tbuckley/cabot-search huggingface dataset:
Everolimus in combination with exemestane in the treatment of postmenopausal women with estrogen receptor-positive metastatic breast cancer who are refractory to letrozole or anastrozole: Preliminary results of the BOLERO-2 trial.
Authors: J. Baselga, M. Campone, M. J. Piccart-Gebhart, H. A. Burris, H. S. Rugo, S. Noguchi, M. Gnant, K. I. Pritchard, F. Lebrun, J. T. Beck, Y. Ito, D. A. Yardley, I. Deleu, A. Perez, T. D. Bachelot, L. Vittori, P. Mukhopadhyay, D. Weber, T. Sahmoud, G. N. Hortobagyi
Journal: Journal of Clinical Oncology (2011)

e11058 Background: The PI3K/Akt/mTOR pathway, a key regulator of cellular proliferation, cellular metabolism, and angiogenesis, is constitutively activated in aromatase inhibitor–resistant breast cancer. Everolimus (EVE), an inhibitor of the PI3K/Akt/mTOR pathway, has single-agent activity and provides additional efficacy to long-term estrogen deprivation when combined with letrozole in the neoadjuvant setting. Combination of EVE and exemestane may improve outcomes for patients ER+ breast cancer refractory to nonsteroidal aromatase inhibitors (NSAI). Methods: In this multinational, double-blind, placebo-controlled phase III study, postmenopausal women ≥18 years old with ER+ locally advanced or metastatic breast cancer whose disease was refractory to NSAI and documented recurrence or progression were stratified by sensitivity to prior hormonal therapy and the presence of visceral metastasis and then randomized (2:1) to EVE (10 mg daily) or matching placebo orally once daily, with both arms receiving exemestane (25 mg daily). Treatment was continued until disease progression or unacceptable toxicity. The primary outcome was progression-free survival (PFS) assessed by the investigators. Secondary outcomes included overall survival, overall response rate, time to deterioration of ECOG performance status, safety, and change in QoL scores over time. Between June 2009 and January 2011, 723 patients were randomized from 24 countries; 84% had hormone sensitive-disease and 56% had visceral disease. An interim analysis based on safety and efficacy reviewed by the independent data monitoring committee will be performed when 317 PFS events have occurred. The IDMC meeting is planned for May 2011.
Abstract P3-07-19: Breast cancer risk perception and adherence to U.S. cancer prevention guidelines
Authors: Erin Hofstatter, Anees Chagpar
Journal: Cancer Research (2015)

Abstract Introduction: In the United States, nearly 200,000 cancer-related deaths each year are attributed to poor diet and physical inactivity. We sought to determine whether perceived personal breast cancer risk was associated with adherence to healthy lifestyle habits in a nationally representative sample. Methods: The National Health Interview Survey (NHIS) is a population-based survey conducted each year by the CDC, designed to represent the non-institutionalized civilian population in the United States. We utilized data from the 2010 NHIS adult and cancer supplements to compare fruit/vegetable intake, alcohol use and exercise habits among women who perceived themselves to be at high risk of developing breast cancer versus those women who perceived themselves to be at average or low risk. Results: In 2010, 12,055 women without a history of cancer were surveyed, representing 94,990,140 people in the population. Perceived risk of breast cancer was not associated with improved adherence to nutrition and physical activity guidelines (see Table). Less than 5% of all U.S. women meet the recommended fruit/vegetable intake regardless of perceived risk, and only one-third of all women achieve recommended physical activity. Approximately 95% of women adhere to guidelines regarding alcohol intake. On multivariate analysis, perceived risk did not affect health habits when controlling for age, ethnicity, education, insurance status, income, region and body mass index (BMI). Conclusion: Thousands of breast cancer diagnoses and deaths could be prevented each year through healthy diet and exercise. Yet, a striking majority of U.S. women do not adhere to cancer prevention recommendations, including those women who perceive themselves to be at high risk of breast cancer. These findings suggest that patient education and awareness of personal breast cancer risk may be essential, but not sufficient, for motivating meaningful behavior change. Univariate AnalysisMultivariate AnalysisPerceived High Risk-% meeting guidelinesPerceived Low/Avg Risk-% meeting guidelinesp-valueOR (95% CI)p-valueFruit/Veg Intake (&amp;gt;=5 svg daily)4.90%4.42%0.56791.14 (0.78-1.66)0.5110Alcohol Intake (&amp;lt;=7 svg/wk)94.22%95.13%0.30930.84 (0.61-1.17)0.3076Physical Activity (75-150 min vig-mod act/wk)30.11%27.74%0.14651.02 (0.87-1.21)0.7921 Citation Format: Erin Hofstatter, Anees Chagpar. Breast cancer risk perception and adherence to U.S. cancer prevention guidelines [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-07-19.
Population-based outcomes of patients (pt) with early-stage HER2-positive breast cancer treated with adjuvant trastuzumab (T).
Authors: Krista Noonan, Joy S. McCarthy
Journal: Journal of Clinical Oncology (2012)

