tbuckley/cabot-search huggingface dataset:
Effect of current smoking on risk of triple negative breast cancer.
Authors: Dhivya Prabhakar, Lyndsay Harris, Cheryl L. Thompson
Journal: Journal of Clinical Oncology (2015)

1592 Background: A number of lifestyle factors have been associated with risk of breast cancer. Studies have suggested that risk factors for triple negative breast cancer (TNBC) are different from other forms of breast cancer, and have suggested that parity, family history and body mass index (BMI) are associated with risk of TNBC. Here we sought to explore these associations and investigate the association of previously underexplored variables with risk of TNBC. Methods: Newly diagnosed breast cancer patients (N = 1236) were recruited from University Hospitals Case Medical Center (UHCMC) from 2007 to 2014. Patients were ineligible if they had a prior cancer or were known to be a BRCA1/2 carrier. Controls (N = 936) were recruited from the mammography center at UHCMC and were eligible if they were not diagnosed with cancer and were not known to be BRCA1/2 positive. All participants completed a lifestyle risk factor survey. Medical records were abstracted to obtain ER, PR and HER2 status. Patients were classified as TNBC if ER, PR and HER2 were negative, or non-TNBC if at least one was positive. Statistical significance of differences in physical activity, family history, parity, smoking, hours of sleep per night and BMI for both TNBC patients and non-TNBC patients compared to controls was assessed using a t-test or chi-square test. A multivariate logistic regression was used to assess significance after adjusting for age, race and BMI. Results: Of the patients, 121 were classified at TNBC and 932 were classified as non-TNBC. We noted a statistically significant association of current smoking with risk of TNBC (OR = 2.67, 95% CI = 1.05-6.76, p = 0.038 in multivariate regression). There was no association between former smoking at risk of TNBC (p = 0.28). There was no association between current smoking at risk of non-TNBC (p = 0.34). We did not note a statistically significant association between any other of the risk factors and TNBC (p > 0.05). Conclusions: There have been mixed results regarding the association of smoking with breast cancer, and, in particular, TNBC. Our data suggests that current smoking is a risk factor for TNBC, but not other subtypes of breast cancer. The lack of association between former smoking and TNBC suggests that quitting smoking may reduce risk.
Utilization of neoadjuvant systemic therapy (NST) for breast cancer.
Authors: Jahan J. Mohiuddin, Allison Mary Deal, Lisa A. Carey, Jennifer Leigh Lund, Brock R. Baker, Timothy M. Zagar, Ellen Jones, Lawrence Bruce Marks, Ronald C. Chen
Journal: Journal of Clinical Oncology (2015)

1027 Background: Multiple clinical trials demonstrated the efficacy of NST to downstage cancers and increase breast conservation. NCCN guidelines recommend NST for clinical stage IIA-IIIA patients who desire breast conservation. Understanding the national patterns of NST use is especially important in light of increasing mastectomy rates. Methods: Women diagnosed 2006-12 were included from the National Cancer Data Base, which contains 70% of incident cancers across the US. Logistic regression was used to examine factors associated with NST use. Results: Among 474,333 women, NST use increased by clinical stage: IIA (15%), IIB (39%), IIIA (52%), and IIIB (77%). Use for inflammatory breast cancer was 89%. NST use also varied by age and receptor status (Table). Mastectomy rates in patients who did not receive NST were: stage IIA (50%), IIB (69%), and IIIA (75%). On multivariable analysis, age, stage and receptor status remained significantly associated with NST. Compared to hormone receptor (HR)+/HER2- patients, adjusted odds ratios (aOR) for other groups were: HR+/HER2+ (1.91, 95% CI 1.83-2.00), HR-/HER2+ (2.56, 2.41-2.72), triple negative (2.62, 2.51-2.74). There was lower use of NST in the community (vs academic centers, aOR 0.58, 0.55-0.61) and in patients with higher vs lower Charlson comorbidity score (aOR 0.77, 0.74-0.81). There was higher use in Black vs White patients (aOR 1.11, 1.06-1.16). Medicaid and uninsured patients did not have lower NST use compared to private insurance. NST use increased over time (2012 vs 2010, aOR 1.20, 1.15-1.24). Conclusions: NST is an increasingly common approach, particularly for high risk clinical and biologic subtypes. However, many stage IIA-IIIA patients undergo mastectomy without attempting NST to downstage their cancers. Percentage of patients receiving NST by stage 2010-2012. IIA Age <50 50-59 60-69 70-79 80+ HR+/HER2- 16 12 9 7 7 HR+/HER2+ 31 23 19 11 9 HR-/HER2+ 35 28 24 16 12 Triple negative 34 29 22 16 16 IIB HR+/HER2- 42 36 29 22 12 HR+/HER2+ 56 49 43 30 23 HR-/HER2+ 62 58 48 39 14 Triple negative 61 58 47 35 17 IIIA HR+/HER2- 60 49 43 30 17 HR+/HER2+ 63 62 51 37 25 HR-/HER2+ 76 66 60 38 24 Triple negative 74 72 62 51 48 IIIB HR+/HER2- 83 81 76 57 33 HR+/HER2+ 91 87 80 65 55 HR-/HER2+ 91 93 87 74 75 Triple negative 89 88 85 83 73
Treatment center (TC) variability in survival of patients (pts) with colorectal cancer (mCRC) treated with bevacizumab (BV): A subanalysis from the BRiTE Observational Study (OCS)
Authors: H. V. Barron, D. M. Purdie, S. Feng, A. P. Sing
Journal: Journal of Clinical Oncology (2009)

