tbuckley/cabot-search huggingface dataset:
Association of IL8 polymorphisms with overall survival in patients with renal cell carcinoma in COMPARZ (pazopanib versus sunitinib phase III study).
Authors: Chun-fang Xu, Toby Johnson, Toni K. Choueiri, Keith C. Deen, Zhengyu Xue, Colin F. Spraggs, Arundathy N. Bartlett-Pandite, Christopher Carpenter, Robert John Motzer
Journal: Journal of Clinical Oncology (2013)

4519 Background: Pazopanib and sunitinib are angiogenesis inhibitors approved for treatment of advanced renal cell carcinoma (RCC). COMPARZ, a phase III randomized clinical trial comparing pazopanib vs sunitinib for RCC, demonstrated similar efficacies for the two therapies but safety profiles differed. Our genetic analyses of previous pazopanib clinical trials found that IL8 polymorphisms may be associated with progression-free survival (PFS) and overall survival (OS). We attempted to validate these associations in the COMPARZ study. Methods: Of the 1110 participants in COMPARZ, 724 (65%) provided consent and DNA for pharmacogenetic analyses (pazopanib, N = 371; sunitinib, N = 353).Associations of IL8 polymorphisms (rs1126647 and rs4073) with PFS and OS were tested using the Cox proportional hazards model with baseline factors as covariates in a combined analysis of all patients and also separately in pazopanib-treated and sunitinib-treated patients. One-tailed P values were calculated for effects in the same direction as previously observed. Results: For PFS there was no significant association in the combined analysis or in pazopanib-treated patients, but there was a significant association in sunitinib-treated patients (P = 0.017). For OS there were significant associations in the combined analysis (P = 0.010) and in sunitinib-treated patients (P = 0.0043) but not in pazopanib-treated patients (P = 0.30). Hazard ratios (HRs) for genetic effects were not significantly different between sunitinib- and pazopanib-treated patients (two-tailed P = 0.23 for genotype-by-treatment interaction). Kaplan-Meier plots suggested a recessive genetic model in the combined data set, with median OS (95% CI) 23.7 months (15.4–29.1) for rs1126647 TT genotype compared to 35.5 months (30.8–∞) for AA or AT genotypes (HR = 1.66, P = 0.0007). Similar associations were seen for rs4073. Conclusions: Germline variants in IL8 are associated with survival outcome in patients with RCC who have received angiogenesis inhibitors. These findings may provide additional scientific insights in making treatment decisions and developing alternative therapies.
Genomic landscape of salivary gland tumors.
Authors: Sheryl Krevsky Elkin, Shumei Kato, Maria Clemence Schwaederle, Brett N. Tomson, Teresa L. Helsten, Jennifer Carter, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2015)

6056 Background: Effective targeted treatment options for advanced salivary gland tumors are lacking. In order to better understand these tumors, we assessed their genomic landscape. Methods: We studied 117 patients with salivary gland tumors that were, on physician request, tested in a Clinical Laboratory Improvement Amendments (CLIA) laboratory (Foundation Medicine, Cambridge, MA) using next-generation sequencing (182 or 236 genes), and analyzed by N-of-One, Inc. (Lexington, MA). Results: There were 354 total aberrations, with 240 distinct aberrations identified in this patient population. Only 10 individuals (8.5%) had a molecular portfolio that was identical to any other patient (with four different portfolios amongst the ten patients). The median number of aberrations/patient was three (range, 0 to 10). The most common abnormalities involved the TP53 gene (36/117 [30.8% of patients]), cyclin pathway (CCND1, CDK4/6 or CDKN2A/B) (31/117 [26.5%]) and PI3K pathway (PIK3CA, PIK3R1, PTEN or AKT1/3) (28/117 [23.9%]). In multivariate analysis, statistically significant co-existing aberrations were observed as follows: TP53 and ERBB2 (p = 0.01), cyclin pathway and MDM2 (p = 0.03), and PI3K pathway and HRAS (p = 0.0001). We were able to identify possible cognate targeted therapies in most of the patients (107/117 [91.5 %]), including FDA-approved drugs in 80/117 [68.4%]. Conclusions: Salivary gland tumors are characterized by multiple aberrations that mostly differ from patient to patient. Significant associations between aberrations in TP53 and ERBB2, the cyclin pathway and MDM2, and HRAS and the PI3K pathway were identified. Most patients had actionable alterations. These results provide a framework for tailored combinations of matched therapies.
The impact of estrogen depletion by aromatase inhibitors on adiponectin serum levels in postmenopausal patients with breast cancer.
Authors: Georg Pfeiler, Robert Konigsberg, Peyman Hadji, Florian Fitzal, Muy-Kheng Maria Tea, Sonja Vogl, Andreas Berger, Ruth Exner, Michael Seifert, Christian F. Singer, Michael Gnant, Peter Christian Dubsky
Journal: Journal of Clinical Oncology (2013)

