tbuckley/cabot-search huggingface dataset:
Discerning predictors for gender differences in survival outcomes for patients treated for bladder cancer.
Authors: Preston Kerr, Jinhai Huo, Sharon Hermes Giordano, Ashish M. Kamat, Edwin Edgard Morales, Justin Edwin Fang, Leslie Ynalvez, Tamer Dafashy, Christopher David Kosarek, Cameron Ghaffary, Stephen Bentley Williams
Journal: Journal of Clinical Oncology (2017)

360 Background: Radical cystectomy is an underutilized option for those with refractory non-muscle invasive and muscle-invasive bladder cancer, however, use of radical cystectomy may differ according to gender. We wanted to discern receipt and timing of radical cystectomy as well as survival outcomes according to gender. Methods: A total of 49,974 patients aged 66 years or older diagnosed with clinical stage I-IV bladder cancer from January 1, 2002 to December 31, 2011 using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data. We used univariate and multivariable regression analyses to identify factors predicting the use of radical cystectomy. Cox proportional hazards models were used to analyze survival outcomes. Generalized linear models were performed to determine association between gender and delayed radical cystectomy. Results: A total of 49,974 patients were diagnosed with stage I to IV bladder cancer. 36,959 (74%) were male patients. Women were older, non-Caucasian race/ethnicity, with increased comorbidities and presented with more advanced disease (all p&lt;0.001). Women were more likely than men to receive radical cystectomy across all clinical stages (stage I, relative risk [RR] 1.53, 95% confidence interval [CI] 1.27-1.84, p&lt;0.001; stage II, RR 1.52, 95% CI 1.37-1.70, p&lt;0.001; stage III, RR 1.26, 95% CI 1.15-1.39, p&lt;0.001; stage IV, RR 1.31, 95% CI 1.17-1.47, p&lt;0.001). Women had lower cancer-specific survival with stage II (hazard ratio [HR] 1.20, 95% CI 1.09-1.32, p&lt;0.001), stage III (HR 1.44, 95% CI 1.23-1.68, p&lt;0.001), and stage IV (HR 1.29, 95%CI 1.17-1.43, p&lt;0.001) disease. Delay from diagnosis to radical cystectomy was associated with worse survival. Conclusions: Gender differences persist with women significantly more likely to undergo radical cystectomy independent of clinical stage. After controlling for tumor characteristics and neoadjuvant chemotherapy, women have significantly worse cancer-specific survival than men. Delay to surgery did not account for this decreased survival among women. These findings support further research discerning bladder carcinogenesis according to gender.
Predicting prognosis in patients with acute myeloid leukemia: The role of next-generation sequencing and mutational profiling.
Authors: Caroline E Sloan, Phyllis A. Gimotty, Anne M Boccuti, Alison Sehgal, Jianhua Zhao, Robert D Daber, Jennifer J. Morrissette, Selina M. Luger, Adam Bagg, Martin Carroll
Journal: Journal of Clinical Oncology (2014)

7068 Background: Although cytogenetics-based prognostication systems are well described in acute myeloid leukemia (AML), Patel et al. (NEJM 2012) recently used data from patients <60 years enrolled in a randomized controlled trial to create a new integrated prognostic (IP) schema using mutations in 9 genes. Our objective was to assess whether the IP schema was relevant in clinical practice. Methods: Our study consisted of 2 cohorts of patients with de novo AML, each from single large academic institutions. We included 181 patients from the Hospital of the University of Pennsylvania and 188 patients from Washington University (The Cancer Genome Atlas) for whom clinical, cytogenetic and genetic data were available. We evaluated survival outcomes among 4 mutational profiles defined by Patel et al. in the IP schema. Results: Clinical characteristics and outcomes were similar in both cohorts (n=369 overall, n=217 age <60), so they were combined for further analysis. Median age was 57 years with 59% <60 years. Patients <60 years with intermediate-risk cytogenetics (n=137) were classified as having favorable, intermediate or unfavorable mutational profiles (see table). In patients >60 years, long-term survival was poor for patients with all 4 mutational profiles and was not further evaluated for this study. Conclusions: The IP schema identifies mutational profiles that have differential survival in younger patients with intermediate-risk cytogenetics. Our findings validate Patel et al.’s IP schema in patients <60 years for some but not all mutational profiles. Performing next-generation sequencing at diagnosis may inform patient management and be cost-effective if gene panels include validated mutations and their use is tailored to patient age. Integrated prognostic (IP) assessment of patients <60 years with intermediate-risk cytogenetics. Mutational profile Prognosis n 3-year overall survival p-value FLT3-ITD negative with mutant NPM1 and IDH1/2 Favorable 13 55% 0.004 FLT3-ITD negative with mutant TET2, MLL-PTD, ASXL1 or PHF6 Unfavorable 32 45% 0.994 FLT3-ITD positive with trisomy 8 or mutant TET2, MLL-PTD or DNMT3A Unfavorable 30 17% 0.039 All others Intermediate 62 35% Reference
Utility of post-therapy surveillance scans in DLBCL.
Authors: Carrie A. Thompson, Matthew J. Maurer, Herve Ghesquieres, William R Macon, Thomas Matthew Habermann, Thomas E. Witzig, James Robert Cerhan, Brian K. Link
Journal: Journal of Clinical Oncology (2013)

