tbuckley/cabot-search huggingface dataset:
Venous thromboembolism in outpatients with cancer receiving chemotherapy for solid tumors.
Authors: L. Gaba, V. Ortega, C. Font, B. Farrús, D. Tàssies, J. C. Reverter, P. Gascon
Journal: Journal of Clinical Oncology (2011)

e19600 Background: Chemotherapy (CT) is recognized as a risk factor for venous thromboembolism (VT) in patients with cancer, although it is not well established which patients could benefit from primary thromboprophylaxis. The aim of this study was to identify potential target subgroups of cancer patients for primary thromboprophylaxis during CT. Methods: A prospective observational registry of consecutive cancer patients who developed VTE was performed between May 2006 and April 2009. Results: A total of 339 cancer patients with VT were recorded. VT occurred in 192 (57%) outpatients actively treated with CT (102 males; mean age 60.6 ± 11 years). The aim of CT was palliative in 128 (67%) patients: lung 43 (34%), breast 22 (17%), colorrectal 16 (12%), gynecologic 13 (10%), urinary tract 12 (9%) and upper gastrointestinal cancers 10 (8%). In this group the VT event was deep vein thrombosis (DVT) in 54 (42%) patients, pulmonary embolism (PE) in 57 (45%) and central catheter-related thrombosis (CVC) in 11 (9%) patients. The CT scheme was neoadjuvant in: 26 (14%) patients: head and neck 9 (35%), Urologic 4 (15%), lung 4 (15%), colorrectal 3 (11%), upper gastrointestinal 3 (11%), gynecologic 2 (8%) and breast 1 (4%). The VT events were: CVC-related thrombosis in 12 (46%), PE in 8 (31%) and DVT in 6 (23%) patients. In 36 (19%) additional patients the CT scheme was adjuvant: colorrectal 17 (45%), breast 10 (26%), lung 3 (8%) and ovary 3 (8%). In this group the VT event was as follows: DVT in 21 (55%), CVC-related in 5 (13%), PE in 5 (13%) and central nervous system thrombosis in 2 (5%) patients. Conclusions: One third of the cancer outpatients in our series developed VTE during intention-to-cure CT (neoadjuvant and adjuvant schemes) while the remaining two thirds did so during palliative CT. Further prospective studies to determine the incidence and risk factors of VT are required in each target population.
The impact of BMI on outcomes of patients with metastatic renal cell carcinoma treated with targeted therapy: An external validation data set and analysis of underlying biology from The Cancer Genome Atlas.
Authors: Laurence Albiges, A. Ari Hakimi, Xun Lin, Ronit Simantov, Emily C. Zabor, Anders Jacobsen, Helena Furberg, Andre Poisl Fay, Daniel Yick Chin Heng, Sabina Signoretti, Rana R. McKay, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2015)

405 Background: Obesity is a risk factor for renal cell carcinoma (RCC) and a poor prognostic factor across many tumor types. However, reports have suggested that RCC developing in an obesogenic environment may be more indolent. We recently reported on the favorable impact of body mass index (BMI) on survival in the International mRCC Database Consortium (IMDC). The current work aims to externally validate this finding and characterize the underlying biology. Methods: We conducted an analysis of 4,657 metastatic RCC (mRCC) patients (pts) treated on phase II-III clinical trials sponsored by Pfizer from 2003-2013. We assessed the impact of BMI on overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). Additionally, we analysed metastatic pts from the clear cell RCC (ccRCC) cohort of TCGA dataset to correlate the expression of Fatty Acid Synthase (FASN) with BMI and OS. Results: At targeted therapy (TT) initiation, 1,829 (39%) pts were normal or underweight (BMI &lt;25 kg/m 2 ) and 2,828 (61%) were overweight or obese (BMI ≥25 kg/m 2 ). Overall, the high BMI group had a longer median OS (23.4 months) than the low BMI group (14.5 months) (hazard ratio (HR) = 0.830, p= 0.0008, 95% CI 0.743-0.925) after adjusting for the IMDC prognostic risk group and other risks factors. In addition, pts with high BMI had improved PFS (HR=0.821, 95% CI 0.746-0.903, p&lt;0.0001) and ORR (odds ratio =1.527, 95% CI 1.258-1.855, p&lt;0.001). These results remain valid when stratified by line of therapy. When stratified by histological subtype, the favorable outcome associated with high BMI was only observed in ccRCC. Toxicity patterns did not differ between BMI groups. In the the Cancer Genome Atlas (TCGA) dataset (n=61), there was a trend towards improved OS in the high BMI group (p=0.07). FASN gene expression inversely correlated with both OS (p=0.002) and BMI (p=0.034). Conclusions: In an external cohort,we validate BMI as an independent prognostic factor for improved survival in mRCC. Given that this finding was observed in ccRCC only, we hypothesize that lipid metabolism may be modulated by the fat laden tumors cells. FASN staining in the IMDC cohort is ongoing to better investigate the obesity paradox in mRCC.
