tbuckley/cabot-search huggingface dataset:
Outcomes of melanoma patients with brain metastases receiving immune checkpoint inhibitor (ICI) therapy.
Authors: Fatemeh Ardeshir-Larijani, Ariel Ann Nelson, Petra Martin, Prateek Mendiratta, Andrew E. Sloan, Serah Choi, David B. Mansur, Christopher J. Hoimes
Journal: Journal of Clinical Oncology (2019)

e21028 Background: The effect of ICI therapy on brain metastasis (mets) in melanoma patients has been described, however the impact of genomic alterations and local treatment (trt) including radiation therapy (RT) on CNS outcomes and overall survival (OS) has not yet been explored. Methods: Under institutional IRB approval, we reviewed our electronic medical record to identify patients (pts) with metastatic melanoma and brain mets who received trt with ICI. Trt history, CNS responses as indicated by the treating physician and available genomic data were recorded. OS was estimated using a multivariable Cox regression model adjusting for genomic alteration, age, ICI regimen and brain mets. Results: A total of 49 pts were identified (65% male). Thirty seven pts had testing for tumor genomic alterations (alt, hotspot and comprehensive genomic testing); BRAFV600E( 30%), cKIT(5%), NRAS(16%), no alt (38%). Prior to initiation of ICI, 78% had known CNS mets, of these, 61% received RT. There was no difference in median OS for pts who started RT prior to ICI compared to those without RT (mOS = 75.71 vs 49.4 weeks, p = 0.75). Median OS was improved for those pts who received RT &gt; 90 days prior to initiation of ICI trt however this was not statistically significant (45.7 vs 136 weeks, p = 0.12) and HR = 0.45 (95% CI 0.08, 2.36). OS was not significantly different in pts with genomic alterations compared with those without alterations (p = 0.264). Of the pts with known brain mets at the time of ICI start, 34% had progressive disease at 3 months and 11% were felt to have pseudoprogression. 18% survived to undergo 6-month disease assessment, of these 12% had further progression. All pts with cKIT mutations survived to 6-month disease assessment. 75% of pts with known brain mets developed new lesions, 15% had increased mass size. Pts who developed new brain mets while on trt with ICI had worse survival than those with preexisting brain mets and developed new brain lesions (28 vs 58 weeks, p = 0.05). 6% of all pts developed CNS immune related adverse effects. Conclusions: Most patients with melanoma and known brain metastasis prior to ICI developed new brain lesions as a site of metastatic spread. The development of new brain mets was associated with worse outcomes. Neither genomic alterations nor RT prior to ICI start were associated with improved survival.
When and how to use data from randomised trials to develop or validate prognostic models
Authors: Romin Pajouheshnia, Rolf H H Groenwold, Linda M Peelen, Johannes B Reitsma, Karel G M Moons
Journal: BMJ (2019)

Prediction models have become an integral part of clinical practice, providing information for patients and clinicians and providing support for their shared decision making. The development and validation of prognostic prediction models requires substantial volumes of high quality information on relevant predictors and patient health outcomes. Primary data collection dedicated to prognostic model (development or validation) research could come with substantial time and costs and can be seen as a waste of resources if suitable data are already available. Randomised clinical trials are a source of high quality clinical data with a largely untapped potential for use in further research. This article addresses when and how data from a randomised clinical trial can be used additionally for prognostic model research, and provides guidance for researchers with access to trial data to evaluate the suitability of their data for the development and validation of prognostic prediction models.
Case 35-1987
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Ronald A. Malt, Carolyn C. Compton
Journal: New England Journal of Medicine (1987)

Presentation of CaseA 21-year-old woman was admitted to the hospital because of a mass in the right hepatic lobe.The patient's menarche began at the age of 16 years, with flow that lasted two or three days and was not preceded by molimina. At the age of 18 years her menses ceased at a time that her weight fell from 50 to 42.3 kg during travel to Europe. Several months later she regained the lost weight, but amenorrhea persisted. During the two years before admission brief courses of various hormonal preparations were administered elsewhere; they included medroxyprogesterone, estrogens, thyroid . . .
Chemoimmunotherapy combination: Potential option for metastatic NSCLC patients with EGFR mutation resistant to osimertinib.
Authors: Bo Yang, Yaping Long, Yi Hu
Journal: Journal of Clinical Oncology (2019)