8504 Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma. The optimal follow-up strategy for patients (pts) in remission is not clear. The goal of this study is to determine the utility of surveillance scans in a large, prospective, multi-institutional cohort of DLBCL pts. Methods: Patients were enrolled in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER), a prospective cohort of newly diagnosed lymphoma pts. All pts were followed for events including relapse, re-treatment, and death with events verified by medical records. Patients eligible for this study had biopsy proven DLBCL and were treated with anthracycline based immunochemotherapy (IC). Initial and post-treatment management was per treating physician. Medical records were re-reviewed in pts with events for clinical details at relapse and relationship to planned follow-up visits and surveillance scans. Results: 644 pts with DLBCL treated with IC were enrolled in MER from 2002-2009. Median age was 63 years (range 18-92), 54% were men, and median f/u was 59 months (range 8-116). 537 pts entered post-treatment observation; 109 (20%) of the 537 pts relapsed and 41 died from other causes. 42% of relapses were in the first 12 months following diagnosis, 27% between 12-24 months, and 31% &gt;24 months. In the 109 who relapsed, 62% of pts (62/100, 9 unknown) presented to their physician earlier than a planned follow-up visit due to symptoms. At the time of relapse, 68% were symptomatic, 42% of pts had abnormal physical exam, and 55% had elevated LDH; 87% of pts had ≥1 of these features. Of the 38 pts with relapse detected at a planned visit, 26 had clinical features of relapse and 12 pts had relapse detected solely by planned surveillance scan; 4 pts had relapse of low-grade or other subtype and 8 had DLBCL relapse (4 of whom had equivocal/positive PET at the end of IC). Thus, surveillance scanning detected DLBCL relapse prior to clinical manifestations in only 8/537 pts (1.5%) observed post DLBCL therapy. Conclusions: The vast majority of DLBCL relapses occur outside of planned follow-up visits and are accompanied by symptoms, physical exam, or laboratory abnormalities. Routine surveillance scans post-therapy add little to detection of DLBCL relapse.
Frequent Genetic Alterations of PI3K-AKT Pathway and Their Clinical Significance in Germinal Center B-Cell-like Diffuse Large B-Cell Lymphoma
Authors: Daisuke Ennishi, Ali Bashashati, Saeed Saberi, Anja Mottok, Barbara Meissner, Merrill Boyle, Susana Ben-Neriah, Robert Kridel, David Dominguez-Sola, Kerry J Savage, Laurie H Sehn, Joseph M. Connors, Ryan D. Morin, Marco A. Marra, Sohrab P. Shah, Christian Steidl, David W. Scott, Randy D Gascoyne
Journal: Blood (2016)
Association of TP53 mutation status with clinical outcomes stratified by sensitive and non sensitive EGFR mutation, in non-small cell lung cancer (NSCLC).
Authors: Saman Ahmed, Charu Aggarwal, Rosemarie Mick, Trisha M Sterlicchi, Stephan Kadauke, Christofer Gault, Roger B. Cohen, Tracey L. Evans, Joshua Bauml, Charuhas Deshpande, Drew A. Torigian, Jayaram Udupa, Corey J. Langer, Jennifer J. Morrissette
Journal: Journal of Clinical Oncology (2015)

