tbuckley/cabot-search huggingface dataset:
Outcomes of thymic neoplasms after the 1999 WHO classification.
Authors: Yousif Yonan, John M. Varlotto, Thomas J Fitzgerald, Abram Recht, Karl Uy, William Vincent Walsh, John Charles Flickinger, Fei Gu, Geoffrey Graeber, Richard Sawyer Pieters, James Edward Liebmann, Nengliang Yao, Syed Quadri, Suhail M. Ali
Journal: Journal of Clinical Oncology (2014)

7604 Background: In 1999 the World Health Organization (WHO) published a histologic sub-typing system for thymoma that divided it in to six classes, which included one category for thymic carcinoma (WHO C, Group 1) and five categories of invasive thymoma (WHO A, AB, B1, B2 and B3, Group 2). Methods: The SEER database was used to retrospectively identify thymic neoplasms from 2000-2010 using the six-tier classification system. Only those patients having thymic neoplasia as their only cancer and undergoing complete (R0) resection were included in the analysis. Overall survival (OS) and thymic-specific survival (TSS) were evaluated by Kaplan-Meier methods. Multivariate analysis(MVA) was performed including group, age, race, Masaoka stage, gender, and adjuvant radiation therapy as key variables. Results: 505 thymic neoplasms were identified including 96 (19%) in group 1 and 409 (81%) in group 2. Median follow-up was 38 months. For patients with early Stage(I/II) group 1 and group 2 tumors, OS at 2, 3, and 5 years was 90.5, 90.5, 67.9% for Group 1 and 98.2, 95.8, 95.8 for Group 2 respectively. Group 1 classication (p<0.0001, HR 1.82), advancing age (p=0.003, HR 1.03) and increasing stage (p=0.04, HR 1.37) were significant predictors of worse OS. TSS was excellent in the overall group with thymus-related death listed as cause of death in only 35 (6.9%) of patients. Any Group 1 and Stage III/IV Group 2 tumors had significantly worse TSS. Histologic sub-typing within Group 2 was not associated with OS, TSS or high-risk of lymph node involvement (all<5%). In early-stage Group 1 patients, 15/34 (44%) did not have a nodal exam and 6/19 (32%) had positive nodes. Conclusions: Early-stage Group 2 patients have an excellent OS and TSS may not benefit from adjuvant therapy. Trials of adjuvant therapy should be considered for advanced-stage Group 2 patients and all Group 1 patients. Thymic carcinomas may be understaged due to lack of lymph node examination and the high percentage with involved nodes.
A validated whole-blood RNA transcript-based prognostic model that predicts survival in men with castration-resistant prostate cancer.
Authors: William K. Oh, Philip Kantoff, Howard I. Scher, Jay Magidson, Karl Wassmann, Gwo-Shu Mary Lee, Leah M. Katz, Sumit Kumar Subudhi, Aseem Anand, Martin Fleisher, Matt D. Galsky, Robert W Ross
Journal: Journal of Clinical Oncology (2012)

4516 Background: Survival for patients with castration resistant prostate cancer (CRPC) is highly variable. We developed a whole blood RNA transcript-based model as a prognostic biomarker in CRPC. Methods: Peripheral blood was collected from 62 men with CRPC in a training set and from 140 patients with CRPC in a validation set on various treatment regimens. A panel of 168 inflammation and prostate cancer-related genes was evaluated using optimized quantitative polymerase chain reaction to assess biomarkers predictive of survival. A 2-class proportional hazard model was developed from time of CRPC diagnosis and time of blood draw. Results: A 6-gene model (consisting of ABL2, SEMA4D, ITGAL, and C1QA, TIMP1, CDKN1A) separated CRPC patients into two classes: higher risk men who died within 2·2 years of developing CRPC and lower risk men who lived over 2·2 years (log rank p=0·00083). The results were similar regardless of the survival time definition (CRPC diagnosis versus blood draw) and did not depend on whether they received chemotherapy in addition to hormone treatment. The model successfully validated in an independent cohort of men with CRPC (p= 0.000001·7). Conclusions: Transcriptional profiling of whole blood yields critical prognostic information in men with CRPC independent of treatment. The 6-gene model suggests possible dysregulation of the immune system, a finding that warrants further study. This model may play an important role in patient counseling, in patient stratification for clinical trials, and potentially as a predictive biomarker for immune-based therapeutic strategies.
