tbuckley/cabot-search huggingface dataset:
Gabapentin for the prevention of chemotherapy-induced nausea and vomiting: A pilot study.
Authors: F. M. Cruz, A. Del Giglio, D. d. I. G. Cubero, P. Taranto, T. Lerner, A. T. Lera, M. C. Miranda, M. C. Vieira, A. B. d. S. Fede, F. Schindler, S. O. Afonseca, H. Pinczowski
Journal: Journal of Clinical Oncology (2011)

9017 Background: Chemotherapy-induced Nausea and Vomiting (CINV) is a distressing side-effect that affects many patients undergoing emetogenic chemotherapy, despite the use of antiemetic medications. The purpose of this trial was to evaluate the efficacy and safety of gabapentin for the prevention of CINV during the first cycle of treatment in patients receiving moderately or highly emetogenic chemotherapy. Methods: Eighty chemotherapy naïve patients scheduled to receive moderately and highly emetogenic chemotherapy were enrolled in this randomized, double-blind, placebo-controlled clinical trial. All patients received intravenous ondansetron 8 mg, dexamethasone 10 mg and ranitidine 50 mg before chemotherapy on day one and oral dexamethasone 4 mg twice a day on days two and three. Patients were randomly assigned to take gabapentin 300 mg or placebo on the following schedule: five and four days before chemotherapy 1 × daily, three and two days before chemotherapy 2 × daily, one day before to five days after chemotherapy 3 × daily. The primary end point was complete overall protection from both vomiting and nausea over the course of the entire study (day 1 through day 5), and complete protection during the delayed period (24 h to 120 h after chemotherapy). Results: The proportion of patients achieving complete response improved from 40% to 62,5%, (p=0,04) when comparing the control group and the gabapentin group, respectively. In the subset of patients who achieved complete control in the acute phase, the percentage of patients who achieved delayed complete control was higher in the gabapentin group (89,3 x 60,7%, p=0,01). Adverse events did not significantly differ between study arms. Conclusions: Gabapentin is a cheap alternative that significantly improved complete control of CINV and appears to be more effective for delayed CINV control.
Ziv-aflibercept (Z) in combination with FOLFIRI for second-line treatment of patients (pts) with metastatic colorectal cancer (mCRC): Interim safety data from the global aflibercept safety and quality-of-life program in pts pretreated with bevacizumab (B).
Authors: David Raymond Ferry, Alberto F. Sobrero, Roberto Bordonaro, Salvatore Siena, Filippo Pietrantonio, Stefan Bauer, Julien Taïeb, Pascale Garreau-Laporte, Sandrine Brette, Emmanuelle Dochy, Gérard Lledo
Journal: Journal of Clinical Oncology (2014)

556 Background: In the VELOUR study, adding Z (known as aflibercept outside the United States) to FOLFIRI resulted in improved OS, PFS, and RR in mCRC pts who had received prior oxaliplatin. Prior treatment with B (~30% of the ITT population) did not appear to impact the safety profile of Z. Results from VELOUR supported initiation of the global Aflibercept Safety and Quality-of-Life (QoL) Program composed of two clinical studies (ASQoP [NCT01571284]; AFEQT [NCT01670721]) to capture QoL and safety data from a population similar to that of VELOUR in a real-life setting. We report early safety data from this interim analysis in pts pretreated with B. Methods: ASQoP and AFEQT are single-arm, open-label trials evaluating safety and QoL of Z in mCRC pts previously treated with an oxaliplatin-containing regimen. Eligible pts receive Z (4 mg/kg) q2wks on day 1 of each cycle followed by FOLFIRI until disease progression, unacceptable toxicity, death, or investigator/pt decision. Initial starting doses and subsequent modifications are at treating physicians’ discretion. The percentage of pts with grade (G) 3/4 adverse events (AEs) in the combined safety population of ASQoP and AFEQT in B-pretreated pts is compared with that of B-pretreated pts in VELOUR. Results: At data cut-off, the safety population comprised 116 pts with ≥1 completed treatment cycle; 67 (57.8%) were pretreated with B. At least 1 G3/4 AE was experienced by 49.3% of pts vs 82.5% in VELOUR. Most G3/4 AEs were G3. There were no reports of G4 hypertension or proteinuria. Conclusions: Thisinterim safety analysis from ASQoP/AFEQT in pts pretreated with B has identified no new safety signals for Z and a trend toward decreased incidence of G3/4 events. The early analysis provides additional safety data and suggests an acceptable toxicity profile in this real-life setting. Clinical trial information: NCT01571284. [Table: see text]
Modeling patient variability in pazopanib-induced hepatotoxicity with iPSC-derived hepatocyte-like cells.
