tbuckley/cabot-search huggingface dataset:
Craniocaudal retroperitoneal node length as a risk factor for relapse from clinical stage I testicular germ cell tumor.
Authors: Stephanie Anne Holler Howard, Kathryn P. Gray, Elizabeth O'Donnell, Fiona M. Fennessy, Clair Beard, Christopher Sweeney
Journal: Journal of Clinical Oncology (2014)

363 Background: To investigate if retroperitoneal craniocaudal nodal length (CCNL) or nodal volume (NV) predicts relapse risk in clinical stage I testicular cancer. Methods: This institutional review board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant study retrospectively reviewed 826 patients with testicular cancer. One hundred eighteen out of 826 patients forming the analytic cohort had stage I disease and either more than or equal to 2 years surveillance or retroperitoneal lymph node dissection with no adjuvant chemotherapy. 3D NVs and CCNL were measured by two attending physicians in consensus. Association between relapse risk and CCNL/NV was evaluated using univariable/multivariable logistic regression analysis adjusted for known prognostic factors. Results: Sixty six out of 118 patients (56%) had nonseminomatous germ cell tumor (NSGCT) and 52 (44%) had seminomatous germ cell tumor (SGCT). Twenty one percent (25 out of 118) of patients relapsed: 24% (16 out of 66) for NSGCT and 17% (9 out of 52) for SGCT. Eighty percent of relapses were limited to the retroperitoneum; 90% of these were at the site of the largest lymph node. CCNL proved to be an independent risk factor in NSGCT using a multivariable logistic regression model adjusting for other potential known risk factors of embryonal predominance (EP) and lymphovascular invasion (LVI). For every 3 mm increase in CCNL, the risk of relapse increased by 52% (odds ratio [OR]=1.52; 95% CI=1.03- 2.25). For patients with SGCT, only the primary tumor size was an independent risk factor for relapse (OR=1.34; 95% CI=1.02-1.75). Conclusions: In NSGCT, CCNL was shown to be associated with increased risk of relapse independently of other known risk factors. If validated in a larger cohort, CCNL could provide important additional information used to inform management decisions in these patients.
Clinical activity of enzalutamide against metastatic castration-resistant prostate cancer (mCRPC) in patients who have progressed on abiraterone acetate: The Princess Margaret experience.
Authors: Francisco Emilio Vera-Badillo, Raya Leibowitz-Amit, Arnoud Templeton, Jo-An Seah, Srikala S. Sridhar, Jennifer J. Knox, Ian Tannock, Anthony Michael Joshua
Journal: Journal of Clinical Oncology (2014)

159 Background: In men with mCRPC enzalutamide and abiraterone acetate have been shown individually to prolong survival after progression on chemotherapy with docetaxel. Little is known about the sequential use of enzalutamide and abiraterone. A PSA response rate of 8% and progression free survival (PFS) of 2.7 months has been reported for 38 men who received abiraterone following enzalutamide [Loriot, Ann Onc, 2013]. Here we report our experience with enzalutamide following abiraterone. Methods: We reviewed all patients with mCRPC treated with enzalutamide following abiraterone and docetaxel at our institution. Primary outcomes were PSA response rate (confirmed decline ≥ 50%) and time to treatment failure (TTF, defined as the time from treatment initiation to treatment discontinuation for any reason, including disease progression, treatment toxicity, patient preference, or death.). Data were analyzed using the Kaplan-Meier method. Results: Twenty-six patients were treated between August 2012 and July 2013. Median age was 72 years (range 56-88); 85% had ECOG performance status 0 or 1; metastatic sites included bone (N=25, 96%), lymph nodes (N=19, 73%) and visceral (N=1, 3.4%). Median number of prior cycles of docetaxel was 8 (range 1 – 12), 6 patients (29%) had previous exposure to ketoconazole, and median duration of previous abiraterone was 8.7 (range 1.4-22.7) months. Seven pts (27%) had a PSA response ≥ 50% and an additional 7 patients (27%) had a ≥ 30% PSA response. Median TTF on enzalutamide was 4.9 (95% CI 3.8-6.2) months. Reasons for discontinuation of enzalutamide were clinical and/or biochemical progression in 24 patients (92%), and toxicity (fatigue grade 3-4) in 3 patients (11.5%). An update of patient numbers and analysis will be presented at the meeting. Conclusions: Treatment of patients with mCRPC with enzalutamide after progression on docetaxel and abiraterone has modest clinical activity.
Prognostic factors in advanced biliary tract cancer treated with first-line chemotherapy with cisplatin and gemcitabine.
Authors: Renata D'Alpino Peixoto, Daniel John Renouf, Howard John Lim
Journal: Journal of Clinical Oncology (2014)

