tbuckley/cabot-search huggingface dataset:
Improving recruitment in 11 challenging oncology RCTs using the QuinteT Recruitment Intervention.
Authors: Jenny Donovan
Journal: Journal of Clinical Oncology (2018)

e18635 Background: Randomized controlled trials (RCTs) are the most rigorous approach for evaluating healthcare interventions, but many fail to recruit to target. Few interventions to improve recruitment have been transferrable across RCTs. The QuinteT Recruitment Intervention (QRI) aims to optimize recruitment and informed consent. It was developed in the recently published ProtecT prostate cancer RCT comparing surgery, radiation therapy and active monitoring in 1,643 men. It has been applied in 10 other challenging Phase III oncology RCTs involving comparisons between surgery, radiation therapy, chemotherapy, and conservative or no active intervention. Methods: In the QRI, data are collected intensively to understand recruitment - patient log data, interviews with investigators/recruiters, and audio-recordings of appointments in which recruiting clinicians/nurses present the RCT to patients and seek their consent to participate. These data are analyzed rapidly, presented to the chief investigator, and together with the QuinteT team, a plan of actions to improve recruitment and informed consent is developed. Actions include facilitating discussions about practical obstacles, exploring difficult issues related to patient eligibility and clinician equipoise, and providing confidential feedback to recruiters about how best to present the RCT and communicate with patients. Data on numbers of eligible patients approached and recruited are reviewed and compared with targets and achievements over time. Results: Recruitment in the initial periods of these 11 oncology RCTs were below target, sometimes threatening closure. After implementation of the QRI, recruitment in eight RCTs improved: five completed recruitment to a main trial or feasibility study and three continue to recruit at or above target. In one main and three feasibility RCTs, QRI data provided clear reasons for the need to cease recruitment promptly (e.g. insurmountable difficulty with equipoise/insufficient numbers of eligible patients). Conclusions: Formal evaluation of the QRI is required, but its results so far suggest it has potential to address recruitment difficulties in some of the most challenging RCTs in oncology.
INPP5a expression as a prognostic marker in cutaneous squamous cell carcinoma (cSCC).
Authors: Helen J Liang, David J DiCaudo, Jessica E Schmidt, Mark R. Pittelkow, Aleksandar Sekulic, Aaron R Mangold
Journal: Journal of Clinical Oncology (2018)

e21567 Background: Inositol Phosphate 5-Phosphatase (INPP5A) is a membrane-associated type I inositol phosphatase that has been shown to play a role in development and progression of cutaneous squamous cell carcinoma (cSCC) and oropharyngeal SCC. The goal of the current study is to explore the utility of INPP5A in predicting clinical outcomes in cSCC, focusing on tumor characteristics and outcome in relation to INPP5A expression. Methods: A total of 155 cases of actinic keratoses and SCCs from 145 patients were identified and immunohistochemical (IHC) staining was performed for INPP5a. All cases were reviewed and INPP5a levels scored by a board-certified dermatopathologist (DJD). INPP5A expression of tumors was defined relative to adjacent normal tissue and if no adjacent normal tissue was present, relative to a normal epidermis control. 0 = complete loss of expression; 1 = significantly diminished; 2 = partially diminished; 3 = normal INPP5a expression. Patient charts were reviewed for demographics, tumor characteristics, and outcome. Results: The majority of tumors (144/155, 92.9%) had an INPP5a score of 2 or 3, while a minority (11/155, 7.1%) had a score of 1. No patients had complete loss of INPP5a. Patients with INPP5a score of 1 were more likely to be immunosuppressed, compared to patients with INPP5a scores of 2 or 3 (54.5% vs. 15.6%, p = 0.0059). Tumors with INPP5a score of 1 compared to scores of 2 or 3 were much more likely to be intermediate to high risk (BWH stage T2a and above 90% vs 11.2%, p < 0.0001), have larger diameter (2.8 cm vs. 1.0 cm, p < 0.0001), moderate to poor differentiation (75% vs. 8.1%, p < 0.0001), and perineural invasion (50% vs. 2.7%, p = 0.0001). The overall survival for patients with tumors with INPP5a score of 1 is significantly worse than patients with tumors with INPP5a score of 2 or 3 with a 3-year survival of 22.2% vs 71.4% (HR = 2.56, p = 0.0126). Conclusions: INPP5a scores on initial tumor biopsy are predictive of aggressive tumors and may be a useful adjunct to guide clinical management of cSCC. Tumors that express low levels of INPP5a are more likely to be high-risk, exhibiting features such as large clinical tumor size, poor differentiation, perineural invasion, and are associated with a poor overall survival.
