tbuckley/cabot-search huggingface dataset:
Hospitalization cost and length of stay in pancreatic cancer population: A national inpatient database study.
Authors: Ikponmwosa Enofe, Manoj P. Rai, Divyesh Reddy Nemakayala, Shilpa Tatineni, Atinuke Aluko, Prabhjot Singh Bedi, Julie Yam, Nazia Naz S Khan, Heather Laird-Fick
Journal: Journal of Clinical Oncology (2019)

e15793 Background: Pancreatic cancer accounts for 7% of all cancer deaths in the U.S. It contributes to burgeoning health care cost and is associated with poor prognosis. The aim of this study was to describe the disease burden, pattern of resource utilization, hospital cost and outcomes among hospitalized pancreatic cancer patients based on the location of disease. Methods: We conducted a retrospective study utilizing the 2014 national inpatient sample database. Adult records with a primary discharge diagnosis of pancreatic cancer were included. Records with no specification on cancer location were excluded. Regression models (logistic and linear) were used to estimate adjusted odds ratios (OR), mean length of stay (LOS) and hospital charges (HC). Covariates included sociodemographic factors, co-morbidities and therapeutic surgical procedures received during hospitalization. Results: A total of 4,799 discharge records met the inclusion criteria. Overall, 74.3% had cancer in the pancreatic head and 25.6% had cancer in the body and tail. Pancreatic head cancers were more common in whites (73%). Patients with cancer in the body and tail more commonly experienced metastasis than patients with pancreatic head cancer (23.8% versus 20.4% p = 0.02). Compared to pancreatic head cancers, patients with body and tail cancers were more likely to have a pancreatectomy during index hospitalization (OR 45, 95% CI 27.8 - 65.2). Alternatively, cancers of the pancreatic head were more likely to have an endoscopic pancreatic procedure during index hospitalization compared to body and tail (OR 7.39, 95% CI 3.9 -13.9). Pancreatic head cancers were associated with a significantly longer mean hospital LOS (8.1 versus 6.4 days, mean difference 1.66, p &lt; 0.001) and higher mean cost of hospitalization (Mean HC $85,263.40 versus $56,156.60 p &lt; 0.001) compared to cancer in the body and tail. Conclusions: Despite lower rate of metastasis and pancreatectomy, patients hospitalized for pancreatic head cancers have longer hospital LOS and higher healthcare cost burden. Our findings may inform physicians, patients, and policymakers and may help channel resources toward specific patient population to reduce healthcare cost and improve outcomes for individuals and healthcare organizations.
Patient-reported outcomes from two global multicenter clinical trials of children and adults with tropomyosin receptor kinase (TRK) fusion cancer receiving larotrectinib.
Authors: Shivaani Kummar, Leo Mascarenhas, Birgit Geoerger, Brian Turpin, Michael Craig Cox, Sandie Yu, Shivani Nanda, Florian Hiemeyer, Karen N Keating, Costel Chirila, Ari Gnanasakthy, Eric Davenport, David S. Hong, Alexander E. Drilon
Journal: Journal of Clinical Oncology (2019)

