tbuckley/cabot-search huggingface dataset:
Liver Transplantation for Fulminant Hepatitis Attributed to Yellow Fever
Authors: Alice Tung Wan Song, Edson Abdala, Rodrigo Bronze de Martino, Luis Marcelo Sá Malbouisson, Ryan Yukimatsu Tanigawa, Guilherme Marques Andrade, Liliana Ducatti, Andre Mario Doi, João Renato Rebello Pinho, Michele Soares Gomes‐Gouvêa, Fernanda de Mello Malta, Rubens Macedo Arantes, Adriana Coracini Tonacio, Lécio Figueira Pinto, Luciana Bertocco Paiva Haddad, Vinicius Rocha Santos, Rafael Soares Nunes Pinheiro, Lucas Souto Nacif, Flávio Henrique Ferreira Galvão, Venancio Avancini Ferreira Alves, Wellington Andraus, Luiz Augusto Carneiro D’Albuquerque
Journal: Hepatology (2018)

Song, Alice Tung Wan; Abdala, Edson; de Martino, Rodrigo Bronze; Malbouisson, Luis Marcelo Sá; Tanigawa, Ryan Yukimatsu; Andrade, Guilherme Marques; Ducatti, Liliana; Doi, Andre Mario; Pinho, João Renato Rebello; Gomes‐Gouvêa, Michele Soares; Malta, Fernanda de Mello; Arantes, Rubens Macedo Jr.; Tonacio, Adriana Coracini; Figueira Pinto, Lécio; Haddad, Luciana Bertocco Paiva; Santos, Vinicius Rocha; Pinheiro, Rafael Soares Nunes; Nacif, Lucas Souto; Galvão, Flávio Henrique Ferreira; Alves, Venancio Avancini Ferreira; Andraus, Wellington; Carneiro D'Albuquerque, Luiz Augusto Author Information
Qualitative assessment of a school-based breast health (BH) educational program to increase breast cancer (BC) awareness in a rural Mexican community: A report of teachers’ perceptions.
Authors: Enrique Soto Perez De Celis, Patricia Rojo-Castillo, Martin A Reyes-Bautista, Yanin Chavarri Guerra
Journal: Journal of Clinical Oncology (2016)

e18030 Background: In order to increase BC awareness, we implemented a school-based educational program for female adolescents in a rural Mexican community, aimed at increasing knowledge and promoting intergenerational transmission of information to their female relatives. Here we report the perspective of the teachers at the target school on the program’s content, as well as their suggestions regarding its implementation and integration into the curricula. Methods: The school teachers attended the one-day program consisting of 5 sessions aimed at increasing knowledge on BH among students and on encouraging the transmission of knowledge in their household. To evaluate the teacher’s opinions and suggestions, open ended questionnaires were applied. Four months later we conducted semi-structured interviews to qualitatively assess the program’s long term impact. Results: 18 teachers participated in the program, of which 13 (72%) were female. The median duration of teaching experience was 9.5 years. All the teachers believed the content to be appropriate for the students’ age and socioeconomic background. 15 (83%) teachers believed the students would discuss BH at home. All the teachers thought BH should be included in the middle school curricula in Mexico. The teachers recommended focusing on third grade students, creating a BH program for males and implementing the program biannually. All the interviewed teachers expressed interest in receiving training in order to implement the program, and some identified breast cancer survivors within their community. Teachers reported students talking about BH at school in the months following the program’s implementation. Conclusions: Obtaining community feedback and promoting active participation of teachers is essential for the implementation of successful school-based education programs in cancer. Teachers at the rural middle school where we implemented our BH intervention not only approved the content, but were eager to participate actively, to offer advice for improvement and to continue with the program. The creation of a training program on BH for Mexican teachers is warranted.