Self-reported burden of lung cancer for patients who experienced considerable weight loss vs. those who did not.
Authors: Ana Maria Rodriguez, Julia Braverman, Pronabesh Dasmahapatra, Elizabeth M Duus, John Friend
Journal: Journal of Clinical Oncology (2016)

e21608 Background: The objective of this study was to compare the self-reported disease burden and experiences of patients with advanced non-small cell lung cancer (NSCLC) who reported considerable weight loss ( ≥ 5% of their body weight in the past 6 months or ≥ 2% for a BMI less than 20 kg/m2) to those who did not. Methods: 95 members of PatientsLikeMe patients community (age mean = 59; 81% females; 81% US residents) with self-reported diagnosis of advanced NSCLC completed an online survey that assessed health-related quality of life (QLQ-C15-PAL), ECOG Performance Status, anorexia-cachexia symptoms/concerns (FAACT A/CS domain), distress levels, clinical/demographic characteristics (including height and past and current weight), and impact of weight loss (open-ended questions). Results from patients with and without weight loss were compared using chi-squared test, a t-test or a Kruskal-Wallis test, as appropriate. Results: 35 (36.3%) patients were classified as having considerable weight loss at the time of the survey and 60 (63.2%) were classified without. 48 (51%) patients self-rated their ECOG Performance Status as 1, and 58 (61%) patients indicated not receiving either chemotherapy or radiotherapy at the time of the survey. Patients with weight loss reported significantly (p < 0.05) lower overall quality of life (55.2 vs. 66.9), worsened anorexia-cachexia symptoms/concerns (30.7 vs. 36.0), and higher symptomology, specifically fatigue (64.8 vs. 49.1), nausea (19.5 vs. 9.2), and appetite loss (41.0 vs. 23.9) – than patients without weight loss. In addition, significantly more patients who lost weight reported moderate/high distress levels than patients who did not (71% vs. 38%). Main worries for patients with weight loss included loss of energy and disease progression. Conclusions: Our results support that weight loss represents a substantial problem for NSCLC patients, associated with lower quality of life, higher distress level and more severe symptoms, particularly in terms of fatigue, nausea, and appetite loss. Interventions targeted at maintaining/increasing body weight may help to improve well-being and reduce key symptoms in advanced NSCLC patients with considerable weight loss.
Prognostic signature of lung adenocarcinoma based on the expression of immune-associated genes.
Authors: Xiaoshun Shi, Di Lu, Siyang Feng, Xiaoying Dong, Xiguang Liu, Jin Li, Allen Menglin Chen, Kaican Cai
Journal: Journal of Clinical Oncology (2018)

e24260 Background: Tumor cells altered certain immune related genes to mimic the function of immune cells, which involving in tumor development and having impact on patient's survival. Though the immunotherapy of tumors has been widespread concerned, prognostic model of lung adenocarcinoma based on immune genes have not been established and reported. Methods: We initially downloaded RNAseq raw data from TCGA lung adenocarcinoma dataset to identify gene expression in significant difference, and then filtered out the immune related genes in the ImmPort database. By using the lasso algorithm and the multi factor Cox analysis, 5 candidate genes was settled as lung adenocarcinoma immune prognosis model. The specificity and sensitivity of the model was tested by comparing published model. Results: We identified 5 markers (MAP3K8, CCL20, VEGFC, ANGPTL4, ADM2) that could predict the overall survival of lung adenocarcinoma patients (HR = 95% CI: P < 0.001).The model is verified by the microarray data and the predictability is superior to previously reported gene models. Conclusions: In this study, we identified an immune-related gene prognostic model, which is expected to become a practical, independent and accurate prognostic model for lung adenocarcinoma. It has potential value in predicting survival and guiding adjuvant chemotherapy.
