroprotection. Methods: Adult female Lewis rats were randomized to 3 arms under equivalent housing: sedentary before injection of vehicle (SedSham), sedentary before 36 mg/kg Ptx (SedPtx), or prehab wheel running 60 min, 5 days/wk X 5 wks pre-Ptx (ExPtx). Outcomes were blinded mobility observation and DigiGait spatiotemporal parameters at baseline, before &amp; after injection, and at euthanasia, with peripheral nerves (sural, sciatic, tibial, fibular) harvested for immunohistochemistry and quantitative histomorphometry with GAP43 (neuroplasticity) &amp; S100 (Schwann) antibodies. Consistent with small pilot design, analyses were primarily descriptive comparisons. Results: A single blinded assessor correctly identified group assignment for 7 of 8 (87.5%) videotaped rats by post-injection mobility observation alone, identifying slowness, frequent paw contact/ reduced forepaw exploration, and flattened paws as Ptx-PN phenotype. Paw changes were confirmed by post-hoc Digigait image comparison. 'Percent propulsion' emerged as a key gait parameter in sensitivity analysis with a prehab non-responder. Levels of S100 appear lower in SedPtx group nerves compared to ExPtx and SedSham animals. Conclusions: Mobility deficits after Ptx are often attributed to peripheral somatosensory changes rather than neuromotor dysfunction, yet these preclinical results echo our growing anecdotal clinical observations. While preliminary, both suggest greater attention to distal strength and motor function after Ptx exposure.
Improvement of chemotherapy induced neuropathy (CIN) in cancer patients using capsaicin 8% patch.
Authors: Christian LE Marec, Julie Berard, Isabelle Queneuille, Karima Mezaib, Francois Croixmarie, Mario Di Palma, Sophie Laurent
Journal: Journal of Clinical Oncology (2016)

e14031 Background: CIN is a common side effect of numerous anti-cancer drugs, with a huge impact on patient's quality of life. Current Pharmacological treatments bring only partial relief with tolerance issues. The capsaicin 8% patch is an approved treatment for localized peripheral neuropathic pain. We report here our experience with this agent in a cohort of patients with CIN. Methods: Patients with CIN treated between January 2013 and December 2015 were included in this study. Pain levels were assessed using an 11-point scale as part of the Brief Pain Inventory questionnaire and the Clinical Global Impressions Scale. Results: 28 patients with CIN, aged 38-83 years, were treated with a 30-minute application of a capsaicin 8% patch on their hands and/or feet. All patients had loco regional block analgesia before capsaicin application to prevent pain worsening during procedure. Neuropathic pain in our cohort was related with several drugs: docetaxel (n=8); paclitaxel (n=5); carboplatin (n=4); bortezomib (n=4); thalidomide (n=3); oxaliplatin (n=2); alkeran (n=2). All patients were resistant to a well conducted neuropathic pain treatment according to French recommendation. All patients reported significant pain relief during the first month after capsaicin use. At 6 months, pain scores were reduced by <30% in 5 patients (18%), 30-50% in 2 patients (7%), 50-70% in 10 patients (36%), 70-90% in 10 patients (36%), and >90% in 1 patients (3%). Capsaicin patch was well tolerated. This procedure was repeated in case of pain recurrence: 19 patients received 1 or 2 applications, 4 patients 4 applications, 4 received 5 or 6, for 1 patient procedure was repeated 9 times. The median delay between two consecutive applications was 7 months in our cohort. Conclusions: Capsaicin 8% patch appears effective and well tolerated in patients with CIN. It must be considered for patients with painful CIN. Pain score reductions in CIN cancer patients treated with the capsaicin 8% patch. CIN <30% 30-50% 50-70% 70-90% >90% Number of treatments n=80 8 13 24 26 9 Number of patients n=28 5 2 10 10 1
Phase 2 study of pembrolizumab in combination with azacitidine in subjects with metastatic colorectal cancer.
Authors: James J. Lee, Weijing Sun, Nathan Bahary, James Ohr, John C. Rhee, Ronald G. Stoller, Stanley M. Marks, Barry C. Lembersky, H. Scott Beasley, Summer Drummond, Natalie Streeter, Yongli Shuai, Yan Lin, James Herman, Hassane M. Zarour, Edward Chu
Journal: Journal of Clinical Oncology (2017)