Abstract 23234: Clinical Outcomes Following Ablation of the Atrioventricular Junction: Impact of Cardiac Resynchronization Therapy
Authors: Suneet Mittal, Dan L Musat, Michael H Hoskins, Julie B Prillinger, Gregory J Roberts, Yelena Nabutovsky, Faisal M Merchant
Journal: Circulation (2016)

Introduction: Many patients (pts) with atrial fibrillation (AF) undergo pacemaker (PM) implant. In some pts, atrioventricular junction (AVJ) ablation (abl) is performed concurrently. We investigate...
IFCT-GFPC-1101 trial: A multicenter phase III assessing a maintenance strategy determined by response to induction chemotherapy compared to continuation maintenance with pemetrexed in patients (pts) with advanced non-squamous (NSQ) NSCLC.
Authors: Maurice Perol, Clarisse Audigier-Valette, Olivier Molinier, Alexis B. Cortot, Jacques Margery, Lionel Moreau, Virginie Westeel, Pascal Dô, Fabrice Barlesi, Eric Pichon, Gerard Zalcman, Patrick Dumont, Nicolas Girard, Michel Poudenx, Julien Mazieres, Jacques Cadranel, Didier Debieuvre, Jérôme Dauba, Denis Moro-Sibilot, Pierre Jean Souquet
Journal: Journal of Clinical Oncology (2017)

9003 Background: Benefit coming from maintenance treatment appears greater for switch maintenance in pts with disease stabilization (SD) while it might be larger for continuation maintenance in pts with objective response (OR). This study assessed a maintenance strategy conditioned by response to cisplatin-gemcitabine (CG): continuation maintenance with G for pts with OR and switch maintenance with pemetrexed (P) for pts with SD compared with a control arm using P continuation maintenance following cisplatin-pemetrexed (CP) induction regimen. Methods: Eligibility criteria included age 18-70 years, PS of 0-1, untreated stage IV NSQ NSCLC without EGFR mutation or ALK rearrangement, ineligibility to bevacizumab. Pts were randomized 1:1 to receive either experimental CG arm: CG (4 cycles) followed by G maintenance in case of OR followed by second-line P or switch maintenance with P for pts with SD, or standard CP arm: 4 cycles CP induction regimen followed by maintenance P. Overall survival (OS) was the primary endpoint; secondary endpoints included PFS, response rate and safety. Results: Between Jul 2012 and Jun 2016, 932 pts were randomized (CG: 467, CP: 465). Pts characteristics were balanced between the arms. 255 pts (54.6%) in the CG arm received maintenance treatment (G: 142, P: 113) while 274 pts (58.9%) received P maintenance in the CP arm. Median number of maintenance cycles was 5 for G and 4 for P in both arms. The OS adjusted HR was 0.97 (95% CI 0.84, 1.13; p=0.72); median OS: 10.9m CG vs. 10.4m CP. The HR for PFS was 0.96 (95% CI 0.84, 1.10; p=0.56); median PFS: 5.0m CG vs. 4.7m CP. Safety profile was as expected during induction chemotherapy. During maintenance, grade ≥3 hematological AEs occurred in 28% and 31% of pts in CG and CP, respectively, with febrile neutropenia (2.4% vs. 1.1%), anemia (9.4% vs. 11.7%), thrombocytopenia (6.7% vs. 5.8%). No grade ≥3 non-hematological AEs occurred in &gt;5% of pts except for asthenia (3.9% CG vs. 5.1% CP). Conclusions: Adapting maintenance strategy according to response to induction chemotherapy does not improve patient outcome. Clinical trial information: NCT01631136.
Host-microbe interactions mediating antitumorigenic effects of MRX0518, a gut microbiota-derived bacterial strain, in breast, renal and lung carcinoma.
