tbuckley/cabot-search huggingface dataset:
A randomized phase III study of duration of anti-PD-1 therapy in metastatic melanoma (STOP-GAP): Canadian Clinical Trials Group study (CCTG) ME.13.
Authors: Tara D. Baetz, Xinni Song, D. Scott Ernst, Elaine McWhirter, Teresa M. Petrella, Kerry J. Savage, Michael Smylie, Ralph Wong, Christopher W Lee, Nicole Look Hong, Diane Logan, Muhammed Saleem Raza, Tahir Abbas, Dora Nomikos, Roger Leung, Bingshu E. Chen, Janet Dancey
Journal: Journal of Clinical Oncology (2018)

TPS9600 Background: Efficacy of the anti-PD -1 agents has been demonstrated in metastatic melanoma in phase I-III trials. During the development of these trials there was no optimal duration of treatment identified. Trials stopped therapy due to unacceptable side effects, investigator's choice, at a specific time point typically at 24 months of therapy or at disease progression. Clinical reports suggest that stopping treatment early due to toxicity may not adversely impact efficacy. In addition, there is evidence that retreatment with immunotherapy may be clinically effective. Unnecessary long term therapy may result in a higher risk of toxicity, diminished quality of life (QoL) and will impact the cost-effectiveness of the therapy. We hypothesize that treatment to maximum tumour response will result in non-inferior overall survival with better QoL, less toxicity and lower cost than continuous therapy. Methods: This is a large, simple randomized phase III trial evaluating the duration of anti-PD-1 therapy in metastatic/unresectable melanoma. Consenting patients must be eligible to receive anti- PD-1 inhibitor as standard of care. Patients are randomized 1:1 to either standard 24 months of therapy in the absence of disease progression versus treatment until maximum tumour response (MTR) with retreatment at the time of progression. MTR is determined by at least two radiologic measurements three months apart. Eligibility criteria are broad to reflect a "real world" patient population. Data collection is streamlined to focus on key endpoints. The primary endpoint is overall survival. Secondary endpoints are PFS, response rate, adverse event rate, health related QoL and economic analysis. Patients are stratified based on line of therapy, stage of disease, BRAF status, LDH level, prior use of adjuvant therapy, anti-PD -1 inhibitor selected and the presence of CNS metastases. The trial will enroll 550 patients with 275 in each arm. It is expected that accrual will last 5.5 years. Currently 78 patients have been enrolled. Clinical trial information: NCT02821013..
SAT0167 Safety of once-weekly alendronate 70 mg in periodontal disease
Authors: T Van Dyke, M Ryder, R Cordero, A Gallagher, G Griffiths, S Offenbacher, G Cizza, W Shih, M Kimberlin, L Meng, A Lombardi
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Periodontal disease, the leading cause of tooth loss in adults, is a chronic inflammatory process which leads to a local imbalance between bone formation and bone resorption. Alendronate sodium (ALN) is a potent and selective inhibitor of osteoclastic bone resorption used for the treatment and prevention of osteoporosis in postmenopausal women. In postmenopausal osteoporotic women, ALN 70 mg once weekly has demonstrated efficacy comparable to those of ALN 10 mg daily and very good safety and tolerability. However, there has been no direct comparison between ALN 70 mg once weekly and placebo. <h3>Objectives</h3> <h3>Methods</h3> To further investigate the safety profile of once weekly ALN, as well as efficacy in periodontal disease, we are conducting a randomised, placebo-controlled, multicenter, 2-year study. Three-hundred and thirty-five patients aged 30 to 79 with periodontal disease were randomised to either placebo (PBO) or ALN 70 mg once weekly. <h3>Results</h3> The overall and upper gastrointestinal (GI) safety and tolerability profile of ALN after one year of treatment was very favourable compared to placebo. Table 1: <h3>Conclusion</h3> In summary, 1-year data show that ALN 70 mg once weekly was very well tolerated in men and women with moderate to severe periodontal disease.
Predicting overall survival (OS) and progression-free (PFS) for oropharynx cancers (OPC) in NRG Oncology RTOG0129/0522 with nomograms.
