tbuckley/cabot-search huggingface dataset:
TCT-717 Impact of percutaneous coronary intervention for chronic total occlusion on long-term outcomes of patients with stable coronary artery disease accompanied by left ventricular dysfunction
Authors: Ryosuke Murai, Masanobu Ohya, Takenobu Shimada, None Katsuya Miura, Hidewo Amano, Shunsuke Kubo, Suguru Otsuru, Seiji Habara, Takeshi Tada, Hiroyuki Tanaka, Yasushi Fuku, Tsuyoshi Goto, Kazushige Kadota
Journal: Journal of the American College of Cardiology (2018)
Laparoscopic sentinel node navigation surgery versus laparoscopic standard gastrectomy with lymph node dissection in early gastric cancer: Results of postoperative morbidity and mortality from a multicenter randomized controlled trial (SENORITA trial).
Authors: Keun Won Ryu, Young Woo Kim, Jae Seok Min, Ji Yeong An, Hong Man Yoon, Bang Wool Eom, Hoon Hur, Young Joon Lee, Gyu Seok Cho, Young-Kyu Park, Mi Ran Jung, Ji-Ho Park, Woo Jin Hyung, Sang-Ho Jeong, Byung-Ho Nam, Mira Han, Nam Hee Kim
Journal: Journal of Clinical Oncology (2018)

e16043 Background: The benefits and hazards of laparoscopic sentinel node navigation surgery (LSNNS), compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection (LND) in early gastric cancer (EGC), are unknown. The SENORITA trial investigated the clinical impact of LSNNS in EGC in terms of short-term surgical outcomes, long-term survival and quality of life (QOL). Methods: Patients with preoperatively diagnosed gastric adenocarcinoma with T1N0 of 3 cm or less in diameter, regardless of histology, except absolute indication for endoscopic resection were eligible. Patients were randomized for LSG with LND or LSNNS using dual tracers. The primary endpoint was 3-year disease-free survival. Morbidity and mortality within 30 postoperative days were evaluated as secondary endpoints and graded by Clavien-Dindo (C-D) classification. Results: From March 2013 to December 2016, 580 patients were randomized (LSG arm 292 vs. LSNNS arm 288). After 49 patients dropped out before surgery, operation was performed in 531 patients (272 vs. 259), representing the full analysis set. Excluding 14 without LSNNS due to various reasons, LSNNS by protocol was performed in 245 patients, and detection of the sentinel basin was possible in 237 patients (96.7%). Stomach-preserving surgery was achieved in 210 (81.1%) patients. Postoperative complications occurred in 47 (17.28%) of LSG and 40 (15.44%) of LSNNS patients (p = 0.568). Severe C-D grade 3 and greater complications were noted in 16 (5.88%) and 13 (5.02%) patients, respectively (p = 0.662). Postoperative mortality occurred in one patient in the LSG arm. Postoperative conversion of LSNNS to LSG was performed in 2 patients due to complications of suture line stenosis and 10 patients according to the study protocol (the involved margin of the resected primary tumor, pT2 or greater, and macrometastasis in the sentinel nodes). Conclusions: LSNNS in EGC is a safe procedure compared with LSG with LND in terms of postoperative morbidity and mortality. Long-term survival and QOL of LSNNS will be determined in the future. Clinical trial information: NCT01804998.
Global oncology fellowship electives: The impact on cancer care and international collaborations.