e11079 Background: Phase III trials have shown clinical efficacy of T when combined with chemotherapy in HER2-positive early stage breast cancer, decreasing recurrence by 50% and increasing survival by 30%. 15-20% of early stage breast cancers demonstrate amplification of the HER2 gene, which is associated with a poor prognosis. The aims of this study were to evaluate the clinical effectiveness of T, and explore potential prognostic factors. Methods: Pts with stage I-III breast cancer overexpressing HER2 from 2005 to 2010, assessed in Newfoundland and Labrador’s cancer centre were retrospectively identified from the Provincial Tumour Registry. Pt, treatment, and tumour characteristics were extracted. Kaplan-Meier curves were used for survival analysis, and Cox Proportional Hazards Models were used to identify prognostic factors and evaluate their impact on outcomes. Results: A total of 148 pts were identified. The median age was 56 years, and 76% received T. At a median follow-up of 25 months, overall survival (OS) was 97% (p=0.0002), and disease-free survival was 96% (p&lt;0.00) for pts receiving T. Younger age, smaller tumour size, and lymph node negativity were favorable prognostic factors. There was an 83% decrease in risk of breast cancer recurrence in the patients receiving T. Discontinuation of T occurred in 6.2% of patients due to a decreased ejection fraction. Conclusions: This population-based analysis demonstrates T’s favorable impact on 25-month DFS, OS, and safety. This adds to the body of literature, showing clinical effectiveness and tolerability of T. [Table: see text]
Prostate-specific antigen as a predictor of radiotherapy response and patterns of failure in localized prostate cancer.
Authors: M A Ritter, E M Messing, T G Shanahan, S Potts, R J Chappell, T J Kinsella
Journal: Journal of Clinical Oncology (1992)

PURPOSE A study of preradiation and postradiation, serial serum prostate-specific antigen (PSA) levels was performed in patients who had clinically localized prostate cancer. The prognostic value of the PSA in pretreatment evaluation and posttreatment follow-up was assessed. PATIENTS AND METHODS Sixty-three patients who presented with clinically localized prostate cancer and who were treated with external-beam radiation therapy were followed-up for a median of 25 months. A serum PSA and physical examination were performed at 3-month intervals, and a bone scan was done yearly. An increase in PSA triggered an additional metastatic workup. Prostate rebiopsy was performed for new, palpable nodules or for a serial increase in PSA in the context of a negative metastatic workup. RESULTS Forty-one patients remained recurrence-free and 22 recurred clinically, 15 distantly and seven locally. The PSA was the strongest, independent, pretreatment prognostic indicator (P = .019) among pretreatment PSA, stage, and grade, but lost significance when the serum prostatic acid phosphatase (PAP) status was included. The initial rate of the PSA decrease after radiation (median half-life, 2.6 months) failed to predict outcome. Recurrence-free patients reached postradiation PSA levels that were equivalent to those reported in disease-free male populations; failure of the PSA to reach such normal levels was a multivariate predictor of subsequent failure (P less than .037). All clinicopathologic documentations of failure were preceded by an increase in PSA levels during follow-up. Delayed versus early PSA increase was associated with clinically localized versus metastatic first recurrence. CONCLUSIONS The serum PSA is an independent pretreatment and posttreatment predictor of outcome. Additionally, for a median follow-up of 25 months, delayed PSA failure is associated with clinically localized rather than metastatic recurrence, a relationship that may help in selection for local salvage therapy.
Patient reported outcomes in a phase 2 trial of SU11248 for metastatic renal cell carcinoma
Authors: J. Beaumont, D. Cella, J. Li, R. Motzer, B. Rini, D. Michaelson, S. Kim, C. Baum
Journal: Journal of Clinical Oncology (2005)