Authors: Yukti Choudhury, Yi-Chin Toh, Yinghua Qu, Jiangwa Xing, Jonathan Poh, Hui Shan Tan, Ravindran Kanesvaran, Hanry Yu, Min-Han Tan
Journal: Journal of Clinical Oncology (2016)

578 Background: The tyrosine kinase inhibitor drug, pazopanib, is commonly prescribed as a first-line treatment option for metastatic renal cell carcinoma (mRCC). Administration of pazopanib can produce severe hepatotoxicity with elevated transaminases and bilirubin levels. The idiosyncrasy of hepatotoxicity suggests individual patient-factors as the key predisposition. Patient-derived induced pluripotent stem cells (iPSCs) bearing individual genetic and other signatures, were interrogated as a novel cell-based approach to model inter-patient drug response variability. Methods: iPSC lines were generated from five mRCC patients who exhibited positive (n = 3) or negative (n = 2) clinical hepatotoxicity to pazopanib. The iPSC lines were differentiated into functional hepatocyte-like cells (HLCs), which were then dosed with pazopanib. Differential cellular viability changes among hepatotoxicity-positive and -negative lines were assessed. To gain insight into the mechanism of idiosyncratic hepatotoxicity, a comparison of transcriptomic changes in HLCs after pazopanib treatment was also done, with accompanying functional assays to investigate mechanisms of toxicity. Results: iPSCs were successfully generated from five patients and could be robustly differentiated into HLCs with uniformly high degrees of hepatocyte function. HLCs from patients with clinical hepatotoxicity exhibited higher in vitro toxicity to pazopanib compared to HLCs from patients without hepatotoxicity (p &lt; 0.01). However, all HLCs showed similar toxicity to known hepatotoxicants. Analysis of transcriptomic changes showed differential early-stress response among pazopanib-sensitive HLCs and suggested oxidative stress as a mechanism of pazopanib toxicity, which was verified by the observed depletion of intracellular glutathione levels in HLCs. Conclusions: We have a developed a novel cellular platform using iPSC-derived HLCs that can recapitulate phenotypes corresponding to clinical variation in pazopanib-induced hepatotoxicity. Furthermore, the patient-derived HLCs are ideal tools for the investigation of specific mechanism of hepatotoxicity.
Open-label prospective study of safety and efficacy of glass-based Y-90 radioembolization for infiltrative HCC with PVT.
