tbuckley/cabot-search huggingface dataset:
NRG-HN003: Phase I and expansion cohort study of adjuvant cisplatin, intensity-modulated radiation therapy (IMRT), and MK-3475 (Pembrolizumab) in high-risk head and neck squamous cell carcinoma (HNSCC).
Authors: Julie E. Bauman, Jonathan Harris, Ravindra Uppaluri, Min Yao, Robert L. Ferris, Josephine Chen, Richard C. Jordan, Nikhil Purushottam Joshi, Srinivas Jujjuvaparu, Dukagjin Blakaj, Mohammad Razaq, Jawad Sheqwara, Loren K. Mell, Neilayan Sen, David Anthony Clump, Madhur Garg, Emrullah Yilmaz, Quynh-Thu Le
Journal: Journal of Clinical Oncology (2019)

6023 Background: Pembrolizumab, an anti-PD1 monoclonal antibody, improves survival in advanced HNSCC. Patients with pathologic high risk, HPV-negative HNSCC have a high recurrence rate despite adjuvant cisplatin-IMRT (CRT), the current standard. Immunosuppression is induced by HNSCC and CRT, and may be reversible by targeting PD1. Methods: We conducted a phase I trial with expansion cohort to determine the recommended phase II schedule (RP2S) for adding fixed-dose pembrolizumab to adjuvant CRT (NCT02775812). Eligibility: oral cavity, pharynx, or larynx primary; HPV-negative; pathologic high risk (positive margin or extranodal extension [ENE]); Zubrod 0-1. During phase I, patients enrolled in descending cohorts of 12 (Table). RP2S was declared if ≤ 3 dose-limiting toxicities (DLT) occurred. DLT was defined as ≥ Grade 3 non-hematologic adverse event (AE) related to pembrolizumab, immune-related (ir)AE requiring &gt; 2 weeks of systemic steroids, or unacceptable delay in IMRT. The expansion cohort enrolled 20. Results: From Nov 2016-Oct 2018, 34 eligible patients enrolled at 22 NRG institutions. During the first cohort, 1 DLT was observed (Grade 3 fever). RP2S was declared as Schedule 3 and the expansion cohort triggered. Among all 34 patients, median age was 60 years (26-83); 68% were male; 74% had Zubrod 1; 85% had oral cavity; 88% had ENE; 21% had positive margin. During expansion, 3 additional patients with DLT were observed: wound infection; diverticulitis; nausea. No DLT unacceptably delayed IMRT. Twenty-eight of 34 (82%) received ≥ 5 doses of pembrolizumab; 17 (50%) got all 8 doses. Thirty-one of 32 (97%) DLT-evaluable patients received all adjuvant RT; 1 withdrew consent after starting protocol. Conclusions: The RP2S is pembrolizumab 200 mg IV q 3 weeks for 8 doses, starting the week before adjuvant CRT. This regimen was safe and feasible in a cooperative group setting. irAE were rare in this population. Clinical trial information: NCT02775812. [Table: see text]
“Not Shared” Need Not Mean “Not Patient Centered”: Deciding That a Patient Is Not a Candidate—Reply
Authors: Susan P. Y. Wong, Ann M. O’Hare
Journal: JAMA Internal Medicine (2019)

