tbuckley/cabot-search huggingface dataset:
Nonadherence of adjuvant radiation in NSCLC patients with N2 disease after lobectomy.
Authors: Yan Xing, Bin S. Teh, Angela Zhu, Weiyuan Mai
Journal: Journal of Clinical Oncology (2014)

7536 Background: National Comprehensive Cancer Network (NCCN) guidelines recommend adjuvant radiotherapy (XRT) for NSCLC patients with N2 disease after lobectomy. The purpose of this study is to identify factors associated with non-adherence if any to NCCN guidelines for the above patients in a large population database. Methods: SEER registry was queried for NSCLC patients with N2 disease and lobectomy, diagnosed between 2004-2010. Patients with distant metastases were excluded. The study period was divided in two eras (2004-2006 and 2007-2010) because the landmark publication in this field by Lally et al. was published on Jun 12, 2006. Multivariate logistic regression analyses were performed to identify factors predicting non-adherence. Results: A total of 2,112 N2 NSCLC patients who had lobectomy were included in the final cohort, 773 (36.6%) of whom received adjuvant XRT according to NCCN guidelines. There were 34.3% and 38.3% of N2 NSCLC patients who received adjuvant XRT in 2004-2006 and 2007-2010 respectively. 40.3% of patients who had larger lymph nodes (LN) burden (≥ 20% LNs removed were positive) received adjuvant XRT compared to 28.2% in patients with small LN burden. Multivariate analyses revealed that age ≥ 70 years, unmarried, west region, diagnosed in early period (2004-2006), T1 and smaller LN burden were associated with non-adherence with guidelines (Table). Conclusions: Although treatment trends are improving since 2007, adjuvant XRT for NSCLC patients with N2 disease continues to be underutilized, particularly in the elderly, unmarried, west regions of the United States, T1 and smaller LN burden. Factors associated with no adjuvant XRT in N2 NSCLC patients after lobectomy. Variables OR 95% CI p Age 60-69 vs. <60 1.37 1.09 - 1.71 0.006 ≥70 vs. <60 2.01 1.61 - 2.53 <0.001 Marital status Unmarried vs. married 1.31 1.08 - 1.59 0.005 Unknown vs. married 1.73 0.87 - 3.44 NS Region West vs. South 1.49 1.19 - 1.86 <0.001 Midwest vs. South 1.32 0.95 - 1.85 NS Northeast vs. South 1.19 0.91 - 1.57 NS Year of diagnosis 2004-2006 vs. 2007-2010 1.23 1.02 - 1.48 0.028 T stage T2 vs. T1 0.95 0.77 - 1.17 NS T3 vs. T1 0.75 0.56 - 0.99 0.045 T4 vs. T1 0.81 0.50 - 1.29 % of positive LN in removed LN < 20% vs. ≥ 20% 1.79 1.46 - 2.20 <0.001 Abbreviations: NS, not significant.
US doctors’ groups call for parties to work together on healthcare reform
Authors: Michael McCarthy
Journal: BMJ (2017)

US doctors’ groups have called for Democrats and Republicans to work together on healthcare reform after the House speaker, Paul Ryan, a Republican from Wisconsin, withdrew a bill to repeal the Affordable Care Act on 24 March when it became clear he did not have enough votes for it to pass. The decision was a stunning defeat for Republicans and President Donald Trump, who had said that they would make repeal of “Obamacare” the first order of business of the new Congress.