Pulse-continuous dose erlotinib as initial targeted therapy for patients with <i>EGFR</i>-mutant lung cancers with untreated brain metastases.
Authors: Mark G. Kris, Kathryn Cecilia Arbour, Gregory J. Riely, Ai Ni, Kathryn Beal, Mariza Daras, Sara A. Hayes, Robert J. Young, Christopher R Rodriguez, William Pao, Helena Alexandra Yu
Journal: Journal of Clinical Oncology (2017)

9039 Background: Clarke (Neurooncol 2010) reported responses with intermittent high pulse doses of erlotinib (leading to higher concentrations in CSF) given to patients with EGFR-mutant central nervous system metastases developing on standard erlotinib doses. In a phase 1 study of pulse-continuous dose erlotinib, no patient developed progression in existing or new brain or leptomeningeal metastases (Yu Ann Oncol 2016). This phase 2 trial tested pulse-continuous dose erlotinib in patients with lung cancers with EGFRmutations with brain metastases. Methods: Patients had no prior EGFR TKI or radiation to the brain and at least 1 target brain metastasis. All received initial daily "pulse" doses of erlotinib 1200 mg days 1&amp;2 and "continuous" 50 mg doses days 3-7 (doses and schedule from the Yu Phase 1 study), weekly until progression. The co-primary endpoints were overall and brain metastasis response by RECIST 1.1. Results: We enrolled 19 patients with EGFR-mutant lung cancers: median age 61yrs (range 45-80), 74% women, 95% Karnofsky PS ≥80%, 1 leptomeningeal disease, 33% prior pemetrexed-based chemotherapy. The median size of target brain metastases was 13 mm (range 10-19 mm). 32% were on dexamethasone for cerebral edema. The partial response rate overall was 74% (95% CI 51-89%) and also 74% in brain metastases. Of 10 patients with progression, 9/10 occurred in non-brain sites (4 EGFRT790M, 1 with progression in brain as well), 1 with leptomeningeal. The median progression free survival was 10 mo (range 7-NR mo). Pulse doses were reduced in 68% (median delivered pulse dose 1050 mg days 1&amp;2, range 600-1200 mg). Incidences of any gradeof rash and diarrhea were 84% and 63% respectively. There were no grade 4 or 5 toxicities. Conclusions: Pulse-continuous dose erlotinib alone controlled brain and leptomeningeal metastases in 89% (95% CI 67-98%) of patients with EGFR-mutant lung cancers with central nervous system spread pretreatment, with an overall response rate of 74% and progression free survival and rates of rash and diarrhea comparable to series with erlotinib 150 mg daily. Supported by Astellas, CA 129243, CA 008748. NCT01967095 Clinical trial information: NCT01967095.
Phase I study of apatinib combined with docetaxel in <i>EGFR</i>-negative advanced non-small cell lung cancer (NSCLC).