Authors: Alex Stevenson, Alessio Panzica, Amy Holt, Delphine Laute Caly, Anna Ettore, Margaret Delday, Emma Hennessy, Philip Cowie, Meenakshi Pradhan, Ian Jeffery, Nicole Reichardt, Emma Raftis, Helene Savignac, Imke Mulder
Journal: Journal of Clinical Oncology (2018)

e15006 Background: The gut microbiota is a key player in therapeutic response to cancer treatment and is linked to the efficacy of checkpoint inhibitors. Proposed antitumorigenic mechanisms of commensal bacteria include expansion of (tumor-specific) T cells, activation of dendritic cells and modulation of the gut microbiota. We examined the antitumor effects of the commensal isolate MRx0518, Enterococcus gallinarum, and analyzed its active compounds and immunotherapy targets. Methods: MRx0518 efficacy on tumor growth was assessed in syngeneic mouse models of breast, renal and lung carcinoma. Tumor flow cytometry, cytokine profiling, transcriptomics, immunohistochemistry and microbiota analysis was performed. MRx0518-induced cytokine production and activation of immunotherapy-relevant cell types was investigated in vitro. Intra-species comparative genomics of MRx0518 was performed, and the transcriptional and proteomic signature associated with host cell activation was assessed. A mono-colonized mouse model was used to study host-microbe interactions in vivo. Results: MRx0518 monotherapy reduced tumor size between 35-51% compared to controls. Tumor reduction corresponded to an increased CD8+ T cells:Tregs ratio and decreased Ki67+ cells. 16S gut microbiota profiling showed a significantly increased diversity for Observed Species. MRx0518 antitumor activity was linked to a strong in vitro immuno-stimulatory phenotype characterized by a distinct transcriptomic signature and induction of inflammatory mediators (IL-8, TNF-α, IL-1ß, IL-6, IL-23, CXCL9, CXCL10). The relative proliferation and activation of CD4+, CD8+ and regulatory T cells was also measured. The MRx0518 genome contained strain-specific regions, and putative immunomodulatory effectors were identified. Mono-colonization studies in germfree mice showed interactions between MRx0518 and activated gut immune cell populations. Conclusions: The gut microbiota-derived strain MRx0518 displays strong antitumor efficacy, and active microbial signaling compounds have been identified. Clinical studies in a variety of solid tumors are planned to commence shortly.
Implementation of a novel application integrating cancer registry data into survivorship care plans.
Authors: Robin C Vanderpool, Jason Jacob, Jordan B. Bispo, Isaac Hands, Bront Davis, Emily Van Meter Dressler, Eric B Durbin
Journal: Journal of Clinical Oncology (2016)

10074 Background: Survivorship care plans (SCP) are comprehensive plans that outline past, present, and future care goals for cancer survivors. As of 2015, delivery of SCP to 10% of eligible patients are mandated for ACOS Commission on Cancer (CoC)-accredited programs; this percentage will incrementally increase to 100% by 2019. Cancer program readiness to implement the new standard is sub-optimal, and tools are needed to improve the efficiency of SCP development, including the use of cancer registry data to prepopulate SCP with existing patient data. In January 2015, University of Kentucky investigators were funded to design, implement, and evaluate a web-based application for prepopulating Journey Forward (JF)SCP templates with patient data collected by hospitals and entered into the Kentucky Cancer Registry’s (KCR) Cancer Patient Data Management System (CPDMS). This presentation will describe activities leading up to the application launch in June 2015 as well as preliminary evaluation findings. Methods: We conducted a detailed process evaluation, including tracking application usage patterns and analyzing qualitative interviews with informatics staff, cancer registrars and patient navigators. Results: Mapping cancer abstract data into JF’s SCP template fields required substantial expertise from KCR and informatics staff. An average of 25% of data fields in JF’s templates can be prepopulated with CPDMS data. Two training webinars were held for 75 registrars and patient navigators. As of December 2015, 479 SCP have been initiated with over two-thirds created for breast cancer (n = 314). Forty-eight individuals representing 19 hospitals have requested access to the application; 15 hospitals (79%) are CoC-accredited. Feedback suggests the application is easy to use, has decreased SCP prep time, and led to new collaborations between cancer registrars and patient navigators. Conclusions: Development of the application was a significant undertaking, but has resulted in a new method for prepopulating SCP with registry data that may ease logistical burdens that hospitals face in meeting CoC-accreditation requirements. Additional data collection and analysis will allow us to study these trends over time.