Authors: Carole Fakhry, Qiang Zhang, Maura L. Gillison, Phuc Duy Nguyen, David Ira Rosenthal, Randal S. Weber, Louise Lambert, Andy Trotti, William Barrett, Wade Thorstad, Sue S Yom, Stuart J. Wong, John A. Ridge, Shyam S. Rao, James A. Bonner, Eric Vigneault, David Raben, Jonathan Harris, Quynh-Thu Le
Journal: Journal of Clinical Oncology (2016)

6024 Background: Therapeutic de-intensification for OPC underscores the need for accurate patient-specific assessment of risk. Current risk stratification is based on HPV tumor status, tobacco use, nodal and tumor stage. These do not include other important predictors of prognosis. Therefore, a patient-specific approach to estimate survival was explored. Methods: Patients with T2-T4, N0-N3 OPC enrolled in RTOG0129 or 0522, available p16 immunohistochemistry (surrogate for HPV) and tobacco history were eligible for retrospective analysis of factors associated with OS and PFS. RTOG0129 compared standard versus accelerated fractionation (AFX) cisplatin based chemoradiation, and RTOG0522 compared cisplatin-AFX ± cetuximab. Nomograms were created based on Cox proportional hazards regression models. Concordance index was used for model discrimination and validation. Results: Study population included 493 patients. Factors independently associated with worse OS included age > 50, poor performance status (Zubrod 1), p16 negativity, ≤ high school education, > 10 pack-years tobacco, anemia, advanced tumor (T4) and nodal stage (N2c-3). Significant interactions were observed including p16 and performance status. All these factors, along with marital status and gender were included into a nomogram to estimate 2- and 5-year OS based upon the absence or presence of each of these patient characteristics. Factors significantly associated with PFS were similar, with the addition of weight loss ≥ 5% and marital status. A nomogram that accounts for the relative contribution of each of these prognostic factors provides 2- and 5-year estimates of PFS. Both nomograms had high concordance indices (0.76 for OS, 0.70 for PFS) and were well calibrated. Conclusions: The developed nomograms incorporate an expanded list of prognostic factors and allow for individual patient-specific estimates of OS and PFS. Use of these nomograms will facilitate decision-making for patients and providers and will refine patient selection criteria for de-intensification trials.
Panobinostat and carfilzomib cytotoxicity in IDH-mutant human chondrosarcoma.
Authors: Gabriel Tinoco, Ana Cristina Paz-Mejia, Luyuan Li, Breelyn A. Wilky, Jonathan C. Trent
Journal: Journal of Clinical Oncology (2016)

11027 Background: Chondrosarcomas are malignant bone tumors that produce cartilaginous matrix and are chemo and radiotherapy resistant. 70% of conventional and 54% of dedifferentiated subtypes harbor IDH1 or IDH2 mutations. This result in elevated levels of the oncometabolite 2-HG. There are no FDA approved agents to treat advanced conventional chondrosarcomas. Panobinostat (pan-HDAC inhibitor) and Carfilzomib (Selective proteasome inhibitor) have shown activity as single agents in human IDH-mutant chondrosarcoma cell lines (HICCL). We hypothesized this two active agents may have a synergistic cytotoxic effect in HICCL Methods: Using quantitative high-throughput drug library screening we identified and validated novel agents with anticancer effects in HICCL. A library of 150 epigenetic drugs was used. Panobinostat and Carfilzomib were chosen for further validation due to their activity. Three HICCL, JJ012 and HT1080 with endogenous IDH1 mutations (R132G and R132C respectively), SW1353 with endogenous IDH2 R172S mutation and a human chondrocyte cell line C28 with wild type IDH were used. Panobinostat (0,4.5,9,18,36,72,144 nM) and Carfilzomib (0,4,8,16,32,64,128) as single or in combination were added in a checker board fashion and viability was assessed after 72 hours using MTS CompuSyn software was used to determine IC50 and synergy. The synergistic combination was used to assess colony formation and apoptosis Results: IC50 for Panobinostat in JJ012, HT1080, SW1353 and C28 was 31.2, 141.3, 17.7 and 19.6 nM respectively; IC50 for Carfilzomib in JJ012, HT1080 and C28 was 58.4, 24.5, 13.7 and 16.6 nM respectively. The best synergistic combination of Panobinostat/Carfilzomib had an effect near to 3% cell viability for JJ012 , HT1080, SW1353 and C28 was 18 nM / 64nM, 36nM /8nM, 36nM /16nM, 18nM /16nM respectively. We found a significant difference in cell viability when the combination was compared with single agent: JJ012 (p < 0.001) , HT1080 (p < 0.0001), SW1353 (p < 0.001). The colony formation and apoptosis were also affected Conclusions: Our study showed that carfilzomib and panobinostat have a significant synergistic cytotoxic effect against HICCL. The effects of these compounds are dose and time dependent
TCT-604 Outcome of High Risk Percutaneous Coronary Intervention: Gender-Based Analysis
Authors: Amir Kaki, M Chadi Alraies, Nimrod Blank, Reema Hasan, Wah Wah Htun, Marvin Kajy, Ahmed Subahi, Mahir Elder, Cindy Grines, Theodore Schreiber
Journal: Journal of the American College of Cardiology (2018)
Health care disparities among octogenarians and nonagenarians with stage III lung cancer.