350 Background: Data regarding prognostic factors in advanced biliary tract cancer (ABTC) remains scarce. The aim of this study was to review our experience in ABTC as well as to evaluate potential prognostic factors for overall survival (OS) as defined in the ABC-02 trial. Methods: 106 consecutive patients with ABTC who initiated palliative chemotherapy with Cisplatin and Gemcitabine from 2009 to 2012 at the BC Cancer Agency were identified using our pharmacy database. Clinicopathologic variables and treatment outcome were retrospectively collected. Potential prognostic factors were assessed by univariate (Kaplan-Meier curves and log-rank test) and multivariate analyses (Cox proportional hazards model). Results: 106 patients (46 males) with a median age of 64 years (range 43 – 88) were included. Median progression free-survival (PFS) was 6.2 months (95%CI: 5.4-7.0). Median OS from diagnosis of advanced disease to death was 12.9 months (95%CI: 10.0-15.7), while median OS from initiation of chemotherapy to death was 10.0 months (95%CI: 7.3-12.6). 34.9% of the patients received 2nd line chemotherapy, with single-agent 5-fluorouracil being the most used drug. On univariate analysis, ECOG performance status (PS) at diagnosis, primary tumor location (gallbladder, intra-hepatic cholangiocarcinoma, extra-hepatic cholangiocarcinoma, ampulla of Vater, unkown), and sites of advanced disease (unresectable locally advanced, regional lymph nodes, liver-limited metastases, extra-hepatic metastases) were significantly associated with worse OS (p &lt; 0.001, 0.003 and 0.009, respectively). Age, gender, CA19-9, CEA, hemoglobin, neutrophil count, prior stent and prior surgery were not significantly associated with OS. On multivariate analysis, predictors of poorer OS were ECOG PS (p&lt;0.001), primary location (p=0.009), site of advanced disease (p=0.006) and CEA (p=0.002). Conclusions: In this population based analysis, outcomes for patients with ABTC were comparable to those noted in the ABC-02 trial. ECOG PS, primary tumor location, site of advanced disease and CEA were all found to be significantly prognostic.
Immunoglobulin Light Chain Repertoire in Chronic Lymphocytic Leukemia (CLL): Recognition of Subsets with “CLL-Specific” CDR3 Regions and Associations with Heavy Chains.
Authors: Kostas Stamatopoulos, Chrysoula Belessi, Anastasia Hadzidimitriou, Evangelia Kalagiakou, Tatjana Smilevska, Niki Stavroyianni, Anastasia Athanasiadou, Aliki Tsompanakou, Theodora Papadaki, Garyfallia Kokkini, George Paterakis, Kalliopi Valianatou, Vassiliki Douka, Riad Saloum, Nikolaos Laoutaris, Achilles Anagnostopoulos, Athanasios Fassas
Journal: Blood (2004)
The Specificity and Isotype of Monoclonal Anti-D Antibodies Dictates Their Ability To Inhibit Opsonized Platelet Phagocytosis.
Authors: John W. Semple, Rukhsana Aslam, Michael Kim, Edwin R. Speck, Donald I.H. Stewart, Erik Weirsma, John Freedman, Mimi Kjaersgaard
Journal: Blood (2006)
Chemoradiotherapy for highly advanced gastric cancer.
Authors: Mai Tsutsui, Tsunehiro Takahashi, Yoshiro Saikawa, Hirofumi Kawakubo, Norihito Wada, Hiroya Takeuchi, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2014)