Effect of CD137 stimulation on ibrutinib antagonism of GA101 dependent NK cell-mediated cytotoxicity.
Authors: Narendiran Rajasekaran, Suparna Dutt, Aurelien Marabelle, Roch Houot, Mohith Sadaram, Johnathan Hebb, Idit Sagiv-Barfi, Sid Ambulkar, Amanda Sandamali Rajapaksa, Cariad Chester, Erin Waller, Holbrook Edwin Kohrt
Journal: Journal of Clinical Oncology (2015)

3075 Background: The clinical successes of BTK inhibitor Ibrutinib and Ofatumumab (GA101), a humanized, glycoengineered mAb against CD20, suggests that a combination therapy may have clinical potential. Our previous study demonstrated that Ibrutinib antagonizes ADCC in CD20+ B-cell lymphoma due to Ibrutinib's irreversible binding to interleukin-2 inducible tyrosine kinase (ITK), which is required for FcR-stimulated NK cell function. (Kohrt et al Blood 2014, 123;12:1957). As GA101 is superior to Rituximab in induction of NK cell mediated ADCC, we hypothesized that-Ibrutinib may not antagonize GA101 and inhibition of NK cell function by Ibrutinib could be overcome by CD137 agonistic mAb enhanced NK cell function. Methods: Purified NK cells were isolated from healthy peripheral blood mononuclear cells and cultured with Ibrutinib for 4 hours together with GA101-coated DHL4 lymphoma cells. For NK cell activation studies, the cells were primed with GA101 coated cells for 20 hours prior to CD137 mAb addition. Secretion of IFN-gamma, CD107a mobilization and cytotoxicity were assessed. Results: The results showed that Ibrutinib inhibited GA101 induced NK cell mediated lysis of lymphoma target cells and degranulation, although IFN gamma release was unaffected. Anti-CD137 mAb enhanced functional GA101 induced NK cell IFN gamma release, restored and enhanced degranulation and lysis of target cells that was impaired by Ibrutinib. Similar results were obtained when autologous peripheral blood mononuclear cells were cultured with CLL cells obtained from circulating tumor cells. The therapeutic efficacy of Ibrutinib and GA101 with anti-CD137 mAb was evaluated in a xenotransplant model of DHL4 lymphoma. Following tumor inoculation, athymic mice received GA101 on day 14 and oral dose of Ibrutinib twice daily and anti-CD137 mAb on day 15 with each treatment repeated weekly for a total of three weeks. Our results demonstrate that GA101 retains its potency in vivo in combination therapy with Ibrutinib and anti-CD137 mAb. Conclusions: Our results support a novel approach to overcome Ibrutinib inhibition of NK cell function by activation of the host immune system by CD137 stimulation that warrants clinical investigation.
Uncharted territory: Life after cancer for young adults.
