tbuckley/cabot-search huggingface dataset:
Predicting response to checkpoint inhibitors in melanoma beyond PD-L1 and mutational burden
Authors: Carl Morrison, Sarabjot Pabla, Jeffrey M. Conroy, Mary K. Nesline, Sean T. Glenn, Devin Dressman, Antonios Papanicolau-Sengos, Blake Burgher, Jonathan Andreas, Vincent Giamo, Moachun Qin, Yirong Wang, Felicia L. Lenzo, Angela Omilian, Wiam Bshara, Matthew Zibelman, Pooja Ghatalia, Konstantin Dragnev, Keisuke Shirai, Katherine G. Madden, Laura J. Tafe, Neel Shah, Deepa Kasuganti, Luis de la Cruz-Merino, Isabel Araujo, Yvonne Saenger, Margaret Bogardus, Miguel Villalona-Calero, Zuanel Diaz, Roger Day, Marcia Eisenberg, Steven M. Anderson, Igor Puzanov, Lorenzo Galluzzi, Mark Gardner, Marc S. Ernstoff
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Immune checkpoint inhibitors (ICIs) have changed the clinical management of melanoma. However, not all patients respond, and current biomarkers including PD-L1 and mutational burden show incomplete predictive performance. The clinical validity and utility of complex biomarkers have not been studied in melanoma. <h3>Methods</h3> Cutaneous metastatic melanoma patients at eight institutions were evaluated for PD-L1 expression, CD8<sup>+</sup> T-cell infiltration pattern, mutational burden, and 394 immune transcript expression. PD-L1 IHC and mutational burden were assessed for association with overall survival (OS) in 94 patients treated prior to ICI approval by the FDA (historical-controls), and in 137 patients treated with ICIs. Unsupervised analysis revealed distinct immune-clusters with separate response rates. This comprehensive immune profiling data were then integrated to generate a continuous Response Score (RS) based upon response criteria (RECIST v.1.1). RS was developed using a single institution training cohort (<i>n</i> = 48) and subsequently tested in a separate eight institution validation cohort (<i>n</i> = 29) to mimic a real-world clinical scenario. <h3>Results</h3> PD-L1 positivity ≥1% correlated with response and OS in ICI-treated patients, but demonstrated limited predictive performance. High mutational burden was associated with response in ICI-treated patients, but not with OS. Comprehensive immune profiling using RS demonstrated higher sensitivity (72.2%) compared to PD-L1 IHC (34.25%) and tumor mutational burden (32.5%), but with similar specificity. <h3>Conclusions</h3> In this study, the response score derived from comprehensive immune profiling in a limited melanoma cohort showed improved predictive performance as compared to PD-L1 IHC and tumor mutational burden.
Evaluating the impact of survivorship models on health system resources and costs.
Authors: Nicole Mittmann, Hasmik Beglaryan, Ning Liu, Soo Jin Seung, Farah Rahman, Julie Gilbert, Jillian Ross, Stephanie De Rossi, Craig Earle, Eva Grunfeld, Jonathan Sussman
Journal: Journal of Clinical Oncology (2018)

1 Background: The provincial cancer agency in Ontario developed and implemented a model of care (MOC) for breast cancer (BC) survivors to transition from oncology-lead care to primary care in a publically funded health care environment (2010-2013). Transition options included direct to primary care and stepped transition. The objective of our study was to examine the health system resources used by the women in the MOC group and compare them to those used by women who did not transition. Methods: A propensity score matched, quasi-experimental approach was used to compare the healthcare resource utilization and costs between BC survivors in the MOC program (case) and those receiving usual care (control). All MOC cases were linked using unique identifiers and linked into the provincial health system databases. Cases and controls were matched 1:1 on year of diagnosis and location of care and were followed from an index date to the earliest of her death date, date of last contact in the database, one day before another cancer diagnosis or the end of study available databases. The primary study outcome was overall health system utilization and mean cost during the follow-up period. Results: There were 2324 women in the MOC program. Demographic information (age, region, stage) were well balanced between cases and controls. Transitioned cases had lower hospitalizations (20.1% vs. 24.4%, p&lt;0.05), fewer cancer clinic visits (6.0% vs. 15.1%, p&lt;0.05), fewer medical oncologist visits (0.39 vs. 1.29, p&lt;0.05) and fewer diagnostics (CT, MRI, ultrasound, x-rays) over an average of 25 months of follow-up. There was a trend for fewer family practice (7.35 vs. 7.91, p=0.08) and internal medical and hematology visits (0.81 vs. 1.03, p=0.08). Annual emergency visits were similar between the two groups (0.76 vs. 0.82, p=0.2). There was a $4300 (2012 $CAN) difference in the mean annual cost between cases and controls. Conclusions: Survivors in the MOC transition program used fewer health system resources and had lower health system costs when compared to controls. These findings provide real world evidence to inform transition policies for cancer survivors.
A cohort study of risk factors, clinical presentations, and outcomes for dermatophyte, nondermatophyte, and mixed toenail infections
Authors: Nuntida Salakshna, Sumanas Bunyaratavej, Lalita Matthapan, Kamonpan Lertrujiwanit, Charussri Leeyaphan
Journal: Journal of the American Academy of Dermatology (2018)
Epidemiology and Outcomes of Granulomatosis With Polyangiitis in Pediatric and Working‐Age Adult Populations In the United States
Authors: Sirada Panupattanapong, Dustin L. Stwalley, Andrew J. White, Margaret A. Olsen, Anthony R. French, Mary E. Hartman
Journal: Arthritis & Rheumatology (2018)

