tbuckley/cabot-search huggingface dataset:
Abstract 12452: Clinical Practice Patterns are Relatively Uniform Between Pediatric Heart Transplant Centers: A Survey Based Assessment
Authors: Chesney Castleberry, Sonja Ziniel, Christopher Almond, Scott Auerbach, Seth Hollander, Lal Ashwin, Matthew Fenton, Joseph Rossano, Melanie Everitt, Kevin Daly
Journal: Circulation (2015)

Background: Randomized control trials (RCT) of immunosuppression are needed in pediatric heart transplantation. However, variations in clinical practice could confound results. We surveyed centers to describe practice variations and understand willingness to modify protocols for the purpose of a RCT. Hypothesis: We hypothesized that though variability in practice exists, there would be a willingness to change protocols as part of a RCT. Methods: Pediatric heart transplant centers were identified based on participation in the Pediatric Heart Transplant Study. One member from each institution was sent an electronic request to complete a survey using a customized Qualtrics tool. Simple descriptive statistics were used. Results: The response rate was 72% (40 responses from 52 contacted centers, 37 complete). Respondents were from the United States (36, 90%), Great Britain (2, 5%), Canada (1, 2.5%), and Brazil (1, 2.5%). Mean center volume was 10 transplants/year (range of 1 to 25). A majority of centers use tacrolimus (36, 95%) and mycophenolate mofotil (36, 95%) as maintenance therapy. Other immunosuppression was cyclosporine (7, 18%), everolimus or sirolimus (3, 8%), and azathioprine (2, 5%). Responses for most clinical practices were over 70% similar except for steroid use and biopsy frequency (Table). Overall, willingness to change clinical practice was greater than 70%. A majority of respondents, 97% (36/37) responded that they would be willing to participate in a RCT and 100% (37/37) said they would be willing to participate in a RCT investigating everolimus or sirolimus. Conclusion: Though practice variations exist between pediatric heart transplant centers, most major components of clinical practice protocols are similar. Importantly, a majority of centers are willing to adopt a common protocol for a RCT and practice variations should not be considered a barrier to trial design. There is overwhelming support for a trial involving everolimus or sirolimus.
Advanced cancer patients' self-reported perception of timeliness of their referral to outpatient supportive/palliative care and their survival data.
Authors: Angelique Wong, David Hui, Margeaux Epner, Vishidha Reddy Balankari, Vera J De la Cruz, Susan Frisbee-Hume, Hilda Cantu, Kresnier Perez Zapata, Diane D Liu, Janet L. Williams, Eduardo Bruera
Journal: Journal of Clinical Oncology (2017)

10121 Background: Palliative Care referral is often thought to be delayed as judged by health professionals and caregivers. However, no studies have ever examined patients’ perception of timeliness of referral. The primary objective of this study was to determine patients’ perception of the timeliness of their own referral to an outpatient palliative care clinic. We also examined the association between perceived timeliness and actual timing of referral. Methods: In this prospective survey, patients with advanced cancer were asked to rate their perceived timeliness of referral using a 5-point Likert scale ranging from much too early to much too late within 7-35 days after their first consultation visit at Supportive Care Center. They were also asked when they felt referral to Supportive Care should occur along 4 points in their disease trajectory. Actual timing of referral was assessed based on survival from the timing of completion of the survey. Results: 200 advanced cancer patients were surveyed. Median age was 64, 111 (55%) were female, and 35 (18%), 32 (16%) and 26 (13%) had gastrointestinal, lung and breast cancer, respectively. The median overall survival was 8.5 months. 144 (72%) patients perceived their referral was “just in time,” 42 (21%) felt it was “late/much too late,” and 14 (7%) felt it was much “too early/early.” 76/193 (39%) felt the referral should occur at the time of diagnosis of cancer, 32 (17%) when they start first-line chemotherapy, 46 (24%) at diagnosis of recurrent disease, 14 (7%) when there are no further treatment options, and 4 (2%) reported never. We found no significant difference in survival among patients who reported their referral was early, just in time, and late (median 9.8 vs. 8.3 vs. 9.0 months, P=0.43). Conclusions: Patients with advanced cancer were referred to our outpatient Supportive Care clinic a median of 8.5 months before death. A vast majority of patients perceived the timing of referral was appropriate, and many agreed that referral should occur early in the disease trajectory. The lack of association between perceived timeliness of referral and survival may be related to the ceiling effect and the small number of patients who felt their referral was late.
Evolution of precision oncology treatment options over time.
Authors: Bat-Ami Gordon, Jared Cotta, Jonathan C. Trent
Journal: Journal of Clinical Oncology (2018)