Authors: Lynda M. Beaupin, Jennifer A Hydeman, Odochi Uwazurike
Journal: Journal of Clinical Oncology (2017)

30 Background: Similar to survivors of childhood cancer, young adult (YA) survivors have distinct and complex medical and psychosocial needs. However, there are no specific follow-up guidelines for patients who were diagnosed as a young adult. Most YA survivors receive inadequate survivorship care with minimal surveillance for late effects. This study aims to examine the concept of survivorship care planning and determine what aspects of post-therapy care is most needed. Methods: Two focus groups were held to investigate the post treatment experience of YA survivors. Participants completed cancer treatment and were diagnosed between 2005 and 2011. They either continued to receive follow-up care or did not. These were further subdivided based on age at diagnosis: 18-24; 25-30; 31-39 years. Participants answered predetermined questions during their session. A demographic questionnaire was given and a SCP (a treatment summary [TS] and its associated long- and late-term risks) developed based on their electronic medical records. Results: 27 YAs participated in the focus groups. SCPs were developed for each participant and required 45 - 180 minutes to complete. 78% felt TS were accurate and 44% learned of long/late-term side effects they were previously not aware of nor receiving surveillance on. Barriers to continued follow-up were related to health insurance status, poor communication with their oncologist, and on-going adjustment challenges. Initial feedback from the SCPs indicates that YAs seek additional information on long/late-term side effects, roadmap for follow-up visit, and information on psychosocial support and YA specific resources. Conclusions: For young adults diagnosed with cancer, there are no guidelines on follow-up care. Young adult survivors are not aware of long- and late-term side effects they may have, and many do not know how often they need to have continued follow-up. Despite great strides made in survivors of childhood cancer, the same cannot be said for young adult survivors.
Effect of prolonged cold ischemic time on immunohistochemical testing of estrogen receptor, progesterone receptor, and HER2 expression in breast cancer.
Authors: Tae-Kyung Yoo, Hyeong-Gon Moon, Jisun Kim, Jun Woo Lee, Min Kyoon Kim, Eunshin Lee, Jongjin Kim, Wonshik Han, Dong Young Noh
Journal: Journal of Clinical Oncology (2014)

e11505 Background: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are the most important predictive and prognostic biomarkers in breast cancer. The American Society of Clinical Oncology/College of American Pathologists recommended that the time from tumor removal to fixation (cold ischemic time) should be kept within 1 hour. Through this study we mean to review the actual cold ischemic time in real practice and analyze whether delayed formalin fixation effects immunohistochemical testing results. Methods: A retrospective review of invasive or in situ breast cancer patients, treated in Seoul National University Hospital, Seoul, Korea, between January 2012 and June 2012, was done. Cold ischemic time was calculated by extracting the time of formalin fixation from the time when surgery ended. All patients were equally divided into two groups (short ischemic group, long ischemic group) with the median cold ischemic time in the middle. Chi-square test was done for ER and PR positive/negative (0% negative, ≥1% positive) and Mann-Whitney U-test was done for ER and PR percentage. Also χ2 test was done for HER2 positive/negative and scoring system ranging from 0 to 3+. Results: A total of 419 patients were included in this study. The median cold ischemic time was 64h 40min (range 3h 17min - 242h 4min). No association between ER, PR expression and cold ischemic time was found in the χ2 test(p=0.459, p=0.511) and Mann Whitney U-test (p=0.689, p=0.129). As for HER2 expression, no significant association with cold ischemia time was seen for HER2 positive/negative (p=0.092). But significant association was seen for HER2 scoring system with more patients having lower HER2 score in the long ischemic group (p=0.042). Conclusions: Our findings show that the actual cold ischemic time in practice is much longer than recommended guidelines. Despite that, ER, PR expression is not associated with cold ischemic time. But as for HER2 expression, longer cold ischemia time was associated with more HER2 negative and lower HER2 score.