In announcing his decision to withdraw the bill, called the American Health Care Act, Ryan said that Republicans have abandoned their efforts to repeal Barack Obama’s 2010 Affordable Care Act for …
Abstract 10274: It’s Complicated: Comorbidity, Self-efficacy, Self-care When Hospitalization and Quality of Life are Outcomes in Heart Failure
Authors: Harleah G Buck, Victoria V Dickson, Roberta Fida, Barbara Riegel, Fabio D’Agostino, Rosaria Alvaro, Ercole Vellone
Journal: Circulation (2015)

Introduction: Essential elements of heart failure (HF) self-care include engagement in daily behaviors that maintain physical stability (self-care maintenance) and recognition of symptoms with a timely response (self-care management). Comorbidity decreases self-efficacy or confidence in the ability to perform self-care which, in turn, impairs self-care behaviors. Comorbidity is also associated with increased hospitalization and poorer quality of life (QOL). Yet the manner in which comorbidity and self-efficacy interact to influence self-care, hospitalization, and QOL remains unclear. Hypotheses: 1) Comorbidity and self-efficacy are determinants of self-care maintenance and management which in turn are determinants of hospitalization and QOL; 2) Comorbidity moderates the relationship between self-efficacy and self-care maintenance and management. Methods: An existing dataset of 628 symptomatic, older (mean age = 73, SD = 11) male (58%) Italian HF patients was analyzed using structural equation modeling and simple slope analysis. Measures used were the Charlson Comorbidity Index; Self-Care of Heart Failure Index (V6.2) for self-efficacy, self-care maintenance and self-care management; medical record review for hospitalization; and Minnesota Living with Heart Failure Questionnaire for QOL. Results: In the model higher comorbidity was associated with lower self-care management but not maintenance. Higher self-efficacy was associated with both higher self-care maintenance and management. Higher self-care maintenance was associated with fewer hospitalizations and better overall QOL. In the moderation analysis comorbidity moderated the relationship between self-efficacy and self-care maintenance. Higher comorbidity weakened the strength of the relationship between self-efficacy and self-care maintenance in post-hoc simple slopes analysis. Conclusions: The strength of the relationship between self-efficacy and self-care maintenance was a function of comorbidity. Self-care maintenance was associated with hospitalization and QOL. Therefore, tailoring interventions to improve self-efficacy at different levels of comorbidity may be key to impacting hospitalization and QOL in HF.
Efficacy of adjuvant trastuzumab (T) compared with no T for patients (pts) with HER2-positive breast cancer and tumors ≤ 2cm: A meta-analysis of the randomized trastuzumab trials.
Authors: Ciara Catherine Maria O'Sullivan, Ian Bradbury, Evandro De Azambuja, Edith A. Perez, Priya Rastogi, Marc Spielmann, Heikki Joensuu, Karla V. Ballman, Joseph P. Costantino, Suzette Delaloge, Dimitrios Zardavas, Martine J. Piccart-Gebhart, JoAnne Zujewski, Eileen McCormick Holmes, Richard D. Gelber
Journal: Journal of Clinical Oncology (2014)

508 Background: Adjuvant T plus chemotherapy improves disease-free survival (DFS) and overall survival (OS) vs. chemotherapy alone for pts with early stage HER2-positive breast cancer. We conducted a meta-analysis to estimate DFS and OS for pts with small tumors (≤2cm) in the T arms from 5 of the 6 randomized adjuvant trastuzumab trials. Pts with tumors ≤2cm, with 0 or 1 positive lymph nodes, and hormone receptor (HR) positive disease had a 5-year DFS of 91% and a 5-year OS of 97% (O’Sullivan, SABCS 2013; abstract:1327). We now plan to conduct an additional meta-analysis to assess the efficacy of T compared with no T for pts with small tumors (≤2cm). Methods: Six randomized controlled trials (RCT) were identified by a Medline search from 2004-2013. Trial groups from 5 phase III RCTs provided data (HERA, NCCTG N9831, NSABP B31, PACS 04, and FinHER).In total, 11,200 pts were randomized in these 5 trials;4,220 of whom had ≤2cm tumors, and known number of positive axillary lymph nodes and HR status(2,588 randomized to T and 1,632 to no T). The individual pt meta-analysis will include pts with tumors ≤2 cm (T1a, T1b and T1c) and 0-1, 2-3 and ≥ 4 positive lymph nodes. Separate analyses will be performed for the two HR cohorts. This analysis will complement the published summary data-based Cochrane Review (Moja et al. 2012) by allowing a detailed investigation of the effect of disease characteristics, such as HR, on treatment effects. In addition to the standard Yusuf-Peto fixed effects model (Yusuf et al. 1985) we will investigate the impact of heterogeneity in study baseline hazards and study treatment effects by fitting random effect models.An intention to treat approach will produce a conservative effect estimate as substantial numbers of control-group pts 'crossed over' to the T arm after positive DFS results were reported. Methods to account for this ‘selective crossover’ are being developed; we plan to extend these methods to the meta-analysis setting to provide less conservative estimates. Results: Pending. Conclusions: A meta-analysis of 5 randomized adjuvant T trials focusing on pts with tumors ≤2cm will be performed and results submitted before the meeting.
Prospective study on the association of depression and anxiety on quality of life, treatment adherence and prognosis in patients with advanced non small cell lung cancer.
Authors: Carolina Nunez-Valencia, Patricia Angulo, Omar Macedo, Yuzmiren Dorantes, Dolores De la Mata, Luis F. Onate-Ocana, Oscar Arrieta
Journal: Journal of Clinical Oncology (2012)