e24179 Background: The landscape of precision oncology is constantly changing. Cancer centers in both the academic and community settings have been implementing Molecular Tumor Boards (MTB) to support the implementation of a site disease agnostic approach. Reports published from these experiences reflect a difficulty in obtaining a targeted therapy, particularly via off label usage. When the NCI-MATCH (MATCH) trial opened at Sylvester Comprehensive Cancer Center (SCCC) in August 2016, it brought an increased awareness to the targeted therapy options available to patients and offered an alternative to off label use. Methods: The MTB at SCCC began in March 2016, and reviews cases by referral from treating physicians. As of February 2018 – 265 cases have been referred to the MTB and 89% have undergone review. 212 cases with ≥12 weeks (through November 2017) post MTB review were analyzed. These cases were divided into 2 groups representing patients reviewed before and after the opening of MATCH at SCCC. Results: 49 cases were reviewed prior to MATCH and 20% of those patients pursued a MTB recommendation. These patients either pursued off label targeted therapies or clinical trials (50% and 50%). 163 cases were reviewed after SCCC opened MATCH and 24% of the patients pursued recommendations. 26% pursued targeted therapies off label, 13% pursued targeted therapies on label, and 62% of patients pursued clinical trial participation. Conclusions: After the opening of MATCH, the MTB saw a 12% increase in clinical trial participation and a 20% decrease in off label usage in reviewed patients. As the options available to patients via molecular driven trials and FDA expanded approvals grow, the need to use therapies in an off label setting decreases. This trend in the field will allow MTBs to provide more actionable guidance to physicians and their patients to pursue precision oncology approaches.
Is physical activity and cardiorespiratory fitness reduced among childhood cancer survivors?
Authors: David Mizrahi, Claire Wakefield, David Simar, Ann Maguire, Gill Hubbard, Joanna Fardell, Jamie McBride, Penny Field, Richard J Cohn
Journal: Journal of Clinical Oncology (2018)

10569 Background: Survivors of childhood cancer experience an increasing incidence of late sequelae with age, with the effect on health likely compounded by limited physical activity and low cardiorespiratory fitness (CRF). This study aimed to determine survivors’ physical activity levels and to objectively measure CRF, compared with controls. Methods: Stage 1: We collected physical activity data from parents of survivors aged 7-18 years, ≥5 years after diagnosis, from 11 Australian and New Zealand hospitals and from age-matched controls (International Physical Activity Questionnaire). We compared moderate-vigorous physical activity with American Cancer Society guidelines (≥300 min/week). Stage 2: We assessed CRF in survivors aged 8-18 years, ≥1 year after treatment completion, by cardiopulmonary exercise test (Bruce Protocol), 6-minute walk test (6MWT), and self-reported fitness (International Fitness Scale). Results: Stage 1: 192 parents of survivors (age = 12.9±2.3 years) and 111 parents of control children (age = 12.3±2.7 years) participated. Parents reported survivors participated in more physical activity than controls (248.4±217.6 vs 184.8±213.6 min/week, p = 0.036), with 31% of survivors meeting physical activity guidelines, compared with 22.7% of controls (p = 0.011). Stage 2: 31 survivors (age = 13.0±3.5 years) and 10 controls (age = 10.6±1.1 years) completed CRF assessments. Survivors appear to have similar CRF compared with controls in terms of VO2max (41.1 vs 46.8ml/kg/min, p = 0.09; 40th vs 60th percentile, p = 0.11) and 6MWT distance percentile (69th vs 78th percentile, p = 0.30). Among survivors, a weak linear relationship existed between self-perceived CRF and VO2max percentile (r2= 0.20, p = 0.017). Conclusions: Only one-third of childhood cancer survivors met physical activity guidelines, whilst survivors and controls reported similar fitness. Considering the late-effects risks during aging in survivors, regularly assessing physical activity and CRF provides clinicians with vital information to monitor survivors. Although survivors accurately perceived their CRF, the weak relationship reinforces the need for accurate assessment to provide insight into cardiovascular risk.
Comparative transcriptomic profiling of renal medullary carcinoma (RMC) to determine distinct signatures and pathways associated with response to chemotherapy.
Authors: Pavlos Msaouel, Gabriel G. Malouf, Xiaoping Su, Hui Yao, Durga N Tripathi, Jianjun Gao, Priya Rao, Rong He, Jose A. Karam, Christopher G. Wood, Cheryl Lyn Walker, Nizar M. Tannir
Journal: Journal of Clinical Oncology (2018)