Phase II trials of cetuximab plus combined modality therapy (CMT) in squamous cell carcinoma of the anal canal (SCCAC) with and without human immunodeficiency virus (HIV) infection.
Authors: Madhur Garg, Fengmin Zhao, Jeannette Y. Lee, Joseph A. Sparano, Joel Palefsky, David H. Henry, William Wachsman, Lakshmi Rajdev, David Michael Aboulafia, Lee Ratner, Lisa A. Kachnic, Edith P. Mitchell, Adedayo A. Onitilo, Ronald T. Mitsuyasu, Al Bowen Benson
Journal: Journal of Clinical Oncology (2016)

3522 Background: SCCAC is a human papilloma virus (HPV) associated cancer that is potentially curable with CMT, commonly associated with HIV infection, and characterized by high local regional failure (LRF) rates. Since cetuximab enhances the effect of radiation in HPV-associated oropharyngeal SCC, we evaluated the efficacy and toxicity of cetuximab plus CMT in SCCAC. Methods: We performed 2 concurrently planned and conducted phase II trials of cetuximab plus CMT in stage I-III SCCAC without (E3205) and with (AMC045) HIV infection. CMT included cisplatin (75 mg/m2) and 5-FU (1000 mg/m2/day x 4 days) x 2 cycles plus RT (45-54 Gy), plus 2 cycles of neoadjuvant cisplatin/5-FU in the first 28 patients in E3205 prior to a study amendment. Cetuximab (400 mg/m2 IV, then 250 mg/m2 IV weekly x 8 weeks) began 1 week prior to CMT. The studies were designed to detect at least a 50% reduction in 3-year LRF rate (35% to 17.5%, 1-sided alpha 0.10, power 90%). Secondary objectives included progression free survival (PFS) and overall survival (OS). Results: The characteristics of the study population and efficacy results are summarized below, indicating higher rates of node positive disease in AMC 045 (47%) and E3205 (54%) compared with R9811 (26%) and ACTII (32%). The majority of patients completed protocol therapy in AMC045 (82%) and E3205 (79%), rates of grade 4 toxicity were similar (32% in E3205, 26% AMC45), and 4% had treatment-associated deaths. Conclusions: Patients with SCCAC with and without HIV infection exhibited similar rates of completing therapy (80%) and clinical outcomes with cetuximab plus CMT. LRF rates were lower compared with historical data using similar definitions. The findings suggest that patients with stage I-III HIV-associated SCCAC should be treated with curative intent similar to immunocompetent patients, and that addition of cetuximab to CMT may reduce LRF. Clinical trial information: 00324415, 00316888. E3205 AMC 045 No. 61 45 Node positive 54% 47% 3 year LRF Rate 23% (95% CI 13%, 36%) P under H0 = 0.03 16% (95% CI 7%, 30%) P under H0 = 0.003 3 year PFS Rate 68% (95% CI 55%, 79%) 82% (95% CI 66%, 91%) 3 year OS Rate 83% (95% CI 71%, 91%) 79% (95% CI 63%, 89%)
Prognostication using molecular (mol) markers and clinicopathological (clpath) features in high-risk stage II/III colon cancer (CC).