e19618 Background: Symptoms of depression and anxiety are common in patients with lung cancer and could produce impact on health-related quality of life (HRQL) and survival. The aim of the present study is to evaluate the association of depression and anxiety on HRQL, treatment adherence and prognosis in patients with non-small cell lung cancer (NSCLC). Methods: This is a prospective study of consecutive patients with stages IIIB-IV NSCLC. Depression and anxiety were measured with the Hospital Anxiety and Depression Scale (HADS) and the International Psychiatric Interview (MINI), and HRQL with the EORTC QLQ-C30 and QLQ-LC13 questionnaires.All instruments were applied before treatment; at three and six months. Lack of adherence to treatment was considered in patients who stopped attending consultation. Overall survival (OS) was calculated with the Kaplan-Meier and Cox methods. Results: Eighty-two patients were included, mean age 58.9 years. Depression and anxiety were found in 32.9 and 34.1% - respectively - at the initial evaluation. Factors associated with depression were: female gender (p=0.034) and poor performance status (p=0.048). Depression showed association to HRQL; particularly Global health status/QoL and functional scales (i.e: Physical, Role, Emotional, cognitive and Social); Anxiety also showed association to HRQL; particularly Global health status/QoL and functional scales (all p≤0.05).Patients with depression presented a median OS of 6.8 months (95% CI 2.4-11.1) whilst non-depressed patients: 14 (10.3-17.6). Anxiety was not associated to OS. By multivariate analysis, depression has a hazard ratio of 1.9 (95% CI 1.03-3.7, p=0.042). Forty-four percent of the patients with depression had poor treatment adherence versus 14% of the non-depressed (p&lt;0.05). Conclusions: One third of patients with advanced NSCLC presented depression and anxiety. Both were associated to decreased HRQL functional scales of QLQ-C30 and treatment adherence. Depression was independently associated to poor prognosis.
Long-term efficacy and safety of enzalutamide (ENZ) monotherapy in hormone-naïve prostate cancer (HNPC): 3-year, open-label, follow-up results.
Authors: Bertrand F. Tombal, Michael Borre, Per Rathenborg, Patrick Werbrouck, Hendrik Van Poppel, Axel Heidenreich, Peter Iversen, Johan Braeckman, Jiri Heracek, Benoit Baron, Andrew Krivoshik, Mohammad Hirmand, Matthew Raymond Smith
Journal: Journal of Clinical Oncology (2017)