Objective The incidence and prevalence of granulomatosis with polyangiitis (GPA) in the US is not well characterized. Owing to its rarity, outcomes data in pediatric‐onset GPA are also lacking. The aims of this study were to describe the epidemiology of GPA and outcomes in GPA patients in the US, and to compare outcomes between pediatric and working‐age adult patients. Methods A retrospective cohort study using the 2006–2014 Truven Health Analytics MarketScan Commercial Claims and Encounters Database was conducted. The incidence and prevalence rates of pediatric and adult GPA (age &lt;65 years) were calculated. Outcomes among the 2 age groups were analyzed. Results A total of 5,562 cases of GPA were identified, of which 214 (3.8%) were pediatric onset and 5,348 (96.2%) were adult onset. The incidence rate of pediatric‐onset GPA was 1.8 cases per 1 million person‐years, compared to 12.8 cases per 1 million person‐years in working‐age adults. There was a slight female preponderance in both groups (63% and 53% among pediatric and adult GPA patients, respectively). Rates of hospitalization and severe infections were high in both children and working‐age adults, but children had more frequent hospitalizations (rate ratio [RR] 1.3 [95% confidence interval (95% CI) 1.1–1.4]) and 2–3‐times higher rates of leukopenia (RR 2.6 [95% CI 1.5–4.3]), neutropenia (RR 2.2 [95% CI 1.2–4.0]), and hypogammaglobulinemia (RR 3.7 [95% CI 2.0–6.4]). Time‐to‐event analyses showed no differences in the time to hospitalization, severe infection, major relapse, or end‐stage renal disease. Conclusion This study represents the largest cohort of GPA reported to date. Pediatric GPA patients experienced more frequent hospitalizations and were more vulnerable to hematologic complications than non‐elderly adult patients.
Progress and challenges in the prevention and control of nonalcoholic fatty liver disease
Authors: Jingjing Cai, Xiao‐Jing Zhang, Hongliang Li
Journal: Medicinal Research Reviews (2018)

Abstract Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide. Individuals with NAFLD have a high frequency of developing progressive liver disease and metabolism‐related comorbidities, which result from of a lack of awareness and poor surveillance of the disease and a paucity of approved and effective therapies. Managing the complications of NAFLD has already begun to place a tremendous burden on health‐care systems. Although efforts to identify effective therapies are underway, the lack of validated preclinical NAFLD models that represent the biology and outcomes of human disease remains a major barrier. This review summarizes the characteristics and prevalence of the disease and the status of our understanding of its mechanisms and potential therapeutic targets.
EA5142 adjuvant nivolumab in resected lung cancers (ANVIL): The newest study in the ALCHEMIST platform.
Authors: Jamie E. Chaft, Suzanne Eleanor Dahlberg, David E. Gerber, Geoffrey R. Oxnard, Shakun M. Malik, Charles B. Simone, Martin J. Edelman, John Heymach, Charles M. Rudin, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2017)