4575 Background: RMC is a highly aggressive renal cell carcinoma (RCC) with poor prognosis and variable response to chemotherapy. It is often treated with cytotoxic regimens used for collecting duct carcinoma (CDC) and upper tract urothelial carcinoma (UTUC). We analyzed the transcriptomic profile of RMC samples and compared it with that of CDC, UTUC, clear-cell renal cell carcinoma (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC). Methods: RNA sequencing (RNA-seq) was performed in primary tumor tissues from treatment-naïve patients with RMC (n = 11), CDC (n = 9), and UTUC (n = 22). We compared these profiles to ccRCC, pRCC, and chRCC samples (n = 20 each) randomly selected from The Cancer Genome Atlas (TCGA). Gene ontology (GO) analysis was performed using DAVID. In vitro cell proliferation was assessed using the MTT assay. Results: Unsupervised hierarchical clustering and principal component analyses showed that 9/11 RMC samples formed a distinct cluster while 2 samples overlapped with CDC (p = 0.0003). There was no overlap between RMC and UTUC, ccRCC, pRCC, or chRCC. Five patients with RMC showed at least partial response to subsequent chemotherapy (4/5 received a paclitaxel-based regimen) and their pre-treatment samples demonstrated upregulation of 62 genes (FDR < 0.05) compared with the other patients. GO analysis revealed that these genes are associated with transmembrane transport pathways (enrichment score 3.87). The most upregulated gene ( > 3-fold) was guanine deaminase (GDA), a regulator of microtubule assembly normally expressed in human kidney collecting ducts. In vitro siRNA knockdown of GDA in the paclitaxel-sensitive RCC cell lines HCR-59 and UOK-146 conferred resistance to paclitaxel but not to drugs that do not target microtubules such as gemcitabine, doxorubicin, or platinum agents. Conclusions: RMC displays a unique transcriptomic signature that is closer to CDC than to UTUC or to other RCC subtypes. RMC tumors more likely to respond to chemotherapy show upregulation of genes such as GDA. Our results provide the first evidence that GDA may be a biomarker of response to microtubule-targeting agents in RMC.
The effect of photo-documentation of the ampulla on neoplasm detection rate during esophagogastroduodenoscopy
Authors: Jae Park, Chul-Hyun Lim, Yu Cho, Bo-In Lee, Young-Seok Cho, Ho Song, Myung-Gyu Choi
Journal: Endoscopy (2018)

Abstract Background A few studies have investigated quality indicators of esophagogastroduodenoscopy (EGD) for identifying upper gastrointestinal (GI) malignancy. The current study aimed to evaluate whether the rate of ampulla photo-documentation could be associated with the detection of upper GI neoplasms. Methods We used data from 111 962 asymptomatic patients who underwent EGD performed by 14 endoscopists at a health promotion center. The rate of ampulla photo-documentation was calculated by reviewing EGD photos archived during each endoscopist’s first year of working at the center. The detection of neoplasms during a 7-year period was investigated. We examined the association between the rate of ampulla photo-documentation and the rate of neoplasm detection. Results The mean rate of ampulla photo-documentation was 49.0 % (range 13.7 % – 78.1 %) during endoscopists’ first year of working at the center. Endoscopists’ rates of ampulla photo-documentation significantly correlated with the detection of total neoplasms (R2 = 0.57, P = 0.03) and small neoplasms (R2 = 0.58, P = 0.03). There was a significant difference in the detection rates of upper GI neoplasms between high (n = 7) and low (n = 7) ampulla observers (odds ratio [OR] 1.31, 95 % confidence interval [CI] 1.03 – 1.68; P = 0.03). The ampulla photo-documentation rate of each endoscopist significantly correlated with the examination time for a normal EGD (R2 = 0.55; P = 0.04). In multivariate analysis, high ampulla photo-documentation rate was a predictor of neoplasm detection (OR 1.33, 95 %CI 1.03 – 1.70). Conclusions The ampulla photo-documentation rate was significantly associated with the detection rate for both total and small upper GI neoplasms. Ampulla photo-documentation should be considered as a quality indicator of EGD.
EA5142 adjuvant nivolumab in resected lung cancers (ANVIL).
Authors: Jamie E. Chaft, Suzanne Eleanor Dahlberg, Onkar V Khullar, Martin J. Edelman, Charles B. Simone, John Heymach, Charles M. Rudin, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2018)