220 Background: A phase 2 study of the androgen receptor inhibitor ENZ as monotherapy in patients with HNPC [NCT01302041] showed a high prostate-specific antigen (PSA) response rate, regardless of baseline metastases, and favorable tolerability. In a 1- and 2-year follow-up, ENZ maintained long-term reductions from baseline in PSA, with minimal impact on total-body bone mineral density (BMD). Herein, results from a pre-specified 3-year follow-up are reported. Methods: A total of67 patients with HNPC and non-castrate testosterone ( ≥ 230 ng/dL) received ENZ 160 mg/day until disease progression or unacceptable toxicity. The primary end point of PSA response ( ≥ 80% decline from baseline) was analyzed at week 25 and 1, 2, and 3 years. Other end points were best overall tumor response, BMD, body composition, quality of life, and safety. Results: At the 3-year visit, 42 (62.7%) patients remained on the study medication. Of those, 38 (90.5%; 95% confidence interval 77.4%, 97.3%) maintained a PSA response. Of the 26 patients with metastases at baseline, 17 (65.4%) had a complete or partial response as best overall response at 3 years. In patients who completed the 3-year visit, minimal changes from baseline were observed in total-body BMD or in BMD of the femoral neck, trochanter, spine L1–L4, or forearm (median and mean changes ranged from –3.6% to 1.3% and –2.7% to –0.1%, respectively). The EORTC QLQ-C30 global health status results showed a small decrease at 3 years versus baseline (–3.96 points), consistent with the 2-year results. At 3 years, measurements for total body fat increased (median, 14.7%; mean, 16.5%) and total body lean decreased (median, –6.3%; mean, –6.5%) from baseline. Physical functioning, fatigue, and dyspnea worsened ( &gt; 10 points) at 3 years, similar to results at 2 years. The most frequently reported adverse events ( &gt; 10%) were gynecomastia, fatigue, hot flush, nipple pain, hypertension, diarrhea, nausea, pain in extremity, back pain, and constipation. Conclusions: In patients with HNPC treated with ENZ for 3 years, the efficacy of ENZ as monotherapy was maintained. Overall, BMD, global health status, and safety results were similar to those at 2 years. Clinical trial information: NCT01302041.
Clinical significance of downstaging in patients treated with chemoradiotherapy for limited-disease small cell lung cancer.
Authors: Se-Il Go, Bhumsuk Keam, Tae Min Kim, Se-Hoon Lee, Dong-Wan Kim, Hak Jae Kim, Hong-Gyun Wu, Doo Hyun Chung, Dae Seog Heo
Journal: Journal of Clinical Oncology (2013)

e18555 Background: Limited-disease small cell lung cancer (LD-SCLC) patients who do not achieve complete remission (CR) have a considerable relapse rate. The change of tumor burden after treatment can be related with prognosis, the change of TNM stage may influence the outcome of treatment. We investigated the impact of downstaging on overall survival (OS) in LD-SCLC patients treated with chemoradiotherapy (CRT). Methods: We retrospectively reviewed the 210 LD-SCLC patients, who were treated with CRT at Seoul National University Hospital from Apr 1999 to Nov 2012. The relationship between downstaging and OS was analyzed, and subgroup analysis on the responders was performed. Results: Patients showing CR, partial remission (PR), and stable disease (SD)/progressive disease (PD) were 37.1% (n=78), 46.2% (n=97), and 16.7% (n=35), respectively. The median OS for CR, PR, and SD/PD were 47.9 months (mo), 21.8 mo, and 11.2 mo, respectively (P &lt;0.001). Patients showing downstaging and no change/upstaging were 61.5% (n=129) and 38.5% (n=81), respectively. The median OS for downstaging and no change/upstaging were 36.5 mo and 14.4 mo, respectively (P &lt;0.001). Among the 97 patients achieving PR, OS were statistically differed by downstaging (26.0 mo in patients with downstaging and 17.7 mo in patients without downstaging [P =0.021]). In the multivariate analyses, female, downstaging, lower initial TNM stage, and prophylactic cranial irradiation were independent good prognostic factors for OS. Conclusions: Downstaging was independent prognostic factor in LD-SCLC. Especially, downstaging is useful for further stratification of patients achieving PR. Additional treatments after CRT may be needed for the patients who achieving PR without downstaging.
SIOPEL 6: A multicenter open-label randomized phase III trial of the efficacy of sodium thiosulphate (STS) in reducing ototoxicity in patients receiving cisplatin (Cis) monotherapy for standard-risk hepatoblastoma (SR-HB).
Authors: Rudolf Maibach, Margaret Childs, Kaukab Rajput, Edward A. Neuwelt, Derek Roebuck, Michael James Sullivan, Veronique Laithier, Milind Ronghe, Liane Lockwood, Patrizia dall'Igna, Eiso Hiyama, Benedicte Brichard, Jane Skeen, Maria Elena Mateos Gonzales, Monique Fabre, Giorgio Perilongo, Piotr Czauderna, Bruce Morland, Penelope Brock
Journal: Journal of Clinical Oncology (2014)