Authors: Nima Kokabi, Juan C. Camacho, Minzhi Xing, John S. Kauh, Bassel F. El-Rayes, Hyun Sik Kim
Journal: Journal of Clinical Oncology (2014)

276 Background: Safety and efficacy of Yttrium-90 (Y90) therapy for infiltrative unresectable hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) require further evaluation. Methods: A prospective single center, open-label, single arm safety and efficacy study recruited patients with unresectable (Barcelona Liver Cancer Stage C) infiltrative HCC with PVT. Safety was assessed according to Common Terminology Criteria for Adverse Events v.3.0 at 1 week and monthly thereafter for 6 months post therapy. Efficacy was assessed by overall survival (OS) as primary endpoint. Tumor response was assessed by dynamic contrast MRI according to Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST at 1, 3, and 6 months (secondary endpoint). To achieve 0.95 power (α=0.05) and predicting prolongation of mean OS by at least 50% over the best supportive care (4 months ± 2 months (SD)), the study was designed to recruit 30 patients. Survival analysis was performed using Kaplan-Meier estimation. Prognostic factors were tested using log-rank and univariate analysis. Results: Thirty (n=30) patients were enrolled and underwent Y90 therapy (median age 63). The median OS was 13 months (CI: 4.1-21.1 months). Six patients had transaminitis (70% grade 1, 30% grade 2) while 8 patients had biliary toxicity (50% grade 1, 10% grade 2, 40% grade 3). Grade 3 bilirubin toxicity occurred in the same 2 patients with grade 2 transaminase toxicity. Although all patients recovered from transient liver toxicities, grade ≥2 liver toxicity was found to be predictor of poor outcome with median OS of 3.6 months for patients with grade ≥2 toxicity vs. 13 months for those with grade 1 or no toxicity (p=0.004). Child-Pugh class B, INR ≥1.5, and grade ≥2 hepatobiliary toxicities were found to be poor prognostic factors by both log-rank and univariate analysis (p&lt;0.05). Upon short-term imaging follow up (mean 34 days post Y90), 80% of patients were found to have complete (13%) or partial (67%) response according to targeted mRECIST criteria, with 93% stable disease according to targeted RECIST. Conclusions: In patients with unresectable infiltrative HCC and PVT, Y90 therapy is a viable and safe treatment option.
Evaluating the impact of a clinical universal mismatch repair screening initiative.
Authors: Michael J. Hall, Kathleen Q. Martin, Christina Rybak, Harry S. Cooper, Karen S. Gustafson, Jeff Boyd, Mary Beryl Daly
Journal: Journal of Clinical Oncology (2012)

194 Background: Immunohistochemistry (IHC)-based universal mismatch repair (UMMR) screening of incident colorectal (CRC) and endometrial (EC) tumors for deficient MMR (dMMR) associated with Lynch syndrome (LS) is supported by expert recommendations and is cost-effective. Heterogeneity in the approach to implementation of UMMR screening nationwide has been observed, suggesting knowledge gaps that could adversely impact anticipated outcomes. Studies of clinical UMMR screening can inform efforts to optimize implementation in the real world setting. Methods: In September 2011, Fox Chase Cancer Center (FCCC) began UMMR screening of incident (surgical) CRC/EC tumors. Providers were emailed a tailored UMMR Results letter intended to facilitate discussion of hereditary cancer risks and for distribution to patients. Content supported genetics consultation for an abnormal UMMR screen or for high-risk history (Hx) regardless of MMR status (i.e., personal Hx of any cancer; or 1st/2nd degree relative with a LS cancer and/or cancer &lt;50). For comparison, clinical data on all CRC/EC surgical cases 3 months prior to implementation of UMMR screening were extracted from the medical record. Results: 55 surgeries for CRC/EC occurred in the 3 months pre-implementation (PRE) and 130 in the 9 months post-implementation (POST). 1 yr PRE and POST data will be presented at the 2012 Quality Symposium. Conclusions: The UMMR screening initiative greatly improved patient outcomes. Provider referral and documentation behavior was highly responsive to an abnormal screening result, but not high-risk cancer history alone. [Table: see text]
25-year survival trends of patients with lymphoma by race/ethnicity as reported to the Nebraska Lymphoma Study Group (NLSG)
Authors: F. R. Loberiza, J. O. Armitage, P. J. Bierman, R. G. Bociek, D. L. Darrington, A. K. Ganti, J. M. Vose, D. D. Weisenburger
Journal: Journal of Clinical Oncology (2008)