Sorafenib (S) and dacarbazine (D) combination in patients (pts) with advanced malignant solid tumors: Phase I study with tumor biopsy genomic analysis and dynamic contrast enhanced ultrasonography (DCE-US)
Authors: J. Soria, V. Lazar, N. Lassau, C. Pena, C. Massard, C. Robert, S. Koscielny, E. Deutsch, E. Zafarana, J. P. Armand
Journal: Journal of Clinical Oncology (2007)

3556 Background: S is a multikinase inhibitor targeting VEGFR-1, -2, -3, PDGFR-a and -β and Raf kinase. The combination of S (400 mg bid) and D (1,000 mg/m 2 , 21-day [d] cycle [C]) was previously defined as maximum tolerated dose. Objectives were to define the pharmacokinetic (PK) profile of D ± S, assess safety of the combination and collect antitumor activity data by genomic analysis and by DCE-US. Methods: All pts received D (1,000 mg/m 2 by 1-hr infusion) with continuous oral S 400 mg bid (except Day1C1). PK was performed during 1 st and 2 nd infusions. RNA expression profiling was performed on sequential tumor biopsies at baseline (BL) and Day 21. DCE-US was assessed at BL and Day 8, 21 of C1. Results: 23 pts treated (median age 59 y) had melanoma (4), leiomyosarcoma (4), adenocarcinoma (5), mesothelioma (3), neuro-endocrine tumor (3) and other (4). 22 had = 1 prior chemotherapy (range, 1–7). Median (range) number of D cycles was 4 (1–9), median (range) duration of S treatment was 15 wks (3–48). Toxicities were manageable and included diarrhea (48% any grade [G], no G3/4), hand-foot skin reaction (48% any G, 4% G3), fatigue (26% G3), thrombopenia (22% G4), and neutropenia (13% G4). Of 22 evaluable pts, 1 (melanoma) had confirmed PR, 13 pts had SD as best response, with a median (range) duration of 161 d (75–258). 7 pts continue with SD. PK (n=15) showed increased mean AUC by 41% and mean Cmax of AIC (an inactive D metabolite that is formed in an equal proportion to the active moiety, diazomethane, that cannot be analytically measured) by 45%. Genomic analysis in 10 pts with PFS =3 mos and in 7 with PFS &lt;3 mos identified a subset of 4 genes whose modulation differentiates these groups with 100% accuracy. 99 DCE-US performed in 17 pts showed 3/7 with short PFS had increased volume on Day 21 and in 3 an increase in maximal intensity &gt;50% on Day 8. Of 10 pts with long PFS, maximal intensity decreased by &gt;50% on Day 21 in 8 pts. Conclusion: Combination of D and S is manageable with clear evidence of antitumor activity. Preliminary data strongly suggest a new paradigm based on sequential tumor genomic analysis allowing early identification of responders. Early stage DCE-US may predict PFS duration. No significant financial relationships to disclose.
Cost of colon cancer care: Results of nationwide inpatient sample (NIS) data.
Authors: Pranshu Bansal, Ian Rabinowitz, Yanis Boumber, Dhruv Bansal
Journal: Journal of Clinical Oncology (2017)

692 Background: Cost of cancer care including colon cancer continues to rise. Most of the recent advances in colon cancer inlcude biologics and targeted agents which are adminstered in an oupatient setting and more commonly thought to be responsible for increasing economic burden. Cost of care for cancer patients in an inpatient setting however continues to be a significant factor that needs to be identified better to help adopt cost effective quality improvement in future. Methods: We used NIS to extract data for patients hospitalized with primary diagnosis of colon cancer using clinical classification software code 14, and corresponding ICD9 codes for the years 2003-2013. ICD codes for colorectal and rectal cancer were eliminated. NIS is a nationally representative survey of hospitalizations conducted by the Healthcare Cost and Utilization Project. It represents 20% of all hospital data in US. Trend of rate of hospitalization, mean length of stay (LOS), mean cost of hospitalization and mean cost of hospitalization based on owner type- government, private not for profit (PNFP) and private for profit (PFP) was performed. Results: From the year 2003 to 2013 rate of hospitalizations for colon cancer decreased from 37.4 to 28.1 per 100,000 hospital admissions. Mean LOS declined from 9.06 to 7.76 between 2003-2013. In the same time period the mean cost of hospital stay increased from $39,430 to $73,219. The mean cost of hospitalization based on owner type in 2003 was government $33,507; PNFP $33,735 and PFP was $55,553 and in 2013 the mean costs were $63,194; $68,555 and $107,428 respectively. Conclusions: In the decade of 2003-2013 the rate of hospitalization decreased by approximately 25%, LOS decreased by 14% but the mean cost of hospitalization continued to increase throughout the decade with a mean increase of approximately 85% in hospital costs. The increase was observed across the spectrum of all owner types with the maximum increase of 104% in PNFP followed by PFP owner type at 93%, national inflation rate was 26% during this time. Progress made in decreasing LOS has not directly translated into reducing hospital costs and further studies focusing on factors in addition to cost of biologic agents that contribute to cancer care costs should be considered.