121 Background: Although the prognosis of early gastric cancer is favorable, the treatment for advanced cases still have difficulty in achieving satisfactory results. Thus, more effective multimodality treatment should be established. Chemoradiotherapy has become a standard treatment for gastric cancer especially as an adjuvant therapy while radiotherapy has been expected as one of the modalities against highly advanced gastric cancer. Methods: Patients with advanced gastric cancer who were treated with chemotherapy of S-1 and cisplatin plus radiation were analyzed retrospectively. Concurrent radiation therapy (5 days/week) at 2 Gy/day was started with chemotherapy and repeated daily on days 1–5, 8–12, 15–19 and 22–26. Irradiation was planned using a computed tomography (CT) simulator for two rectangular portals with a pair of 45-degree wedge filters and was targeted at the primary tumor and surrounding lesions, including lymph nodes. Results: A total 109 patients were treated with chemoradiotherapy between 2002 and 2013 at our institute. The median age was 64 years. Histological type included 45 differentiated and undifferentiated 64 subtypes. The TNM stage before the treatment was diagnosed as IIIA: 11; IIIB: 10; IIIC: 14; IV: 74. Of the 98 evaluable patients, 69 patients had partial responses while no patients had a complete response, resulting in an overall response rate of 70%. Progressive disease (PD) occurred in 2 patients (4%). The most frequent adverse events more than grade 3 were hematologic toxicities, including leukocytopenia (47%), neutropenia (25%), and thrombocytopenia (24%). Non-hematologic toxicities such as general fatigue, renal-related events, and gastrointestinal toxicities were manageable with no treatment-related death. The median survival time was 537 days. Conclusions: While there were disadvantages of radiotherapy including the difficulty of confirming the area of irradiation due to peristaltic movement, risk of perforation and ulceration, recent technological advancement of radiation therapy has enabled pinpoint accuracy in treatment of primary gastric lesions and regional lymph nodes. There has been much anticipation that chemoradiotherapy will be a part of multidisciplinary treatment for advanced cancer.
Pharmacological Inhibition of Hsp90 Destabilizes the Histone Methyltransferase Ezh2 in Alloreactive T Cells and Reduces Graft-Versus-Host Disease While Retaining Anti-Leukemic Effects in Mice
Authors: Qingrong Huang, Shan He, Yuanyuan Tian, Changhong Li, Yuting Gu, Pan Chen, Jiefang Huang, Yongnian Liu, Min Jin, Qi Cao, Ran Reshef, Yi Zhang, Yanyun Zhang
Journal: Blood (2015)
Breast cancer patients’ trust in their physicians: Do patient information, perceived involvement in care, and organizational characteristics have an impact?
Authors: H. Pfaff, A. Nitzsche, F. Scheibler, P. Steffen, C. Kowalski
Journal: Journal of Clinical Oncology (2008)

9528 Background: Patients´ trust in physicians is a central aspect of the patient-physician relationship in oncological treatment. Therefore it is necessary to know what factors influence patients´ trust. The hypothesis is that patient information, perceived involvement in care, and organizational characteristics of the hospital have a significant impact on patients´ trust. Methods: In a retrospective, cross-sectional correlative study we obtained data from 3,131 patients (response rate: 89 %) with primary breast cancer who had undergone breast surgery at one of the 49 breast centers (BCs) in North Rhine-Westphalia, Germany. All BCs in this state participated in the study. During February and July 2006 all patients (N=3535) at these centers were asked to fill in a standardized postal questionnaire. The study endpoint was patients´ trust in the physicians at the BCs. The independent variables were information provided on disease and treatment, perceived involvement in care, and organizational characteristics (perceived quality of the hospital organization; accessibility of the physicians). In addition, we obtained clinical data from the attending physicians to control for disease severity. Multivariate linear regression was used to test the hypothesis. Results: Patients’ trust in physicians was largely explained by the variables in our model (N = 2479; R2adj. = 0.45; p < 0.001). Breast cancer patients’ trust in their physicians largely depended on the behaviour of the physicians. The more the physicians provided the patients with information on disease and treatment options (beta = 0.161; p < 0.001), and the more the physicians facilitated involvement in decision-making processes (beta = 0.186; p < 0.001), the more the patients trusted their physicians. The accessibility of the physicians (beta = 0.384; p < 0.001) and the perceived quality of the hospital organization (beta = 0.100; p < 0.001) also contributed significantly to patients’ trust. Conclusions: Our findings show that patient information, perceived involvement in care, and organizational characteristics have a significant impact on patients‘ trust in physicians. No significant financial relationships to disclose.
Bone effects of adjuvant tamoxifen (T), letrozole (L), or L plus zoledronic acid (Z) in early breast cancer (EBC): The phase III HOBOE study.
Authors: F. Perrone, C. Gallo, S. Lastoria, F. Nuzzo, A. Gravina, G. Landi, E. Rossi, C. Pacilio, V. Labonia, F. Di Rella, M. De Laurentiis, M. C. Piccirillo, M. Di Maio, P. Giordano, G. Daniele, G. De Feo, R. Fiore, S. Signoriello, G. Esposito, A. de Matteis
Journal: Journal of Clinical Oncology (2011)