Authors: Richard John Cassidy, Xinyan Zhang, Pretesh R Patel, Joseph W Shelton, Sibo Tian, Conor Ernst Steuer, Rathi Narayana Pillai, Suresh S. Ramalingam, Taofeek Kunle Owonikoko, Seth D Force, Felix G Fernandez, Theresa Wicklin Gillespie, Walter J Curran, Kristin Ann Higgins
Journal: Journal of Clinical Oncology (2017)

e18075 Background: Octogenarians and nonagenarians with stage III lung cancer are underrepresented in randomized trials that established the standard of care therapy of concurrent chemoradiation (CRT). The purpose of this study was to investigate factors predictive of and the impact on overall survival (OS) following CRT among patients ≥80 years old with stage III non-small cell lung cancer (NSCLC) in the National Cancer Data Base (NCDB). Methods: In the NCDB, patients ≥80 years old from 2004 to 2013 with stage III NSCLC were queried. Logistic regression, Kaplan-Meier method, and Cox-proportional hazard regression analyses were performed as well as propensity-score matched (PSM) analysis to reduce treatment selection bias. Results: A total of 12,641 stage III NSCLC patients ≥80 years old were identified with complete treatment and OS records; 7,921 (62.7%) received no treatment, 1,153 received definitive radiation alone (9.1%), and 3,567 (28.2%) received CRT. On multivariable analysis (MVA), black race, female gender, advancing age, residence in a lower-educated county, adenocarcinoma histology, and patients with stage IIIB tumors were associated with receiving no anti-cancer therapy while treatment at an academic facility and lower comorbidity status were associated with receiving anti-cancer treatment (all p &lt; 0.05). On MVA, male gender, advancing age, non-adenocarcinoma histology, higher tumor grade, larger tumors, advancing T and N stage, stage IIIB tumors (vs. IIIA), delayed start to CRT, and not receiving CRT were associated with worse OS (all p &lt; 0.05). OS rates at 1 and 5 years was 53.7% and 10.1% respectively for patients receiving CRT compared to 16.4% and 3.3% respectively for all other therapies (p &lt; 0.01). PSM analysis confirmed that not receiving CRT was associated with worse OS (HR = 1.23, 95% CI 1.11-1.34; p &lt; 0.01). Conclusions: A significant portion of patients ≥80 years old with stage III NSCLC do not receive treatment. Black race, female gender, advancing age, and residence in a lower-educated county were associated with not receiving therapy. In this NCDB series, OS is higher in patients ≥80 years old receiving CRT, even when adjusting for patient- and tumor-related factors.
Association of pre-existing thyroid autoimmunity with the development of thyroid dysfunction induced by nivolumab.