Authors: Jianchun Duan, Jie Wang, Zhijie Wang, Lin Lin, Junling Li, Yan Wang, Xingsheng Hu, Yutao Liu
Journal: Journal of Clinical Oncology (2018)

e21184 Background: Chemotherapy combined with antiangiogenic agents such as bevacizumab and ramucirumab has been shown to bring overall survival benefit for advanced NSCLC patients (pts). Apatinib is a small-molecule TKI mainly targeting VEGFR-2. This phase I trial was designed to determine the optimal dose of apatinib and potential efficacy in pts treated with this agent plus docetaxel combination for advanced NSCLC. Methods: This phase I dose escalation study enrolled pts with EGFR-negative stage IV NSCLC who were treated with platinum-based doublet previously. Pts received oral apatinib daily in a 3+3 dose escalation design (250, 500 and 750 mg) plus docetaxel at 60 mg/m² every 3 weeks. Previous study (Oncotargets Ther, 2017(10): 1821-1825) demonstrated the safety and efficacy of apatinib at 500 mg in advanced NSCLC. Thus, apatinib dose was not escalated to 750 mg in this study. Dose-limiting toxicity (DLT) was defined as the presence of grade 4 hematological and/or grade ≥ 3 non-hematological toxicities during the first cycle. Results: Between May 2016 and April 2017, 9 pts, with median age of 49 years, were enrolled to 2 dose levels: 250 mg (n = 3), 500 mg (n = 6, with 3 additional pts recruited for safety concern). The median duration of combined treatment was 2.7 (2.6-2.8) mos. No dose modification occurred, and 4 pts experienced dose interruption (2 in 250 and 2 in 500 mg). No 1-cycle DLT was reported in both dose groups. The most commonly occurred adverse events (AEs) of all grades were blood bilirubin increased (66.7%), hypertension (44.4%) and γ-glutamyltransferase increased (44.4%). 2 pts were found with grade 3 hypertension, which was the most common grade 3/4 AEs. All 9 pts were available for response evaluation: 3 had partial response and 6 had stable disease, achieving an objective response rate of 33.3% and a disease control rate of 66.7%, at beast response. The median progression-free survival of 9 pts was 2.9 (95%CI, 1.7-3.3) mos. Conclusions: Apatinib at 500 mg is safe and tolerable in pts with advanced NSCCL when combined with docetaxel. The preliminary results also demonstrated the efficacy of apatinib plus docetaxel in previously treated advanced NSCLC. Clinical trial information: NCT02691871.
Comparison of biochemical recurrence free survival after radical prostatectomy triggered by grade reclassification on active surveillance, and men newly diagnosed with similar grade disease.
Authors: Clarissa P. Diniz, Ballentine Carter, Jonathan I. Epstein, Mufaddal Mamawala
Journal: Journal of Clinical Oncology (2017)

5047 Background: Evaluate the biochemical recurrence free survival (bRFS) in men after radical prostatectomy (RP) triggered by Gleason score (GS) grade reclassification (GR) during active surveillance (AS) in order to inform patient decisions. Methods: We conducted a retrospective analysis of men undergoing RP from 1995 - 2015 at Johns Hopkins and identified 4 groups; 94 men in AS that underwent RP following GR from Gleason score (GS) 6 to GS ≥ 7(3+4) [grade groups ≥ 2], 3,504 men that underwent IRP following a diagnosis of grade groups ≥ 2, 56 men in AS that underwent RP following GR to GS 7(3+4) [grade group 2], and 1,979 men that underwent IRP following a diagnosis of grade group 2. The outcome of interest was bRFS, assessed using Kaplan Meir analysis and a multivariate Cox regression model. Results: Men on AS had a lower PSA density distribution (0.11 vs. 0.13, p = 0.022; 0.12 vs. 0.12, p = 0.043), and a higher proportion of low volume cancers (46.2% vs. 15.3%, 46.4% vs. 16.7%, both p &lt; 0.001) as compared to the IRP groups for both biopsy grade groups ≥ 2 and biopsy grade group 2, respectively. The proportions of men with biochemical recurrence (BCR) in the AS and IRP groups were 13.8% vs. 29.1% (p = 0.008 for grade groups ≥ 2) and 8.9% vs. 21.7% (p = 0.022 for grade group 2), respectively. One, 5, 10-year bRFS for men in the AS group vs the IRP group was 97.9%, 76.6%, 69.0% vs 85.5%, 65.1% ,54.2%%, respectively for biopsy grade groups ≥ 2 (log-rank test, p = 0.009), and 96.4%, 89.6%, 89.6% vs 91.2%, 74.0%, 63.9%, respectively for biopsy grade group 2 (log-rank test, p = 0.071). For biopsy grade groups ≥ 2, there was no significant difference in BCR between groups after adjustment for age at treatment, biopsy extent of cancer, and PSA density; HR = 0.78 (95% CI 0.43 – 1.43, p = 0.426). Conclusions: AS patients that are reclassified to grade groups ≥ 2 have no greater risk of treatment failure as compared to men newly diagnosed with similar grades. These data could help inform decisions regarding management of low grade prostate cancer.