517 Background: Treatment with L can reduce bone mineral density (BMD) in patients (pts) with EBC. However, the addition of Z may protect against bone loss. Methods: We performed a 1:1:1 randomized phase III trial to compare the bone effects of adjuvant T, L or L+Z in pre- and postmenopausal pts with hormone-receptor positive EBC. Premenopausal pts also received triptorelin. Primary end point was T-score at lumbar spine (LST) measured by DXA-scan 1 year after randomization. The study had 80% power to detect a 0.35 effect size. Two comparisons were planned: L vs T and L+Z vs L; for each one, a linear model was applied to test treatment effect adjusted by age, menopausal status, previous chemotherapy and baseline LST. Two exploratory analyses were done to test whether baseline body mass index (BMI) and 6-month estradiol level were associated with L vs T effect. NCT00412022. Results: From March '04 to December '09, 483 patients were enrolled; 459 (247 pre- and 212 postmenopausal) were available for primary analyses. Median age was 50 (range 28-80); 320 (70%) pts had received adjuvant chemotherapy. At baseline 35%/23% of the pts were overweight/obese. At 1-year, mean (SD) change of LST from baseline was −0.27 (0.64) with T, −0.57 (0.66) with L and +0.02 (0.59) with L+Z. Both L vs T and L+Z vs L comparisons were highly statistically significant, p<0.0001. In premenopausal pts, but not in postmenopausal ones, bone effect of L (vs T) decreased with increasing values of baseline BMI (interaction test p=0.004 and p=0.47, respectively). There was no interaction between 6-month estradiol level and bone treatment effect, in both menopausal subgroups (p=0.31 and p=0.22, respectively). Conclusions: The HOBOE study confirms that L decreases BMD as compared with T, and that the addition of Z protects against this side effect. Interestingly, BMI seems predictive of L effect on bone health among premenopausal but not postmenopausal pts; these findings are consistent with previous observations. HOBOE has been extended and is now recruiting only premenopausal pts, to test disease-free survival effects. Novartis kindly supplied Z (for all pts) and L (for premenopausal pts). Partially supported by AIRC.
Role of combined germline pharmacogenomic and somatic genomic analysis in personalized cancer therapy: Non-small cell lung cancer (NSCLC) case study.
Authors: Pratheesh Sathyan, Prem Gurnani, David Lasecki, Kevin Hicks, Charis Eng, Kevin P Rosenblatt
Journal: Journal of Clinical Oncology (2015)

e18551 Background: Personalized cancer therapy, utilizing either germline pharmacogenomic or somatic mutation analyses, can increase therapeutic success and improve outcomes. To date, few integrated studies of germline pharmacogenomics and somatic mutations in cancer patients have been undertaken. The long-term aim of the study is to determine whether the identification of both somatic mutation and germline variation that govern pharmacodynamic and pharmacokinetic responses to cancer chemotherapy can be used concurrently to achieve better patient outcomes. Methods: We utilized the molecular and clinical data for 404 lung adenocarcinoma patient samples found in The Cancer Genome Atlas (TCGA). Statistical analysis was performed using Kaplan-Meier curves with the Wilcoxon test for overall survival. We identified patients with well-known mutations that affect NSCLC. We further divided these patients based on the presence or absence of variation in any of 6 CYP450 genes (CYP-1A2, 2D6, 3A4, 2C19, 2C9 and 3A5) to identify a possible correlation that can be associated with increased survival. Results: Analysis revealed a statistically significant survival benefit (n = 326, p = 0.029) for the patient population not carrying CYP450 variants compared to the group expressing CYP450 variants. Analysis on the most common genes targeted in lung cancer (EGFR, ROS1, ALK and MET) uncovered a similar survival advantage (n = 323, p = 0.029) for the population without CYP450 variants. Further analysis by stage indicated that a survival benefit is associated with the absence of CYP450variants in stage I patients; patients with adv stage II and III did not show a similar correlation but did show the same trend. Conclusions: Our results suggest a correlation between a patient’s pharmacokinetic handling of cancer drugs, as determined, in part, by genetic variability, and somatic driver mutations. A caveat to our approach using the TCGA is that germline data are not available and one would have to assume that the CYP450 variants in each tumor represent the germline and not de novo somatic mutations. Further prospective clinical studies will be needed to evaluate the above conclusions.
Phase II protocol with docetaxel plus prednisone in patients with hormone refractory prostate cancer
Authors: E. Silva, F. M. Calais Da Silava, F. E. Calais Da Silava
Journal: Journal of Clinical Oncology (2005)