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AB1366-HPR THE EFFECTS OF LAND AND WATER BASED MULTIDIMENSIONAL FUNCTIONAL MOBILITY EXERCISES ON PULMONARY FUNCTIONS IN ANKYLOSING SPONDYLITIS PATIENTS
Authors: Baris Gurpinar, Nursen Ilcin, Sema Savci, Nurullah Akkoc
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Pulmonary manifestations are common in ankylosing spondylitis (AS) yet there is not enough evidence about the results of different interventions on pulmonary functions. <h3>Objectives</h3> The aim of this study was to evaluate the pulmonary effects of land and water based multidimensional functional mobility exercises on pulmonary functions in AS patients. <h3>Methods</h3> This is a single-blinded, randomized and experimental study conducted in outpatient clinic and thermal center. A total of 38 patients with definite ankylosing spondylitis according to the modified New York criteria were recruited for the study Patients were randomly allocated to aquatic (AG) and land (LG) exercise group twice in a week for 8 weeks. Pulmonary Function Tests (PFT), maximal inspiratory mouth pressure (MIP), and maximal expiratory mouth pressure (MEP) were measured before and after the intervention. <h3>Results</h3> 3 patients from AG and 6 from LG missed 4 sessions consecutively. In AG, PEF (p=0.004), VC (p=0.025), MVV (p=0.006) and MIP (p=0.001) improved significantly on the other hand in LG FEV1/FVC (0.049), PEF (p=0.007) and MVV (p=0.004) significantly increased. <h3>Conclusion</h3> Performing multidimensional functional mobility exercises in water and on land could have different results. Exercising in water could have additional benefits such as increasing inspiratory muscle strength. <h3>References</h3> [1] Berdal G, Halvorsen S, van der Heijde D, Mowe M, Dagfinrud H. Restrictive pulmonary function is more prevalent in patients with ankylosing spondylitis than in matched population controls and is associated with impaired spinal mobility: a comparative study. Arthritis research &amp; therapy. 2012;14(1):R19. [2] Gyurcsik ZN, Andrs A, Bodnr N, Szekanecz Z, Sznt S. Improvement in pain intensity, spine stiffness, and mobility during a controlled individualized physiotherapy program in ankylosing spondylitis. Rheumatology International. 2012;32(12):3931-6. [3] Altan L, Bingl, Aslan M, Yurtkuran M. The effect of balneotherapy on patients with ankylosing spondylitis. Scandinavian Journal of Rheumatology. 2006 2006/01/01;35(4):283-9. [4] van Tubergen A, Hidding A. Spa and exercise treatment in ankylosing spondylitis: fact or fancy? Best Practice &amp; Research Clinical Rheumatology. 2002 2002/09/01;16(4):653-66. [5] Seckin U, Bolukbasi N, Gursel G, Eroz S, Sepici V, Ekim N. Relationship between pulmonary function and exercise tolerance in patients with ankylosing spondylitis. Clinical and experimental rheumatology. 2000;18(4):503-6. <h3>Disclosure of Interests</h3> None declared
Patient-reported outcomes of patients treated with (neo)adjuvant immune checkpoint combination therapy in high-risk stage III macroscopic melanoma: A matched cohort study.
Authors: Annelies H. Boekhout, Katarzyna Józwiak, Elisa A. Rozeman, Silvie HM Janssen, Lonneke V van de Poll-Franse, Christian U. Blank
Journal: Journal of Clinical Oncology (2019)

9588 Background: Results from the phase 1b (OpACIN) study comparing neoadjuvant to adjuvant ipilimumab (3mg/kg) plus nivolumab (1mg/kg) demonstrated a high clinical activity of neoadjuvant treatment in high-risk melanoma. However, the toxicity was high, with 90% grade 3 to 4 toxicity. These findings raise questions about long-term quality of life (QoL) in these patients (pts) who were treated with curative intent. Here we present the first analysis of patient-reported outcomes of patients treated with (neo)adjuvant immune checkpoint combination therapy. Methods: Sixteen of 20 pts had completed study treatment and were currently in follow-up (FU). Pts were asked to fill in The European Organisation for Research and Treatment of Cancer QoL questionnaire-C30 (QLQ-C30). The QLQ-C30 was used to assess health-related QoL and is composed of functional, symptomatic dimensions and a dimension of global health/QoL. A reference population (controls without a diagnosis of cancer) was obtained from the ‘Patient Reported Outcomes Following Initial treatment and Long term Evaluation of Survivorship’ registry. Pts were individually matched on age, gender, education and marital status with up to 9 controls. Pts and controls were compared on QLQ-30 scores using univariable linear regression analyses. Results: Thirteen out of 16 invited pts (81% response) returned a completed questionnaire. Median FU was 30 months after randomization. Pts scored significantly lower in emotional (std coeff. = -1.0, p = .007), role (std coeff. = -0.7, p = .08), cognitive (std coeff. = -0.8, p = .018) and social (std coeff. = -1.0, p = .014) functioning and higher in symptom burden of fatigue (std coeff. = .9, p = .024) compared to controls, which were all clinically relevant. The physical functioning and global QoL score did not differ between pts and controls. Conclusions: High risk stage III melanoma pts treated with (neo)adjuvant immune checkpoint combination therapy showed significantly lower emotional, role, cognitive and social functioning scores than controls. Pts reported higher levels of fatigue, however, there was no difference on physical functioning and global QoL between pts and controls.
Low-fat dietary pattern and long-term breast cancer incidence and mortality: The Women’s Health Initiative randomized clinical trial.
Authors: Rowan T. Chlebowski, Aaron K Aragaki, Garnet L Anderson, Kathy Pan, Marian L Neuhouser, JoAnn E Manson, Cynthia A. Thomson, Yasmin Mossavar-Rahmani, Dorothy Lane, Karen Johnson, Jean Wactawski-Wende, Snetselaar Linda, Thomas E Rohan, Juhua Luo, Ana Barac, Ross L Prentice
Journal: Journal of Clinical Oncology (2019)