e17532 Background: Treatment options and overall survival (OS) rates for pts with mCRC have increased markedly over the past decade. However, the variability in OS across TCs, and possible contributing factors (measured and unmeasured), remain unclear. We present an analysis from the BRiTE OCS assessing variability in OS as a function of TC, and sought to identify site factors that may predict better outcomes. Methods: BRiTE enrolled 1,953 pts with mCRC receiving a first-line BV-based regimen, from 248 U.S. sites, mostly community practices (Grothey et al. J Clin Oncol. 2008 26:5326). A Cox proportional hazard model was used to identify predictors of OS (age, PS, albumin, alkaline phosphatase, site of primary tumor) and calculate the expected number of deaths (E) compared to the observed number of deaths (O) within each TC. The ratio O/E was calculated and its distribution is presented. Sites with high O/E (top 25%) vs low O/E (lowest 25%) were titled “worst” (W) and “best” (B), respectively. B and W sites were compared by type (academic vs community, hospital vs clinic, urban vs rural), number of pts treated, choice of first-line chemotherapy, postprogression (PD) therapy, and duration of BV. TCs with ≥3 pts were included in the analysis (198). Results: Significant variation in the O/E ratio was observed across TCs ( Table ). The differences between W and B TCs were that pts at W TCs were less likely to receive a first-line oxali containing regimen (65% vs 67%), had shorter overall duration of BV (8 m vs 12 m) and were less likely to use BV following PD (33% vs 39%). Measured site, pt, and treatment variables explained ∼7% of the variability in O/E, suggesting most TC variability was due to unmeasured factors. Conclusions: Significant variability in OS exists across BRiTE TCs, which appears partly related to the specific therapies received by pts. Further work is needed to determine whether W TCs can be optimized and improve outcomes in pts with mCRC. [Table: see text] [Table: see text]
Improving the quality of breast cancer surgical treatment decisions.
Authors: Steven J. Katz, Jennifer J. Griggs, Nancy K. Janz, Sarah T. Hawley
Journal: Journal of Clinical Oncology (2012)

6024 Background: Ensuring breast cancer treatment decisions are high quality (i.e., informed and preference-concordant) is a key component of patient centered care. Methods: A web-based decision tool, including an interactive preference clarification exercise, was developed over a one-year period with input from health communication experts, clinicians, and women with breast cancer. Newly diagnosed early stage breast cancer patients from two cancer centers were recruited and randomized to view the tool before or after completing a survey. Mean scores for key outcome measures, including surgical treatment knowledge (4 true/false questions), decision satisfaction (12 questions each with a 5-point Likert scale from strongly agree to strongly disagree), and preference-concordant decisions, were compared between the groups using t-tests. Concordance between preferences and surgical choices was evaluated using the chi-square test. Results: 110 subjects were recruited and 105 completed the study. Their mean age was 57 years, 60% had a college degree or more, and 81% were white. Those viewing the website first had higher scores on several decision outcomes than those taking the survey first (Table). Knowledge scores were also higher among those viewing the website before the survey (3.0 vs. 2.61, p=.23). The risk of recurrence was the most important treatment attribute, followed by retaining the natural breast, in both groups. Concordance between treatment choice and computer generated treatment was 65% for website first and 61% for survey first groups. Conclusions: A tool focused on improving knowledge and preference-concordant decisions produced positive results on breast cancer surgical treatment decision making. Further work should assess the impact of the tool in larger and more diverse populations. [Table: see text]
Multicenter phase II trial of temsirolimus (TEM) and bevacizumab (BEV) in pancreatic neuroendocrine tumor (PNET): Results of a planned interim efficacy analysis.
Authors: Timothy J. Hobday, Rui Qin, Diane Lauren Reidy, Malcolm J. Moore, Jonathan R. Strosberg, Andreas Kaubisch, Manisha H. Shah, Hedy Lee Kindler, Heinz-Josef Lenz, Helen Chen, Charles Erlichman
Journal: Journal of Clinical Oncology (2012)