e19076 Background: EGFR mutations (MT) located on exons 19 and 21confer a better prognosis and survival due to their sensitivity to tyrosine kinase inhibitors (TKIs) compared to exon 18 and 20 MTs. The relationship of these MTs to TP53 status and the impact of their co-existence on survival remains unclear. Methods: We conducted a retrospective analysis of Stage IV NSCLC pts treated at the Abramson Cancer Center with established EGFR and TP53 MT status using gene sequencing obtained through our Center for Personalized Diagnostics. Overall Survival (OS) and Progression Free Survival (PFS) were determined for the p53 MT and wild type (WT) cohorts in TKI sensitive (exon 19, 21;SEN) and TKI non-sensitive (exon 18, 20, non- SEN) EGFR MT cohorts Results: Of 51 pts analyzed, there were 37 SEN and 14 non- SEN pts; 38 had TP53 MT and 13 were p53 WT pts. TP53 MT and WT groups were similar for median age (67 vs. 63 yrs), PS (90% ECOG 0-1), smoking status (47% vs. 46% smokers) and T790M status (16% vs. 23%) and female pre dominance (55% and 69% respectively). Exon 19 deletions (69% vs. 29%), brain (69% vs 55%) and bone (69% vs. 39%) metastasis were more common in TP53WT group. At median follow-up of 20.7 mos (15.1 for 37 living pts), the overall median PFS was 15.5 mos (95% CI = 12.8 – 18.2 mos) and OS 46.3 mos (95% CI = 31.7 – 60.8 mos). Conclusions: Coexistence of TP53 MT may be associated with worse clinical outcomes in NSCLC pts with either SEN or non- SEN EGFR MTs, but larger sample sizes are needed to firmly establish whether associations exist. Cohort No Med PFS mos (95% CI) Med OS mos (95% CI) Non-SEN TP53 WT 2 Not estimable Not estimable TP53 MT 12 11.5 (10.8-12.2) 28.3 (4.3-52.4) SEN TP53 WT 11 33.2 (3.3 – 63) Not reached (no deaths) TP53 MT 26 17.1 (13.8 -20.5) 46.3 (38.9-53.7) Log rank test p = 0.52 p = 0.12
Quality of life (QOL) measurement in patients receiving neoadjuvant therapy in the I-SPY 2 trial.
Authors: Michael Hwang, Roxanne E Jensen, Julia Lyandres, Jane Perlmutter, I–SPY Two Trial Coordinators and Research Nurses, Laura Esserman, Michelle E. Melisko
Journal: Journal of Clinical Oncology (2014)

TPS9656 Background: The I-SPY 2 TRIAL is a phase 2 trial investigating novel, targeted therapies in combination with standard chemotherapy in the neoadjuvant setting for stage 2 and 3 breast cancer. While the toxicities of chemotherapy alone are well characterized, introduction of experimental agents may significantly alter the toxicity profiles of these regimens, and could lead to short-term and long-term changes in QOL for patients. During the screening process, the trial informs patients of having either a tumor with a “low risk” (not eligible for the I-SPY 2 treatment phase) vs. “high risk” (eligible) profile, allowing the opportunity to study the impact on QOL of providing prognostic information prior to and throughout treatment. Methods: Patients who consent to the screening phase of I-SPY 2 are asked to participate in the QOL sub study. Patients complete a QOL questionnaire at baseline prior to treatment. For those patients who consent to the treatment phase of I-SPY 2, additional questionnaires are completed on the first day of treatment, after 12 weeks, prior to surgery, and then 1, 6, 12 and 24 months post-surgery. Questionnaires include established QOL measurements: the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and Breast 23 (EORTC QLQ BR23), the National Comprehensive Cancer Network Distress Thermometer and Fear of Recurrence scale, and items from the NCI Patient-Reported Outcomes Measurement Information System (PROMIS) in domains of physical, psychological, cognitive, and sexual function. The study will evaluate changes in QOL, distress, and fear of recurrence prior to surgery to two years post-operatively. The study will also allow comparison and validation of QOL measurement using PROMIS, a publicly available Web-based resource supported by the National Cancer Institute, to legacy EORTC QOL instruments. Since initiation of the QOL sub study, 520 patients have participated in the screening phase, with 311 patients initiating I-SPY 2 study treatment. With the accrual goal of 800 patients to the main I-SPY 2 TRIAL, up to 585 may be accrued to the prospective portion of the QOL sub study. Clinical trial information: NCT01042379.
A Structural Basis for p53-Deficiency, Deregulated Cell Cycle and Unfavorable Outcome in Diffuse Large B-Cell Lymphoma
Authors: Bjoern Chapuy, Stefano Monti, Kunihiko Takeyama, Scott J Rodig, Yansheng Hao, Kelly T Yeda, Haig Inguilizian, Craig Mermel, Treeve Currie, Ahmet Dogan, Jeffery Kutok, Rameen Beroukhim, Donna S. Neuberg, Thomas M Habermann, Gad Getz, Andrew L. Kung, Todd R. Golub, Margaret A. Shipp
Journal: Blood (2012)
Identification of new susceptibility genes in familial breast cancer by exome sequencing.
Authors: Henry T. Lynch, Hongxiu Wen, Yeong Kim, Carrie Snyder, Yulia Kinarsky, Pei Xian Chen, Kenneth H. Cowan, David Goldgar, San Ming Wang
Journal: Journal of Clinical Oncology (2012)