Polymorphisms as markers of sunitinib efficacy and toxicity in first-line treatment of renal clear cell carcinoma: Final results of a multicentric prospective study by the Spanish Oncology Genitourinary Group.
Authors: J. Garcia-Donas, E. Esteban, L. J. Leandro-García, D. E. Castellano, A. Gonzalez del Alba, M. A. Climent, J. A. Arranz, E. Gallardo, J. Puente, J. Bellmunt, B. Mellado, E. Martínez, F. Moreno, A. Font, M. Robledo, C. Rodriguez de Antona
Journal: Journal of Clinical Oncology (2011)

4559 Background: Sunitinib is a tyrosin kinase inhibitor with proven efficacy in renal clear cell carcinoma (RCCC). However properly validated molecular predictors of response or toxicity are still lacking. This study aims to identify such genetic markers focusing on the pharmacokinetics and pharmacodynamics pathways of the drug. Methods: An observational prospective study involving 15 centers of the Spanish Oncology Genitourinary Group (SOGUG) was designed to collect DNA from RCCC sunitinib-treated patients. Eligibility criteria included patients with locally, advanced or metastatic clear renal cell carcinoma treated with sunitinib in a daily practice setting and no prior systemic treatment (neither chemotherapy nor immunotherapy). A total of 15 key polymorphisms in 8 genes involved in the pharmacokinetics (CYP3A4, CYP3A5, ABCB1 and ABCG2) and pharmacodynamics (VEGF, VEGFR2, VEGFR3 and PDGFRa) of the drug were selected to perform a genotype-phenotype analysis. Results: From February 2008 trough December 2010, 100 patients have been included. Regarding clinical factors prognostic classification of the MSKC showed a significant correlation with TTP (p=0.014). Among the polymorphisms studied, two VEGFR3 SNPs presented statistically significant associations with sunitinib TTP (HR=4.3, 95%CI= 2.1-8.8, P=6x10-5 and HR=3.6, 95%CI=1.9-6.8, P=10-4, per allele in multivariate analysis), clinical benefit (HR=12.4, 95%CI= 2.0-77, P=0.007 and HR=5.9, 95%CI= 1.3-28, P=0.024, per allele in multivariate analysis) and one of them with OS (HR=7.5, 95%CI= 1.6-35, P=0.01) favouring wild type patients. Two ABCB1 SNPs also showed a significant association with TTP. In relation to toxicities, one CYP3A5SNP showed a trend towards an increased risk for grade 3/4 toxicity (P=0.052). Conclusions: To the best of our knowledge this is the first time a relevant role of VEGFR3 polymorphisms in response to first line treatment for renal clear cell carcinoma is found. If confirmed, inhibition of this target could have therapeutic implications.
Final results of a phase II study of voreloxin in women with platinum-resistant ovarian cancer.