8167 Background: SU11248 is a novel, oral multi-targeted tyrosine kinase inhibitor with both anti-angiogenic and anti-tumor activity. In a phase 2 study (014) of SU11248 for the treatment of metastatic renal cell carcinoma following failure of 1 prior cytokine treatment, a 40% tumor response rate (25/63) has been reported (Motzer et al., ASCO 2005, submitted). This analysis describes the patient reported outcomes (PROs) in this trial. Methods: PROs were assessed using the FACIT-Fatigue scale (FACIT-Fatigue, score range = 0–52) and the EQ-5D health status visual analogue scale (EQ-VAS, score range = 0–100) in the first four 6-week cycles (4 weeks on treatment, 2 weeks off), weekly for FACIT-Fatigue and at the start and end of each 4-week treatment period for EQ-VAS. Of 63 patients enrolled, 62 participated in the baseline PRO assessment and 37 (59%) provided complete or near-complete data across four 6-week cycles. Results: At baseline, FACIT-Fatigue and EQ-VAS scores of these patients were slightly lower than those of the general population. Baseline FACIT-Fatigue and EQ-VAS scores were associated with baseline performance status (FACIT-Fatigue p<0.001; EQ-VAS, p=0.001) and, marginally, with subsequent response to therapy (partial response/stable disease was associated with less fatigue or better health state; FACIT-Fatigue p=0.169; EQ-VAS p=0.033). FACIT-Fatigue and EQ-VAS scores declined across these four cycles (average change from baseline: FACIT-Fatigue = -2.2, EQ-VAS = -5.87) but these changes are smaller than what is considered ‘minimally important’ for these measures. A pattern of decline and recovery coincided with the 4-week on/2-week off periods in each cycle. Average change from baseline in FACIT-Fatigue and EQ-VAS scores did not differ with response to therapy. Conclusions: SU11248 did not cause significant changes in PROs in this group of patients, although FACIT-Fatigue and EQ-VAS scores declined slightly while patients were on treatment and improved while they were off treatment in the first four cycles. These changes were not correlated with tumor response. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer
Three simple rules to ensure reasonably credible subgroup analyses
Authors: James F Burke, Jeremy B Sussman, David M Kent, Rodney A Hayward
Journal: BMJ (2015)

The limitations of subgroup analyses are well established—false positives due to multiple comparisons, false negatives due to inadequate power, and limited ability to inform individual treatment decisions because patients have multiple characteristics that vary simultaneously. In this article, we apply Bayes's rule to determine the probability that a positive subgroup analysis is a true positive. From this framework, we derive simple rules to determine when subgroup analyses can be performed as hypothesis testing analyses and thus inform when subgroup analyses should influence how we practice medicine.
Impact of pegfilgrastim on early all-cause mortality in patients receiving cancer chemotherapy
Authors: G. H. Lyman, N. M. Kuderer, J. Crawford, D. A. Wolff, E. Culakova, M. S. Poniewierski, D. C. Dale
Journal: Journal of Clinical Oncology (2008)