6547 Background: We studied the survival trends over a period of 25 years for patients with lymphoma to explore possible disparities in clinical outcome according to race/ethnicity. Methods: Patients at least 19 years old with non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) and reported to the NLSG from 1981 to 2006 were analyzed. Progression-free (PFS) and overall survival (OS) between whites (W) and non-whites (nW) were compared using Cox proportional hazards regression analysis to adjust for other prognostic clinical variables. Results: A total of 3,626 patients with NHL or HL were eligible for study. 3,511 (97%) patients were W, whereas 115 (3%) patients were nW. Of the nW, 49% were blacks, 26% Hispanics, 10% Asians, 9% Native Americans and 6% others. Whites were older (median age 63y vs 53y for nW, p<0.001). At diagnosis, W were more likely to have advanced disease. Non-whites were more likely to have B symptoms and have elevated LDH. No differences according to sex, performance status, disease type (low or high grade NHL, or HL), size of tumor, or number of prior chemotherapy cycles were noted between W and nW. Multivariate analyses adjusted for age, disease type, and other prognostic factors, showed that PFS and OS between W and nW varied across time periods (1981–1992, 1993–1999, 2000–2006). There was a significant improvement in 5y PFS (35% to 40% to 51%) and OS (50% to 56% to 71%) across time periods among W. Improvements in PFS and OS were, however, not noted among nW. Furthermore, during 2000–2006, the risk of treatment-failure and death was significantly higher for nW (RR 1.70, 95% CI 1.13–2.55, p=0.01 and RR 2.09, 95% 1.29–3.37, p=0.003, respectively) compared to W. Conclusion: The expected improvement in clinical outcome over time as more treatment modalities become available for patients with lymphoma appears to occur among W, but not among nW. Distinguishing whether biology or socio-economic status best explains this disparate outcome is being evaluated. No significant financial relationships to disclose.
The PROFILE feasibility study: Genetic prostate cancer risk stratification for targeted screening.
Authors: Christos Mikropoulos, Elena Castro, Elizabeth Bancroft, Elizabeth Page, Natalie Taylor, Tokhir Dadaev, Zsofia Kote-Jarai, Antonis C. Antoniou, Nandita DeSouza, Diana Keating, Edward Saunders, Doug Easton, Nigel Borley, Mahbubl Ahmed, Andrew Lee, Ros A. Eeles
Journal: Journal of Clinical Oncology (2014)

22 Background: Prostate cancer (PC) screening is controversial and a better assessment of individualized PC risk is needed. Several single nucleotide polymorphisms (SNPs) conferring a cumulative risk of PC have been identified. We have explored the potential role of genetic markers for targeted screening in a population with increased risk of PC due to family history (FH). Methods: PROFILE was developed as a pilot study to determine the feasibility of targeted PC screening using prostatic biopsy (PB) and its association with specific genetic profiles in men with FH. We also evaluated the role of PSA and Diffusion Weighted MRI (DW-MRI) as screening tools. One hundred sixteen men age 40 to 69 with FH of PC were enrolled between October 2009 and December 2012. Cumulative SNP risk scores were calculated by summing 59 risk alleles for each locus using the weighted effect (log-additive model). DW-MRI was performed in 50 patients. Participants were asked to undergo a 10 core PB regardless of baseline PSA. Results: Median age 53 (40 to 69) and median PSA was 1.15. One hundred and two men accepted to undergo a PB as primary PC screening. Twenty-three tumours were found (22.5% of biopsies) as well as seven men diagnosed with atypical small acinar proliferation (ASAP) (6.8%) and eight men with high-grade prostatic intraepithelial neoplasia (HG-PIN) (7.8%). In total 37.1% received an abnormal result. Out of the diagnosed PC 41% were intermediate or high risk and requiring treatment, which compares with 24% in general population screening. The predictive performance of DW-MRI, PSA, genetic model and genetic model plus PSA measured by AUC were: 0.85, 0.73, 0.57 and 0.74, respectively. The genetic model performed best in men with a normal PSA of &lt;3(AUC 0.63). Analyses of a 78 SNP profile from the recent COGS results are underway. Conclusions: Ourresults indicate that PB is acceptable for PC screening in men with FH of PC. The significant AUC for DW-MRI would warrant a larger study. The incidence of ASAP is higher in this group than the general population.The SNP risk score was more predictive in men with PSA less than three where PB would not normally be undertaken, therefore an expanded study to investigate the role of genetic profiling in directing PB in PC screening is indicated.