520 Background: Observational studies of dietary fat intake and breast cancer have inconsistent findings. To address this issue, the Women’s Health Initiative (WHI) Dietary Modification (DM) clinical trial assessed a low-fat dietary pattern influence on breast cancer incidence and outcome. Methods: The WHI DM trial is a randomized, controlled clinical trial conducted at 40 US centers, where 48,835 postmenopausal women, aged 50-79 years, with no previous breast cancer and dietary fat intake ≥32% of total energy, were randomly assigned, from 1993-1998, to a usual diet comparison group (60%) or dietary intervention group (40%) with goals to reduce fat intake to 20% of energy and increase vegetables, fruit, and grain intake. This study is registered as: NCT00000611. Results: The dietary intervention significantly reduced fat intake; increased fruit, vegetable and grain intake with modest weight loss (3%) (all P&lt; 0.001). During 8.5 years of dietary intervention, there were 8% fewer breast cancers and deaths from breast cancer were somewhat lower in the intervention group but the rates were not significantly different. However, deaths after breast cancer (breast cancer followed by death from any cause) were significantly reduced in the intervention group, both during intervention (hazard ratio [HR] 0·65 95% confidence interval [CI] 0·45-0·95) and through 16.1 year (median) cumulative follow-up. Now, after long- term, cumulative 19.6 year (median) follow-up, with 3,374 incident breast cancers, the significant reduction in deaths after breast cancer continued (with 1,011 deaths, HR 0·85 95% CI 0·74-0·96) and a significant reduction in deaths from breast cancer (breast cancer followed by death attributed to the breast cancer) emerged (with 383 deaths, HR 0·79 95% CI 0·64-0·97). Conclusions: Adoption of a low-fat dietary pattern associated with increased vegetable, fruit, and grain intake, demonstrably achievable by many, significantly reduced the risk of death from breast cancer in postmenopausal women. To our review, these findings provide the first randomized clinical trial evidence that a dietary change can reduce a postmenopausal woman’s risk of dying from breast cancer. Clinical trial information: NCT00000611.
A phase I study of MGMT-P140K transfected hematopoetic progenitor cells (HPC) combined with TMZ/O6BG dose escalation for newly diagnosed, MGMT unmethylated glioblastoma: Tolerance and evidence of survival benefit.
Authors: Andrew E. Sloan, Lisa Roger, Chris Murphy, Jane Reese, Hillard M. Lazarus, Boro Dropulic, Stanton L. Gerson
Journal: Journal of Clinical Oncology (2019)