Authors: H. W. Hirte, W. P. McGuire, R. P. Edwards, A. Husain, P. Hoskins, J. E. Michels, U. Matulonis, C. Sexton, J. A. Fox, G. Michelson
Journal: Journal of Clinical Oncology (2010)

5002 Background: Voreloxin (VOR), an anticancer quinolone derivative, has clinical activity in ovarian cancer and acute leukemia. Final phase II results are reported for 3 regimens of single-agent VOR in patients (pts) with primary or secondary platinum (plat)-resistant ovarian cancer (n = 137). Methods: Eligible pts had platinum-resistant ovarian cancer, prior treatment (tx) with 1-3 plat regimens plus 1 nonplat or biologic allowed, and disease progression within 6 mos. VOR was administered by ≤10 min IV infusion in 3 schedules for up to 6 cycles and in tx extension: A, 48 mg/m2 every 3 weeks (q3wk); B, 60 mg/m2 q4wk; or C, 75 mg/m2 q4wk. Response determined by GOG-RECIST. Results: Overall response rate (ORR = CR + PR) was 11% for all dose levels: A (n = 65), 2CR, 5PR; B (n = 37), 1CR, 3PR; C (n = 35), 4PR. ORR was 9% for pts (n = 44) with prior pegylated liposomal doxorubicin (PLD, Doxil) treatment failure. Disease control (CR+PR+SD for ≥ 12 wks) was seen in 59% of A, 43% of B, 57% of C, and 64% of PLD failures; ∼25% of pts continued in tx extension after cycle 6. No overt signs of congestive heart failure (CHF) were seen in pts completing multiple cycles. Two pts (B) are ongoing at 21 cycles and 1 pt (C) at 14 cycles. Median progression-free survival (PFS) was 84 days (d) (95% CI, 67-104 d) overall; A, 82 d; B, 84 d; C, 109 d; PLD failures, 90 d. Overall PFS for B was better than A (p = 0.03); C versus A was p = 0.08 and B versus C was p = 0.75. PFS was comparable for pts with or without PLD failure (p = 0.94). Across all doses, grade ≥ 3 AEs with ≥ 5% incidence included febrile neutropenia (FN) (12%), nausea (7%), vomiting (5%), fatigue (19%), and hypokalemia (5%). FN was low in A (9%) and B (5%); higher in C (23%). FN was manageable with supportive care and/or VOR dose reduction. Conclusions: The clinical safety and efficacy profile of VOR is encouraging for pts with heavily pretreated plat-resistant ovarian cancer, including pts with PLD failure. Overall ORR was 11% and median PFS was 84 d. Prolonged SD was noted across doses with no overt signs of CHF. The safety profile was consistent across doses, but FN incidence increased at 75 mg/m2. Clinical activity is optimal at 60 mg/m2 based on PFS and low incidence of FN (5%), and is recommended for further clinical development in this pt population. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sunesis Pharmaceuticals Sunesis Pharmaceuticals Sunesis Pharmaceuticals
Surging footprints of mathematical modeling for prediction of transdermal permeability
Authors: Neha Goyal, Purva Thatai, Bharti Sapra
Journal: Asian Journal of Pharmaceutical Sciences (2017)

In vivo skin permeation studies are considered gold standard but are difficult to perform and evaluate due to ethical issues and complexity of process involved. In recent past, a useful tool has been developed by combining the computational modeling and experimental data for expounding biological complexity. Modeling of percutaneous permeation studies provides an ethical and viable alternative to laboratory experimentation. Scientists are exploring complex models in magnificent details with advancement in computational power and technology. Mathematical models of skin permeability are highly relevant with respect to transdermal drug delivery, assessment of dermal exposure to industrial and environmental hazards as well as in developing fundamental understanding of biotransport processes. Present review focuses on various mathematical models developed till now for the transdermal drug delivery along with their applications.
Assessment tools for palliative care.