Authors: Shiro Kimbara, Yutaka Fujiwara, Shintaro Iwama, Ken Ohashi, Aya Kuchiba, Hiroshi Arima, Naoya Yamazaki, Shigehisa Kitano, Noboru Yamamoto, Yuichiro Ohe
Journal: Journal of Clinical Oncology (2018)

9091 Background: Thyroid dysfunction (TD) induced by immune checkpoint inhibitors is not sufficiently understood. The purpose of this study was to identify risk factors and the clinical course of TD induced by nivolumab. Methods: Patients with advanced solid tumors who were treated with nivolumab from March 2009 through March 2016 at the National Cancer Center Hospital were eligible. Thyroid function and anti-thyroid antibodies from the preserved serum samples among patients treated with nivolumab were evaluated retrospectively. The biochemical diagnosis of TD was determined in accordance with the guidelines of ATA, AACE, and the Endocrine Society. We defined thyroid autoimmunity as presence of anti-thyroid antibodies including anti-thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb) before nivolumab. Results: One-hundred and eighty-nine patients with advanced solid tumors who were treated with nivolumab from March 2009 through March 2016 at the National Cancer Center Hospital were eligible for this study. Twenty-three (12%) of 189 patients developed TD, including 17 cases of hypothyroidism and 20 of thyrotoxicosis. Thyrotoxicosis followed by hypothyroidism occurred in 14 cases. There were significant difference between patients who developed TD (n = 23) and who did not (n = 166) in thyroid autoimmunity (p < 0.001) and elevated TSH (p = 0.01) at baseline. Next, we performed further analysis among 168 patients with sufficient assessment of anti-thyroid antibodies. Fourteen of 35 patients (40%) with thyroid autoimmunity developed TD, versus nine of 133 (7%) without (odds ratio 9.19; 95% confidence interval [CI]: 3.53-23.9). In multivariate analysis, elevated TSH and TgAb at baseline were significantly associated with the development of TD, with odds ratios of 7.36 (95% CI: 1.66-32.7) and 26.5 (95% CI: 8.18-85.8), respectively. Interestingly, thyrotoxicosis followed by thyrotoxicosis did not develop in 5 of 6 patients who received steroid therapy on the onset of thyrotoxicosis due to any reasons such as other irAEs and a symptom relief for brain metastasis. Conclusions: Patients with preexisting TgAb and elevated TSH before nivolumab treatment were at high risk for TD.
Efficacy and safety of low-dose everolimus in Chinese HR-positive, HER2-negative metastatic breast cancer patients.
Authors: Xiying Shao, Yabing Zheng, Zhan-Hong Chen, Guangliang Li, Wang Xiao Jia
Journal: Journal of Clinical Oncology (2018)

e13035 Background: Everolimus has been testified to be effective among women with hormone receptor-positive human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (MBC). However, everolimus at dose of 10mg was accompanied by a higher incidence of mTOR-inhibitor class-effect adverse events (AEs) which usually leading to dose reduction or interruption. Additionally, some studies suggested that there was no correlation between dose intensity (5 vs. 10 mg labeled dose) and efficacy. Consequently, we conducted the present study aiming to explore the efficacy and safety of everolimus at dose of 5 mg plus endocrine therapy in Chinese population. Methods: 68 HR+/HER2- MBC patients were included in this exploratory study who received everolimus at the dose of 5mg in Zhejiang Cancer Hospital between September 2014 and September 2017. Progression free survival(PFS) and overall survival(OS) were estimated by the Kaplan- Meier method, and the hazard ratios(HRs) and corresponding 95% confidence intervals(CIs) were estimated using the Cox proportional harzard model. Objective response rate(ORR), clinical benefit rate(CBR) and safety profile were also evaluated. Results: After a median follow up of 14 months, PFS was 5.3months (95%CI 4.2-6.4), and OS was immature. 16(23.5%) were at the first or second-line, 52(76.5%) were at third-line or later. PFS for the first and second-line is significantly longer than that for the third-line or later (12.9months vs. 4.6months, P= 0.009, HR = 0.395, 95% CI = 0.192-0.811). 11(16.2%) achieved partial response (PR), 42(61.7%) had stable disease (SD), and 15(22.1%) reported progressive disease (PD). The ORR and CBR were 16.2%, 35.2%, respectively. Most common all grade adverse events were stomatitis(26.5%), fatigue(10.0%), infection(11.8%), thrombocytopenia(5.9%), anemia(4.4%), hyperglycemia(4.4%). The most common ≥3 grade adverse events were stomatitis(4.4 %), infection(2.2%). Conclusions: The combination of low-dose everolimus and endocrine therapy was highly effective especially at the earlier line in Chinese population. And the safety profiles were similar to previous studies but the incidences were greatly lower.
Identifying chemotherapy-induced peripheral neuropathy (CIPN) and its treatment using claims data: A URCC NCORP and NIH Collaboratory study.