Authors: John Butonzi, Cyprien Shyirambere, Frederick Lansigan, Christian Rusangwa, Thomas H. Davis, Addie Hill, Kelly Rose, Rebecca Jane DeBoer, Deogratias Ruhangaza, Mary D. Chamberlin
Journal: Journal of Clinical Oncology (2018)

11009 Background: To meet the rising demand for cancer care in low-middle-income countries (LMIC’s), an accredited Global Health track in Hematology-Oncology Fellowship programs (HOFP) is needed. To determine feasibility, the Geisel School of Medicine at Dartmouth (GSMD) HOFP piloted a bi-annual, one-month elective in Rwanda supervised by GSMD faculty. Objectives included exchange of knowledge in a resource-stratified setting and engagement in scholarly collaborations. Methods: Program objectives were implemented by GSMD HOFP in partnership with the Rwandan Ministry of Health, the NGO Partners In Health, and the Butaro Hospital Cancer Center of Excellence (BCCOE) in Butaro, Rwanda. Mentorship opportunities, formal lectures, organizational changes, research projects and funding sources were tracked. Fellows were evaluated using ACGME clinical competencies. Results: The 2-year pilot program was 100% enrolled by fellows from 3 US HO programs and one rising first year HO fellow (N = 4). Seven educational, research and quality improvement projects and three organizational changes were implemented. Three grant proposals for research collaborations are in process. Fifty percent of participating fellows plan to pursue careers in Global Health. The HO fellows gained perspective on cancer care and capacity-building in a LMIC, and confidence in teaching. BCCOE staff gained knowledge and mentorship, ideas for quality improvement, and increased expertise with treatment protocols. Rwandan colleagues valued the solidarity generated by a long-term partnership. Faculty were funded by a combination of CME, Fellowship and Vacation time. Conclusions: A global oncology fellowship elective is feasible and has a qualitative impact on care delivery and collaboration in LMICs influencing fellows’ career choices and professional growth of colleagues at partner sites. Long-term partnerships complement the task-sharing approach to cancer care. Financial sustainability requires formal institutional support for faculty participation. A Global Health track in HO that includes international applicants from LMICs will encourage multi-disciplinary collaboration and expand our capacity for quality global cancer care.
Barriers to cancer care pathways in France: A qualitative case study.
Authors: Fatima Yatim, Marie Ferrua, Aude Fourcade, Mario Di Palma, Etienne Minvielle
Journal: Journal of Clinical Oncology (2016)

e18032 Background: Modern cancer care requires the development of care pathways. Many studies point out the importance of cancer care pathways to reduce discontinuities of care. However, there are few descriptive studies about their effective implementation. Objectives: To identify barriers to effective implementation of cancer care pathways in France, drawing from the perspective of patients and healthcare providers. Methods: The case study was conducted at Gustave Roussy (Villejuif, France), as a part of a Capri research program, which experiments and evaluates coordinated cancer care pathway. Three categories of participants were selected: patients and caregivers; professionals of Gustave Roussy (e.g. hospital practitioners, nurses, transverse services); and primary care providers (e.g. physicians, private nurses, pharmacits). Data collection was done from November 2014 to May 2015 (job shadowing, internal documentation and semi-structured interviews). Data were systematically analyzed according to the theoretical frame defining from literature review: (i) lack of resources, (ii) coordination problems, (iii) problems relative to professional and organizational practices, (iv) public education. Results: 24 hours (3days) of job shadowing, 57 semi-structured interviews and different documents were analyzed. The interviewees were: patients (17); professionals of Gustave Roussy (29); and primary care providers (11). Six categories of barriers identified: (i) coordination problems (55/57); (ii) insufficienty of patient education (47/57); (iii) lack of resources (38/57); (iv) difficulties related to professional and organizational practices (32/57), (v) technical limits related to data transmission (20/57); and (vi) lack of a common and agreed standards on cancer care pathway (17/57). Conclusions: The majority of barriers to cancer care pathway implementation are related to a lack of coordination between healthcare providers and within each healthcare facility (e.g. non-transmission of patient medical records, lack of communication). They require the implementation of new professional managerial skills, especially among nurse navigators and other existing and new professions for improving the care coordination.
Molecular and clinical implications of <i>CHD1</i> loss and <i>SPOP</i> mutations in advanced prostate cancer.