Cost-minimization analysis (CMA) of capecitabine plus oxaliplatin (XELOX) compared with modified FOLFOX6 (mFOLFOX6) for the adjuvant treatment of resected colon cancer in British Columbia.
Authors: S. Yunger, B. Mistry, W. Y. Cheung, D. Ksienski, A. Urspruch
Journal: Journal of Clinical Oncology (2011)

e16538 Background: Evidence suggests that XELOX (NO16968 XELOXA) may have similar efficacy as mFOLFOX6 in the adjuvant treatment of colon cancer. Because XELOX is partly administered orally and is associated with a 3-week rather than a 2-week treatment cycle, we conducted a CMA from the healthcare payer and societal perspectives in order to evaluate the potential cost savings of replacing mFOLFOX6 with XELOX in the province of British Columbia, Canada. Methods: Applying treatment and toxicity data from phase III clinical trials of XELOX and FOLFOX-based regimens to the adjuvant colon cancer population in British Columbia, the CMA compared total costs associated with chemotherapy medications, drug administration and delivery, hospital and clinic visits, treatment-related toxicities, and need for central venous access devices (CVADs). Costs to patients in terms of lost time and decreased travel were also considered. We assumed that patients would receive either 8 cycles of XELOX or 12 cycles of mFOLFOX6 in our cost models. Results: The different costs by type are summarized in the table. From the payer perspective, the use of XELOX resulted in cost savings of $5,339 per patient when compared to mFOLFOX6. From a societal perspective, XELOX was also associated with savings of $6,082 per patient. The greatest cost savings with XELOX were attributed to fewer visits for chemotherapy treatment and decreased CVAD usage. XELOX was also associated with less loss of time and decreased travel for patients because of fewer clinic visits. Conclusions: Replacing mFOLFOX6 with XELOX in the adjuvant treatment of colon cancer may be associated with potential cost savings from both the payer and societal perspectives. Cost items (all in CAD currency) XELOX mFOLFOX6 Incremental difference Drug costs $24,280 $25,399 Administration costs $1,647 $3,302 Hospitalization costs $2,172 $3,163 Clinic costs $107 $121 Toxicity costs $82 $78 Central venous access costs $194 $1,757 Total costs - payer $28,484 $33,823 - $5,339 Patient time costs $2,745 $3,257 Patient travel costs $1,116 $1,345 Total costs - societal $32,345 $38,427 - $6,082
Prospective follow-up of 96 patients with breast cancer with leptomeningeal metastasis recruited from 2007 to 2010.