4047 Background: PNET has long had few effective therapies other than chemotherapy. Recent placebo-controlled phase III trials of the mTOR inhibitor everolimus and the VEGF/ PDGF receptor inhibitor sunitinib noted improved progression-free survival (PFS). However, objective response rates (RR) with these agents are still &lt;10%. Preclinical studies suggest enhanced anti-tumor effects with combined mTOR and VEGF targeted therapy. Methods: We conducted a phase II trial of the mTOR inhibitor TEM (25 mg IV q week) and the VEGF-A monoclonal antibody BEV (10 mg/kg IV q 2 weeks) in patients (pts) with well or moderately differentiated PNET and progressive disease by RECIST within 7 months of study entry. Co-primary endpoints were RR and 6-month PFS. Planned enrollment is 50 patients, with interim analysis for futility after the first 25 evaluable pts. Pts had no prior mTOR or VEGF targeted agents, ECOG PS 0-1, and adequate hematologic and organ function. Continued octreotide was allowed, but not required. Prior interferon, embolization, and ≤ 2 chemotherapy regimens were allowed. Results: Confirmed PR was documented in 13 of the first 25 (52%) evaluable patients. 21 of 25 (84%) patients were progression-free at 6 months. Both endpoints exceeded the protocol-defined criteria to continue enrollment. For 36 evaluable patients, the most common grade 3-4 adverse events attributed to therapy were hypertension (14%), leukopenia (11%), lymphopenia (11%), hyperglycemia (11%), mucositis (8%), hypokalemia (8%), and fatigue (8%). Conclusions: The combination of TEM/BEV has substantial activity in a multi-center phase II trial with RR of 52%, well in excess of single targeted agents in PNET. 6-month PFS was a notable 84% in a population of patients with RECIST criteria progression within 7 months of study entry. Accrual is ongoing.
Proportional shortfall due to pancreatic cancer in Europe: Survival and quality of life analysis based on a systematic review.
Authors: Alfredo Carrato, Alfredo Falcone, Michel Ducreux, Juan W. Valle, Adam Parnaby, Kamel Djazouli, Kym Alnwick-Allu, Adam Hutchings
Journal: Journal of Clinical Oncology (2014)

e15253 Background: Proportional shortfall (PS) analysis has been proposed as a quantitative methodology to compare the relative burden of different diseases for the purposes of informing resource allocation (van de Wetering et al. 2013). The study applied the PS methodology to pancreatic cancer – a disease associated with a very poor prognosis and a high patient burden. Methods: PS is represented by a number from 0 (no loss of healthy life) to 1 (complete loss of remaining healthy life) and estimated as a ratio of the disease-related quality-adjusted life year (QALY) loss as a proportion of the remaining patient QALY expectation in the absence of disease. Parameter values for the analyses were derived from a systematic literature review of epidemiology, survival, and quality of life in pancreatic cancer in Europe. Results: QALY expectation in the absence of pancreatic cancer was calculated based on the mean life expectancy of patients aged 64 in 28 countries of the EU (20.5 years) adjusted for the average quality of life in this age group (0.8 utility). The EU general population aged 60-65 can therefore expect to live 16.4 additional years of life at full health (Table).The pancreatic cancer-related QALY expectation was calculated using a median survival of 0.4 years (5.3 months; mean of 4 studies; median age 62-66). This was adjusted by the patient quality of life reported in a German study of 45 pancreatic cancer patients (0.65 utility; mean age, 64 years). A patient with pancreatic cancer can therefore only expect to live 0.29 years of life in full health.The PS for pancreatic cancer is 0.98, indicating a 98% loss of remaining healthy life. This is largely attributable to the very low median life expectancy in these patients compared with the life expectancy of the average European of the same age. Conclusions: The Proportional Shortfall approach incorporates quality of life and survival to quantitatively assess the relative burden of disease. In pancreatic cancer it demonstrates the nearly complete loss of healthy life associated with the disease. Age 64 Proportional shortfall Healthy population PanC patients Average survival 20.5 years 0.4 years (5.3 months) Quality of life 0.8 0.65 QALYs 16.4 0.29 0.98
Multiplex testing of potentially ‘actionable’ alterations in small cell lung cancer (SCLC).
Authors: Shirish M. Gadgeel, Aliccia Bollig-Fischer, Ann G. Schwartz, Antoinette J. Wozniak, Michele L Cote, Ammar Sukari, Wei Chen, Laura Mantha, Gerold Bepler
Journal: Journal of Clinical Oncology (2014)