6602 Background: TRK fusions involving NTRK1, NTRK2, and NTRK3 occur in diverse tumor types in children and adults. Larotrectinib, a selective TRK inhibitor, was recently approved by the FDA based on high objective response rates, durable disease control, and a favorable toxicity profile in in patients with tumors harboring TRK fusions (Drilon et al, NEJM 2018; Laetsch et al, Lancet Oncol 2018). To explore the impact of larotrectinib on quality of life (QoL), patient-reported outcomes (PROs) are reported here for pediatric patients (SCOUT; NCT02637687) and adolescents and adults (NAVIGATE; NCT02576431). Methods: Patients completed questionnaires assessing QoL (i.e., PedsQL, FACES, EORTC QLQ-C30, EQ-5D-5L) at baseline and planned cycle visits. Data were analyzed using descriptive statistics, longitudinal data models, and graphical displays. Results: As of July 2017, 37 patients (13 pediatric and 24 adolescent or adult) completed questionnaires at baseline and had at least one post-baseline measurement. Improvements compared to baseline in PROs were seen in both groups of patients in all functional domains of the PedsQL (physical, emotional, social, and school) and of the EORTC QLQ-C30 (physical, role, cognitive, emotional, and social). Number of patients with MID-improvement for PedsQL (Total Score), EORTC QLQ-C30 (Global Health Score), and EQ-5D-5L (VAS) are presented in the table below. Improvements were rapid (by cycle 3 or 5), seen across most tumor types and sustained a minimum of 2 cycles. Conclusions: Although necessarily viewed with caution due to relatively small sample sizes, these results nonetheless show a meaningful early improvement in QoL in pediatric and adult patients with TRK fusion cancer treated with larotrectinib. Clinical trial information: NCT02637687 and NCT02576431. [Table: see text]
Efficacy and safety of the combination of nivolumab (NIVO) plus ipilimumab (IPI) in patients with symptomatic melanoma brain metastases (CheckMate 204).
Authors: Hussein Abdul-Hassan Tawbi, Peter A. J. Forsyth, F. Stephen Hodi, Christopher D. Lao, Stergios J. Moschos, Omid Hamid, Michael B. Atkins, Karl D. Lewis, Reena Parada Thomas, John A. Glaspy, Sekwon Jang, Alain Patrick Algazi, Nikhil I. Khushalani, Michael A. Postow, Anna C. Pavlick, Marc S. Ernstoff, David A. Reardon, Agnes Balogh, Jasmine I. Rizzo, Kim Allyson Margolin
Journal: Journal of Clinical Oncology (2019)

9501 Background: We previously reported efficacy and safety of NIVO+IPI in patients (pts) with untreated, asymptomatic, melanoma brain metastases (MBM) from the CheckMate 204 study. Here, we provide the first report of NIVO+IPI in pts with symptomatic MBM, and report updated data in pts with asymptomatic MBM. Methods: In this phase II trial, pts with ≥1 measurable, nonirradiated MBM 0.5–3.0 cm were enrolled into two cohorts: (1) those with no neurologic symptoms or steroid Rx (asymptomatic; cohort A); and (2) those with neurologic symptoms, whether or not they were receiving steroid Rx (symptomatic; cohort B). In both cohorts, pts received NIVO 1 mg/kg + IPI 3 mg/kg Q3W × 4, then NIVO 3 mg/kg Q2W until progression or toxicity. The primary endpoint was intracranial clinical benefit rate (CBR; proportion of pts with complete response [CR] + partial response [PR] + stable disease [SD] ≥6 mo). As of the clinical cutoff date on May 1, 2018, all treated pts (101 in cohort A and 18 in cohort B) had been followed for ~6 mo or longer. Results: In this updated analysis of cohort A (median follow-up of 20.6 mo), the CBR was 58.4% (Table). In cohort B, pts received a median of 1 NIVO+IPI dose and 2 of 18 pts (11%) received all 4 doses. At a median follow-up of 5.2 months in cohort B, intracranial objective response rate was 16.7% and the CBR was 22.2%. Grade 3/4 adverse events occurred in 54.5% of pts in cohort A and in 55.6% of pts in cohort B (6.9% and 16.7% in the nervous system, respectively), with one death related to treatment in cohort A (immune-related myocarditis). Conclusions: In pts with asymptomatic MBM, our updated results show a high rate of durable intracranial responses, further supporting NIVO+IPI as a first-line treatment in this population. Intracranial antitumor activity was observed with NIVO+IPI in pts with symptomatic MBM, but further study is needed to understand the biologic mechanisms of resistance to immunotherapy and to improve treatments in this challenging population. Clinical trial information: NCT02320058. [Table: see text]
Enhancing community capacity to improve cancer care delivery and the effect on patient-reported outcomes, healthcare utilization and total costs of care.
Authors: Manali I. Patel, David Ramirez, Richy Agajanian, Hilda H. Agajanian, Jay Bhattacharya, Tumaini Coker
Journal: Journal of Clinical Oncology (2019)

