tbuckley/cabot-search huggingface dataset:
Predictors of survival in patients with HER2+ metastatic breast cancer (MBC) treated with trastuzumab.
Authors: E. M. Olson, J. S. Najita, J. Sohl, A. Arnaout, E. P. Winer, N. U. Lin
Journal: Journal of Clinical Oncology (2011)

e11100 Background: Trastuzumab (T) is associated with improvements in overall survival (OS) among patients (pts) with HER2+ MBC; however disease course in individual pts is highly variable. We aimed to identify predictors of OS in pts with HER2+ MBC who were treated with a T-based regimen. Methods: Using pharmacy records, 113 HER2+ pts diagnosed with MBC from January 1999 to May 2005 who received T-based therapy at Dana-Farber Cancer Institute were retrospectively identified to allow for a minimum of 5 years (yrs) of follow up. Median OS and 95% CI were determined using Kaplan-Meier methods; group comparisons utilized the log-rank test. Hazard ratios (HR) were obtained using a Cox proportional hazards model adjusting for age at recurrence, era of first line therapy, hormone receptor status and disease-free interval (DFI). Results: Median follow up was 6.7 yrs (range 0.7-20.8) from diagnosis of primary breast cancer. Median number of metastatic T-based regimens was 3 (range 1-12). Median OS was 3.5 yrs (95% CI 3.0-4.4). On univariate analysis, median OS was worse in pts with a DFI < 2 yrs (3.0 yrs, CI 1.6-3.9) compared to ≥ 2 yrs (4.4 yrs, CI 3.1-5.5; p=0.03); and in pts with ≥ 2 metastatic sites (2.6 yrs, CI 2.0-3.3) vs. pts with only 1 site (4.1 yrs, CI 3.2-6.0; p=0.01). CNS disease at first recurrence was associated with a shorter OS compared with liver and/or lung mets or other sites (CNS: 1.9 yrs CI 0.1-5.9, liver/lung: 3.2 yrs CI 2.5-4.2, other: 4.6 yrs CI 2.7-8.0; p=0.05). CNS mets developed in 62 (55%) pts by the time of death or last follow up; of the pts alive at 1, 3 and 5 yrs, CNS disease was present in 20%, 39%, and 41% of pts respectively. To explore a potential selection bias, we evaluated a subset of 56 pts diagnosed with primary breast cancer ≥ 1999 (i.e. after the adoption of routine HER2 testing); CNS mets at first recurrence in these pts predicted for worse median OS compared to other sites (CNS: 1.1 yrs CI 0.1-2.7, liver/lung: 2.1 yrs CI 1.3-3.5, other: 4.4 yrs CI 0.5-6.3; p=0.004) with a HR 6.3 (CI 1.2-33.0; p=0.03). Conclusions: The natural history of HER2+ MBC has evolved with T-based therapy, with median OS now exceeding 3 yrs. CNS metastases are common, and the presence of CNS disease predicts for a worse outcome.
Genotype-based gene signature of glioma risk
Authors: Yen-Tsung Huang, Yi Zhang, Zhijin Wu, Dominique S. Michaud
Journal: Neuro-Oncology (2016)

Glioma accounts for 80% of malignant brain tumors, but its etiologic determinants remain elusive. Despite genetic susceptibility loci identified by genome-wide association study (GWAS), the agnostic approach leaves open the possibility that other susceptibility genes remain to be discovered. Here we conduct a gene-centric integrative GWAS (iGWAS) of glioma risk that combines transcriptomics and genetics. We synthesized a brain transcriptomics dataset (n = 354), a GWAS dataset (n = 4203), and an advanced glioma tumor transcriptomic dataset (n = 483) to conduct an iGWAS. Using the expression quantitative trait loci (eQTL) dataset, we built models to predict gene expression for the GWAS data, based on eQTL genotypes. With the predicted gene expression, iGWAS analyses were performed using a novel statistical method. Gene signature risk score was constructed using a penalized logistic regression model. A total of 30527 transcripts were analyzed using the iGWAS approach. Four novel glioma susceptibility genes were identified with internal and external validation, including DRD5 (P = 3.0 × 10–79), WDR1 (P = 8.4 × 10–77), NOMO1 (P = 1.3 × 10–25), and PDXDC1 (P = 8.3 × 10–24). The genotype-predicted transcription pattern between cases and controls is consistent with that between tumor and its matched normal tissue. The genotype-based 4-gene signature improved the classification between glioma cases and controls based on age, gender, and population stratification, with area under the receiver operating characteristic curve increasing from 0.77 to 0.85 (P = 8.1 × 10–23). A new genotype-based gene signature of glioma was identified using a novel iGWAS approach, which integrates multiplatform genomic data as well as different genetic association studies.
Brief versions of the FACIT-fatigue and FAACT subscales for patients with non-small cell lung cancer cachexia.
Authors: John M Salsman, Jennifer L Beaumont, Katy Wortman, Ying Yan, John Friend, David Cella
Journal: Journal of Clinical Oncology (2014)