e20618 Background: Osimertinib has been emerged as the standard selection in EGFR T790M-positive NSCLC patients who failed prior treatment with EGFR TKIs. However, acquired resistance to osimertinib is a growing clinical challenge. Despite the significant antitumor activity of Chemoimmunotherapy (CIT) combinations in NSCLC, clinical benefit in patients with EGFR mutations has not been shown obviously. Our objective was to assess the effectiveness and tolerability of CIT for metastatic EGFR-mutant NSCLC patients with acquired resistance to Osimertinib. Methods: We conducted a retrospective study in patients with sensitizing EGFR-mutant NSCLC who were resistant to Osimertinib and received anti-PD1 immunotherapy combined with chemotherapy at Chinese PLA General Hospital. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and toxicities were examined. Results: Between Oct 2015 and Nov 2018, 11 patients were available for analysis, 45.5% male, 45.5% ECOG PS 0-1, median age 54 years, all pts who failed treatment with Osimertinib had received previously targeted therapies. In this CIT combination group, 6 [54.5%] of 11 pts received pembrolizumab and 5[54.5%] of 11 pts received Nivolumab anti-PD1 therapy, 8 [72.7%] of 11 pts received mono-chemotherapy and 3 [27.3%] of 11 pts received platinum-based doublet chemotherapy. The median PFS was 7.47 months (95% CI 3.04 to 11.89). Despite Median OS was not reached, the OS rate at one year was 6 [54.5%] of 11. The ORR was 5 [45.5%] of 11. Treatment-related adverse events (TRAE) of grade 3 or higher were reported in 6 [54.5%] of 11 patients. The most common grade 3 or worse TRAEs were fatigue (3 [27.3%] of 11) and anemia (3 [27.3%] of 11); The following ≥Grade 3 TRAEs occurred once: decreased neutrophil count, acute kidney injury, gastrointestinal bleeding. One patient discontinued treatment because of immune-associated gastroenteritis. Conclusions: In metastatic NSCLC patients with activating EGFR mutation resistant to Osimertinib, our single institution real-world experience in Chemoimmunotherapy combination shows promising activity and acceptable toxicity profile. Given the small number of patients studied, further clinical trials are warranted.
Significance of degree of destructive stromal invasion in early stage endocervical adenocarcinoma.
Authors: Jayanthi Sivasothy Lea, Steven Holloway, Wenxin Zheng, Hao Chen, Glorimar Rivera
Journal: Journal of Clinical Oncology (2019)

e17023 Background: Recent evidence has suggested that stratifying endocervical adenocarcinomas based on degree of destructive stromal invasion and desmoplastic response may help further identify risk of lymph node metastasis (1,2). We sought to explore the prognostic influence of the above histopathologic stratification in women undergoing treatment for early stage cervical adenocarcinoma. Methods: Women with stage IA1 – IB2 endocervical adenocarcinoma who underwent radical hysterectomy were included. Demographics and clinico-pathologic data were collected. Three independent gynecologic pathologists performed pathology review for all specimens and tumors were categorized into patterns A, B, and C based on the criteria described by Silva et al (2). Briefly, these criteria include adenocarcinoma without destructive stromal invasion or desmoplastic response (pattern A), minimum destructive invasion (pattern B), and frank invasion (pattern C). Clinico-pathologic data were reviewed and all cases were stratified as either low, intermediate (GOG 92 criteria) or high-risk (positive nodes, parametria, margins). Chi square and Fisher exact test were used for statistical analysis. Results: 46 patients with cervical adenocarcinoma were identified with the following stage distribution: 6 stage IA, 34 stage IB1 and 6 stage IB2. All patients with stage IA disease had pattern A or B tumors. Ten patients with pattern A or B tumors had stage IB1 (N = 9) or IB2 (N = 1). 30 patients had pattern C tumor, all of which were stage IB1-IB2. LVSI was identified in 40% of pattern C versus 6% of pattern B tumors (p &lt; 0.02). All patients who were high-risk for recurrence had pattern C tumors. 16/17 patients who were intermediate-risk had pattern C versus 1/17 with pattern B tumor (p &lt; 0.01). Lymph node metastasis was identified in 11% of pattern C and none in patterns A and B tumors (p &lt; 0.01). All recurrences were diagnosed in patients with pattern C tumors (p &lt; 0.01). Conclusions: Recurrent cervical adenocarcinoma was seen only in patients with pattern C tumors, while no patient with pattern A or B tumors recurred. This histopathologic stratification could be utilized to propose individualized therapy for women with newly diagnosed endocervical adenocarcinoma. References: 1. Diaz De Vivar A al. Int J Gynecol Pathol. 2013;32(6):59;22. Roma AA. Et. al. Gynecol Oncol. 2016; 141: 36.
Clinical impact of tissue of origin testing and mutation profiling in the Solving Unknown Primary Cancer (SUPER) national prospective study: Experience of the first two years.
Authors: Linda R. Mileshkin, Tharani Sivakumaran, Dariush Etemadmoghadam, Richard Tothill, Andrew Fellowes, Stephen B. Fox, Lisa Guccione, Alison E. Freimund, Anna deFazio, Nicholas Wilcken, Bo Gao, Madhu Sudan Singh, Ian M. Collins, Gary Edward Richardson, Christopher B. Steer, Mark Andrew Warren, Christos Stelios Karapetis, Cindy Bryant, Penelope Schofield, David Bowtell
Journal: Journal of Clinical Oncology (2019)