Authors: E. Le Rhun, N. Kotecki, F. Zairi, I. Rodrigues, A. Mailliez, M. Baranzelli, M. Faivre-Pierret, P. Devos, J. Cazin, J. Bonneterre, F. Dubois
Journal: Journal of Clinical Oncology (2011)

2089 Background: Around 5% of patients with breast cancer (BC) develop leptomeningeal metastasis (LM). Incidence of LM may increase. The aim of this study was to report the outcome of patients diagnosed with BC LM. Methods: 96 consecutive female BC patients diagnosed with LM were prospectively followed up in our institution from 2007 to 2010. Characteristics and outcomes of patients were reported. Correlations between characteristics and overall survival (OS) were analyzed using usual statistical methods (Kaplan Meier, Log-rank, Cox). Results: Median time between BC and LM was 42,5 months. BC were invasive ductal carcinoma in 72%. Estrogen and progesterone receptors were detected in respectively 61,5 and 43% of the tumors. HER2 expression was observed in 26,5%. 24% were triple negative. At LM diagnosis, median age was 52 and median Performance Status (PS) was 2. CSF cytology and cerebrospinal MRI were positive in respectively 72% and 87%. Median time between LM diagnosis and 1st intrathecal (IT) was 3 days. 80 LM patients received IT liposomal cytarabine (ventricular device in 55%) associated with systemic treatment in 52 cases and whole brain radiotherapy in 12 cases. Clinical stabilization or improvement was observed in 46%, CSF response in 37%, MRI stabilization or improvement in 67,5%. 12 patients were staying alive. Median OS of the whole cohort and the 80 treated patients were respectively 2,8 and 3,5 months. Initial PS was the mainly variable correlated with OS (p<0,0001). Median OS of the whole cohort was 5 months in 0-2 PS patients (n=56), 24 days in 3-4 PS patients (n=40). Median OS of the treated patients was 5,6 months in 0-2 PS patients (n=50), 31 days in 3-4 PS patients (n=30). Other significant predictors of survival were: RP and triple negative status RP (p=0,01/p=0,004), time between LM diagnosis and 1st IT injection (p), systemic and IT treatment (p<0,0001/p=0,0002), radiotherapy (p=0,0076), clinical, cytological and MRI responses (p<0,0001/p=0,0366/p=0,0343). Conclusions: Our results confirm the importance of an early diagnosis and the interest of the association of IT and systemic treatment in treating BC LM.
The choice of IMRT for early-stage right breast cancer.
Authors: Sophia Edwards-Bennett, Stephen Andrews, Patrick Francke, Frank Vicini
Journal: Journal of Clinical Oncology (2013)

81 Background: The benefit of Intensity Modulated Radiation Therapy (IMRT) has been established for left breast cancer. However, IMRT is not routinely employed for right breast cancer. The purpose of this study is to (1) compare dosimetric parameters in women with early stage right breast cancer undergoing whole breast radiation therapy using 3-dimensional conformal radiation (3DCRT) versus intensity modulated radiation therapy (IMRT) (2) determine treatment planning and/or anatomical correlates for patients who may benefit from IMRT. Methods: IMRT versus 3DCRT treatment plans were compared for 20 consecutive female patients with early stage (T1-T2 N0M0 ) right breast cancer treated at our center from 1/2012 to 12/2012. The planned target volume (PTV), contoured according to the RTOG atlas guidelines, was prescribed to 46-8-50.4 Gy in 26-28 fractions with PTV coverage goal of ≥ 95 % receiving the prescription dose. Dosimetric and anatomic parameters: % right lung receiving 20 Gy (lung V20), maximum breast dose (Dmax), maximum skin dose (Dmax skin), chest wall separation (CWS) and medial gantry angle (MGA) were determined for each paired treatment plan. Wilcoxon-signed rank test was utilized to compare IMRT and 3DCRT dosimetric parameters. Univariate analysis was used to identify planning or anatomic correlates associated with favorable dosimetric outcomes. Results: The lung V20Gy for IMRT ( 10.86±2.81%) was significantly lower than for 3DCRT (12.92±3.45 %, p &lt; 0.043). IMRT significantly reduced Dmax to 53.79 ± 2.17 Gy from 56.7 ± 2.24 Gy with 3DCRT (p 0.001). 3DCRT yielded significantly higher Dmax skin (33.47±3.21 Gy) than IMRT (24.16 ±2.65 Gy, p&lt; 0.0001). Mean CWS and MGA were 22.4 ± 2.6 cm and 126 ± 5.1° respectively. There was a significant association between CWS and Dmax for 3DCRT (p &lt; 0.026). Conclusions: The most significant impact of IMRT for right breast cancer was the reduction of Dmax and Dmax skin, with a more tempered advantage in the reduction of lung V20. Reduction of maximum breast and skin dose harbors clinical relevance as it relates to acute skin toxicity, long- term fibrosis and adverse cosmetic outcomes. Chest wall separation may be a potential planning surrogate marker to determine which right-sided breast cancer patients may benefit from IMRT.