Authors: Pasquale Rescigno, Gunther Boysen, Daniel Nava Rodrigues, George Seed, David Dolling, Ruth Riisnaes, Mateus Crespo, Diletta Bianchini, Semini Sumanasuriya, Ines Figueiredo, Rossitza Christova, Veronica Gil, Jane Goodall, Adam Sharp, Mark A. Rubin, Wei Yuan, Christopher Barbieri, Joaquin Mateo, Suzanne Carreira, Johann S. De Bono
Journal: Journal of Clinical Oncology (2018)

5064 Background: CHD1 deletions (CHD1del) and SPOP mutations (SPOPmut) frequently co-occur in prostate cancer (PCa) with lower frequencies observed in castration-resistant PCa (CRPC). Responses to standard treatments in this subset of patients have not been previously reported. We studied the molecular and clinical characteristics of CHD1del/SPOPmut metastatic CRPC (mCRPC) analyzing CHD1 presence/loss during disease progression and correlation to response to Abiraterone acetate (AA). Methods: We identified mCRPC patients who had hormone naïve (HNPC) and CRPC tumor samples available: these were analyzed for CHD1, PTEN and ERG expression by immunohistochemistry (IHC). SPOP status was determined by targeted next generation sequencing (NGS). Correlations with CHD1/SPOP status and clinical outcomes and responses to AA were analysed using Cox-regression and Log-Rank analyses. Results: Tumor samples from 89 patients who had progressed from HNPC to CRPC were analyzed in a cohort enriched for SPOPmut. CHD1 protein loss was detected in 11 (15%) and 13 (17%) of HNPC and mCRPC biopsies, respectively. Comparison of CHD1 protein levels were feasible in 56 matched, same patient HNPC and mCRPC biopsies. CHD1 protein status correlated in 55 of 56 cases of the matched samples (98%). We identified 22 patients with somatic SPOPmut, with 6 of these mutations not reported previously in PCa, including one (p.A187T) located in the BTB domain in an area reported to be necessary for homodimerisation and other two located in residues (E50, R121) previously associated with endometrial cancer. SPOPmut and/or CHD1 loss was associated with a higher response rate to AA (SPOP: OR = 14.50 p = 0.001; CHD1: OR = 7.30, p = 0.08) and a longer time on abiraterone (SPOP: HR = 0.37, p = 0.002, CHD1: HR = 0.50, p = 0.06). Conclusions: SPOP mutated mCRPCs are strongly enriched for CHD1 loss and seem to be likely sensitive to AA. We envision that determination of SPOP/CHD1 status might serve treatment selection in mCRPC.
Phase 1b safety and antitumor activity of PLM60 (pegylated liposomal mitoxantrone) in NHL.
Authors: Simon Li, Yuhuan Gao, Guangyu Ma, Mingxia Wang, Zhangying Feng, Kun Lou, Yueyin Peng, Shan Chen, Jing Yuan, Sheng Hao, Vivien Shi, Ronald Walls, Luana Pesco Koplowitz, Chunlei Li
Journal: Journal of Clinical Oncology (2018)

e19503 Background: PLM60 is a novel liposomal pegylated nanoparticle formulation of conventional mitoxantrone (cMI) that showed improved PK properties, good tolerability, and potential efficacy versus cMI in patients with advanced lymphoma and sarcoma at doses of 14 and 16 mg/m2, providing a rationale for further evaluation. Methods: Randomized, open-label, Phase 1b dose escalation study to characterize safety and antitumor activity of PLM60 (18, 20, 22, 24 mg/m2) once every 28 days up to 4 cycles in patients with advanced/refractory NHL confirmed by pathology and/or cytology. Tumor assessments per Cheson 2007 criteria were at baseline and end of 2nd and 4th cycle. Results: Heavily pretreated Asian subjects (mean age 54 yrs; range 29-71 yrs; 9 males/8 females) were treated; 17 were evaluated for safety and 11 for response (4 withdrew, 2 lost to follow-up). Prior cumulative anthracycline use: 41 to 448 mg/m2. There was 1 SAE (Gr3 multiple lacunar infarction considered doubtfully related to treatment) at 24 mg/m2 and 1 DLT (Gr4 neutropenia) at 20 mg/m2; no MTD was reached at doses of 18-24 mg/m2. Most AEs were Gr1-2, few were Gr3, and 1 was Gr4 during the DLT observation period. Most common AEs were expected myelosuppression that tended to be more frequent and severe with higher doses. No subject had clinically significant decreases in LVEF from baseline or ECG abnormalities during or post treatment. Responses were seen in 4 of 11 evaluable subjects including 2 CRu at 22 mg/m2 and 2 PR at 18 mg/m2. Conclusions: PLM60 had good tolerability and therapeutic effect with no cardiotoxicity findings in patients with advanced NHL. AEs were minimal compared with those expected in a heavily pretreated population with previous anthracycline use. Number Gr3 Hematologic Events 18 mg/m2 N = 3 20 mg/m2 N = 7 22 mg/m2 N = 4 24 mg/m2 N = 3 WBC count ↓ 1 2 2 1 Neutrophil ↓ 2 3 2 2 Lymphocyte ↓ 2 4 2 1 Platelet ↓ 0 1 0 1
Engaging pediatric patients and caregivers in an oral chemotherapy safety assessment.