e11601 Background: Adiponectin impacts on breast cancer risk and prognosis. Obesity and insulin resistance are correlated with low adiponectin serum levels, which increase breast cancer risk and lead to a worse outcome regarding breast cancer. Additionally a cross talk between the adiponectin and estrogen signaling system has been suggested. Here we prospectively investigated the impact of estrogen depletion via aromatase inhibitors (AI) on adiponectin serum levels in postmenopausal patients with breast cancer. Methods: 68 postmenopausal ER positive patients with breast cancer, scheduled to receive anastrozole or letrozole as adjuvant endocrine treatment were prospectively included in this study. Serum was taken before (T1) and 3 months after start with aromatase inhibitors (T2). Non-fasting serum levels of adiponectin, FSH, LH, E2, glucose and insulin were analyzed immediately in the clinical routine lab and in a dedicated central lab able to measure E2 in serum at low concentrations with high sensitivity. Results: At baseline, a strong significant negative correlation between adiponectin and body mass index (BMI) as well as a positive correlation between adiponectin and FSH serum levels could be observed (r=-0.43, p=0.01 and r=0.38, p=0.03, respectively). Taking the previously proposed cut off of 15.5μg/ml, patients with low adiponectin serum levels had a significantly higher BMI and significant lower FSH serum levels. No interaction between adiponectin and estradiol serum levels could be detected. As previously shown, AI treatment significantly decreased estradiol serum levels and consequently increased FSH serum levels. However, 3 months of AI treatment did not alter adiponectin, insulin and c-peptide serum levels, respectively. Conclusions: Short term estrogen depletion via aromatase inhibitors does not impact on non-fasting adiponectin, insulin and c-peptide serum levels in postmenopausal patients with breast cancer.
Trends in chemotherapy-related treatment of late-stage colon and rectal cancer.
Authors: Cathy Bradley, K. Robin Yabroff, Joan L Warren, Neetu Chawley, Chris Zerutoc, Elizabeth B. Lamont
Journal: Journal of Clinical Oncology (2013)

6604 Background: The appropriate intensity of treatment for patients with advanced incurable cancer remains uncertain. Our study examines trends in population-based treatment following diagnosis for metastatic colon and rectal cancer in elderly adults. Methods: We used the Surveillance, Epidemiology, and End Results – Medicare database to identify persons aged 65 and older who were diagnosed with distant stage colon (N=12156) and rectal cancer (N=3071) between 2000 and 2007. We assessed treatment patterns over the year after diagnosis with a focus on chemotherapy and related services. For each year, we report the percent of patients receiving chemotherapy, hematopoietic growth factors, and antiemetics/premedication. For those patients who received chemotherapy, we estimated, by year, the median number of days from the first to the last chemotherapy claim. Results: From 2000 to 2007, the percent of patients receiving chemotherapy increased from 39.6% to 44.4% for colon patients and from 46.6% to 59.2% for rectal patients. The median duration of chemotherapy increased by more than 40 days. The type of chemotherapy used changed dramatically. Oxaliplatin and Bevacizumab were not available in 2000, but by 2007, a substantial portion of colon and rectal cancer patients received Oxaliplatin (28.4% and 37.6%) and Bevacizumab (24.4%. and 33.2%). The percent of patients receiving hematopoietic growth factors rose appreciably from 3.7% to 23.2% for colon patients and from 5.2% to 27.4% for rectal patients. From 2000-2007, use of antiemetics/premedication increased from 27.2% to 44.3% for colon patients and from 32.9% to 56.9% for rectal patients. Conclusions: The use and intensity of chemotherapy related treatment for CRC patients with advanced cancer has increased markedly from 2000 to 2007. Many of these therapies are very expensive. ASCO has encouraged realistic conversations about the potential benefits and limitations of disease-directed therapy with the hope of improving patients’ quality of life while reducing medical treatment costs. Our findings demonstrate the need for physicians to assess their treatment practices relative to health care costs and patient prognosis.
A phase 1 study of phospholipid ether [<sup>131</sup>I]-CLR1404 in patients with advanced solid tumors.
Authors: Sam Joseph Lubner, Jacqueline Ann Mullvain, Lance T. Hall, Michael Pishavian, Joanne E. Mortimer, Katherine Oliver, Jennifer Heideman, Jamey Weichert, Glenn Liu
Journal: Journal of Clinical Oncology (2014)