2062 Background: GBM is the most common malignant brain tumor with a median survival of 15 months despite surgery and radio-chemotherapy. The most important mechanism of TMZ resistance is the O 6 -methylguanine-DNA methyltransferase (MGMT) gene which repairs temozolamide-induced DNA methylation. The MGMT inhibitor O 6 -benzylguanine (BG) demonstrated efficacy in depleting MGMT and maximizing tumor response in early phase clinical trials. However, MGMT expression is also low in hematopoietic cells, so this approach led to unacceptable bone marrow toxicity and thus has been abandoned. We hypothesized that chemoprotection of hematopoietic HPC with an MGMT mutant (MGMT-P140K) characterized by normal methyltransferase activity, coupled with low affinity for BG would maximize anti-tumor response while enabling patients to tolerate TMZ &amp; BG dose escalation with minimal toxicity. A phase I trial was performed to test this hypothesis. Methods: 10 adults with newly diagnosed MGMT unmethylated, IDH-1 WT, GBM underwent standard surgery and radiation, followed by transplantation with autologous CD34 + HPC engineered to express MGMT-P140K using a lentiviral vector. We tested tolerance and efficacy of three different paradigms for conditioning bone marrow and re-infusion of HPC. To assess chemo-protection, patients’ blood counts and transgene marking were monitored during and after treatment, as was toxicity, response, and progression-free and overall survival. Results: Treatment was moderately toxic with 3/10 patients suffering grade 3-4 hematologic toxicity; no high grade non-hematologic toxicity was observed . Viral transduction rates ranged from 3-75% and were clearly improved in Arm III utilizing BCNU conditioning and intra-patient dose escalation of TMZ/O6GB. In patients tolerating 3 cycles or more, P140K-MGMT gene markings in peripheral blood and bone marrow cells increased 3-26-fold with only mild (Grade 2-3) mylosuppression consistent with chemo-protection as hypothesized. Median PFS and OS was 22 and 31 months respectfully, and three patients in Arm III are healthy and progression free at 36-39 months. OS exceeded RPA predicted survival by 3.3-fold suggesting clinical benefit. Viral insertion site analysis demonstrate lack of clonal dominance. Conclusions: P140K-MGMT transfected HPC enables TMZ/ BG dose escalation with acceptable toxicity and increased survival in a small cohort of selected patients. A phase II study is ongoing. Clinical trial information: NCT01269424.
PL3.3 Second interim and first molecular analysis of the EORTC randomized phase III intergroup CATNON trial on concurrent and adjuvant temozolomide in anaplastic glioma without 1p/19q codeletion
Authors: M J van den Bent, S Erridge, M A Vogelbaum, A K Nowak, M Sanson, A A Brandes, W Wick, P M Clement, J F Baurain, W Mason, H Wheeler, M Weller, K Aldape, P Wesseling, J M Kros, C M S Tesileanu, V Golfinopoulos, T Gorlia, B G Baumert, P J French
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The 1st interim analysis of the CATNON trial showed benefit from adjuvant (adj) temozolomide (TMZ) on overall survival (OS) but remained inconclusive about concurrent (conc) TMZ. A 2nd interim analysis was planned after 356 events. MATERIAL AND METHODS The 2x2 factorial design phase III CATNON trial randomized 751 adult patients with newly diagnosed non-codeleted anaplastic glioma to either 59.4 Gy radiotherapy (RT) alone; the same RT with concTMZ; the same RT and 12 cycles of adjTMZ or the same RT with both concTMZ and adjTMZ (doi: 10.1016/S0140-6736(17)31442-3). MGMT promoter methylation (MGMTmeth) status was re-assessed with the Infinium Methylation EPIC Beadchip using the MGMT_STP27 model. Isocitrate dehydrogenase 1 and 2 (IDH) mutation (mt) status was assessed with glioma targeted Agilent SureSelect baits sequence using an Illumina HiSeq2500 Rapid PE100. RESULTS With a median follow-up of 56 months and 356 events, the hazard ratio (HR) for OS adjusted for stratification factors after concTMZ was 0.968 (99.1% CI 0.73, 1.28). 5-year OS was 50.2% with and 52.7% without concTMZ (95% CI [44.4, 55.7] and [46.9, 58.1]). An IDHmt was found in 335 of 480 assessed cases (70%). Median OS was 19 mo (95% CI 16.3, 22.3) in IDHwt tumors and 116 mo (95% CI 82.0, 116.6) in IDHmt tumors. The interaction test based on IDH status was significant (p=0.016) in the univariate HR analysis for OS after concTMZ (IDHwt, n=145, events=120, HR = 1.27, 95% CI 0.89, 1.82, p=0.19; IDHmt, n=335, events=92, HR= 0.67, 95% CI 0.44, 1.03, p=0.06). IDHmt was predictive of benefit from adjTMZ (IDHmt HR: 0.41, 95% CI 0.27, 0.64; IDHwt: HR 1.05, 95% CI 0.73, 1.52; interaction test p = 0.001). In IDHmt patients that received adjTMZ, the HR for OS after concTMZ was 0.71 (95% CI 0.35, 1.42, p=0.32). MGMTmeth was found in 288 of 410 assessed cases (70%), interaction test for concTMZ (p = 0.092) and adjTMZ (p = 0.166) did not reach statistical significance. CONCLUSION In the entire study cohort, concTMZ did not increase OS. However, in IDHmt tumors a trend towards benefit of concTMZ is present. AdjTMZ increased OS in IDHmt but not in IDHwt tumors. Further analyses and follow-up will allow full assessment of efficacy in the molecular subgroups.
Birmingham trust and Babylon Health discuss pre-A&amp;E triage app
Authors: Elisabeth Mahase
Journal: BMJ (2019)

An NHS trust in Birmingham has said that it is in talks with the technology company Babylon Health about expanding its services to the city, including whether its software could be used to triage patients attending emergency departments.

University Hospitals Birmingham NHS Foundation Trust is considering whether a modified version of Babylon’s AI symptom checker,1 currently designed for primary care, could be used to “triage out” avoidable attendances that present at emergency departments, to combat growing demand.