3072 Background: Cancer of unknown primary (CUP) has a poor prognosis with a median survival of less than 12 months. SUPER is a prospective cohort study designed to create a national biobank of patients (pts) with no confirmed primary site following diagnostic work-up. Tumor and blood samples undergo mutational profiling for actionable mutations using the 386 gene PeterMac Comprehensive Cancer Panel (CCP) plus CUPGuide, a microarray gene-expression site-of-origin assay. We aimed to determine the clinical impact of CUPGuide and CCP profiling. Methods: 172 pts were enrolled between 2013-2015. Baseline demographics, treatments, investigations and clinico-pathological characteristics were collected over 12 months. Clinicians completed clinical management questionnaires before and after receiving results. Results: Molecular analysis was performed for 124/172 (72.1%) pts with sufficient DNA and/or RNA. CUPGuide was completed for 97/124 (78.2%); primary site predictions were made in 84/97 patients (86.6%). The most common primary site predictions were lung, gastric, ovary and breast. CUPGuide predictions resulted in a change in management in 10/84 (12%) of cases and confirmed current management already commenced by the clinician in 53/84 (63%). Mutation profiling was completed in 103/124 (83.1%) pts with actionable mutations found in 11 pts, 4 of whom received subsequent targeted therapy. Testing was considered to have a clinical impact in 70/120 cases (58%): either resulting in a change in treatment (n = 14), diagnosis of a pathogenic germline finding (n = 8) or a moderate/high confidence tissue of origin prediction (n = 58). There were two deaths prior to the availability of the CUPGuide results and eleven deaths prior to availability of the CCP results. Conclusions: Molecular analysis for CUP pts has clinical impact in the majority of cases. Timeliness of return of results, drug access and insufficient tissue for testing are barriers to greater impact that need to be addressed to improve the care of pts affected by CUP.
Clinical outcomes of patients with stage IV cancer receiving immune checkpoint inhibitors in the inpatient setting.
Authors: Sienna Durbin, Leyre Zubiri, Andrzej Niemierko, Laura A Petrillo, Aditya Bardia, Ryan J. Sullivan, Corey McEwan, Therese Marie Mulvey, Ian Matthew Allen, Donald P. Lawrence, Justine Vanessa Cohen, Ephraim P. Hochberg, David P. Ryan, Kerry Lynn Reynolds
Journal: Journal of Clinical Oncology (2019)