6552 Background: Myelosuppression is a major cause of dose-limiting toxicity in patients receiving cancer chemotherapy. A meta-analysis of randomized controlled trials of prophylactic colony-stimulating factors (CSFs) reported significant reductions in all-cause mortality during the period of chemotherapy (Kuderer JCO 2007). The impact of the CSFs in cancer patients with multiple comorbid conditions has not been closely studied. Methods: A prospective observational study of 4,458 consecutive adult patients receiving cancer chemotherapy was conducted at 115 randomly selected U.S. practices. Clinical and treatment measures were captured at baseline and during treatment. Progression-free survival (PFS) and overall survival (OS) and adjusted hazard ratios (HRs; 95% CI) were estimated using an extended Cox regression model with time-dependent covariates. Results: Patient age ranged from 18 to 97 with 41% >65 years, ECOG PS >1 in 46% and stage 4 in 38%. During the period of observation (median=75 days;range 1–385), 298 (6.7%) patients progressed and 137 (3.1%) died including 88 of presumed progressive disease. Other causes of death included infection (13), cardiopulmonary (12) and other/unknown (24). Pegfilgrastim was administered on an individual basis to 1,209 patients including 620 as primary prophylaxis starting in cycle 1 (PPP). Patients receiving PPP experienced better PFS (HR=0.65 [0.46–0.92] P=.0109) and OS (HR=0.41 [0.21–0.81] P=.0079) than those without such support. In univariate analysis incorporating any use of pegfilgrastim as a time-dependent covariate, improvements in both PFS (HR=0.54 [0.40–0.72] P<.0001) and OS (HR=0.40 [0.23–0.68] P<.0001) were observed. In multivariate analysis, pegfilgrastim use was associated with improved PFS (HR=0.62 [0.44–0.88] P=.0070) and OS (HR=0.44 [0.23–0.84] P=.0120) after adjustment for other significant covariates including ECOG PS, Charlson comorbidity index, age, body mass index, cancer type, stage and year on study with stratification for practice site. Conclusions: While pegfilgrastim use was individualized, the results presented here suggest that patients with a range of comorbid conditions receiving such support may experience improved PFS and OS during chemotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Amgen Amgen
P-275 Phase II study of oral tegafur/uracil and leucovorin plus bevacizumab as a first line therapy for elderly patients with advanced or metastatic colorectal cancer
Authors: H. Tamagawa, T. Mizushima, C. Matsuda, K. Murata, M. Fukunaga, H. Ohta, J. Hasegawa, M. Tsujie, T. Fukuzaki, T. Hata, I. Takemasa, M. Ikeda, H. Yamamoto, M. Sekimoto, R. Nezu, Y. Doki, M. Mori
Journal: Annals of Oncology (2015)
Cost effectiveness of androgen suppression plus radiation therapy for clinically localized prostate cancer
Authors: S. J. Wang, T. S. Herman, C. R. Thomas
Journal: Journal of Clinical Oncology (2005)

6010 Background: In addition to studying traditional clinical outcomes, examination of both quality of life and economic outcomes of new treatment regimens is warranted, particularly for those that may be considered expensive and/or associated with significant toxicities. We constructed a model to predict long-term quality-adjusted outcomes and cost-effectiveness of adding androgen suppression therapy (AST) to radiotherapy (RT) for clinically localized prostate cancer. Methods: Based on 5-yr clinical trial data from D’Amico, et al. (JAMA 2004; 292(7):821–827), we constructed a Markov process to compare outcomes for RT alone vs. RT plus 6 mos of AST, for pts with clinically localized prostate cancer. Quality-of-life utility measures and cost data were obtained from published literature. We included costs associated with hormone treatment, toxicity, and disease progression. The analysis was performed from the health care payer perspective, with results reported in 2004 U.S. dollars. A 15-yr time horizon and 3% discount rate were used, and one-way sensitivity analyses were performed. Since optimal AST duration is still unclear, we also analyzed the effects of increasing AST duration. Results: The projected 15-yr progression-free survival was 33% vs. 11%, for RT+AST vs. RT, respectively, while the projected 15-yr overall survival was 52% vs. 26%. At 15 years, the RT+AST group showed a net gain of 1.65 quality-adjusted life years (QALYs) and no net cost compared with RT alone (total costs $15,000 for RT+AST vs. $15,500 for RT alone). Results were most sensitive to changes in time horizon, discount rate, and utility for progression. At time horizons of greater or less than 15 years, the incremental cost-effectiveness ratio (ICER) was positive, but never more than $6500/QALY. If AST treatment duration was extended to 3 years, the 15-yr gain in QALYs was 1.58 and the ICER was $7400/QALY. Conclusions: The addition of AST to RT for the treatment of clinically localized prostate cancer is cost effective over a wide range of parameters. The magnitude of the cost-effectiveness is highly dependent upon time horizon. No significant financial relationships to disclose.
Outpatient-Based Bone Marrow Transplantation for Hematologic Malignancies: Cost Saving or Cost Shifting?
Authors: J. Douglas Rizzo, Georgia B. Vogelsang, Sharon Krumm, Barbara Frink, Victoria Mock, Eric B. Bass
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine whether a shift in care from an inpatient-based to an outpatient-based bone marrow transplantation (BMT) program decreased charges to payers without increasing clinical complications or out-of-pocket costs to patients. PATIENTS AND METHODS: This nonrandomized prospective cohort study compared clinical and economic outcomes for 132 consecutive BMT patients with hematologic malignancies who received either inpatient- or outpatient-based BMT care. RESULTS: Seventeen of 132 BMT patients underwent outpatient-based BMT. Compared with the inpatient-based group, the outpatient-based group had a markedly lower mean number of inpatient hospital days (22 v 47; P &lt; .001) and decreased mean inpatient facility charges ($61,059 less per patient; P &lt; .0001) but had higher mean outpatient facility charges ($49,732 higher; P &lt; .0001). Total professional fees were similar for the groups. The mean total charge to payers was only 7% less ($12,652; P = .21) for outpatient-based BMT than for inpatient-based BMT, but total charge was 34% less for outpatient compared with inpatient BMT ($54,240; P = 0.056) in a subset of patients who had a standard rather than high risk of treatment failure. There was no significant difference between groups in out-of-pocket costs for transportation, lodging, meals, home nursing, household assistance, child care, medication expenses, or unreimbursed medical bills. There also was no significant difference between groups in reported income lost, involuntary unemployment, or months of disability. The two groups had similar rates of major complications, including death, significant acute graft-versus-host disease, and veno-occlusive disease of the liver. CONCLUSION: Increased use of outpatient-based BMT should produce substantial cost savings for payers without adverse effects on patients for those patients who do not have a high risk of treatment failure.
Recent trends in tobacco consumption--Canada and other countries.
Authors: Collishaw N, Mulligan L
Journal: MMWR Morbidity and Mortality Weekly Report (1984)