Authors: Sarina Isenberg, Rebecca Aslakson, Sydney Morss Dy, Renee Wilson, Julie Waldfogel, Allen Zhang, Alex B. Blair, Karen Robinson
Journal: Journal of Clinical Oncology (2016)

66 Background: Recent reviews have not comprehensively addressed palliative care (PC) assessment tools. This project summarizes the extent of evidence about PC assessment tools for patients and families, and how tools have been used for clinical care, quality indicators, and evaluation of interventions. Methods: We searched MEDLINE, CINAHL, and Cochrane Database of Systematic Reviews for systematic reviews of assessment tools for PC, from January 2007 to March 2016. We searched the grey literature for domains without systematic reviews, and for domains with systematic reviews &gt; three years old. Paired investigators independently screened search results and grey literature to determine eligibility, and assessed risk of bias of systematic reviews. The team selected the most recent and highest-quality systematic reviews for each domain. One investigator abstracted information, and a second investigator checked the information. Results: Using the National Consensus Project Palliative Care Guidelines domains, we included nine systematic reviews with 167 tools, and six tools from grey literature. Most tools were in physical, psychological, psychiatric, and social aspects of care, care at the end of life, and tools that cross domains (quality of life and caregiver-reported experience). Only two tools directly addressed spiritual aspects and none addressed cultural or patient-reported experience. Internal consistency reliability was evaluated for almost all tools; most reported construct validity; and few reported responsiveness (sensitivity to change). Few studies evaluated the use of assessment tools in quality indicators or clinical practice. A systematic review of 38 PC interventions and the assessment tools used found that at least 25 interventions included physical, psychosocial and psychiatric, and quality of life tools, but the tools varied extensively, and only nine included patient experience tools. Conclusions: Although assessment tools exist in many PC domains, tools are needed to assess spiritual and cultural aspects of care, and patient-reported experience. Research is needed concerning: tools in clinical practice and quality of care; comparison of existing tools; and evaluation and dissemination tools with evidence of responsiveness.
Prospective trial of proton reirradiation of locally recurrent esophageal cancer.
Authors: Abigail T. Berman, Annemarie Therese Fernandes, Stefan Both, Kristi Varillo, Edgar Ben-Josef, James M. Metz, John Peter Plastaras
Journal: Journal of Clinical Oncology (2014)

159 Background: Local recurrences of esophageal cancer occur in approximately 25% of patients and cause significant morbidity. Their treatment after esophagectomy and chemoradiation is particularly challenging. A second course of radiotherapy in a previously radiated field carries the risk of radiation-induced tissue injury. Proton therapy (PRT) may offer an advantage in the re-irradiation setting due to the lack of exit dose and potential sparing of normal tissues. Methods: Between 6/2011 and 8/2013, 10 adult patients (pts) with locally recurrent esophageal cancer, initially cT1b-T4N0-1, in or near prior treatment fields began reirradiation. Toxicity was graded according to the Common Toxicity Criteria version 4.0. Acute toxicity was defined as occurring within 90 days from start of PRT. Results: The median follow-up was 7.9 months (1-23) from the start of retreatment, and 15 months (2.4-27.8) from the development of local recurrence. Mean age was 70 (53-91). ECOG PS was 0 (n=4), 1 (4), 2 (2). Eight pts had intraluminal and two had paratracheal nodal recurrences. Eight of the pts had adenocarcinoma and two squamous cell carcinoma. Median CTV size was 138 cc (32-390). Seven received concurrent chemotherapy. The median total dose was 54.0 Gy (50.4-61.2); all pts were treated with PRT exclusively (9 double scatter and 1 uniform scanning), except for two pts who were treated with 15-30% IMRT. The median prior dose was 55.8 Gy (45-70). The median interval between radiation courses was 31.4 mos (12-105). Maximum acute toxicity was grade 2 (30%), 3 (30%), and 4 (40%). Of the grade 4 toxicities, one was an esophagopleural fistula and respiratory failure unlikely related to RT, and 3 were neutropenic toxicities possibly related to RT. Three pts developed metastatic disease at a median of 28 mos after starting RT. Three pts developed in-field locoregional recurrence at a median of 13 mos. Five pts died after a median of 13 mos. Conclusions: Preliminary results using PRT for reirradiation of esophageal cancers shows that local control can be achieved in a large proportion of pts with moderate but acceptable acute toxicity. Further follow-up on these pts is needed to assess the long-term utility of PRT reirradiation. Clinical trial information: NCT01126476.