259 Background: Cancer anorexia-cachexia syndrome (CACS) is common in advanced cancer patients and associated with weight loss, fatigue, impaired quality of life (QoL), and poor prognosis. The goal of this project was to identify the most responsive items and evaluate their validity from two QoL measures in the ROMANA 2 (NCT01387282) Phase III global study evaluating anamorelin HCl in the treatment of non-small cell lung cancer (NSCLC) cachexia: the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) and the Functional Assessment of Anorexia/ Cachexia Therapy (FAACT). Methods: In the ROMANA 2 trial, 477 patients with unresectable Stage III or IV NSCLC and cachexia were to be enrolled and randomized (2:1) to receive anamorelin HCl or placebo once daily for 12 weeks. All 383 patients who reached the Week 12 visit at the time of this blinded data analysis were included. Co-primary endpoints were change from baseline in lean body mass and handgrip strength. QoL was a key secondary outcome with FACIT-F and FAACT questionnaires administered at baseline and at weeks 3, 6, 9, and 12. Results: Two 4-item scales (referred to as the Simplified Evaluation of Fatigue [SEF] &amp; Simplified Evaluation of Appetite [SEA]) from the FACIT-F and FAACT, respectively, demonstrated good internal consistency reliability with Cronbach’s alphas &gt;0.70. In analysis of known group validity, scores significantly differed between groups defined by performance status and appetite (with effect sizes ≥0.34). Convergent validity analysis showed significant correlations with general QoL/functioning scales (correlation coefficients 0.41–0.77), further demonstrating validity. In terms of responsiveness, changes from baseline to week 12 in SEF and SEA scores were associated with changes in general QoL/ functioning, appetite, weight, and lean body mass (correlations &gt;0.20). The estimated important difference for each scale was ~1-2 points. Conclusions: These brief scales are valid and responsive measures that provide psychometric properties necessary to promote future research in NSCLC patients with CACS. Additional work should examine clinical utility of these scales and their impact on treatment decision-making.
Short-term outcomes of implementation of a computer-based breast cancer risk assessment program during screening mammography.
Authors: Debra Ray, Sherry Grumet, Portia Lagmay-Fuentes, Lolita Jacob, Annette Terzo, Alex Puma, Shirley Hwang
Journal: Journal of Clinical Oncology (2012)

298 Background: Major barriers to high risk breast cancer risk assessment include inadequate documentation of family history, complexity of risk calculation and model selection, and lack of awareness. We have established a high risk breast cancer assessment program using a computer-based real time risk calculation at time of screening mammography. Objectives were to facilitate identification of high risk patients needing genetic counseling/testing and MRI breast screening. Methods: Beginning 11/23/2010, prior to screening mammogram all patients completed a self reported risk assessment using a wireless tablet. With real time risk calculation for risk of genetic mutation (Myriad and BRCAPRO models) as well as life time risk of breast cancer (Gail, Claus, Tyrer-Cuzick, and BRCAPRO models) using HughesRiskApps patients were categorized into high risk ( ≥ 10% gene mutation risk or ≥ 20% life time breast cancer risk) or average risk groups and received a risk assessment letter. The risk data was integrated into mammography information system (Penrad) simultaneously. High risk patients were contacted by a coordinator to facilitate high risk clinic evaluation. Results: As of June 30, 2012, 24,213 patients without a cancer history completed HRA; 2,196 patients (9.1%) have been identified as high risk- for genetic mutation 1,051 pts, (4.3%), life time risk 1,570 pts, (6.5%), and both risks 425 pt, (1.8%). 416 patients (18.9%) of those high risk patients have been evaluated in the high risk clinic. 231 patients have been evaluated by genetic counselor and 97 have had genetic testing and 9 with positive results (9.3%). Yearly screening breast MRI has been recommended to 254 patients. Conclusions: We have successfully implemented breast cancer risk assessment through screening mammography service. Results suggest that 9.1% of our patients can benefit from high risk clinic assessment and 4.3% should have consideration for gene mutation testing. 6.5% of our patients may benefit from screening breast MRI. We strive to improve the number of patients who proceed with high risk clinic assessment by education of our patients regarding benefits of screening and risk reducing strategies.
Usefulness of FDG-PET in the evaluation of tumor response to proton beam therapy for locally advanced pancreatic ductal adenocarcinoma.
Authors: Sachiyo Shirakawa, Ippei Matsumoto, Kazuki Terashima, Makoto Shinzeki, Sadaki Asari, Tadahiro Goto, Hideyo Mukubo, Masaki Tanaka, Hironori Yamashita, Toshimitsu Iwasaki, Jun Ishida, Taro Okazaki, Masahiro Kido, Masanori Takahashi, Atsushi Takebe, Kenji Fukushima, Tetsuo Ajiki, Takumi Fukumoto, Yonson Ku
Journal: Journal of Clinical Oncology (2013)