TPS10094 Background: The SIOPEL 3 trial of Cis monotherapy and surgery in SR-HB showed a 3yr OS of 95% at 5 years. SR-HB is defined as tumor extension limited to PRETEXT I, II or III, no involvement of portal or hepatic veins, no intra-abdominal extrahepatic disease, AFP >100ng/ml and no metastases. At commonly used doses and schedules, Cis can cause permanent bilateral high-frequency hearing loss. Several pre-clinical and clinical studies in adults and children (particularly from the Oregon group) suggest that STS may reduce the risk of ototoxicity. There are however concerns that STS could reduce the anti-tumor efficacy of Cis, hence the time separation of Cis and STS and the close monitoring of the trial. Methods: Newly diagnosed patients with SR-HB are treated with 4 chemotherapy courses every 2 weeks before surgery and 2 courses after surgery. Patients are randomly assigned to receive Cis alone or Cis followed by STS. Cis 80mg/m2 is administered i.v. over 6 hrs. STS is administered i.v. exactly 6 hrs after stop of Cis over 15 minutes at 20g/m2. Serum sodium is monitored 1 hr, 6 hrs and 18 hrs post STS. Tumor response is assessed after 2 and 4 cycles preoperatively with serum AFP and liver imaging. In case of lack of response after 2 cycles, STS is stopped and chemotherapy is changed to combination therapy with Cis and doxorubicin 60mg/m2 continuous infusion over 48 hrs. A DNA sample for central analysis of ototoxicity predisposition factors and a tumor sample are requested. The primary endpoint of the trial is centrally reviewed absolute hearing threshold, at the age of ≥3.5 yrs, by pure tone audiometry. With a sample size of 102, the trial has 80% power to detect a reduction of the rate of hearing loss defined as Brock grade ≥ 1 from 60% under Cis alone to 35% under Cis and STS. In case of concerns of an adverse effect of STS on the efficacy of the Cis chemotherapy, the trial may be stopped early. Interim efficacy results on response to chemotherapy are evaluated after every 20 patients and submitted immediately to the IDMC. The IDMC has recommended continuing the trial after review of the results on 20, 40 and 60 pts. Clinical trial information: NCT00652132.
A study of autologous dendritic cell therapy targeting mucin-1 for treatment of patients with epithelial ovarian cancer in first remission.
Authors: Jonathan S. Berek, Jeffrey C. Goh, Heidi J. Gray, James Fiorica, James R. Mason
Journal: Journal of Clinical Oncology (2012)