4787 Background: Although treatment of hormone-refractory prostate cancer (HRPC) is difficult, the use of docetaxel every 21 days plus prednisone has been reported as a promising regimen for patients with HRPC. The purpose of this study was the investigation of the efficacy of docetaxel for patients with HRPC and toxicity Methods: 26 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily and 75 mg of docetaxel per square meter every three weeks. Inclusion criteria hormone refractory prostate cancer patients, PSA> 20, performance status WHO<2 .The primary end point was prostate-specific antigen (PSA) levels, pain and the performance status WHO. There mean (range) age was 74 (55–88) years and mean prostate-specific antigen (PSA) level 402 (38–1100) ng/mL, Gleason Socore median 8 (7 to 9). Five patients had had previous chemotherapy (mitoxantrone-prednisolone in two, vinorelbine in three) Results: Of the 26 patients 6 where non-evaluated with less than 2 cycles. Twenty patients received a mean (range) of 7.3 (6–10) cycles of therapy, the median follow up was 12,2 months, there was two reported drug-related toxicity grade 3, dermatological. Only three patients required a blood transfusion and no skeletal related events were reported. Seven had a reduction in PSA by more than 50% at 2 months and two of these had a PSA less than 4; seven were stable at six months; and six progressed and died Conclusions: Docetaxel plus prednisone is a safe regime in HRPC and more trials are needed to assess response and efficacy. No significant financial relationships to disclose.
Analysis of mutational status in recurrently mutated genes in clear cell renal cell carcinoma and overall survival in patients with metastatic disease at time of nephrectomy.
Authors: Brandon Manley, Jozefina Casuscelli, Daniel Tennenbaum, A. Ari Hakimi, James Hsieh
Journal: Journal of Clinical Oncology (2016)

520 Background: Using the genetic profile of a tumor, clinicians may be able to give insight in to the aggressiveness or indolence of a patient’s disease. The choice to initiate or hold systemic therapy for those with metastatic disease may be aided by knowing which mutations put a patient at an accelerated risk of death from their disease. Identifying genomic markers in clear cell renal cell carcinoma (ccRCC) for patients with metastatic disease at time of nephrectomy may assist in the decision to initiate early systemic therapy even in those with stable clinical disease. Methods: Using available data from The Cancer Genome Atlas (TCGA), The International Cancer Genome Consortium (ICGC), The Cancer Genomics Project Tokyo, Japan and our intuitional database we identified 157 patients who had metastatic disease at time of nephrectomy. We performed statistical analysis to compare the presence of mutations in five recurrently mutated genes (VHL, PBRM1, SETD2, BAP1 and KDM5C) in ccRCC and overall survival. For each gene, Kaplan-Meier estimates for patients with and without mutations were generated and compared using the Log-rank test and Cox proportional hazards regression. Results: Out of the five recurrently mutated genes analyzed, we found that only mutations in BAP1 showed a statistically significant decrease in overall survival for patients who had metastatic disease at time of nephrectomy. Patients without a mutation in BAP1 had an estimated median overall survival of 32.2 months, whereas patients with a mutation in BAP1 had an estimated median overall survival of 15.4 months, HR 1.717 (CI 1.038 –2.839), p-value=0.0326. Conclusions: Patients with mutations in BAP1 show a statistically significant decrease in overall survival compared to those without mutations in these patients with terminal disease. Given these findings early initiation of systemic therapy may be considered even in those with small or stable residual disease.