7592 Background: Therapy and outcomes of SCLC patients have not changed for many years. Recently, driver mutations have been identified in many cancers and targeting these mutations can provide clinical benefit. Recent data from whole genome sequencing suggest that driver mutations may exist in SCLCs. We conducted multiplex testing of SCLCs to identify mutations potentially predictive of response to novel and established therapeutics. Methods: We identified tumor tissues of 30 SCLC patients collected as part of two different institutional review board approved studies. Using the Sequenom MassArray system and a multiplexed panel, we analyzed tumor DNA for 214 mutations in 26 genes associated with the pathogenesis of lung cancer. Gene copy number analysis utilized a 180K oligonucleotide microarray and comparative genomic hybridization assay. Results: The median age at diagnosis of patients was 63 years; 66 % of were males; 23% were African-Americans; 57% patients had extensive stage SCLC at diagnosis. Point mutations were identified in 5 (17%) patients, 2 patients had p53 mutations, 1 each had PI3K, EGFR and Kras mutation. Of the 21 tumors for which gene copy number analysis has been completed, the median number of genes, listed in the Sanger Institute Cancer gene census, that were altered was 135 (range 0-299). Only 1 tumor had no gene copy number alterations. Of the genes that are targets for novel anticancer agents, PI3K (76%) and DDR2 (48%) amplifications were the most frequent alterations. Among the 21 tumors analyzed for both point mutations and gene copy number variations, one or more potentially actionable alterations were identified in 19 (90%) tumors. Conclusions: Our analysis indicates that potentially
Next-generation sequencing in a cohort of metastatic breast cancer (MBC) patients.
Authors: Tadeu Frantz Ambros, Grzegorz Gurda, Adrian V. Lee, Adam Brufsky, Steffi Oesterreich, Rohit Bhargava, Marina Nikiforova, Yuri Nikiforov, Shannon Puhalla
Journal: Journal of Clinical Oncology (2015)

e22053 Background: MBC eventually becomes resistant to available therapies. The diverse genomic alterations in breast cancer present an opportunity for identification of actionable genomic variations and discovery of new disease drivers. Methods: A de-identified search of all clinical patient data at UPMC yielded 30 MBC whose cancer samples underwent next-generation sequencing (NGS) via in house Ion Torrent PGM from January, 2013 to June, 2014, performed at the physician's discretion. A standard 46 or 50 cancer gene panel with approximately 2,800 mutations was reported. Patients were included if they had histological confirmation of MBC and available NGS data. Results: Our search resulted in 30 cases. Median age was 54 years (range 35-75). Breast cancer subgroups were mostly represented by ER+/HER2- with 16 patients (53.3%), triple negative breast cancer (TNBC) with 11 (36.7%) patients, ER+/HER2+ with 2 patients (6.7%) and ER-/HER2+ with 1 (3.3%) patient. NGS was obtained from a metastasis biopsy in 25 patients (83.3%). Median follow-up time post NGS was 5.5 months (range 0-18). Patients received a median of 3 (range 0-14) lines of therapy before NGS. Fifteen (50%) patients had at least one variant affecting function (VAF), while 22 (83.3%) had at least one variant of unclear significance. The mean number of VAF was 0.9 and VUS was 1.6. A total of 75 unique aberrations were detected, including: PIK3CA (n = 10), TP53 (n = 9), KRAS (n = 1), APC (n = 1), PTEN (n = 1), STK11 (n = 1), EGFR amplification (n = 1), ERBB4 (n = 1) and FGFR1 (n = 1). Higher frequency of PIK3CA mutations was associated with ER+ disease (p = 0.06) and longer DFI (p = 0.03). Six patients received targeted therapy based on the NGS results although no patients were included in clinical trials. Conclusions: It is feasible to use NGS in patients with MBC to find potential actionable targets of therapy and as a tool for hypothesis generation for new prognostic and predictive genomic markers. Genome driven clinical trials will likely make these results more usable, as current therapeutic options may be limited in routine clinical practice.
Lamellar Ichthyosis in Sub-Saharan Africa
Authors: Celestin Ahogo Kouadio, Jacob Enoh, Patrice Gbery Ildevert, Laciné Cissé, Ange Sylvain Allou
Journal: JAMA Dermatology (2017)