271 Background: Evaluation of tumor response to radiation therapy in pancreatic ductal adenocarcinoma (PDA) using conventional radiological tests is difficult due to generally small size and inflammatory or fibrotic changes of radiated tissue. Although increasing evidence has shown that 18-F-fluorodeoxyglucose-positoron emission tomography (FDG-PET) can assess functional changes in various tumors, available data in PDA with radiation therapy is scarce. In this study, we investigated the role of FDG-PET in long-term monitoring tumor response to proton beam therapy (PBT) for PDA. Methods: Thirty-four locally advanced PDA patients with pre- and post-PBT FDG-PET data were included in this study. Local tumor responses by computed tomography (CT) and FDG-PET were defined as below: response group in CT (complete response: CR, partial response: PR, stable disease: SD, progressive disease: PD) was defined according to Response Evaluation Criteria in Solid Tumors, but only evaluation of primary tumor; and in FDG-PET, CR was defined as disappearance of FDG uptake, PR as decrease, SD as unchange, and PD as increase, compared to pre-PBT data. We evaluated tumor response at three different time points: 0-3, 3-6, and 6-12 months after PBT. Also serum CA19-9 values were evaluated. Results: Radiation doses were 50.4-70.2 GyE and 28 (82%) patients received concomitant chemotherapy. During the follow-up period (median 19 months), a total of 90 FDG-PET tests were performed. At the first time point, SD was noted in 90% (9/10) of patients by CT, whereas CR or PR in all by FDG-PET. At the second point, 39% (7/18) of patients demonstrated PR by CT, whereas 91% CR or PR by FDG-PET. Two patients with PD by FDG-PET were diagnosed as SD by CT, while one patient with PD by CT was diagnosed as PR by FDG-PET. At the third point, four patients with PD by FDG-PET were diagnosed as PR or SD by CT. Serum CA19-9 values supported FDG-PET findings. In four of 14 patients with serial FDG-PET, the maximum effects were noted at the second point. Conclusions: Serial FDG-PET can detect changes in local tumor response to PBT for PDA earlier and more sensitively than CT. Of note, there is the risk for false positive in early post-PBT FDG-PET.
Value of FDG-PET for detecting metastatic lesions in head and neck cancer
Authors: S. E. Fogh, C. Champ, G. J. Kubicek, C. Intenzo, R. A. Axelrod, W. M. Keane, M. Machtay
Journal: Journal of Clinical Oncology (2008)