Impact of marital status on prognostic outcome of women with breast cancer.
Authors: Shaheenah S. Dawood, Xiudong Lei, Rebecca Dent, Paul N. Mainwaring, Sudeep Gupta, Javier Cortes, Ana M. Gonzalez-Angulo
Journal: Journal of Clinical Oncology (2014)

594 Background: The objective of this study was to examine the impact of marital status among patients with breast cancer. Methods: We searched the SEER registry to identify 549589 patients (pts) with stage I to IV breast cancer diagnosed between 1990 and 2010. Patients were divided into two groups depending on the marital status at diagnosis: a) married, b) unmarried (included never married, separated, divorced and widowed). Breast cancer specific survival (BCSS) was computed using the Kaplan Meier product limit method. Multivariable cox models were then fit to look at the association of marital status and BCSS adjusted for various pt and tumor characteristics. Results: Married pts accounted for 56.8% of the cohort. Married pts tended to be younger (median age of diagnosis 56 yrs vs. 65 yrs), have lower stage of disease, smaller tumor size, node negative disease and be of white/other race compared to unmarried pts. 5-year BCSS was 89% and 82% among married and unmarried pts respectively (p<0.0001). Among patients of either black or white/other race a 7% significant improvement in 5-year BCSS was observed among married compared unmarried pts. Among pts with stage I, II, III and IV disease a significant improvement in 5-year BCSS of 1%, 3%, 9% and 7% respectively was observed among married compared to unmarried pts. In the multivariable cox model unmarried pts had a higher risk of death from breast cancer compared to married pts (HR=1.2; 95%CI: 1.18-1.22;p<0.0001). An interaction term between marital status and age at diagnosis was significant, such that as age increases by one year unmarried pts had increasing risk of death compared to unmarried pts (HR 1.004, 95% CI 1.003-1.005, p<0.0001). Conclusions: Being married at the time of diagnosis of breast cancer improves survival regardless of pt and tumor characteristics. The impact of marital status appears to be greater among older pts compared to younger patients, which may be explained partly by a more aggressive biology generally seen among younger pts and the increasing need for a support system among older patients.
The impact of UGT1A1 and SLCO1B1 genetic polymorphisms and pharmacokinetics of axitinib on clinical safety and efficacy in patients with metastatic renal cell carcinoma.
Authors: Shintaro Narita, Ryoma Igarashi, Norihiko Tsuchiya, Takamitsu Inoue, Nobuhiro Fujiyama, Kazuyuki Numakura, Hiroshi Tsuruta, Hideaki Kagaya, Mitsuru Saito, Takenori Niioka, Masatomo Miura, Shigeru Satoh, Tomonori Habuchi
Journal: Journal of Clinical Oncology (2017)

448 Background: We investigated the impact of genetic polymorphisms and pharmacokinetics of axitinib on adverse events, objective responses, and survival in patients with metastatic renal cell carcinoma (mRCC). Methods: In total, 53 patients with mRCC treated with axitinib were analyzed. Patient was classified as favorable (n = 5), intermediate (n = 36), and poor (n = 12) using the MSKCC risk classification system. High-performance liquid chromatography was used to measure serum axitinib levels. AUC 0 – 12 (ng∙h/mL) was calculated using various serum levels at 0 to 12 h (C 0 –C 12 ) following administration on day 7 of treatment. The genetic polymorphisms related to the drug pharmacokinetics, including SLCO1B1, SLCO1B3, SLCO2B1, ABCB1, ABCG2, CYP2C19, CYP3A5, and UGT1A1, were analyzed using PCR-RFLP analysis. Results: The most frequently reported ≥ G3 adverse events were hypertension (43.3%), proteinuria (30.2%), and anorexia (20.1%). The axitinib trough levels (C 0 ) were significantly correlated with AUC 0–12 of axitinib. Patients with axitinib C 0 ≥ 10 ng/mL had a significantly higher rate of hand-foot syndrome ≥ G2 and hypothyroidism ≥ G2 than those with axitinib C 0 &lt; 10 ng/mL (p = 0.013, p = 0.005). The overall survival in patients with axitinib C 0 ≥ 5 ng/mL was significantly better than that in those with axitinib C 0 &lt; 5 ng/mL (p = 0.022). The mean C 0 and AUC 0–12 values in patients with a poor metabolizer (*6/*6, *6/*28, and *28/*28) of UGT1A1 polymorphism were significantly higher than those in patients with an extensive metabolizer (p = 0.045, p = 0.035, respectively). The mean AUC 0–12 value in patients with the SLCO1B1 *15 was significantly higher than that in those without the SLCO1B1 *15 (p = 0.038). Conclusions: Serum axitinib levels were associated with adverse events and overall survival of patients with mRCC. The genetic polymorphisms in UGT1A1 and SLCO1B1 may affect serum axitinib levels in patients with mRCC. Pharmacokinetics and genetic polymorphisms play important roles in the outcomes of patients with mRCC treated with axitinib.
ERALOP study: Hair regrowth after adjuvant FEC-docetaxel chemotherapy for early breast cancer in the real life.
Authors: Hugues Pierre Bourgeois, Aurelie Jamet, Francoise Grude, Carole Adounkpe, Pierre Kerbrat, Remy Delva, Helene Simon, Philippe Deguiral, Bertrand Diquet, Pascale Laine
Journal: Journal of Clinical Oncology (2014)

e12014 Background: During 2008 we have collected one hundred observations of persisting alopecia (PA). The FEC 100-docetaxel 100 mg/msq regimen was mostly concerned. We therefore decided to evaluate exact incidence of this relevant side effect through women points of view. Methods: ERALOP is a retrospective study using a self-questionnaire targeting patients (pts) treated with this sequential regimen from 2008 to 2009. The primary objective was to estimate the incidence of a PA at 6 months after last course of docetaxel with CTCAE 4.0 classification: grade 1: hair loss of up to 50% not obvious from a distance, a different hair style may be required to cover the hair loss, grade 2: hair loss > 50% with a psychosocial impact. The sample size calculation of 635 patients took into account: PA incidence of 3.2% (TAC regimen), precision of 0.015, α risk at 0.05, 20% patients lost for follow up. ERALOP study was approved by local ethic comitee. Results: from July 2012 to October 2012, 829 pts received a self-questionnaire. 176 pts (21%) did not answer and were considered as without PA. 653 (79%) answers with medical data fully documented were collected. Median age of patients was 56 years. Six months after last docetaxel course, PA incidence grade 2: 8.6% (71 pts/829), grade 1: 32.6% (271 pts), grade 0: 35% (290 pts), NA: 2.5% (21 pts). 73% of pts with PA received hormonotherapy. At the time of the inquiry (median follow up of 3.7 years), PA incidence grade 2 was 3.5% (29 pts), grade 1: 30% (248 pts), grade 0 42.6% (353 pts), for a global PA incidence of 33.4%. Between 6 months after docetaxel and inquiry, appears slight or total regrowth for 40 pts with PA grade 2 and 187 with PA grade 1. Three pts still wore a wig, and many pts had suboptimal regrowth of eyelash (31%), eyebrow (47%), pubic hair (27%), and nail disorders (27%). A multivariate analysis was performed to look for risk factors of PA. Conclusions: This high level of PA, lead us to conduct ALOPREV trial to investigate the preventative properties of cooling cap prevention trial during docetaxel infusion in spite of FEC induced alopecia and results are encouraging.