The collaboration between the trust and …
Burden and etiologies of 30-day readmission after bone marrow transplant: Insights from National Readmission Database.
Authors: Naveen Premnath, Karan Sud, Sathish Kumar Pondaiah, Arjun Gupta
Journal: Journal of Clinical Oncology (2019)

e13106 Background: With more centers getting accredited as a bone marrow transplant (BMT) unit, attention has shifted to healthcare care quality metrics such as readmissions. Previous studies have shown high rates of 30-day readmission to be associated with worse long term survival. Except a few single center studies there is no viable data for readmissions for patients undergoing BMT. Methods: This is a retrospective cohort study using the National Readmission Database (NRD) for 2014. All adults with index admission for BMT (autologous and allogenic) were included. Exclusion criteria was age &lt; 18 years, mortality during index admission and inter-hospital transfers. ICD 9 codes were used to identify diagnoses and procedures. Results: A total of 3,972 admissions for BMT were identified. Among these 2,462 underwent autologous (AU) and 1,510 underwent allogenic (AL) transplant, respectively. 30-day readmission rate was 8.6% in AU and 8.2% in AL group. The mean age was 55.9 years and 47.8 years in the AU and AL group, respectively. About 40.5% were females in the AU group and 44.4% in the AL group. Major co-morbidities included Smoking (22.7% in AU and 19.1% in AL), diabetes (13.8% in AU and 12.4% in AL), chronic kidney disease (10% in AU and 4.3% in AL) and prior irradiation (5.7% in AU and 4.5% in AL). Mean length of stay during the index admission was 18 days in AU and 26 days in AL group. Principle diagnosis for undergoing transplant was found as multiple myeloma (59.2% in AU) and AML (25.2% in AL). Major etiologies for readmission were neutropenia (26.9% in AU and 15.8% in AL) followed by Infectious etiologies 26% in AU and 20.4% in AL group, nausea and vomiting 4.3% in AU and 3.2% in AL group. Dehydration accounted for 5.7% in AU group and mucositis 5.7% in AL group. Conclusions: There is a significant readmission rate in this study population. 30-day readmissions in this population are primarily due to neutropenia and infectious etiologies including sepsis and pneumonia. Nausea, vomiting and dehydration played a major role in both categories and remain a major targetable group. We believe there is a dire need for major studies to further evaluate risk factors and predictors for readmission and their impact on overall survival. [Table: see text]
Trends in immunotherapy use and survival impact in stage IV non-small cell lung cancer.
Authors: Zachary Otaibi, Amir Kamran, Rodney E Wegner, Athanasios Colonias, Benny Weksler, Gene Grant Finley
Journal: Journal of Clinical Oncology (2019)

e20715 Background: Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. 5-year survival rate for metastatic non-small cell lung cancer (NSCLC) is estimated at 4%. For patients who lack a driver mutation, platinum based chemotherapy had been the cornerstone treatment, but the addition of immunotherapy has altered the treatment landscape for many advanced NSCLC patients. Immunotherapy, with or without chemotherapy, has been demonstrated in many clinical trials to extend survival in both the first-line setting as well as subsequent lines of therapy. While the clinical trial data over the past several years has been robust, less is known about how these agents have fared in routine clinical practice. To understand this better, we utilized the National Cancer Data Base (NCDB) to examine the survival of patients who received immunotherapy for stage IV NSCLC. Methods: We queried the NCDB from 2004-2015 for patients with stage IV NSCLC treated with chemotherapy and at least 3 months of follow-up. Multivariable logistic regression was used to determine predictors of immunotherapy use. Multivariable cox regression was used to determine predictors of overall survival. A propensity score was calculated and used to mitigate indication bias. Results: Of 203,069 eligible patients, 5,877 received immunotherapy. The median age was 65 years (40-90). The median follow up was 10.6 months (3-154). Patients were more likely to receive immunotherapy if they were younger, had a lower comorbidity score, received treatment at an academic facility, had adenocarcinoma histology, private insurance, Caucasian race, and a more recent treatment year. The use of immunotherapy rose steadily across the dataset years, rising from 1% to 12%. Predictors of survival were younger age, lower comorbidity score, lower grade tumor, treatment at an academic facility, higher education, higher income, private insurance, metropolitan location, immunotherapy use, adenocarcinoma histology, and more recent year of treatment. On propensity-matched Kaplan-Meier analysis patients treated with immunotherapy in addition to chemotherapy had improved survival, 13.7 months compared to 11.8 months, p &lt; 0.0001. Conclusions: This analysis demonstrates improved overall survival in stage IV NSCLC patients who received immunotherapy. There are inherent limitations of retrospective analyses of data from large databases, however the survival improvement noted in this study is concordant with the more robust prospective clinical research published to date.