Authors: Jessica A. Zerillo, Constance M Barysauskas, Erin Santacroce, Mary Ann Zimmerman, Melissa Freeman, Teresa Lau Greenberg, Phuong Nguyen, Daniel J Wallace, Elizabeth A Hill, Susan N. Chi, Pratiti Bandopadhayay, Sharon Lane, Audrea Szabatura, Kathleen Houlahan, Paul J. Catalano, Amy Billett
Journal: Journal of Clinical Oncology (2016)

e18156 Background: While established processes ensure safe utilization of parenteral chemotherapy, oral chemotherapy is usually prescribed by a single clinician on blind-faith that it is dispensed and administered as intended. There has been little assessment of pediatric oncology patient and parent-reported oral chemotherapy errors and needs. Our aim was to pilot an oral chemotherapy safety assessment before administering it to a larger population. Methods: Patients and caregivers completed a questionnaire on oral chemotherapy prescribing instructions, how oral chemotherapy medications are actually administered, and any self-perceived errors or near misses during prescribing, dispensing, or administration. Surveys were piloted in Dana-Farber/Boston Children’s Cancer and Blood Disorders Center over one month. Surveys were repeated to assess for internal consistency and semi-structured interviews were performed to assess validity. Results: Six of seven parents and one of two patients completed the two rounds of surveys and interviews. Survey completion took a median of 7 minutes (IQR 4, 9.5). Over the two surveys, there was 100% consistency on perceived prescribing errors, the primary outcome of interest. 93% felt the questions were easy to understand. There were no reported differences between the medication label and its administration. One parent reported an error in how the child took prednisolone and identified that it was because she had not received education on how to fill the medication dispenser. Parents desired additional information on how to improve medication taste and accurately administer liquid medications, as well as resources (e.g. calendars) to assist with medication adherence. Conclusions: The administration of a survey to obtain patient and parent-reported information on oral chemotherapy errors and needs was feasible. Surveys have been modified to incorporate suggestions and a larger survey analysis with concurrent adherence data will be reported. Such surveys may assist in identifying errors or near misses that may be underreported to the care team. The inclusion of the patient and caregiver in reporting of oral chemotherapy errors and needs has the potential to improve safety for patients.
Real-world data on overall survival (OS) impact of anti-EGFR sequence in patients (pts) with microsatellite stable (MSS) all-RAS and <i>BRAF</i><sup>V600E</sup> wild-type metastatic (met) colorectal cancer (CRC).