P40 Analysis of Family Clustering in Lung Cancer (LC): Genetic Cancer Risk Assessment (GRCA) into the Thoracic Oncology Unit
Authors: G. Pacheco Cuellar, S. Campos-Gomez, K. Campos-Gomez, J.J. Valdés-Andrade, J.L. Barrera Franco
Journal: Journal of Thoracic Oncology (2018)
TCT-412 Side Branch Intervention for Non-Left Main True Bifurcation Lesions: Pooled Analysis of Korean Multicenter Drug-Eluting Stent Cohort
Authors: Gyu Chul Oh, Jeehoon Kang, Jung-Kyu Han, Han-Mo Yang, Kyung Woo (KW) Park, Bon-Kwon Koo
Journal: Journal of the American College of Cardiology (2018)
Emotion and Symptom-focused Engagement (EASE): A randomized pilot trial of an integrated psychosocial and palliative care intervention for individuals with acute leukemia (AL).
Authors: Gary Rodin, Carmine Malfitano, Anne Rydall, Christopher Lo, Aaron David Schimmer, Charles Marmar, Camilla Zimmermann
Journal: Journal of Clinical Oncology (2017)

7041 Background: Individuals diagnosed with AL may experience severe physical and psychological distress due to the illness and its treatment, the threat of relapse and treatment failure, and a high risk of mortality. To alleviate psychological and physical distress in this population, we developed a novel, 8-week, manualized intervention called EASE. This includes: 1) EASE-psy- a tailored psychotherapeutic component to reduce psychological distress; and 2) EASE-phys-symptom screening, with moderate to severe physical symptoms triggering early palliative care. Methods: To assess the feasibility and preliminary efficacy of EASE, patients were recruited within 2 weeks of admission to a comprehensive cancer center and randomized to receive either EASE or usual care (UC). Physical and psychological symptoms were assessed at baseline, 4, 8 (primary endpoint), and 12 weeks. Intervention patients received 6-10 psychotherapy sessions over 8 weeks, weekly assessment of physical symptoms, and consultation and follow-up by palliative care, when needed. One-way ANOVA was performed to assess mean change scores over time between groups. Results: Forty-two patients were randomized to EASE (n = 22) or UC (n = 20). Predefined feasibility outcomes were all met: &gt; 86% (19/22) of EASE participants (goal &gt; 64%) completed &gt; 50% of proposed EASE-psy sessions; 64% (14/22) completed symptom screenings (goal &gt; 50%); and 100% of those with moderate to severe symptoms had &gt; 1 meeting with the EASE-phys team (goal 100%). There were statistically significant findings favoring EASE vs. UC for satisfaction with care at 8 and 12 weeks (Δ: -3.12 vs 7.39, p &lt; 0.04; -6.1910 vs 0.0125 p &lt; 0.03). There were trends favoring EASE vs. UC for traumatic stress symptoms, depressive symptoms, quality of life, attachment security, and number, severity, and distress related to physical symptoms at 4, 8, and 12 weeks. Conclusions: Although not powered for statistical significance, this randomized pilot trial of EASE for AL showed promising reductions in psychological and physical distress and supports the feasibility and need for a larger randomized controlled trial. Clinical trial information: NCT02353559.
Elevated circulating NKT cells in penile carcinoma.