TPS8575 Background: There have been no advances in the systemic treatment of resected lung cancers in the last decade. This is in contrast to advanced disease where molecularly targeted therapies for patients with oncogene-driven tumors have replaced and/or delayed chemotherapy and where immunotherapy drugs that target the programmed death receptor pathway (PD-1 or PD-L1) are now utilized in first and second line. The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) is a National Cancer Institute (NCI) sponsored National Clinical Trials Network (NCTN) initiative to address the role of genomic testing and personalized therapies in the adjuvant treatment of non-small cell lung cancers. EA5142 is the newest of the ALCHEMIST studies, 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). In ALCHEMIST-Screening, up to 8,000 patients with pathologically confirmed stage IB (≥ 4 cm)-IIIA NSCLC will be enrolled either before or 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 utilizing immunohistochemistry (DAKO 28-8). Adjuvant therapy is allowed but not required. Patients are randomized to nivolumab 240 mg IV over 3 minutes every 2 weeks for up to 1 year versus standard of care observation, stratified by stage, histology, prior adjuvant treatment, and PD-L1 status ( &gt; / = 1% or &lt; 1%). ANVIL has enrolled 52 of 714 planned patients to detect co-primary endpoints of a 30% improvement in overall survival and/or a 33% reduction in disease free survival favoring nivolumab. EA5142 is currently open at over 400 centers nationwide. Clinical trial information: NCT02595944.
Effect of neoadjuvant chemotherapy and recombinant tumor necrosis factor -thymosin – α 1 (TNF-T) on overall survival in patients with triple negative breast cancer (TNBC).
Authors: Liubov Yu Vladimirova, Oleg I. Kit, Ludmila A. Ryadinskaya, Natalia Podzorova, Kristina A. Novoselova, Natalya A Abramova, Irina L. Popova, Natalya Mikhailovna Tikhanovskaya, Anna E Storozhakova, Aza A. Lyanova
Journal: Journal of Clinical Oncology (2018)

e12625 Background: The data on TNF - drugs used in neoadjuvant treatment in breast cancer patients especially on its effect on survival is very few. Meanwhile some trials show that immunotherapy could be effective in patients with TNBC .The purpose of the study was to evaluate the 5-year OS in patients with TNBC receiving neoadjuvant chemotherapy (NACT) with TNF-T. Methods: Eligibility criteria were IIB-IIIB stages of TNBC , ECOG≤1, adequate liver, kidney and bone marrow function, no brain metastases. Recombinant protein of TNF-T 200000 IU was used peritumorally (injected around the tumor) on D1-5 (30 min before cytostatics injection), combined with standard FAC or PA regimens. RFC and OS were evaluated by the Kaplan- Meier method and assessed by the log-rank test in the STATISTICA 12.0 program (StatSoft Inc.). Results: 82 women were recruited between April 2012 – October 2013 (mean age 53.3±1.1 years). Group A (30 pts) received recombinant protein of TNF-T combined to PA (17) and FAC (13) up to 6 courses. Group B (52pts) received standard PA (21) and FAC (31). Tumor response (TR) in Group A was 80% and in Group B 71.9% (p < 0.05), including CR 15% and 6.25%, correspondingly (p < 0.05). All pts of the main group received surgery, with no TNF-T-associated complications. Median of RFS in Group A was 57 ± 1,4 mos, in Group B was 48± 1,4 mos. (Log-Rank test p = 0,03). Median OS in Group A was 59±1,8 (29-65 mos.), in Group B was 53±1,3 (6-59 mos.) (Log-Rank test p = 0,02). Conclusions: TNF-T injected peritumorally allows to increase the antitumor activity of cytostatics (pCR) which is of great importance for survival in TNBC. NACT combined with TNF-T is found to effect on RFS as well as OS in these patients.
Ridesharing and Text Messaging for Patients With Medicaid—Further Information
Authors: Katherine Rediger, Michael Albert, D. R. Bailey Miles
Journal: JAMA Internal Medicine (2018)

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Non-melanoma skin cancer in childhood cancer survivors previously treated with radiotherapy: Clinical findings, histology, and management.
Authors: Stefanie Thorsness, Azael Freites-Martinez, Mario E. Lacouture, Michael A. Marchetti, Christian P. Navarrete-Dechent, Emily S. Tonorezos
Journal: Journal of Clinical Oncology (2018)

131 Background: Radiotherapy is a well-known risk factor for non-melanoma skin cancer (NMSC), but whether diagnosis, histologic features, or natural history of NMSC after radiotherapy resemble those observed in the general population is unknown. This study aims to describe clinical findings, histology, and management of NMSC on the skin of childhood cancer survivors previously treated with radiotherapy. Methods: A retrospective chart review (2000-2017) was performed including adult survivors of childhood cancer referred to the Adult Long-Term Follow-Up Program or the dermatology service at Memorial Sloan Kettering Cancer Center. Data was obtained from electronic medical records, including demographics, histologic subtype and treatment received for NMSC (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)). Clinical features were assessed with clinical images. Results: 960 (mean age 40 years, SD ± 13) patients were assessed for the diagnosis of BCC/SCC after radiotherapy for cancer. The mean age of cancer diagnosis was 15 years (range: birth-39 years). The most common primary diagnosis was Hodgkin lymphoma. 82 patients developed NMSC; 67 of these developed NMSC in the field of prior radiotherapy. 283 in-field lesions were counted, of which 275 were BCC and 8 were SCC. Of the 275 BCC, 261 (95%) were primary lesions and 14 (5%) were recurrent lesions. All SCC were primary lesions. Based on clinical images, 30% of BCC were clinically pigmented; the most common presentation was macule (46%). The mean intervals for BCC and SCC from time of radiotherapy to diagnosis of the first in-field lesion were 24 years (range, 2-44 years) and 32 years (range, 14-46 years), respectively. Histologically, superficial subtype was most prevalent in the BCC subgroup, comprising 47% of all cases. Mohs surgery was the most common therapy (43% of BCC cases; 37% of SCC cases). Conclusions: Among survivors of childhood and young adult cancer, BCC was the most prevalent NMSC. Most of BCC arising in sites of prior radiotherapy for cancer treatment were of low-risk histologic subtype and had low rates of recurrence. An expanded role for topical therapy may be appropriate, but further research is needed.
Beating the odds: programming proliferation in the mammalian heart
Authors: Rajan Jain, Andrey Poleshko, Jonathan A. Epstein
Journal: Genome Medicine (2018)