6522 Background: To curb rising expenditures and improve patient-reported outcomes (PROs), we designed an intervention with patient, caregiver, provider, and payer input. The intervention is based on prior work using a lay health worker (LHW) to assess advanced cancer patients' symptoms. In this study, we trained the LHW to refer patients to palliative care and/or behavioral health services in response to positive assessments and expanded the intervention to all cancer stages. We implemented the intervention with a health plan and a community oncology group serving elderly racially/ethnically diverse patients to test the effect on symptoms, healthcare use, and total costs. Methods: We enrolled all newly diagnosed health plan beneficiaries with solid and hematologic malignancies from 10/2016 to 11/2017 and compared outcomes to all cancer patients diagnosed in the year prior to the intervention (control arm). Our primary outcome was change in patient-reported symptoms using the Edmonton Symptom Assessment Scale and Personal Health Questionnaire-9 at baseline, 6 and 12 months post-enrollment. Secondarily, we compared 12 month healthcare use and costs. All generalized linear regression models were adjusted for age, stage, comorbidities, diagnosis, and follow-up. Results: 425 patients were in the intervention; 407 in the control. In both groups, mean age was 79 years; 48% were non-Hispanic White, 43% Hispanic, 3% Black, 6% Asian/Pacific Islander; 60% had advanced stages; 28% had breast, 28% had gastrointestinal, and 10% had thoracic cancers. Intervention patients had significantly decreased symptom burden over time as compared with the control (Mean Difference: intervention (-0.77 +/- 0.28 p = 0.01) vs. control: (0.45 +/- 0.25 p = 0.06)); difference in difference: (-0.68 +/- 0.25 p = 0.007)). Depression scores also significantly decreased over time among intervention patients as compared with the control (Mean Difference: intervention (-1.10 +/- 0.38 p = 0.04)) vs control: (1.21 +/- 0.34 p = 0.01); (difference in difference: -2.03 +/- 0.3 p &lt; 0.001)). As compared to the control arm, intervention patients had lower inpatient admissions (0.7 vs. 0.5 p = 0.01) and emergency department visits per thousand patients per year (0.6 vs. 0.42 p = 0.02), and lower median total healthcare costs ($32,270 versus $25,512 p = 0.01). Conclusions: An LHW intervention significantly improved patient-reported outcomes and the value of cancer care delivery and may be a solution to improve burdensome and costly care for patients.
Genetic Testing After a Terminal Diagnosis—Providing Purpose
Authors: Julie Solimine
Journal: JAMA Oncology (2019)

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Case 52-1984
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Harley A. Haynes, Ben R. Bronstein
Journal: New England Journal of Medicine (1984)

Presentation of CaseAn 86-year-old woman was admitted to the hospital because of facial swelling.She was well until eight years earlier, when an IgA kappa M component was found at another hospital. Microscopical examination of an aspirated specimen of bone marrow was reported to show no plasma-cell infiltrate. A diagnosis of IgA multiple myeloma was made. One year later a left carpal-tunnel division was performed. During the ensuing years the patient remained asymptomatic; no medication was given, and no further examination of the bone marrow was performed. Four years before admission she was treated at another hospital for cellulitis . . .
Mechanisms of the beneficial effects of MSC on human hepatocytes for use in the treatment of acute liver failure: Tunneling nanotube-based transfer of MSC mitochondria to hepatocytes
Authors: Raquel Fernandez-Dacosta, Anil Dhawan, Charlotte A. Lee, Valeria Iansante, Simon Walker, Sharon Lehec, Emer Fitzpatrick, Celine Filippi
Journal: Hepatology (2016)
Immunogenicity and tolerability of personalized mRNA vaccine mRNA-4650 encoding defined neoantigens expressed by the autologous cancer.
Authors: Gal Cafri, Jared J. Gartner, Kristen Hopson, Robert S. Meehan, Tal Z. Zaks, Paul Robbins, Steven A. Rosenberg
Journal: Journal of Clinical Oncology (2019)