Authors: Felipe Da Silva Marinho, Felipe Barros, Leuridan Torres, Fernando A Soares, Gustavo Cardoso Guimaraes
Journal: Journal of Clinical Oncology (2016)

e23019 Background: Natural killers T (NKT) cells are a subset of lymphocytes that with activation and effector properties and they share some similarities with NK cells. This group of cells can react against tumour cells and the antitumour imune response. NKT cells have a role in tumours immunosurveillance.The aim of the study was to evaluate the percentile values of circulating NKT cells in patients with penile carcinoma. Methods: Were evaluated 18 patients with penile cancer (aged above 35) followed in the Uro-oncology unit of HCP from January to September/2015. Was performed collection of peripheral blood of patients and 10 healthy controls men. We used monoclonal antibodies anti-CD3, anti- anti-CD56 and anti-CD16 for immunophenotyping of Natural Killer T cells (NKT). The analyses were performed in FACSVERSE equipment (BD Bioscience). Statistical analysis between groups, was used Mann Whitney test using Graphpad 6.0 program.Was considered significant P < 0.05. Results: Patients with penis cancer had elevated percentile values of NKT cells (p = 0.0036) when compared to healthy controls (Figure 1A). The patients presented similar percentile values of T cells (p = 0.81) and NK cells (p = 0.16) to healthy controls Conclusions: Patients with advanced penile cancer have elevated circulating NKT lymphocytes. This suggests that patients may present reduced levels of these cells in the tumor infiltrate and is associated with a poor prognosis. In the tumor microenvironment, NKT cells influence antitumor responses by secreting cytokines and direct tumoricidal activity with significant inhibition of tumor growth, even in the absence of other cytotoxic lymphocytes.
Long-term results of a prospective phase II study of androgen deprivation therapy, external radiation, cs-131 brachytherapy, and adjuvant docetaxel in high-risk prostate cancer.
Authors: Stephanie Rice, Gloribel K Le, Arif Hussain, Heather Dorothy Mannuel, Michael K Naslund, Pradip P. Amin, Young Kwok
Journal: Journal of Clinical Oncology (2017)

5079 Background: We report the long-term results of a prospective, Phase II study of 2 years androgen deprivation therapy (ADT), 45 Gy bone marrow sparing pelvic radiation (BMS-PR), Cs-131 brachytherapy boost (85 Gy), and 4 cycles of adjuvant docetaxel (75 mg/m2 q21d + prednisone) in high risk, localized prostate cancer. Methods: From2006-2014,38 patients were enrolled. Acute hematologic as well as acute and chronic gastrointestinal (GI) and genitourinary (GU) toxicities were scored based on the CTCAE v3.0 criteria. Biochemical recurrence was defined as a nadir + 2 rise in PSA. Actuarial freedom from PSA failure (bNED) and overall survival (OS) were calculated using SPSS v24. Median Gleason score was 8 (74% Gleason 8-10). Median PSA was 11.2 (range 2.8-96). Results: A total of 38 patients were enrolled on the trial. Median age was 62 years (range 45-82). 82% of patients completed all protocol specified treatments, while 84% completed all 4 cycles of docetaxel. After a median follow up of 44 mo (range 3.4-118), the 5-year bNED rate was 86% while 5-year OS was 80%. Acute grade ≥ 2 GI and GU toxicity rates were 12.5% and 21.9%, respectively. Chronic grade ≥ 2 GI and GU toxicity rates were 3.1% and 3.1%, respectively. 25.6% (n = 10) patients receiving docetaxel developed grade 4 hematologic toxicity. There were no grade 5 toxicities. Conclusions: We found this aggressive multi-modal approach to be feasible, safe, well-tolerated, and effective. It does not appear that BMS-PR decreases hematologic toxicity. Cs-131, with its 9.7 day half-life, does not appear to increase acute or late toxicity. These data build upon the ASCENDE-RT and RTOG 0521 trials that demonstrate the added benefits of brachytherapy boost and adjuvant docetaxel, respectively, in high-risk prostate cancer.