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Restrictive versus liberal blood transfusion for gastrointestinal bleeding: a systematic review and meta-analysis of randomised controlled trials
Authors: Ayodele Odutayo, Michael J R Desborough, Marialena Trivella, Adrian J Stanley, Carolyn Dorée, Gary S Collins, Sally Hopewell, Susan J Brunskill, Brennan C Kahan, Richard F A Logan, Alan N Barkun, Michael F Murphy, Vipul Jairath
Journal: The Lancet. Gastroenterology & hepatology (2017)
Efficacy of bevacizumab in combination with doublet chemotherapy as first-line therapy in metastatic colorectal cancer according to KRAS status.
Authors: Katsuyuki Murai, Toshiki Masuishi, Hiroya Taniguchi, Satoshi Hamauchi, Keiji Sugiyama, Takahiro Tsushima, Seiichiro Mitani, Akiko Todaka, Kazunori Honda, Tomoya Yokota, Yukiya Narita, Nozomu Machida, Shigenori Kadowaki, Akira Fukutomi, Takashi Ura, Yusuke Onozawa, Masashi Ando, Hirofumi Yasui, Kei Muro, Kentaro Yamazaki
Journal: Journal of Clinical Oncology (2017)

744 Background: Bevacizumab (BV) plus fluoropyrimidine-based chemotherapy is a standard treatment as first-line therapy for metastatic colorectal cancer (mCRC). In phase 3 studies, addition of BV to doublet chemotherapy significantly improved progression-free survival (PFS), otherwise overall survival (OS) differences didn’t reach statistical significance. There are only a few reports that assess the efficacy of BV containing chemotherapy according to KRAS status. Methods: We retrospectively reviewed the data of mCRC patients who received doublet chemotherapy (FOLFOX/CapeOX/SOX/FOLFIRI/IRIS) with or without BV as first-line therapy in Aichi Cancer Center or Shizuoka Cancer Center between Apr. 2007 and Aug. 2014. Patients fulfilled following criteria: histologically proven adenocarcinoma, ECOG PS 0-1, adequate organ functions. Exclusion criteria were as follows: KRAS status unknown, adjuvant chemotherapy within less than 6 months (M) before relapse, doublet chemotherapy with other biologics. We analyzed the efficacy of doublet chemotherapy with BV (Group A) and without BV (Group B), dividing into KRAS exon 2 wild type (WT) and mutant (MT). WT-A means Group A in WT. Results: Patients met the selection criteria were 578 (WT-A/WT-B 276/55, MT-A/MT-B 202/45). Patients’ backgrounds were as follows; median age (range) 63 (20-88) years old, male/female 60/40%, ECOG PS 0/1 66/34%, tumor location right colon/left colon and rectum 29/71%, number of metastases 1/ ≥ 2 48/52%, KRAS status WT/MT 57/43%. PFS in Group A/B was 13.0/8.4 m (HR 0.49, 95%CI 0.39-0.61, p &lt; 0.0001), and OS was 32.4/27.1 m (HR 0.70, 95%CI 0.56-0.88, p = 0.0024). PFS was 12.7/8.5 m in WT-A/WT-B (HR 0.51, 95%CI 0.38-0.69, p &lt; 0.0001), 14.5/8.0 m in MT-A/MT-B (HR 0.46, 95%CI 0.33-0.64, p &lt; 0.0001). OS was 32.6/29.8 m in WT-A/WT-B (HR 0.85, 95%CI 0.62-1.17, p = 0.32), 31.7/25.8 m in MT-A/MT-B (HR 0.55, 95%CI 0.39-0.77, p = 0.0005), adjusted HR (variables: age, sex, ECOG PS, tumor location, et al) was 0.74 in WT (95%CI 0.53-1.05, p = 0.089), 0.69 in MT (95%CI 0.48-1.00, p = 0.047). Conclusions: Addition of BV to doublet chemotherapy as first-line therapy might prolong OS in patients with mCRC regardless of KRAS status.