1538 Background: Familial breast cancer was described in the early 1970s with its syndromy confirmed by the discovery of BRCA germline mutations in the 1990s. BRCA mutations account for less than 10% of affected families. Efforts made in the past two decades have resulted in limited results in identifying additional susceptibility genes for familial breast cancer. Methods: Using exome sequencing, we analyzed eight members in a BRCA1-, BRCA2-, p53- and PTEN-negative breast cancer family; five with breast cancer and three unaffected. Mutation candidates were idenified by bioinformatics analysis, experimentally validated by Sanger sequencing and their damaging effect was predicted by the SIFT program. Validated mutations were also tested in 42 additional breast cancer samples from BRCA-negative breast cancer families. Results: We identified 55 non-synonymous germline mutations affecting 49 genes in multiple members of this family, 20 of 22 selected mutations predicted to cause damaging effects were validated. As an exemplar, two mutations in the MYST4 gene were detected at the C terminal (p.D1516Y and p.R1577C), validated, and predicted to cause damaging consequences. MYST4 is a histone acetyltransferase (Champagne, N. et al. JBC. 274, 28528-28536,1999). It contains a C2HC-type finger and a PHD-type zinc finger. Its N-terminal is involved in transcriptional repression while its C-terminal is involved in transcriptional activation and interacts with important transcriptional regulators RUNX1 and RUNX2. MYST4 is involved in DNA replication, transcriptional regulation, and epigenetic modification of chromatin structure. A translocation t(10;16)(q22;p13) between CREBBP and MYST4 was identified in acute myeloid leukemia. The 20 validated germline mutations were tested by Sanger sequencing in 42 additional breast cancer cases from 26 BRCA-negative families. None of the 20 mutations were detected. Conclusions: Results show that remaining unknown susceptibility genes are likely family-specific and can be detected in each affected family using genome sequencing approaches. These results may be the first reported in an exome sequencing study of BRCA-negative breast cancer families.
Will breast cancer survivors receive the same content and assessment in survivorship care plans at non-COC sites?
Authors: Christine B. Weldon, Julia Rachel Trosman, Betty Roggenkamp, Emily Lucille Malin, William John Gradishar, Melissa A. Simon
Journal: Journal of Clinical Oncology (2015)

e20634 Background: The Commission on Cancer (COC) standard 3.3 requires survivorship care plans (SCP) in pilot for 10% of patients completing curative intent treatment, with a tiered requirement for implementation to 100% of survivorship by 01/01/2019. In preparation for a workshop on breast cancer (BC) survivorship care, we analyzed the content and assessments in existing and planned survivorship care plans and programs. Funded by Susan G. Komen. Methods: Web survey conducted with 30 hospitals that provide BC treatment and have registered for a BC survivorship care workshop. Using guidelines / recommendations for survivorship care (ASCO, COC, NCCN, NAPBC), we developed a pre-workshop survey on current and planned content and assessments. Results analyzed by simple frequencies and Fisher's exact test. Results: Response rate: 97% (29/30 sites). All sites plan to provide survivorship care for indicated BC patients. Currently, 22% (5/22) of COC sites and 0% of non-COC sites provide BC survivorship plans. Treatment plan summaries are provided to patients by 27% (6/22) of COC sites and 0% of non-COC sites. The table indicates inclusion or plan for specific survivor care plan content and assessments. Conclusions: While all sites have or plan to have SCPs, not all sites plan to include the content and assessments indicated in ASCO and NCCN survivorship guidelines. We found significant difference between COC accredited sites and non-accredited sites in four areas (see table*). Findings indicate the need for technical support and education on how to incorporate guideline suggested content and assessments for SCPs into practice. SCP Content / Assessment COC sites % Non-COC sites % p-value *BC treatment summary 100 43 0.002 *Current disease status, late- and long-term effects 91 43 0.02 *Surveillance and monitoring activities 91 29 0.003 Anxiety / distress / depression 86 57 ns (not significant) *Summary of current medications 82 29 0.02 Cognitive function 77 57 ns Fatigue 77 43 ns Functional / performance status, areas of patient concern 73 29 ns Pain 73 43 ns Patient lifestyle and behaviors 68 57 ns Description of co-morbidities 68 29 ns Immunization and infections 64 43 ns Sexual function 64 43 ns Sleep disorder 64 43 ns
Development and validation of a prognostic score to predict the survival in adult patients with solid tumors and bone marrow metastases.
Authors: Wen-Chi Chou, Mengting Peng, Chien-Ting Liu, Kun-Yun Yeh, Chang-Hsien Lu, Yung-Chang Lin, Chuang-Chi Liaw
Journal: Journal of Clinical Oncology (2015)