Authors: Rodrigo Dienstmann, Sabine Tejpar, Frank A. Sinicrope, Amanda I. Phipps, Brian Bot, Stephen Henry Friend, Mauro Delorenzi, Polly A. Newcomb, Daniel J. Sargent, John M Jessup, Justin Guinney
Journal: Journal of Clinical Oncology (2016)

3519 Background: AJCC v.7 staging and clpath covariates do not accurately predict outcome of CC patients (pts) eligible for adjuvant chemotherapy (adjCh). Mol markers, microsatellite instability (MSI) and mutations (mut) in BRAF and KRAS, may further improve prognostication in high-risk CC. Methods: Data from 4,796 stage II/III pts accrued to phase 3 trials PETACC3 and N0147 (train set) were used to construct Cox models for overall survival (OS). Variables included stage (pT, pN); clpath (# lymph nodes [LNs] positive, # LNs assessed, tumor grade, primary site, age, gender, adjCh); and mol (MSI, BRAF and KRAS mut). Final models (1. TNM; 2. TNM + mol; 3. TNM + clpath; 4. TNM + clpath + mol) were internally (train set) and externally (test set) validated on 597 stage II/III treated pts from non-clinical trial cohorts. Results: All examined traits were statistically significant for OS prediction (Table 1). We found significant interaction between site and MSI (p=.03) in multivariate models, with worse OS for MSI vs MSS left CC (HR 1.22) and better OS for right CC (HR 0.70). Models 1 to 4 associated with C-indices of 0.65, 0.68, 0.70, 0.72, respectively, in train set; and 0.68, 0.71, 0.73, 0.74 in test set. Corresponding time-dependent AUCs (5 years summary) were 0.54, 0.66, 0.73, 0.74 in train set; and 0.55, 0.68, 0.72, 0.73 in test set. Conclusions: Incorporation of mol markers (MSI, BRAF and KRAS mut) improves prognostic estimation in stage II/III CC pts treated with adjCh. We propose their prospective assessment in larger clinical cohorts, including untreated pts, and development of online calculators that could aid in prognostication (model-based staging) and patient/physician communication. Multivariable OS Cox model in train set. Variable HR CI95% pT2 vs pT1 1.06 0.52 2.19 pT3 vs pT1 2.22 1.24 4.36 pT4 vs pT1 4.23 2.32 8.33 pN1 vs pN0 1.76 1.17 2.39 pN2 vs pN0 2.88 1.74 3.72 # LNs positive 1.07 1.05 1.08 >=12 vs <12 LNs assessed 0.70 0.59 0.82 High vs Low/Moderate grade 1.29 1.09 1.51 Right vs left 1.53 1.33 1.81 Age (years) 1.01 1.00 1.02 Male vs female 1.36 1.16 1.54 FOLFIRI vs 5FU 1.01 0.80 1.30 FOLFOX vs 5FU 0.70 0.59 0.92 MSI vs MSS 0.72 0.57 0.90 BRAF mut vs wt 1.80 1.48 2.28 KRAS mut vs wt 1.45 1.26 1.72
Relationship between expression of hypoxia-inducible factor-1α and activity of transcription factors in patients with oral mucosa cancer.
Authors: Ekaterina Komarova, Oleg Ivanovich Kit, Aleksey Yurievich Maksimov, Vladimir Kononenko, Aleksandra Demidova
Journal: Journal of Clinical Oncology (2016)

e17528 Background: The condition for activation of other transcription molecules conducive to tumor cell division by means of hypoxia-inducible factor is the factor penetration to the nucleus. In this regard, the relationship between HIF-1α expression and nuclear factors of NF-kB family transcription in the tumor tissue and histologically intact tissue in patients with oral mucosa cancer, was studied. Methods: The level of hypoxia-inducible factor-1α (HIF-1α) and nuclear factors of NF-kB family transcription (p50 and p65 forms) was evaluated in 41 patients with oral mucosa cancer (T2N0-2M0) in the supernatant of frozen tumor tissue (100 mg) obtained in the course of surgical treatment, by enzyme linked immunosorbent assay. It was controlled by histologically intact tissue of the oral mucosa (n = 41) located at a distance of not less than 2 cm from the tumor. The relationship between these factors was identified using Spearman correlation analysis. Results:. HIF-1α content in the tumor tissue as compared to the histologically intact one increased by 2.2 times (p < 0.05), NF-kB p50 - 3 times (p < 0.05), NF-kB p65 - 6 times (p < 0,05). NF-kB p65/p50 factor increase in the tumor tissue proved the prevalence of activated forms of NF-kB. The correlation between the content of HIF-1α and NF-kB p50 in the tumor tissue was the highest in patients with low grade G3 (R = 0.56, p < 0.0001) and tumor nodal involvement (R = 0.53, p = 0.0001). The correlation between HIF-1 α and NF-kB p65 was less close than that between HIF-1α and NF-kB p50, which is probably explained by the discrepancy between the growth gradient of HIF-1α, NF-kB p50 and NF-kB p65 with the development and progression of oral mucosa cancer. Conclusions: Hence, there is a close relationship between activation of HIF-1α and NF-kB p50 and NF-kB p65 transcription factors in the tumor tissue in the progression of oral mucosa cancer. HIF-1α factor modifies activation of nuclear factors of NF-kB family transcription.