2557 Background: Preclinical data suggest that tumor cells of many types selectively accumulate and retain phospholipid ethers. To capitalize on this, a radiolabeled phospholipid ether [131I]-CLR1404 was developed with the goal of improving tumor imaging specificity and as a novel approach to therapy. Experiments with [131I]-CLR1404 in mouse models demonstrated safety and efficacy. We conducted a phase 1 study of escalating doses of [131I]-CLR1404 in patients with advanced solid tumors. The primary objective of this study was to determine a recommended dose of [131I]-CLR1404 for treating advanced solid malignancies. The secondary objectives were to expand the safety and pharmacokinetic profile, determine anti-tumor activity, and obtain tumor imaging with [131I]-CLR1404. Methods: Patients were first given a dosimetric dose followed by a treatment dose 1-2 weeks later in an algorithmic escalation design. Toxicity follow up included q 7 day lab and clinical assessment. Patients had single photon emission computed tomography (SPECT) scans to assess [131I]-CLR1404 biodistribution. Results: Twelve patients were enrolled (7 male, 5 female, age range 40-70) at 3 open centers. Two patients withdrew from study before receiving drug; 10 patients (3 colon, 2 breast, 2 prostate, 2 esophagus, 1 ovarian) received protocol therapy. The per-protocol dose-limiting toxicities (DLT) were grade 4 thrombocytopenia (PLT) and grade 4 neutropenia (ANC) at 37.5mCi/m2. For further safety analysis, an intermediate dose level was opened at 31.25 mCi/m2; 2 DLTs (grade 4 PLT, grade 3 ANC with fever) were encountered. Clinical activity was shown with 4 patients with stable disease (SD) up to 6 months. SPECT imaging confirmed selective [131I]-CLR1404 accumulation in known tumors. Conclusions: At a dose of 31.25 mCi/m2, DLTs were low PLT and ANC. Studies exploring the mechanism(s) of action of [131I]-CLR1404 toxicity are ongoing to minimize myelosuppression. Disease-specific studies are also underway to identify patients most likely to benefit from [131I]-CLR1404 monotherapy. In this study, there was evidence of [131I]-CLR1404 anti-tumor activity (4 pts with SD) and sustained uptake in tumors by SPECT imaging. Clinical trial information: NCT01495663.
Areas of Consensus and Differences Among a Panel of Experts on the Optimal Use of Newly Approved Agents to Treat Multiple Myeloma (MM): Results from an Annually Updated Online Decision Support Tool
Authors: Timothy A Quill, Kristen M Rosenthal, Shaji Kumar, Suzanne Lentzsch, Sagar Lonial, G. David Roodman, Kevin L Obholz, Kenneth C. Anderson
Journal: Blood (2016)
Safety of eribulin in Korean patients with metastatic breast cancer.
Authors: Yeon Hee Park, Young-Hyuck Im, Keun-Seok Lee, In Hae Park, Joohyuk Sohn, Soohyeon Lee, Tae Yong Kim, Seock-Ah Im, Jee Hyun Kim, Se Hyun Kim, Soo Jung Lee, Su-Jin Koh, Ki Hyeong Lee, Yoon Ji Choi, Eun Kyung Cho, Suee Lee, Seok Yun Kang, Jae Hong Seo, Sung-Bae Kim, Kyung Hae Jung
Journal: Journal of Clinical Oncology (2015)