Authors: Elena Elez, Guillem Argiles, Raquel Comas, Ariadna Garcia, Nuria Mulet, Alba Noguerido, Jaume Capdevila, Ignacio Matos, Giulia Martini, Juan Francisco Grau Bejar, Guillermo Villacampa, Paolo Nuciforo, Javier Hernandez-Losa, Stefania Landolfi, Ana Vivancos, Teresa Macarulla Mercade, Josep Tabernero, Rodrigo Dienstmann
Journal: Journal of Clinical Oncology (2018)

3551 Background: Pts with MSS all-RAS and BRAFV600E wild-type met CRC are more likely to respond to anti-EGFR drugs, irrespective of treatment (tx) line, particularly if left-sided primaries (prim). The best sequence of targeted agents is still under investigation in molecularly-selected pts. Methods: From a prospective clinical-molecular cohort of CRC pts, the subset with all-RAS and BRAFV600E wild-type tumors (2010-2016) plus MSS status (2015-2016) was used to investigate the impact of anti-EGFR sequence (1st vs. 2nd/3rd lines) in OS after met diagnosis. A propensity-score-weighted (PSW) Cox proportional hazard model was built to adjust for tx selection bias based on stage at diagnosis (dx), number and site of met, type of first-line chemotherapy (chem), and curative resection of met. Results: In total, 913 pts were registered in the database and 416 (45%) fulfilled the molecular criteria. From these pts, 98% received two chem regimens, 70% anti-EGFR tx, 60% anti-angiogenic tx and 45% had surgery of met. Clinical variables associated with no administration of anti-EGFR tx were older age at dx, single met site and surgery of met (p < .05). The only factor linked to preference for anti-EGFR tx as 1st line was year: 30% from 2010-2014 and 56% from 2015-2016 (p < .01). In anti-EGFR treated pts not eligible to curative surgery of met (n = 152), OS in pts with left-sided prim (splenic flexure-rectum, 85% of all cases) was 47.5 months and in those with right-sided prim (cecum to transverse, 15%) it was 33.6 months (HR 1.58; CI95% 1.03-2.41; p = .04). In a PSW Cox model with molecularly-selected pts (n = 275), offering an anti-EGFR regimen at 1st line in pts with left-sided prim did not impact on OS (HR = 0.96, CI95% 0.8-1.2, p = .72). The same was true for right-sided prim (HR = 1.26, CI95% 0.8-2.1, p = .36; interaction p = .32). Conclusions: In a real-world cohort before the “sidedness” era we found that anti-EGFR sequence did not affect OS of pts with left-sided prim, but 1st line therapy was preferred setting in more recent years. Only 15% of molecularly-selected pts have poor outcome right-sided prim, limiting subgroup analysis.
Combination of PDL-1 and PARP inhibition in an unselected population with metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Fatima Karzai, Ravi Amrit Madan, Helen Owens, Amy Hankin, Anna Couvillon, Lisa M Cordes, Farhad Fakhrejahani, Nicole D. Houston, Jane B. Trepel, Clara Chen, Daniel C. Edelman, Paul S. Meltzer, Seth M. Steinberg, James L. Gulley, William L. Dahut, Jung-min Lee
Journal: Journal of Clinical Oncology (2017)

5026 Background: About 30% of sporadic mCRPC has defects in DNA repair pathways which may confer sensitivity to PARP inhibition. There is limited data about PDL1 inhibition in mCRPC. We hypothesize increased DNA damage by olaparib (O) will complement anti-tumor activity of immune checkpoint blocking antibody, durvalumab (D), in mCRPC:NCT02484404. Methods: Single arm pilot study with accrual of 25 patients (pts) with mCRPC and biopsiable disease. Prior treatment with enzalutamide and/or abiraterone is required. D is given at 1500 mg iv q28 days + O 300 mg po q12 h. Primary endpoint is PFS. Pretreatment and on-study core biopsies undergo mutational analysis. Results: 10 pts have enrolled (median age 65 yr [range 51-79], median baseline PSA: 85.78 [22.17-809.9 ng/mL]). 7 pts have GS ≥ 8. Grade 3/4 adverse events include anemia 2/7 (29%), thrombocytopenia, lymphopenia, neutropenia, nausea, fatigue, UTI, and lung infection [1/7 each, (14%)]. 5/7 pts (71%) on-study &gt;2 months (mos) have PSA declines &gt; 50%. Median PFS is 7.8 mos (95% CI: 1.8 mos-undefined). Conclusions: Preliminary data shows D+O is well tolerated with activity in an unselected population. Accrual is ongoing with biomarker analysis. Clinical trial information: NCT02484404. [Table: see text]