6634 Background: Immune checkpoint inhibitors (ICI) represent a major leap in the treatment of many cancers. Use has rapidly expanded in recent years, yet it is unknown whether hospitalized patients, who are often sicker than those who were studied in clinical trials, derive benefit from ICI. The primary objectives of this study were to characterize the clinical features and outcomes of inpatients receiving ICI at a single institution, and to identify predictors of survival. Methods: After IRB approval, we conducted a retrospective chart review of inpatients with Stage IV solid tumors receiving ICI between 2015 – 2018 at a tertiary care referral hospital. Patients receiving ICI on clinical trial were excluded. We examined the clinical characteristics, readmission rate, and post-discharge survival. We then conducted a Cox multivariable regression analysis to identify predictors of post-discharge survival. Results: A total of 103 patients with Stage IV solid tumors were treated with ICI as inpatients between 2015 – 2018. Average age was 57 years (range = 26 to 85); 57% were male; 27% had ECOG performance status (PS) 3-4; average Charlson Comorbidity Index score was 8.3. Most common tumor types were melanoma (35%) and lung (22%). Seventy-six percent began ICI as an inpatient and 24% received ICI as continuation of outpatient therapy. Seventeen percent experienced an immunotherapy related adverse event, most commonly colitis and pneumonitis. The 30 day readmission rate was 41%. The median post-discharge survival was 31 days; 47% of patients died during admission or within 30 days of discharge; 14% survived more than 6 months. Factors predictive of shorter post-discharge survival were PS of 3-4 relative to PS 0-2 (HR 2.0, p &lt; 0.004), and lung cancer (HR 2.0, p &lt; 0.024) and other tumor types (HR 2.1, p &lt; 0.004) relative to melanoma. Conclusions: While the majority of inpatients receiving ICI died during admission or within 30 days of discharge, a subset of patients with stage IV disease were alive at 6 months. Tumor type and ECOG PS predict post-discharge survival and may be used to identify inpatients more likely to benefit from ICI. These novel findings, which are unique to a single institution, require additional validation.
A phase II study of concurrent nimotuzumab and intensity-modulated radiotherapy in elderly patients with locoregionally advanced nasopharyngeal carcinoma.
Authors: Caineng Cao, Qiaoying Hu, Xiaozhong Chen
Journal: Journal of Clinical Oncology (2019)

e17562 Background: The purpose of this study was to evaluate the feasibility of concurrent nimotuzumab to intensity-modulated radiotherapy (IMRT) in elderly patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: According to the eighth edition of the American Joint Committee on Cancer staging system, elderly patients with stage III–IVA NPC were given concurrent nimotuzumab (200 mg/week, starting 1 week before IMRT) with IMRT. They completed a geriatric assessment tool (function, comorbidity, cognition, psychological state, social activity/support, and nutritional status) before initiation of protocol therapy. Results: Thirty patients [median age of 70.5 (65-95) years] with stage III (60%), and IVA (40%) NPC were enrolled between March 2017 and November 2018. The mean scores on the comorbidity scale and instrumental activities of daily living scale were 7 (range, 1 to 12) and 12 (range, 8 to 14), respectively. Grade 3 mucositis occurred in 10 (33%) patients and 1 (3%) patient had grade 3 radiotherapy-related dermatitis. Grade 3 pneumonia occurred in 3 patients (10%) and no patients had nimotuzumab-related acneiform rash. There were 20 complete responses and 10 partial responses 1month after the completion of IMRT. Conclusions: Concurrent administration of nimotuzumab and IMRT is effective and well-tolerated for elderly patients with locoregionally advanced NPC. Clinical trial information: NCT03025958.
Phase 1 trial of anti-CD19 chimeric antigen receptor T (CAR-T) cells with tumor necrosis alfa receptor superfamily 19 (TNFRSF19) transmembrane domain.
Authors: Paolo Fabrizio Caimi, Jane Reese, Folashade Otegbeye, Dina Schneider, Kamal Chamoun, Kirsten M Boughan, Brenda W. Cooper, Erin Galloway, Molly Gallogly, Winfried Kruger, Andrew Worden, Michael Kadan, Ehsan Malek, Leland L. Metheny, Benjamin K. Tomlinson, Rafick-Pierre Sekaly, David Wald, Rimas Orentas, Boro Dropulic, Marcos J.G. De Lima
Journal: Journal of Clinical Oncology (2019)