TPS8581 Background: There have been no advances in the systemic treatment of resected lung cancers in the last decade. In contrast, targeted therapies and immunotherapies have demonstrated benefit in advanced disease. Furthermore, adjuvant immunotherapy after concurrent chemoradiation in locally advanced non-small cell lung cancer (NSCLC) has demonstrated improvement in progression free survival. The role of adjuvant immunotherapy after surgery remains unknown. The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) is a National Cancer Institute sponsored National Clinical Trials Network initiative to address the role of genomic testing and personalized therapies in the adjuvant treatment of NSCLC. EA5142 is the arm of the ALCHEMIST investigating adjuvant nivolumab in patients not eligible for the EGFR or ALK directed trials. Methods: ALCHEMIST is a clinical trial platform that consists of integrated protocols: ALCHEMIST Screening (A151216; NCT02194738), ALCHEMIST-EGFR (A081105; NCT02193282), ALCHEMIST-ALK (E4512; NCT02201992), and ALCHEMIST-nivo (EA5142; NCT02595944; ANVIL). In ALCHEMIST-Screening, up to 8,000 patients with pathologically confirmed stage IB (≥ 4 cm)-IIIA NSCLC will be enrolled after surgical resection. Tumors that are non-squamous histology will be centrally genotyped for EGFR mutations and ALK rearrangements. Patients with EGFR or ALK-positive tumors are offered enrollment in trials evaluating adjuvant erlotinib or crizotinib, respectively. In the ~80% of patients enrolled with tumors that have wildtype EGFR and ALK or those with squamous histology, central testing will be performed for PD-L1 by immunohistochemistry (DAKO 28-8). Adjuvant chemotherapy and/or radiotherapy is allowed but not required. Patients are randomized to nivolumab versus standard of care observation, stratified by stage, histology, prior adjuvant treatment, and PD-L1 status (≥1% or < 1%). ANVIL is active at over 600 US sites and is actively enrolling. The study statistical plan is to detect co-primary endpoints of a 30% improvement in overall survival and/or a 33% improvement in disease free survival favoring nivolumab. EA5142 design changes under review at CTEP will be presented. Clinical trial information: NCT02595944.
Lung-MAP (S1400) Lung Cancer Master Protocol: Accrual, demographics, and molecular markers.
Authors: Vassiliki Papadimitrakopoulou, Mary Redman, David R. Gandara, Fred R. Hirsch, Philip C. Mack, Hossein Borghaei, Corey J. Langer, Jeffrey A. Engelman, Martin J. Edelman, Kathy S. Albain, Primo Lara, Charu Aggarwal, Mark A. Socinski, Scott N. Gettinger, Lyudmila Bazhenova, Shakun M. Malik, Vincent A. Miller, Ellen V. Sigal, Karen Kelly, Roy S. Herbst
Journal: Journal of Clinical Oncology (2016)