Abstract 359: Autosis is Triggered by Ischemia/Reperfusion in the Heart
Authors: Jihoon Nah, Peiyong Zhai, Beth Levine, Junichi Sadoshima
Journal: Circulation Research (2017)

Although autophagy generally acts as a protective function in cardiomyocytes (CMs), uncontrolled or excessive activation of autophagy can be detrimental to CMs under some conditions. However, whether autophagy mediates cell death for CMs remains largely unknown. Recently, it has been shown in HeLa cells that excessive activation of autophagy induces cell death with characteristic morphological and biochemical features, and this form of cell death is termed autosis. Here we investigated whether death of CMs is induced by autosis in the presence of TAT-Beclin1, an autophagy-inducing peptide, and ischemia/reperfusion. TAT-Beclin1 treatment dose-dependently increased the level of LC3-II and decreased that of p62. TAT-Beclin1-treated CMs showed increases in trypan-blue-positive cells suggesting that autophagy-related cell death is induced by TAT-Beclin1. TAT-Beclin1-treated CMs showed the typical morphological features of autosis, including increased autophagic vacuoles and empty vacuoles, perinuclear spaces w...
TCT-660 Prevalence, Treatment Options, and Influence of a Training Program on Clinical Outcome in Patients With ST-Elevation Myocardial Infarction Between 1999 and 2016 in China: The Prospective, Multicenter Registry MOODY Trial
Authors: Jing Kan, Shao-Liang Chen, Junjie Zhang, Nailiang Tian, Fei Ye, Song Yang
Journal: Journal of the American College of Cardiology (2018)
Quality-adjusted life years (QALY) for inotuzumab ozogamicin vs standard of care for relapsed/refractory acute lymphoblastic leukemia (R/R ALL).
Authors: Ilse van Oostrum, Yun Su, Bart Heeg, Thomas Wilke, Alexander Smith, Fausto Rodriguez Loberiza
Journal: Journal of Clinical Oncology (2017)

e18506 Background: Inotuzumab Ozogamicin (InO), an anti-CD22 antibody-calicheamicin conjugate, has demonstrated superior clinical activity versus standard of care (SOC; intensive chemotherapy), including clinically meaningful improvement in overall survival (OS), high rates of complete remission (CR) and stem cell transplantation (SCT), and favorable patient-reported outcomes for R/R ALL in the phase 3 INO-VATE trial. Quality of life is an important consideration for R/R ALL patients in both short- and long-term survival. This study aimed to estimate mean overall survival adjusted for QoL (QALY) for patients treated with InO v SOC. Methods: A Markov model was developed with five health states - No CR, CR, post-SCT, progression, and death. Transition probabilities between health states and mortality rates were based on the InO-VATE trial. These rates were extrapolated to a lifetime horizon using parametric survival curves fitted to available OS data, and published literature for survival after SCT. Utilities (QoL valuations) for each health state were based on the patient-reported EQ-5D scores collected in the InO-VATE trial and a literature review. Adverse events experienced during and after treatments, including as a result of subsequent SCT, were taken into account in overall QoL. Outcomes were discounted at 1.5% and half-cycle corrected. Results: The estimated mean LY and QALY in each health state for InO and SOC and their differences are shown in Table. Most gains in LY and QALY for InO over SOC were from Post-SCT. Conclusions: This analysis taking into account both quantity and quality of life estimates InO offers an average of nearly 2 more years of QALY compared to SOC in R/R ALL, based on higher CR and SCT rates and better QOL. This is mainly driven by long-term gains of SCT. This can help inform patients, physicians and payers in decision making. [Table: see text]