e17730 Background: Bone marrow metastases in patients with solid cancers represent an advanced and dismal malignant disease. There are limited reports regard their clinical features and outcomes. We aimed to develop a scoring system to predict survivals in these patients to help with clinical decisions making. Methods: A total of 165 adult patients diagnosed with solid cancers and bone marrow metastases confirmed by bone marrow biopsies at the Chang Gung Memorial Hospital Linkou Medical Center between 2000 and 2014 were selected as derivation cohort. A risk model was developed using multivariate logistic regression from the derivation cohort and a marrow metastases prognostic score (MMPS) was generated. An independent cohort of 156 patients from three other hospitals was selected using the same recruiting criteria to validate the MMPS in predicting the survival. Results: MMPS was constructed by four independent prognostic variables: Eastern Cooperative Oncology Group performance status (0, 1.5, 3, and 6 points for performance status 1, 2, 3 and 4, respectively), site of cancer (0 point for breast, prostate or nasopharynx, 2.5 points for the others), platelet count (0, 1.5, and 2.0 points for count < 50, 50-100, and > 100 x 109/L, respectively) and neutrophil to lymphocyte ratio ( 0 point for ratio < 4, 1 point for ratio ≥ 4). Patients in both the derivation and validation cohorts were stratified into good (score = 0-4), intermediate (score = 4.5-7.5) and poor (score ≥ 8) prognostic groups based on their MMPSs. The median (95% confidence interval) survival in each risk group of the derivation cohort was 241 days (152-330, n = 57), 58 days (43-73, n = 59) and 11 days (4-18, n = 49), respectively; while 305 days (216-394, n = 54), 65 days (51-79, n = 69) and 9 days (3-15, n = 33) of the validation cohort. The c-statistic in predicting survival less than one year was 0.89 in the derivation cohort and 0.88 in the validation cohort. Conclusions: This study developed a risk model that accurately predicted survival in adult patients with solid cancers and bone marrow metastases. This scoring system may be used to help patients and their family, as well as clinicians in deciding appropriate treatments.
A gene expression profile test that distinguishes ovarian from endometrial cancers.
Authors: Anita Lal, Rebecca Panos, Mira Marjanovic, Michael Walker, Eloisa Fuentes, Daniel Stuart Kapp, William David Henner, Ljubomir J Buturovic, Meredith Halks Miller
Journal: Journal of Clinical Oncology (2012)

10576 Background: The differential diagnosis between primary epithelial ovarian and endometrial cancers is often unresolved because the histologic subtypes of these two tumor types can have very similar histology and immunohistochemical appearance. Here we report the development and validation of a gene expression profile (GEP) diagnostic test (Pathwork Tissue of Origin Endometrial Test) that distinguishes ovarian and endometrial cancers in formalin-fixed, paraffin-embedded (FFPE) specimens using a 316–gene classification model. Methods: The test was clinically validated in a blinded study using a pre-specified algorithm and microarray data files for 75 metastatic, poorly differentiated or undifferentiated primary FFPE tumor specimens that had either a known clinical diagnosis of ovarian or endometrial cancer and belonged to one of the 14 ovarian and endometrial WHO histologic subtypes on the test panel. Results: Classification biomarkers, empirically selected by machine learning, included several genes such as homeobox transcription factors and kallikrein peptidases with known function in the biology of ovarian and endometrial cancers. The Tissue of Origin Endometrial Test accurately identified the primary site for 94.7% (95% CI, 87% to 99%) of ovarian and endometrial cancers. Other measures of test performance include an area under the ROC curve of 0.997 and a diagnostic odds ratio of 406. Test performance did not change significantly when stratified by specimens from metastases (90.5%) or by poorly differentiated and undifferentiated primary tumors (96.3%). All stages of ovarian and endometrial cancers were included in the validation study and had agreements of 85% to 100% with the clinical diagnosis. In a precision study, concordance in test results was 100%. Reproducibility in test results between three laboratories had a concordance of 94.3%. Conclusions: The GEP test identified specific ovarian and endometrial cancer morphologies even when a clear distinction could not be made by histologic criteria. The GEP test can aid in resolving an important differential diagnostic question in gynecologic oncology and may impact clinical management of these patients as well as entry opportunities into clinical trials.