9088 Background: Lung-MAP (S1400), coordinated by SWOG on behalf of NCTN, is a first-in-kind master “umbrella” protocol in partnership between government, academia, patient advocacy organizations, and industry, designed to simultaneously and independently test multiple biomarker-driven therapies for patients (pts) with chemo-refractory squamous cell lung cancer (SCCA). Methods: Lung-MAP currently includes 3 biomarker-driven sub-studies and one non-match study for pts not eligible to enroll onto a biomarker-driven sub-study. If genomic screening identifies a molecular match, pts are assigned to: S1400B evaluating taselisib, a PI3K inhibitor, S1400C evaluating palbociclib, a CDK 4/6 inhibitor and, S1400D evaluating AZD4547, an FGFR inhibitor. The recently activated non –match sub-study S1400I tests nivolumab + ipilimumab vs. nivolumab alone (S1400E evaluating rilotumumab an HGF monoclonal antibody + erlotinib closed 11/26/2014 and S1400A evaluating MEDI4736 in non-match ptsclosed 12/18/2015). Results: From June 16, 2014 to January 20, 2016, 418 sites opened, 525 pts registered to the screening component of the trial, and 210 pts registered to a sub-study: 116 to S1400A, 17 to S1400B, 36 to S1400C, 24 to S1400D, 9 to S1400E and 6 to S1400I. Demographics: Median age 67(range 35-92); male 68%; ECOG PS 0-1 80%, PS 2 16%; Caucasian 85%, Black 8%, other 8%; never/former/current smokers 3%/60%/33%. Of 507 pts genomically screened, 450 (89%) were successful . Table 1 displays biomarker prevalence and overlap; 60% of pts had no match and 0.2% had all 3. Conclusions: This novel master protocol designed to challenge current drug development paradigms and expedite drug registration, is demonstrating feasibility of genomic screening and confirms anticipated prevalence of targeted alterations in SCCA. Support: Supported in part by NIH/NCI (CA180888, CA180819, CA180820, CA180821), and by Amgen, AstraZeneca, Bristol-Myers Squibb Company, Genentech and Pfizer through the Foundation for the National Institutes of Health, in partnership with Friends of Cancer Research. Clinical trial information: NCT02154490.Biomarker prevalence and overlap. Total FGFR CDK PIK3CA FGFR (16.8%) 14.3% 2.3% 0.2% CDK (18%) 13.9% 1.8% PIK3CA (9.1%) 7.1%
Addressing the burden of cancer in East Africa through cascaded training and education by local doctors.
Authors: Jennifer Eastin, Omoding Abrahams, Ruth Board, Graham G. Dark, Uschi Hofmann, Johnathan Joffe, George Kogolla, Khamza KY Maunda, Walter Otieno Mwanda, Susannah Jane Stanway, Katie Wakeham
Journal: Journal of Clinical Oncology (2018)

11000 Background: Development of cancer services in low and middle income countries (LMIC) is a challenge. The Medical Education, Training and Fellowship (METAF) program aims to improve early detection, research and treatment of cancer in East Africa (EA). Through clinical training courses, participating physicians will be better equipped to diagnose, triage and manage cancer within local hospitals. Methods: The EADB, which is responsible for the development of infrastructure in EA, through the British Council, appointed the RCP as the technical partner in this 4-year project. During Year 1, a needs assessment was carried out in Kampala with oncologists from Kenya, Tanzania, Uganda and Rwanda. Course conveners were recruited, curricula developed and two intensive “training of trainers” (TOT) courses delivered with RCP volunteers teaching alongside local faculty. In Year 2, 5 training courses were delivered, including the first round of ‘cascaded’ courses, facilitated by trainers who participated in the previous TOT workshops, supported by a member of local faculty and an RCP volunteer. Quantitative feedback to evaluate learning was gathered using multiple choice tests at the beginning and end of training. Qualitative feedback was gathered from written evaluations at the end of each course. Course content is continually amended based on country specific needs and participant and faculty feedback. Results: Since the launch of the program in 2016, 7 clinical training activities have been delivered; 3 oncology ToT workshops and 4 oncology cascaded training courses. During Years 1 and 2 the total number of doctors trained across East Africa as part of the METAF programme was 137. Participant feedback suggests that over 935 clinical staff will benefit from the knowledge gained on the clinical courses through mentoring by course participants at home facilities. Conclusions: The TOT solution to the need for a rapid cascade of knowledge has been well received and demonstrated to be effective within this multinational program. The methodology may be applicable to similar needs in LMIC settings. Lessons learned to date will be implemented during Years 3 & 4.