e12031 Background: EMBRACE/Study305 demonstrated the efficacy of eribulin for the treatment of advanced breast cancer after two-to-five lines of chemotherapy. Only 1% of patients were from Asia Pacific regions in this study. It is important to evaluate the safety and efficacy profiles of eribulin in Korean patients taking into account the potential effects of ethnic and cultural differences on them. Therefore, we decide to evaluate the safety and efficacy of eribulin in Korean patients with locally advanced or metastatic breast cancer who have previously received at least two chemotherapeutic regimens which should have included an anthracycline and a taxane by this phase 4 clinical trial, ESKIMO study. Methods: In this phase IV single arm open-label study, women with locally advanced or metastatic breast cancer and 2-5 prior chemotherapy regimens in the advanced setting were enrolled to receive eribulinmesylate. Prior anthracycline and taxane treatment, and ECOG PS 0-2 were required. Treated and stable brain metastases were allowed to include. Results: At a median follow up of 14.1 (range 8.3-17.7) months, in total, 101 patients were included, and among them, 96 patients who have completed the study were included in this analysis. Triple negative breast cancer patients and late-line treatment of 3rd-line or more were more common than EMBRACE study (30.2% vs. 18%, and 80.2% vs. 53%). The median age was 51 years. A median of three cycles (range 1-15) was received per patient. The most common adverse events were neutropenia (88.5%), and followed by decreased appetite (39.6%), and alopecia (37.5%), and the most common grade 3/4 adverse event was neutropenia (86.5%). However, febrile neutropenia occurred in 1 patient (1.0%). Grade 2 or 3 neuropathy was observed in 6.3% of patients of all 24.0% of neuropathy. 2 patients (2.0%) discontinued drug administration due to AEs of peripheral neuropathy and subcutaneous abscess. Serious adverse events other than death occurred in 18 patients (18.7%) and one death occurred without causal relationship to eribulin. Conclusions: This analysis showed that higher rates of neutropenia and decreased appetite were observed than EMBRACE study. Eribulin showed tolerable and manageable safety profiles in Korean patients. Clinical trial information: NCT01961544.
Racial disparities in depressive symptom prevalence and selective serotonin reuptake inhibitor (SSRI) utilization in cancer patients: An analysis from ECOG E2Z02: Symptom Outcomes and Practice Patterns (SOAPP).
Authors: Fengmin Zhao, Lynne I. Wagner, William F. Pirl, Andrew H. Miller, Michael Fisch
Journal: Journal of Clinical Oncology (2012)

6076 Background: Rates of diagnosis and treatment of depression in primary care vary widely by race. It is unclear whether such disparity exists in oncology. Methods: 3106 patients with cancer of the breast, prostate, colon/rectum, or lung were enrolled from multiple sites in a longitudinal study of symptoms. Patient-reported depressed mood (PRD) on a 0-10 numerical rating scale and clinician-reported psychological distress (CRD) were used to identify depressive patients at baseline. Patients also rated depressed mood 4-5 weeks after baseline. A 2-point change was considered clinically significant for change in PRD. Logistic regression models were used to examine the effect of race on prevalence of depression and antidepressant use. Ordinal logistic regression models examined the effect of race on changes in depression. Results: Of the 3106 patients, 2648 were white, 364 were black, and 94 were other race. At baseline, 20% had moderate/severe PRD; CRD was 28%. Black patients had higher rates of depression than whites, but the difference was not significant after adjusting for other covariates (PRD: 24% vs. 20%, adjusted OR=1.1, P=0.6; CRD: 30% vs. 27%, adjusted OR=1.06, P=0.8). Improvement in depressed mood varied by baseline PRD score (57% with severe depression, 51% with moderate, and 14% with mild). In patients with moderate/severe depression at baseline, blacks were less likely to have depression improvement than whites (adjusted OR=0.41, P=0.008 for moderate depression, adjusted OR=0.35, P=0.01 for severe depression). Among patients with depression defined by CRD, 29% were taking an SSRI (blacks: 14%, whites: 31%), Blacks were less likely to take an SSRI than whites (adjusted OR=0.38, P=0.01). Conclusions: Less than one third of patients with depressive symptoms are taking SSRI antidepressants. Black race is not only associated with less improvement in depressive symptoms over time but also lower probability of SSRI utilization.
Secondary chemoprevention using short period (3 months) of LHRHa as an option for men with low-risk localized prostate cancer (LRPC) before active surveillance (AS).
Authors: Olivier Cussenot, Sarah Drouin, Christophe Egrot, Jean-Nicolas Cornu, Philippe Sebe, Pierre Mozer, Pierre Conort, Christophe Vaessen, Francois Haab, Marc-Olivier Bitker, Morgan Roupret
Journal: Journal of Clinical Oncology (2012)