2539 Background: AntiCD19 CAR-T cells have shown encouraging anti-lymphoma activity. Decreasing the time from apheresis to CAR-T infusion can make this therapy available to pts with rapid progression. We present the interim results of a phase I clinical trial using on-site CAR-T manufacture. Methods: Adult pts with r/r CD19+ B cell lymphomas who failed ≥ 2 lines of therapy were enrolled. Autologous T cells were transduced with a lentiviral vector (Lentigen Technology, Inc,LTG1563) encoding an antiCD19 binding motif, CD8 linker and TNFRSF19 transmembrane region, and 4-lBB/CD3z domains. GMP-compliant manufacture was done using CliniMACS Prodigy, in a 12-day culture. Dose levels were 0.5, 1 and 2 x 10 6 CAR-T cells/kg. Lymphodepletion was done with cyclophosphamide (60mg/kg x 1) and fludarabine (25mg/m 2 /d x 3). Results: 7 pts (4 women, 3 men) were enrolled. Median age was 60y [range 43-69]. Diagnoses were DLBCL (n = 3) PMBCL, follicular lymphoma (FL), transformed FL, and transformed lymphoplasmacytic lymphoma; with a median of 4 previous treatments. Six pts had symptomatic refractory disease. CAR-T cell product manufacture was successful in all pts. Mean transduction rate was 44% [range 29-57]. CAR-T cell doses were 0.5 x 10 6 /kg (n = 3) and 1 x 10 6 /kg (n = 4). Median apheresis to infusion time was 13 days [range 13–20], 5 products were infused fresh. CAR-T persistence based on vector sequence, peaked in peripheral blood MNCs between days 14-21. Five pts are evaluable for safety. CRS grade 1 - 2 (Lee) occurred in 4 pts; with 3 requiring treatment. Grade 4 CRES (CARTOX-10) occurred in 1 pt, with resolution after corticosteroids; considered a DLT as it lasted more than 72 hours. No treatment-related mortality has occurred. 4/5 evaluable pts have achieved complete response. One pt did not respond and died. After a median follow up 3 months, all responding pts are alive and 1 relapsed 6 mo after treatment. Conclusions: Second generation antiCD19 CAR-T cells with TNFRS19 transmembrane domain have clinical activity against refractory NHL. Short manufacture time achieved by local CAR-T cell manufacture with the CliniMACS Prodigy enables treatment of a very high risk NHL population. Clinical trial information: NCT03434769.
Physical activity platform to improve bone health in cancer survivors.
Authors: Cathy Skinner
Journal: Journal of Clinical Oncology (2020)

e24054 Background: Cancer treatment-induced bone loss and the risk of fractures is a significant burden on national health care with the annual cost of osteoporosis at $25.3 billion. Clinical studies report that moderate-intensity resistance exercises prevent a decline in bone health and reduce complications such as fatigue, muscle wasting, and bone loss. Only a small percentage cancer survivors engage in exercise. Several factors account for this low level of engagement such as poor awareness of the benefits, lack of motivation, and access to exercise programs for cancer survivors. Web- and mobile app-based programs that encourage physical activity can potentially address these problems and can be scaled for dissemination. Methods: Thrivors plus Bone Health (Thrivors+BH) is first-of-its-kind, clinically validated platform of bone health exercises that adapts to a cancer survivor's pain and energy levels with several interactive feedback features. The product has physical activity, mindfulness, nutrition, survivorship resources, and bone health education. The platform's back-end tracks and reports module activity. We conducted a single-blind RCT of 142 breast cancer survivors adherence to a 20-week program of resistance and impact exercises. Participants in the control arm accessed Thrivors Basic which lacked interactive feedback. Results: The primary outcome was higher adherence. High adherence equals completion of at least 40 of 60 recommended exercise sessions during the 20-week intervention. The intervention group showed higher measures of platform usage, duration and activity. Intervention group completed the validated jumping protocol after an 8-week program of strength training to prepare for increased intensity exercises. Although some participants discontinued due to various reasons (time constraints or health complications), the supportive modules and feedback from the PI influenced participants to resume exercise after a period of inactivity. The mean scores in the PAM and SF-36v surveys were higher for the intervention group. Conclusions: The study demonstrates breast cancer survivors' willingness to utilize a digital platform with prescribed exercise routines. Feedback suggests that more personalized and interactive features may encourage a higher frequency of engagement in bone-health specific physical activity. A follow-up study will examine the impact of the exercise program on bone health and the role of coaching to impact sustainable behavior change. Clinical trial information: NCT03651037 .