Authors: Jennifer S. Gewandter, James Marshall, Jeffrey Brown, Lesley H. Curtis, Robert H. Dworkin, Ian Kleckner, Noah Kolb, Gary R. Morrow, Karen Michelle Mustian, Supriya Gupta Mohile
Journal: Journal of Clinical Oncology (2018)

e18707 Background: Investigating CIPN prevention and treatment strategies is a high priority that could be pursued with claims data. However, no studies have investigated the feasibility of identifying CIPN cases using claims, possibly due to a perception of low billing for CIPN by oncologists. We investigated the feasibility of using claims and administrative data from 1 national and 2 regional insurers participating in the NIH Health Care Systems Research Collaboratory Distributed Research Network to identify patients who developed neuropathy or began taking 3 neuropathic analgesics after starting chemotherapy. Methods: Patients with no record of any of 20 ICD-9/10 codes related to peripheral neuropathy (PN codes) 6 months prior to their first chemotherapy dose were eligible (data from Jan 2006 – Dec 2016; n = 352,528). The percentage of patients with any PN code up to 6 months after chemotherapy initiation was calculated for patients receiving neurotoxic chemotherapies (i.e., platinums, taxanes, vinca alkaloids, bortezomib) and non-neurotoxic chemotherapies. National drug codes were used to identify new prescriptions for gabapentin, pregabalin, and duloxetine within 6 months of chemotherapy initiation. Results: Patients receiving neurotoxic chemotherapy had a higher incidence of PN codes than those receiving non-neurotoxic chemotherapy (20% vs. 7%, p < 0.0001). The percentages of patients receiving neurotoxic vs. non-neurotoxic chemotherapies who were dispensed the analgesics were as follows: (1) gabapentin: 7% vs. 1.7% (p < 0.0001); (2) pregabalin: 0.7% vs. 0.3% (p < 0.0001); and (3) duloxetine: 0.8% vs. 0.8% (p = 0.5). Analyses separated by year yielded similar results. Conclusions: This study is the first to show that it is feasible to identify CIPN cases using national and regional claims data. Further investigation of the sensitivity and specificity of this method by comparing claims and clinical data is necessary. This study showed that duloxetine, the only drug with demonstrated efficacy for CIPN (published in 2013), was prescribed 8.7 times less frequently than gabapentin after initiation of a neurotoxic chemotherapy. Funding: UG1CA189961 / U24AT009676-01
Pooled Analysis of Nine Cohorts Reveals Breast Cancer Risk Factors by Tumor Molecular Subtype
Authors: Mia M. Gaudet, Gretchen L. Gierach, Brian D. Carter, Juhua Luo, Roger L. Milne, Elisabete Weiderpass, Graham G. Giles, Rulla M. Tamimi, A. Heather Eliassen, Bernard Rosner, Alicja Wolk, Hans-Olov Adami, Karen L. Margolis, Susan M. Gapstur, Montserrat Garcia-Closas, Louise A. Brinton
Journal: Cancer Research (2018)

Abstract Various subtypes of breast cancer defined by estrogen receptor (ER), progesterone receptor (PR), and HER2 exhibit etiologic differences in reproductive factors, but associations with other risk factors are inconsistent. To clarify etiologic heterogeneity, we pooled data from nine cohort studies. Multivariable, joint Cox proportional hazards regression models were used to estimate HRs and 95% confidence intervals (CI) for molecular subtypes. Of 606,025 women, 11,741 invasive breast cancers with complete tissue markers developed during follow-up: 8,700 luminal A–like (ER+ or PR+/HER2−), 1,368 luminal B–like (ER+ or PR+/HER2+), 521 HER2-enriched (ER−/PR−/HER2+), and 1,152 triple-negative (ER−/PR−/HER2−) disease. Ever parous compared with never was associated with lower risk of luminal A–like (HR, 0.78; 95% CI, 0.73–0.83) and luminal B–like (HR, 0.74; 95% CI, 0.64–0.87) as well as a higher risk of triple-negative disease (HR, 1.23; 95% CI, 1.02–1.50; P value for overall tumor heterogeneity &amp;lt; 0.001). Direct associations with luminal-like, but not HER2-enriched or triple-negative, tumors were found for age at first birth, years between menarche and first birth, and age at menopause (P value for overall tumor heterogeneity &amp;lt; 0.001). Age-specific associations with baseline body mass index differed for risk of luminal A–like and triple-negative breast cancer (P value for tumor heterogeneity = 0.02). These results provide the strongest evidence for etiologic heterogeneity of breast cancer to date from prospective studies. Significance: These findings comprise the largest study of prospective data to date and contribute to the accumulating evidence that etiological heterogeneity exists in breast carcinogenesis. Cancer Res; 78(20); 6011–21. ©2018 AACR.