e15105 Background: Definition of LRPC and candidates for AS remains problematic. Relevant markers that reflect tumor aggressiveness are still to be determined. When AS is used it can be difficult to assess disease progression despite surveillance with PSA and repeat biopsies. Moreover, 20-50% of patients on AS were over the windows of curability when radical treatment was triggered. The current knowledge of PC suggests that aggressiveness should be assessed not only in terms of clinical features but also in terms of response to Androgen Deprivation Therapy (ADT). Methods: 83 men with LRPC (T1c or T2a PC; PSA ≤10ng/ml; Gleason score ≤6) whom have chosen prostate cancer management without radical therapy were included. They then underwent AS after receiving one injection of ELIGARD-22.5. AS consisted of PSA every 3 months (mo) and biopsies (≥12 cores) every 12mo. Patients were stratified at diagnosis according to age at diagnosis, PSA, PSA density, PSA nadir, bio-testosterone, dynamic MRI staging, % positive cores and length of tumor on the diagnosis biopsy. Predictive factors of recurrent PC observed on biopsy were tested using a Cox regression and Markov models. Results: Mean age at diagnosis of LRPC was 64 years, (standard deviation, 6.2 years). Median time to follow-up after diagnosis biopsy was 31mo. Surveillance biopsies were positive for 37 men (44%) (7 with Gleason score&gt;6). In the subgroup of insignificant PC according EPSTEIN criteria surveillance biopsies were positives for 17/48 men (35%) (2 with Gleason score&gt;6). Expected results from literature on classical AS were 60-70% of positive biopsy and 10-21% of upgraded biopsy at the first repeat biopsy. Predictive factors of prostate cancer observed on biopsy were: PSA nadir at 3mo &lt;0,1ng/ml (OR=1.8; 95%CI 1.0 to 3.3 p=0.04), positive core biopsy&gt;1(OR=1.7; 95%CI 1.0 to 2.9; p=0,03), and &gt;T1c detectable tumor on MRI (OR=2.9; 95%CI 1.4 to 5.9; p=0.003). Conclusions: Results obtained with 3mo of LHRHa for LRPC suggest that ADT response can be used firstly to reduce prevalence of primary PC lesions and secondly in order to identify PC able to castration resistance and consequently which require radical treatment.
Association of increased body height with BRAF mutations in male melanoma patients.
Authors: Eve Maubec, Maria Geay, Elodie Regnier-Rosencher, Charlotte Fite, Francoise Boitier, Nora Kramkimel, Julie Chrisment Di Lucca, Agnes Carlotti, Lydia Deschamps, Eduardo Marinho, Benoit Couturaud, Sebastien Albert, Athanasios Kalampokas, Xavier Sastre, Etienne Rouleau, Marie- Odile North, Jerome Lamoril, Beatrice Crickx, Nicolas Dupin, Marie-Françoise Avril
Journal: Journal of Clinical Oncology (2013)

e20032 Background: Somatic BRAF mutations occur in approximately 40-50% of patients (pts) with unresectable cutaneous melanoma (CM) and are more common in young pts. The objective of this study was to determine if body height and body mass index (BMI) are associated with BRAF mutation status. Methods: 212 consecutive BRAF-tested patients with unresectable stage IIIC or IV CM were analysed. Tumor samples from two departments of dermatology were screened by high-resolution melt curve analysis of BRAF exon 15; abnormal results were confirmed by DNA sequencing. Associations between BRAF mutation status and height, BMI and age of pts were examined using univariate and multivariate logistic regression analyses in the whole sample and according to sex. Results: The BRAF mutation frequency was 42%. On univariate analysis in the whole sample, BRAF mutated status was not associated to BMI (p=0.9) but was associated to age and height (p≤0.027). The BRAF mutation frequency was higher in taller pts reaching 59% in pts &gt; 180 cm (p=0.003, χ² test). According to sex, this association was significant in males (p=0.004) but not in females (p=0.39). Size did not differ significantly in the 4 quartiles groups of age (&lt;50, 50-62, 62-72 and &gt;72 years; p &gt;0.07). On multivariate analysis, in the whole sample, only age was associated to mutated BRAF status (p&lt;0.001); but in the male subgroup, age and height were independent factors predicting BRAF mutations (p&lt;0.04). Conclusions: Tallness was significantly associated with BRAF mutations in male melanoma pts. This is in agreement with published data for colorectal carcinoma. This study might suggest a genetic susceptibility to somatic BRAF mutations, increased height and melanoma. [Table: see text]
American College of Cardiology/American Heart Association 2006 Update of the Clinical Competence Statement on Invasive Electrophysiology Studies, Catheter Ablation, and Cardioversion
Authors: Cynthia M Tracy, Masood Akhtar, John P DiMarco, Douglas L Packer, Howard H Weitz, Mark A Creager, David R Holmes, Geno Merli, George P Rodgers
Journal: Circulation (2006)