Differential side effects profile in mCRPC patients treated with abiraterone or enzalutamide: A meta-analysis of randomized controlled trials.
Authors: Raphael Brandao Moreira, Marcio Debiasi, Fernando C. Maluf, Joaquim Bellmunt, Andre Poisl Fay, Toni K. Choueiri, Fabio Augusto Barros Schutz
Journal: Journal of Clinical Oncology (2016)

73 Background: Abiraterone and enzalutamide are currently approved for mCRPC patients. Both drugs have distinct mechanisms of action and may have different toxicity profile. There are limited data comparing the side effects of abiraterone and enzalutamide. We performed a meta-analysis of randomized controlled trials (RCT) to better characterize the risk of adverse events associated with both drugs. Methods: We performed a literature search on MEDLINE for studies reported from January 1966 to July 31, 2015. Abstracts presented at ASCO meetings from 2004 to 2015 were selected manually. Phase III RCT were included in analysis. We assessed the risk of adverse events reported in RCT by performing two meta-analysis: abiraterone-prednisone vs. placebo-prednisone (2,283 pts) and enzalutamide vs. placebo (2,914 pts). Summary of incidence, relative-risks (RR), and 95% confidence intervals (CI) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: Overall, enzalutamide was not associated with all-grade (RR 1.06 - 95% CI 0.67-1.65) or grade ≥3 (RR 0.81 - 95% CI 0.28-2.33) cardiovascular events, but was associated with increased risk of all-grade fatigue (RR 1.29 - 95% CI 1.15-1.44). On the other hand, abiraterone was associated with increased risk of all-grade (RR 1.28 - 95% CI 1.06-1.55) and grade ≥3 (RR 1.76 - 95% CI 1.12-2.75) cardiovascular events, but was not associated with all-grade (RR 0.85 - 95% CI 0.58-1.23) or grade ≥3 (RR 1.07 - 95% CI 0.97-1.19) fatigue. No evidence of publication bias was observed. Conclusions: In this meta-analysis, abiraterone was associated with an increased risk of cardiovascular events, while enzalutamide was associated with an increased risk of fatigue.
Hepatocellular carcinoma and end-of-life care.
Authors: Natasha Hunter, Jamie Erin Potosek, Rebecca A. Miksad
Journal: Journal of Clinical Oncology (2014)

278 Background: Patients with hepatocellular carcinoma (HCC) usually present with incurable tumors and advanced underlying liver disease. Although guidelines exist to assess the quality of end of life (EOL) care for cancer patients, little is known about EOL care for HCC patients. Due to the complexity and multidisciplinary nature of the disease, we hypothesized that EOL care for HCC patients differs from that delivered to other cancer patients and may be heterogenous based on patient characteristics and primary clinician specialty. Methods: We assessed EOL HCC care through medical chart review of 188 consecutive HCC patients treated at an academic tertiary care hospital who died between 2007 and 2013. Based on available data, EOL care and documentation was assessed per published guidelines. Patient, HCC and liver disease characteristics, cancer treatments, symptom burden, and EOL care and documentation was compared by provider specialty. The odds of receiving aggressive EOL care by provider specialty, patient characteristics, and documentation measures were calculated. Using data from the Dartmouth Atlas Project, we compared results with EOL data for cancer patients overall at our institution and nationally during a similar time frame. Results: Fewer HCC patients enrolled in hospice compared with cancer patients overall at our institution, and nationally (36%, 49% and 55%, respectively). In addition, HCC patients spent fewer days on hospice, spent more time in the hospital, and experienced more (and longer) intensive care unit admissions. Compared to those primarily cared for by other specialties, HCC patients seen by an oncologist were more likely to have goals of care (GOC) documentation and to enroll in hospice. Patients never seen by an oncologist were more likely to have a psychiatric illness. English as a non-primary language and code status documentation were among factors associated with more aggressive EOL care. Conclusions: At our institution, EOL care for HCC patients is more aggressive compared to cancer patients overall and nationally. The subset of HCC patients seen by oncology were more likely to meet EOL quality guidelines (GOC documentation and hospice enrollment). A better understanding of EOL practices for HCC may impact multidisciplinary care.