Lenalidomide, doxorubicin hydrochloride and dexamethasone versus bortezomib, lenalidomide, and dexamethasone prior to scheduled stem cell transplant in newly diagnosed myeloma.
Authors: Stefan Knop, Christian Langer, Monika Martha Engelhardt, Johanne Wangemann, Lars Olof Muegge, Florian Bassermann, Kerstin Schaefer-Eckart, Igor W. Blau, Denise Wolleschak, Albrecht Reichle, Ivana von Metzler, Bernd Metzner, Christoph Röllig, Bernd Hertenstein, Michael Pfreundschuh, Tim H. Brümmendorf, Martin Gramatzki, Matthias Ritgen, Swantje Held, Hermann Einsele
Journal: Journal of Clinical Oncology (2017)

8001 Background: In younger, medically fit patients (pts) with newly diagnosed (ND) multiple myeloma (MM), autologous stem cell transplant (SCT) remains a standard of care. Prior to SCT, induction triplets with at least one of the newer compounds are recommended. Bortezomib (V), lenalidomide (R) and dexamethasone (D; VRD) ranks amongst the most effective treatments. VRD + SCT proved superior over VRD alone in a randomized, controlled trial (RCT). We found encouraging efficacy and low toxicity with RAD (RD and adriamycin) + SCT and decided to compare RAD versus VRD induction in an RCT. Methods: The DSMM XIV study was set up according to a double 2x2-factorial design to enroll NDMM pts up to 65 years (yrs). Post-induction (PI) CR rate was the efficacy endpoint for the initial study phase. We hypothesized CR rate with RAD would be non-inferior to an estimated 20% CR with VRD. The study was powered to confirm non-inferiority of RAD at a 10% margin with a one-sided α level of .05. Minimal residual disease (MRD) was analyzed by eight-color flow cytometry (EuroFlow standards) on marrow samples. Results: 476 pts were randomized between 05/2012 and 06/2016, 469 of whom (median age 55 (range, 32–65) yrs) received at least one dose of study drug. 18.3% of pts had ISS stage III MM and 17.2%, elevated LDH. 11.3% of pts had del17p; 11.1% had t(4;14); and 4% had t(14;16). 232 pts were randomized to 3 four-week RAD cycles and 237 to 3 three-week VRD cycles, respectively. 89.7% of RAD versus 93.2% of VRD pts completed all induction cycles. PI CR rate was 11.8% (90% CI, 7.9%-16.3%) with RAD versus 13.0% (90% CI, 8.9-18.0) with VRD, (P = .697). 72/317 pts (22.7%) with paired baseline/PI samples achieved negative MRD at a median sensitivity level of 6.73x10 -6 . 47 (20.3%) RAD versus 35 (14.8%) VRD pts experienced treatment-emergent SAEs (P = .144). Treatment-related induction mortality was 0% in either arm. Conclusions: To the best of our knowledge, this is the first RCT to compare two lenalidomide-based triplets prior to SCT. The endpoint was met with comparable PI CR rates for RAD and VRD, respectively. Tolerability was encouraging in both arms. Follow-up data is needed to analyze time-dependent endpoints. Clinical trial information: NCT01685814.