TPS5113 Background: Cvac (Cvac) is an autologous dendritic cell immune stimulant targeting mucin-1 positive tumors. A phase IIa study demonstrated potential for treating mucin-1 positive epithelial ovarian carcinoma (EOC). A phase IIb study was designed to determine on a pilot basis if Cvac could demonstrate an effect on progression free and overall survival in patients with EOC in first or second remission. The current study, CANVAS (CANcer VAccine Study) is evaluating Cvac treatment of EOC patients in first remission after surgery and standard chemotherapy, with at least three cycles of platinum and taxane therapy. Endpoints include progression free survival, overall survival, safety evaluation and quality of life scores. Methods: Patients are eligible if they have stage III or IV mucin-1 positive EOC and have had optimal cytoreductive (&lt;1cm residual disease) surgery. Apheresis to obtain immature dendritic cells occurs prior to chemotherapy. Cvac is manufactured during chemotherapy. Patients remain eligible for the study if they have a complete response to standard chemotherapy after surgery. Cvac or placebo is dosed every four weeks for three doses, and every twelve weeks for three additional doses. 1000 patients will be randomized to Cvac or placebo in 22 countries, with 800 expected to receive vaccine or placebo. CT or MRI imaging determines progression, and is centrally read prior to inclusion and at each timepoint. Recruitment commenced January 2012. Over 100 centers are participating in the study globally, with majority in Europe. Enrollment is expected to take 18-24 months. An interim analysis is planned after 400 PFS events, and final analysis after 620 PFS events. Observation of 620 events would have approximately 90% power to detect a hazard ratio of 0.77 in PFS at a significance level of p=0.049 (approximately a 30% increase in median PFS in the Cvac group compared with the placebo group).
Survival results of a multicenter phase II study of trastuzumab with S-1 alone in elderly patients with HER-2 positive advanced gastric cancer (JACCRO GC-06).
Authors: Kazuhiro Nishikawa, Yutaka Kimura, Toshiki Masuishi, Chikara Kunisaki, Satoshi Matsusaka, Yoshihiko Segawa, Masato Nakamura, Kinro Sasaki, Narutoshi Nagao, Yukimasa Hatachi, Yasuhiro Yuasa, Shinya Asami, Masahiro Takeuchi, Hiroshi Furukawa, Masashi Fujii, Toshifusa Nakajima
Journal: Journal of Clinical Oncology (2017)

100 Background: S-1 plus cisplatin (SP) is a standard regimen for advanced gastric cancer (AGC) in Japan. In patients with HER-2 positive AGC, combined administration of fluoropyrimidine plus cisplatin and trastuzumab is the standard treatment. However, cisplatin has several important drawbacks, including nausea, vomiting, and renal toxicity. Especially, these disadvantages of cisplatin are noticeable in elderly patients. We have already reported the results of the efficacy and safety of trastuzumab combined with S-1 alone in elderly patients with HER-2 positive AGC. In this time, we report the survival results of this study. Methods: Patients, 65 years or older, with HER-2 positive AGC received S-1 (80-120mg per day) orally on days 1-28 of a 42-day cycle and trastuzumab (first time: 8 mg/kg, from 2nd onward: 6 mg /kg) intravenously on day 1 of a 21-day cycle. Results: A total of 51 patients were enrolled. One patient was ineligible, one patient did not receive study treatment, therefore in the full analysis set of 49 patients, the median age was 71 years (range: 65-85) and ECOG PS was 0/1/2: 32/14/3. The confirmed RR (CR/PR/SD/PD: 2/18/21/8) was 40.8% (80% confidence interval (CI): 31.8-49.8%, 95% CI: 27.1-54.6%), and the null hypothesis was rejected. Median follow up period was 10.6 months. Median OS was 15.8 months (95%CI: 9.13-20.37). Median PFS was 5.1 months (95%CI: 3.78-5.55), and TTF was 4.0 months (95%CI: 3.09-5.39). Major grade 3 or 4 adverse events included neutropenia (12.0%), anemia (24.0%), diarrhea (10.0%) and anorexia (12.0%). There was one treatment-related death. Conclusions: Trastuzumab in combination with S-1 alone demonstrated promising antitumor activity and manageable toxic effects, as well as promising survival results in elderly patients with HER-2 positive AGC. Clinical trial information: 000007368.