The heart is one of the least regenerative organs in the human body; adult cardiac myocytes divide at extremely low frequency. Therefore, meaningful induction of cardiac regeneration requires in-depth understanding of myocyte cell-cycle control. Recent insights into how myocytes can be coaxed into duplicating in vivo might inform emerging therapeutics.
Surveillance for Late Effects in Childhood Cancer Survivors
Authors: Wendy Landier, Roderick Skinner, W. Hamish Wallace, Lars Hjorth, Renée L. Mulder, F. Lennie Wong, Yutaka Yasui, Nickhill Bhakta, Louis S. Constine, Smita Bhatia, Leontien C. Kremer, Melissa M. Hudson
Journal: Journal of Clinical Oncology (2018)

Many childhood cancer survivors carry a significant risk for late morbidity and mortality, a consequence of the numerous therapeutic exposures that contribute to their cure. Focused surveillance for late therapy-related complications provides opportunities for early detection and implementation of health-preserving interventions. The substantial body of research that links therapeutic exposures used during treatment of childhood cancer to adverse outcomes among survivors enables the characterization of groups at the highest risk for developing complications related to specific therapies; however, methods available to optimize screening strategies to detect these therapy-related complications are limited. Moreover, the feasibility of conducting clinical trials to test screening recommendations for childhood cancer survivors is limited by requirements for large sample sizes, lengthy study periods, prohibitive costs, and ethical concerns. In addition, the harms of screening should be considered, including overdiagnosis and psychological distress. Experts in several countries have developed guideline recommendations for late effects surveillance and have collaborated to harmonize these recommendations internationally to enhance long-term follow-up care and quality of life for childhood cancer survivors. Methods used in these international efforts include systematic literature searches, development of evidence-based summaries, rigorous evaluation of the evidence, and formulation of consensus-based surveillance recommendations for each late complication. Alternate methods to refine recommendations, such as cumulative burden assessment and risk prediction and cost-effectiveness modeling, may provide novel approaches to guide survivorship care in this vulnerable population and, thus, represents a worthy objective for future international survivorship collaborations.
Yoga as a survivorship tool in cancer patients and caregivers.
Authors: Winston Tan, Meghna Ailawadhi
Journal: Journal of Clinical Oncology (2018)

90 Background: Preliminary data suggest that yoga is one of the most popular complementary and alternative therapies and most likely to improve quality of life. In spite of the methodologic limits,studies suggest an improvement in a range of symptoms of patients with cancer among those who did yoga. The absence of side effects and the excellent cost-benefit ratio make it a very interesting symptom management tool. Methods: We advertised to our cancer patients the availability of a free yoga class twice a week. (August 2016-present). This was run by one trained instructor. All patients with different cancers were allowed to participate including caregivers. A post session survey was done at one time point to evaluate the benefits of the class. Results: Usually between 8-15 individuals attend the class. In one session a written survey was conducted, 13 patients/caregiver agreed to fill up the survey. 9 were patients (breast , sarcoma, lymphoma, brain tumor melanoma and spine tumor) and 5 were caregivers.4 never had any prior yoga class before, the reasons for attending the class included stress relief, improve balance, help pain, support spouse, suggestion by MD and exercise. Among those who answered the question 7 were new to yoga 0-3 month, they mainly did restorative and gentle yoga. The perceived benefits among attendees included being more relaxed, calm down, peaceful, increase strength, more mindful and better health. 8/13 perceived that it did improve quality of life very much, 3/13 quite a bit 1 a little. All were very satisfied with the yoga sessions. Conclusions: In an undifferentiated group of cancer patients, yoga classes participants have positive perceived benefits in majority of the individuals who did restorative/gentle yoga. This led to symptom control and also had significant participant satisfaction.