3054 Background: Microsatellite stable (MSS) metastatic colorectal cancer (mCRC) has relatively poor tumoral infiltration of CD8 + T cells and is resistant to pembrolizumab (Pembro) when compared to MSI-H mCRC. DNA hypomethylating agent induces epigenetic expression of multiple genes including cancer-testis antigens in CRC, which are recognized by cytotoxic CD8 + T cells in vitro and in vivo. This trial tested whether concurrent treatment with azacitidine (Aza) could enhance the anti-tumor activity of Pembro. Methods: This is a phase 2 trial to evaluate anti-tumor activity and safety of Pembro plus Aza in patients (pts) with previously treated mCRC without any further standard chemotherapy option. Pts received Pembro 200 mg IV on day 1 of each cycle Q3W and Aza 100 mg daily SQ injection on days 1-5 of each cycle Q3W. Primary endpoint was response rate (ORR) using RECIST v1.1. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Tumor tissues were collected for correlative studies. Results: Thirty-one pts were enrolled [median age, 61 years (range, 30-79); 17 M/14 F; ECOG PS 0/1 (58%/42%); 30 pts with MSS mCRC]. Pts received at least 2 lines of prior systemic chemotherapy for mCRC (median, 3; range, 1-5). Thirty pts received at least one dose of study therapy (median, 3 cycles; range, 1-8). Ten pts could not complete the first 3 cycles due to rapid symptomatic tumor progression. One pt with MSS mCRC achieved PR and 3 pts had SD as best response. The ORR was 3% (1/30; 95% CI, 0.1-17%). Seven pts with PD at the end of cycle 3 continued on study therapy, and 2 pts had stabilization of tumor progression. Median PFS was 2.1 months (95% CI, 1.8-2.8), and median OS was 6.2 months (95% CI, 3.5-8.7). While treatment-related adverse events (TRAEs) were reported in 63% of pts, most of the TRAEs were Gr 1/2 (96%). Frequent TRAEs possibly related to Aza were anemia (n = 5), constipation (n = 5), and leukopenia (n = 4); and possibly related to both Aza and Pembro were nausea (n = 5) and fatigue (n = 5). Gr 3 TRAEs included anemia (n = 1), ALT elevation (n = 1), and alkaline phosphatase elevation (n = 1). Conclusions: Pembro plus Aza is feasible with a tolerable safety profile but appears to have minimal anti-tumor effect for MSS mCRC. Clinical trial information: NCT02260440.
Onset of neutropenia as an indicator of treatment response in the phase III RECOURSE trial of TAS-102 vs placebo in patients with metastatic colorectal cancer.
Authors: Atsushi Ohtsu, Takayuki Yoshino, Alfredo Falcone, Rocio Garcia-Carbonero, Guillem Argiles, Alberto F. Sobrero, Marc Peeters, Lukas Makris, Fabio Benedetti, Alberto Zaniboni, Yasuhiro Shimada, Kentaro Yamazaki, Yoshito Komatsu, Howard S. Hochster, Heinz-Josef Lenz, Ben Tran, Mona Wahba, Kenichiro Yoshida, Eric Van Cutsem, Robert J. Mayer
Journal: Journal of Clinical Oncology (2016)

3556 Background: TAS-102 is comprised of an antineoplastic thymidine-based nucleoside analog, trifluridine (FTD), and a thymidine phosphorylase inhibitor, tipiracil. Primary results of the RECOURSE trial demonstrated a significant improvement in overall survival (OS) and progression-free survival (PFS) with TAS-102 vs placebo (pbo) in patients (pts) with metastatic colorectal cancer refractory/intolerant to standard therapies. Neutropenia is a common TAS-102–associated adverse event and it has been hypothesized to be associated with a relatively high FTD concentration in pts. Methods: RECOURSE data were analyzed post hoc for correlations between onset of neutropenia (Grade 3/4) and survival benefit. Results: Of 533 pts given TAS-102, 75 (14%) developed Grade 3/4 neutropenia in treatment cycle 1, 86 (16%) in cycle 2, and 39 (7%) in cycle ≥3. Onset of neutropenia at any cycle was associated with longer median OS and PFS compared with no neutropenia. A consistent survival benefit was observed regardless of the cycle of initial onset of neutropenia, as demonstrated by the hazard ratio (against cycle-matched pbo control groups) and corresponding median OS differences (Table). Conclusions: An association between occurrence of Grade 3/4 neutropenia and survival benefit was observed. The data indicate that such survival benefit occurred regardless of whether the initial onset of neutropenia occurred after cycle 1, cycle 2, or later. Further analyses are required to fully determine whether FTD pharmacokinetics correlate with TAS-102 efficacy and onset of neutropenia, and whether cycle initiation delays affect response. Clinical trial information: NCT01607957. TAS-102/Pbo* n (%) TAS-102/Pbo* Median OS (months) Hazard Ratio (95% CI) All RECOURSE (as treated) 533 (100)/265 (100) 7.1/5.3 0.68 (0.58-0.81) Earliest cycle of Grade 3/4 neutropenia onset in TAS-102 arm 1 75 (14)/265 (100) 9.7/5.3 0.45 (0.32-0.64) 2 86 (16)/215 (81) 8.7/6.3 0.56 (0.41-0.78) ≥3 39 (7)/48 (18) 13.8/10.2 0.36 (0.17-0.75) None 333 (62)/265 (100) 5.5/5.3 0.97 (0.81-1.16) *Number of pbo pts who entered cycle; no pbo pts exhibited neutropenia.