2643 Background: Therapeutic vaccination against cancer has proven very challenging with little clinical benefit. Vaccines against non-viral tumors have mainly targeted differentiation antigens, cancer testis antigens, and over-expressed antigens. However, negative selection in the thymus against these normal non-mutated antigens severely limits the ability to generate high avidity anti-cancer T-cells. The importance of neoantigens to each patient’s unique cancer as targets for immunotherapy has been extensively studied, by our group and others. It is now clear that neoantigen-specific T-cells are present in most cancers and these neoantigens derived from somatic mutations offer a specific and highly immunogenic target for personalized vaccination. We developed a process to identify immunogenic T-cell epitopes derived from tumor-specific mutations using tumor-infiltrating lymphocytes. Methods: We combined, for the first time, validated defined neoantigens, predicted neoepitopes and mutations in driver genes into a single mRNA concatemer (mRNA-4650) to vaccinate patients with metastatic common epithelial cancers. We are conducting a phase I/II trial in patients with metastatic melanoma, gastrointestinal, or genitourinary cancers with at least one lesion that is resectable. Patients must have an ECOG status of ≤1 with adequate organ and bone marrow function. Patients are vaccinated intramuscularly at two-week intervals for four cycles, and dosing may be repeated for a second course of vaccination. Key primary endpoints are safety, tolerability and the development of T-cell reactivity as well as objective response rate. Results: mRNA-4650 is safe at all dose levels studied to date with no reported DLTs or drug related SAEs. Neoantigen specific CD8 and CD4 T cells responses against neoepitopes included in the vaccine have been observed and no tumor regressions were seen. Conclusions: Our data show that such a personalized mRNA vaccination is feasible and can elicit neoantigen specific T cell responses. Combination of vaccines with checkpoint inhibitors or adoptive T cell therapy can open the possibility to develop effective immunotherapies for patients with the common epithelial cancers. Clinical trial information: NCT03480152.
The clinical features of extragonadal germ cell tumors: A SEER analysis.
Authors: Yanal Mufeed Alnimer, Khalil Katato
Journal: Journal of Clinical Oncology (2019)

e16064 Background: Extragonadal germ cell tumor is an uncommon type of malignancy. We aim to identify the clinical features and the prognosis in various histological subtypes in these patients using the Surveillance, Epidemiology, and End Results Program (SEER) database. Methods: We used the (SEER) database to identify the patients with non-gonadal germ cell tumors between 1998-2015. 1299 patients were identified and included in our analysis. Results: 1299 patients had non-gonadal germ cell tumors between 1998-2015. The mean age was 26 years-old. 568 patients (44%) were females and 731 patients (56%) were males. 276 patients (21%) died after a mean follow up time of 41.16 months (1-60 months). The mean overall survival (OS) was 49.4 months (95%CI 48.21-50.52) with the median being unreached. The Females had better OS compared to the males with a Hazard ratio (HR) = 0.50 (95%CI 0.40-0.63). Age more than 60 years-old at the time of diagnosis was associated with a substantially significant increase in mortality with an HR = 43 (95% CI 19.17-94.41). The mediastinal germ cell tumors were associated with worse OS compared to other sites with a HR = 4.69 (95%CI 3.37-6.52). The median OS for Embryonal cell carcinoma was 22 months, and it was associated with worse OS compared to seminoma and other histological subtypes with a HR = 4.10 (95% CI 1.69-9.72) and 2.77 (95% 1.16-6.58) respectively. On the other hand, Seminoma was associated with better OS compared to other histological subtypes with an HR = 0.66 (95%CI 0.52-0.84). Moreover, tumor size less than 80 mm was associated with better OS with a HR = 0.42 (95%CI 0.30-0.64). In multivariate analysis, patients above the age of 60 had worse OS with an HR = 4.04 (95%CI 1.71-9.58), patients with mediastinal germ cell tumors had poorer OS compared to other sites with an HR = 2.38 (95%CI 1.51-3.79). Furthermore, embryonal carcinoma, mixed germ cell tumors and choriocarcinoma were associated with worse OS compared to seminoma and immature teratoma with an HR = 10.39 (95% CI 4.36-24.72), HR = 2.07 (95% CI 1.23-3.46) and HR = 6.16 (95%CI 2.98-12.74) respectively. Conclusions: Non-gonadal seminoma and immature teratoma carry better prognosis compared to other histological subtypes. Also, among non-gonadal germ cell tumors, non-mediastinal seminoma has the best survival outcome.
Genome-wide cell-free DNA fragmentation profiling for early cancer detection.
Authors: Alessandro Leal, Stephen Cristiano, Jillian Phallen, Jacob Fiksel, Vilmos Adleff, Daniel C. Bruhm, Sarah Østrup Jensen, Jamie E. Medina, Doreen N. Palsgrove, Noushin Niknafs, Valsamo Anagnostou, Patrick M. Forde, Julie R. Brahmer, Remond Fijneman, Julia S. Johansen, Hans J. Nielsen, Gerrit A. Meijer, Claus Lindbjerg Andersen, Robert B. Scharpf, Victor E. Velculescu
Journal: Journal of Clinical Oncology (2019)