A Retrospective Analysis of Pneumocystis Jirovecii Pneumonia Infection in Patients Receiving Idelalisib in Clinical Trials
Authors: Laurie H Sehn, Michael Hallek, Wojciech Jurczak, Jennifer R. Brown, Paul M. Barr, John Catalano, Steven E. Coutre, Richard R. Furman, Nicole Lamanna, Ysebaert Loïc, Andrew D. Zelenetz, Jeffrey P. Sharman, Sven DeVos, Adeboye Henry Adewoye, Yeonhee Kim, Ian W. Flinn, Gilles A. Salles
Journal: Blood (2016)
Effectiveness study of gemcitabine, oxaliplatin, and capecitabine as first-line treatment for nonresectable biliary tract cancer.
Authors: Lars Henrik Jensen, Anne Haahr Mellergaard, Dan Hoegdall, Ole Larsen
Journal: Journal of Clinical Oncology (2014)

334 Background: Since 2010, the doublet gemcitabine and cisplatin has been standard first-line systemic treatment for non-resectable biliary tract cancer. In a phase I-II trial of the well-tolerated triplet of gemcitabine, oxaliplatin, and capecitabine, the median progression free survival (PFS) and overall survival (OS) were 6.9 and 12.5 months, respectively. Overall response rate was 34%. Since 2005 the regimen has been used in Denmark. We wanted to investigate the effectiveness of the triplet regimen given in daily clinic. Methods: We included 192 patients from two institutions. Patients had to have non-resectable biliary tract cancer and to be suitable for combination chemotherapy on doctor’s discretion. Gemcitabine 1000 mg/m 2 and oxaliplatin 60 mg/m 2 were given every two weeks followed by capecitabine 1000 mg/m 2 b.i.d. for one week. At one institution the oxaliplatin dose was 50 mg/m 2 and capecitabine dose 650 mg/m 2 b.i.d. continuously. One cycle included two treatments and was typically administered for up to six cycles/months, but was allowed for longer time until progression. Results: At institution A, 117 patients were included and 73 (62%) were women. Median age was 66 years (range 25-80). Median treatment duration was six cycles/months (range 1-12). Thirty-five, 69, 12, and one patient(s) were in performance status 0, 1, 2, and 3, respectively. Ninety patients were evaluable for response and 6 (7%) had complete response, 18 (20%) partial response, 53 (59%) stable disease, and 13 (14%) progression as best response. Median PFS was 9.7 months (95% CI 8.5-11.7) and median OS 11.7 months (9.8-14.0). The results were comparable to institution B, where the response rate in 56 patients with measurable disease was 30%. In 75 patients evaluable for survival analysis, PFS was 8.1 months and OS 12.0 months for performance status 0-1 (n=55). Patients in performance status 2 (n=25) had a PFS and OS of only 1.7 and 2.8 months, respectively. Conclusions: A triplet of gemcitabine, oxaliplatin, and capecitabine given in daily clinic was well tolerated and has effectiveness comparable to results from a phase II trial and the pivotal phase III trial of gemcitabine and cisplatin.