6047 Introduction: The role of PET scans in the staging of head and neck cancer (HNC) is unclear. The NCCN guidelines do not recommend routine metastatic workup beyond physical exam, CXR and laboratory tests. The purpose of this report is to examine the incidence and accuracy of staging PET scans for detecting metastatic disease in patients with HNC. Methods: Retrospective review of all newly diagnosed HNC patients who had a staging PET scan at Thomas Jefferson University between 2003 and 2007. 182 patients with SCC (171), or adenocarcinoma (11) histologies were analyzed in this study, none of whom had known metastatic disease prior to staging PET exam. Clinical stage prior to the PET scan was stage I-II in 26 patients (14%), stage III in 24 patients (14%), and stage IVa or b in 107 patients (59%). 25 patients had recurrent disease. Results: The overall incidence of confirmed metastatic disease in this study population was 6.0%. Twenty-five (13.5%) of the staging PET scans had areas suspicious for a metastatic lesion(s). Twenty-two patients were further evaluated with subsequent confirmatory imaging and/or biopsy, revealing 10 (45.5%) true positives, and 12 (54.5%) false positives. Of the 157 negative PET scans there was 1(0.5%) false negative and 156 (98.7%) true negatives. Thus, the sensitivity of PET was 91% and specificity was 93%. Positive predictive value is 45% and negative predictive value is 99.5%. No patients with pre-PET clinical stage II or I cancer had confirmed distant metastases. Patients with metastatic disease had stage III (1 patient) or stage IV (10) - nodal stages were N0 (2), N2 (1), N2 (4), and N3 (3). The only statistically significant predictor for metastatic disease was clinical stage IV versus all other stages (p <0.028). Conclusions: The incidence of metastatic disease in HNC is low, but finite. Given the marked differences in the treatment of locally advanced/non-metastatic HNC versus metastatic HNC, we recommend metastatic workup with PET for clinical stage III/IV disease. Although the sensitivity, specificity and negative predictive value rates were acceptable, the positive predictive value was suboptimal. Patients found to have a PET scan ‘positive‘ for metastatic disease require confirmatory imaging or ideally biopsy. PET scan is not necessary for patients with clinical stage I/II disease. No significant financial relationships to disclose.
Genetic ancestry and odds of prostate cancer diagnosis in African American and European American men.
Authors: Yaw A. Nyame, Adam Murphy, Ken Batai, Ebony Shah, Maria Ruden, Courtney M.P. Hollowell, Andre Kajdacsy-Balla, William Catalona, Rick Kittles
Journal: Journal of Clinical Oncology (2016)

86 Background: Although ethnic differences in disease incidence among African American (AA) men may reflect differences in screening behaviors and behavioral and socioeconomic factors, genetic ancestry may be a factor. This study will investigate the association between West African and Native American genetic ancestry and PCa diagnosis. Methods: We enrolled 40-79 year-old men who were undergoing prostate biopsy or routine PSA screening at outpatient urology clinics in Chicago, IL. Blood was drawn at the time of enrollment for the genotyping of 105 ancestry informative markers. West African (WAA), European (EA), and Native American (NAA) genetic ancestry was estimated using the Bayesian Markov Chain-Monte Carlo method implemented in the program STRUCTURE. Univariate analysis was performed by Wilcoxon rank-sum test for continuous variables. Unconditional binary logistic regression models were used to estimate odds ratios for the likelihood of PCa diagnosis and for the odds of having high-risk PCa relative to controls, adjusting for age, body mass index (BMI), alcohol-use, and family history of PCa. Results: 857 men were enrolled; 34.5 % were diagnosed with PCa, 50.9 % were controls and 14.6 % were men with negative prostate biopsies. AAs comprised 27% of the sample. The median was 63 years (IQR 57 – 68). Among AA men, the median genetic WAA proportion was 0.78 (IQR 0.69 – 0.83) and NAA was 0.04 (IQR 0.02 – 0.09). There was no significant difference in genetic WAA among AA men with and without PCa diagnosis (p = 0.54); however, genetic NAA was significantly lower among PCa cases (median 0.034 vs 0.057,p = 0.03) compared to controls. Among EA men, the media NAA was 0.067 (IQR (0.03 – 0.10). Similarly among EA men, genetic NAA was significantly lower among cancer cases (0.04 vs. 0.08, p &lt; 0.001). On logistic regression, WAA ≥ 88% was associated with increased odds of PCa in AA men (OR 2.6 95% CI 1.1 – 6.7). In both AAs (OR 0.5, 95% CI 0.2 – 1.1) and EAs (OR 0.3, 95 % 0.2 – 0.6), men in the highest genetic NAA quintile had a decreased risk of PCa on logistic regression compared to men in the lowest quintile. Conclusions: Our study reveals that NAA is protective against PCa diagnosis among all men. Additionally, AA men with a high degree of WAA demonstrate an increased risk of PCa. Future work will focus on determining the association of known prostate cancer risk SNPs such as the 8q24 regions and genetic ancestry.
A Novel Evolutionary Pattern Revealed Using Deep Sequencing of Immunoglobulin Loci at Diagnosis and over the Course of Treatment in Multiple Myeloma Patients
Authors: Nikhil C. Munshi, Joaquin Martinez-Lopez, Victoria Carlton, Stephanie Minvielle, Yu-Tzu Tai, Mariateresa Fulciniti, Mehmet K. Samur, Paul G. Richardson, Michel Attal, Philippe Moreau, Florence Magrangeas, Kenneth C. Anderson, Malek Faham, Herve Avet-Loiseau
Journal: Blood (2016)
Etoricoxib and anastrozole in adjuvant early breast cancer: ETAN trial (phase III).
Authors: M. S. Rosati, M. Di Seri, G. Baciarello, V. LO Russo, P. Grassi, L. Marchetti, S. Giovannoni, M. L. Basile, L. Frati
Journal: Journal of Clinical Oncology (2011)