Canada ranks 4th among all nations and leads the major industrialized nations in per capita consumption of manufactured cigarettes -- the dominant although not the only form of tobacco consumed worldwide.  Per capita tobacco consumption declined slightly in Canada from 1974-82 but total consumption actually increased -- but not as rapidly as population growth.  Preliminary data for 1983 show that Canadian tobacco consumption decreased substantially.  For 12 months in 1981-82 the price of tobacco products in Canada increased faster than the rate of inflation likely accounting in large measure for decreased consumption.  In the US per capita cigarette consumption for individuals 18 years or older has decreased at an annual rate of 0.6% from 1963-78 even less than the rate of decline reported for Canada.  Additionally the proportion of smokers has declined at an annual rate of 1.6% from 1965-80 (42% to 33%).  The relatively high rate of decline in the percentage of smokers compared with that in per capita cigarette consumption indicates that the average number of cigareetes smoked per smoker has increased.  The increase in the number of cigarettes consumed per smoker has averaged approximately 1% per year.  The decline in the percentage of persons in the US who smoke has been at least partially offset by an increase in the percentage who use  tobacco.  The use of smokeless tobacco products has increased at an annual rate of approximately 11% per year since 1974.  An estimated 22 million persons use smokeless tobacco.  Tobacco use is a significant public health problem in the US and many other countries and is responsible in the US for an excess of 350000 premature deaths annually.
Pharmacogenomic analysis of needle biopsies obtained before preoperative docetaxel/capecitabine/FEC (TX/FEC) chemotherapy for breast cancer
Authors: F. A. Holmes, J. A. O’Shaughnessy, B. Hellerstedt, J. Pippen, S. Vukelja, D. Kocs, L. Asmar, E. Fenske, F. Lin, W. F. Symmans, L. Pusztai
Journal: Journal of Clinical Oncology (2006)

10595 Background: Our goal was to evaluate the feasibility of obtaining fine needle biopsies, for pharmacogenomic analysis, in community based oncology practices and develop gene expression-based predictors of pathologic complete response (pCR) to preoperative sequential docetaxel/capecitabine and 5-fluorouracil, epirubicin, cyclophosphamide chemotherapy. Methods: One hundred seventy-five patients were accrued at 29 sites in the US Oncology Research network. FNA specimens were mailed to a central laboratory (MDACC) and gene expression profiling was performed on Affymetrix U133A chips. Results: RNA extraction was started on 140 specimens, 112 of these (80%) yielded ≥1 μg total RNA, 69 were hybridized and 65 (94%) gene expression profiles have passed quality control as of abstract submission date. The analysis plan is to develop a multigene predictor of pCR from the first 80 cases and test its performance independently in the remaining cases. Conclusions: Collection of mandatory research FNA biopsies for pharmacogenomic research is feasible in community practice. Approximately 80% of biopsies yield sufficient RNA for gene expression profiling. In 20% of patients, either technical factors, which can be addressed, or tumor biology (necrotic, rapidly growing tumors) were limiting. Supported by Roche Laboratories, Inc., Nutley, NJ; Pfizer, New York, NY; and Precision Therapeutics, Pittsburgh, PA. [Table: see text]