3018 Background: Analyses of cell-free DNA (cfDNA) in the blood provide a noninvasive diagnostic avenue for patients with cancer. However, cfDNA analyses have largely focused on targeted sequencing of specific genes, and the characteristics of the origins and molecular features of cfDNA are poorly understood. We developed an ultrasensitive approach that allows simultaneous examination of a large number of abnormalities in cfDNA through genome-wide analysis of fragmentation patterns. Methods: We used a machine learning model to examined cfDNA fragmentation profiles of 236 patients with largely localized breast, colorectal, lung, ovarian, pancreatic, gastric, or bile duct cancer and 245 healthy individuals. Estimation of performance was determined by ten-fold cross validation repeated ten times. Results: cfDNA profiles of healthy individuals reflected nucleosomal patterns of white blood cells, while patients with cancer had altered fragmentation patterns. The degree of abnormality in fragmentation profiles during therapy closely matched levels of mutant allele fractions in cfDNA as determined using ultra-deep targeted sequencing. The sensitivity of detection ranged from 57% to &gt; 99% among the seven cancer types at 98% specificity, with an overall AUC of 0.94. Fragmentation profiles could be used to identify the tissue of origin of the cancers to a limited number of sites in 75% of cases. Combining our approach with mutation-based cfDNA analyses detected 91% of cancer patients. Conclusions: This effort is the first study to demonstrate genome-wide cell-free DNA fragmentation abnormalities in patients with cancer. Results of these analyses highlight important properties of cfDNA and provide a facile approach for screening, early detection, and monitoring of human cancer.
Multi-omics profiling of upper-tract urothelial carcinomas.
Authors: Gabriel G. Malouf, Hui Yao, Roger Mouawad, Morgan Roupret, Jean-Emannuel Kurtz, Jean-Philippe Spano, INSTITUT CANCEROLOGIE Meyer KHAYAT, Eva Comperat, Xiaoping Su
Journal: Journal of Clinical Oncology (2019)

4560 Background: Upper-tract urothelial carcinomas (UTUC) may harbor similar genetic profile as compared to bladder cancer, although frequencies of mutated genes have been shown to differ between them. However, to the best of our knowledge, the epigenetic landscapes of UTUC and their association with genetic alterations and clinico-pathological tumor features remain unknown. Methods: We collected 40 UTUC samples (20 non-muscle invasive (NMI) and 20 muscle-invasive (MI) and carried out whole-exome sequencing (n = 30), DNA methylation using Infinium EPIC arrays (n = 35) and RNA sequencing (n = 20). Validation was performed on TCGA bladder cancer dataset. Results: We identified 3232 putative somatic mutations with an average of 2.1+/-2.6 mutations per megabase. Significantly mutated genes were FGFR3 (50%), KDM6A (27%), MLL2 (27%) and ARID1A/B (23%). No difference in term of genetic alterations were identified between MI- and NMI- UTUC. Unsupervised hierarchical clustering using most variable DNA methylation probes uncovered two robust DNA methylation epi-clusters. Epi-cluster C1 (n = 23; 65.7%) displayed markedly higher DNA methylation relative to Epi-cluster C2 (n = 12; 34.3%). Notably, all muscle-invasive samples were enriched in C1 (16/17, 94.1%); conversely, C2 was enriched with non-muscle-invasive samples (p = 0.0009). Overall, 14.209 probes were significantly hypermethylated in C1 as compared to C2 epi-cluster; Gene Set Enrichment Analysis (GSEA) demonstrated that those were enriched for PRC2 targets (p = 6x10 -65 ). Integrative analysis with tumor genetic landscape showed that C1 epi-cluster was enriched for mutations in SWI/SNF complex as compared to C2 (p = 0.02). We then applied our epi-signature to bladder TCGA cohort and obtained two similar epi-clusters associated with patients overall survival (p = 0.035). Conclusions: Our study demonstrate for the first time that difference between MI- and NM- invasive UTUC might be related to epigenetic rather than genetic alterations. This might pave the way for testing epigenetic therapies in non-muscle invasive tumors with the aim to prevent recurrence and distant metastasis.