533 Background: Preclinical data clearly demonstrated that cyclooxigenase activates growth-promoting and anti-apoptotic pathways as well as aromatase. However, data from clinical trial are poor, mainly due to the severe restrictions that the FDA has imposed to the COX-2 inhibitors in 2004 because of their serious adverse events. Methods: We designed a phase III, placebo-controlled prospective trial in which postmenopausal hormone-receptor positive early breast cancer (EBC) women were randomized 1:1 to receive anastrozole (1 mg/die) upfront in combination with placebo or etoricoxib (60 mg/die). Combined treatment was planned for 24 months. Patients were allowed to discontinue the etoricoxib or placebo for toxicity (censored). Anastrozole was continued for 5 years. The primary end-point was the 5-years event free survival (EFS). The secondary end-point was to compare the risk of fracture and the muscle-skeletal events in the two groups. Chi-Square tests for categorical data and time to event provided two-sided p values. Results: Since 2003 to 2006 we enrolled 182 patients. A number of 93 patients was enrolled in the treatment arm and N=89 in the control. The median treatment duration was 14 months in ETAN group and 12 in PAN group. A number of 37 patients in the treatment arm and 33 in the control discontinued etoricoxib after the FDA alert on COX-2 inhibitors. To a 5 years follow-up, the median EFS was 56.9 and 53.14 months [HR: 1.9; 95%CI (1.03 – 3.59), p= .03] in the treatment arm and control, respectively. There were no significative differences in terms of fractures [RR: 0.58, 95%CI (0.14-2.38), p= .45]. Muscle-skeletal pain was significative lower in the treatment arm (50/73) than the control (16/67) [RR: 2.1, 95%CI (1.29-3.43), p= .002]. None of the patients in the treatment arm developed serious adverse event. Conclusions: Our data demonstrated a small but significative advantage in terms of EFS and muscle-skeletal events when etoricoxib is added to anastrozole in adjuvant setting. Data are strongly limited from the study drop-out, but the very long follow-up and the absence of major toxicity encourage larger phase III confirmatory trials.
Chemotherapy use during the last 30 days of life in patients with cancer.
Authors: Maria Alma Rodriguez, Yvette DeJesus, Lee Cheng
Journal: Journal of Clinical Oncology (2012)

231 Background: Treatment options are increasingly available to patients with advanced cancer. Appropriately timed cession of chemotherapy is a quality-of-care measure in the Quality Oncology Practice Initiative of the American Society of Clinical Oncology. To gain insight into whether communication about end-of-life (EOL) issues might need to be improved, we analyzed chemotherapy use during the 30 days at the EOL (EOLCx) among patients at large cancer center. We also analyzed the presence of electronic DNR (eDNR) orders at the time of death in hospital as a surrogate indicator of EOL discussions. Methods: We reviewed the records of cancer patients (age≥18 years) who received their care at The University of Texas MD Anderson Cancer Center and died between December 2010 and May 2012. Logistic regression was used to measure associations of EOLCx and age, gender, ethnicity, comorbidities, cancer type, and cancer progression. Results: A total of 7,399 patients met the inclusion criteria. The median age was 64 years; 46% were female and 18% had hematologic malignancies (HM). 996 patients (14%) received EOLCx, and of these, 554 died in the hospital (7%, 554/7,399). Of those who died in the hospital, 93% had eDNR orders (no difference between solid tumors [ST] and HM). The EOLCx was higher for patients who died in the hospital than for those who died elsewhere (44% vs 7%) and higher for patients with HM than for those with ST (38% vs 8%). EOLCx was more common in patients with ST with metastases, HM without relapse, and HM with relapse than in those with ST without metastases [odds ratios (ORs), 3.3, 13.9, and 32.8, respectively; all p&lt;0.05]. EOLCx was less common in older patients (≥65 years) than younger patients (OR, 0.6; p&lt;0.05) and was more common in patients with comorbidities than in those without (OR, 1.3; p&lt;0.05) and in patients who were not black or Hispanic than in white patients (OR, 1.6; p&lt;0.05). No difference of EOLCx between genders was found. Conclusions: EOLCx was more common in patients with HM with or without relapse than in patients with ST. Most patients had eDNR orders at the time of death in hospital. The results suggest that communication about prognosis and advanced planning about the goals of medical care is becoming critical part in overall oncologic care plan.