tbuckley/cabot-search huggingface dataset:
Abstract 13816: Readmission in Patients With Atrial Fibrillation Treated With Dofetilide versus Other Anti-arrhythmic Drug Therapy
Authors: Zhun Cao, Dale Rublee, Dorothy Baumer, Scott B Robinson, Richard Chambers, Rebecca Ashkenazy, Craig B Lipkin
Journal: Circulation (2016)

Introduction: An estimated 3 million people in the U.S. are affected by atrial fibrillation (AF), and its prevalence is projected to increase significantly as the population ages. This study examined time trends of 30-day hospital readmission rates in AF patients treated with dofetilide vs those treated with other antiarrhythmic drug therapy (ADT) and those without ADT (controls). Methods: A retrospective cohort study was conducted using Premier Healthcare Database. The first adult inpatient discharge with ICD-9 diagnosis code 427.31 between 1/1/2007-11/30/2014 was included. Unadjusted descriptive analysis was used to describe the trends of 30-day all-cause and AF-related readmission rates in patients treated with dofetilide, compared to patients with other ADT (amiodarone, sotalol, flecainide, propafenone and dronedarone) and those without ADT. Logistic regressions were used to estimate the association between 30-day readmission and type of anti-arrhythmic treatment. Results: 2,664,043 AF discharges were included. 30-day all-cause readmission rate for dofetilide patients decreased from 10.42% in 2007 to 6.75% in 2014, compared to 3.35% for patients with other ADT, and 3.40% for controls. 30-day AF-related readmission rates dropped by 3.28% in dofetilide, compared to 1.85% in other ADT cohort and 2.42% in controls. Using the no-ADT cohort as reference, the adjusted odds ratios (OR) of 30-day all-cause readmission were 0.76 (95% CI: 0.73-0.80, p&lt;0.001) for dofetilide and 1.10 (95% CI: 1.09-1.11, p&lt;0.001) for other ADT. The adjusted OR of 30-day all-cause readmission were 0.91 (95% CI: 0.86-0.97, p=0.002) for dofetilide and 1.13 (95% CI: 1.12-1.14, p&lt;0.001) for other ADT. The adjusted 30-day all-cause readmission rates were 12.20% for dofetilide, 16.62% for other ADT, and 15.41% for controls. The adjusted AF-related readmission rates were 10.81% for dofetilide, 13.05% for other AA, and 11.71% for controls. Conclusions: There was an 8-year decline in 30-day readmission rates for all cohorts (p&lt;0.001), with a faster decrease in dofetilide patients (p&lt;0.001). The dofetilide treated patients had the lowest adjusted risk of 30-day all-cause and AF-related readmission, while patients undergoing other ADT had the highest readmission rates.
Differential use of complementary and alternative medicine (CAM) in cancer patients at a single institution.
Authors: Prabhsimranjot Singh, Makardhwaj Shrivastava, Sidney Morris Stoll, Waseem Cheema, Rukhsana Hossain, Laura Covolus, William B. Solomon
Journal: Journal of Clinical Oncology (2016)

e21582 Background:: It is appraised that 30-40% of people use some form of complementary and alternative medicine (CAM) in the United States. Immigrants face barriers to conventional oncology treatments including lack of insurance, language variances. We hypothesized that, as compared to their US-born counterparts, recent immigrants are expected to have greater use of CAM. Methods: We designed a comprehensive survey questionnaire of self-reported CAM use in patients treated for any cancer at our multi-cultural institution. This included data on demographics, cancer stage, anxiety level and whether these patients pursued second medical opinions. Statistical analysis was performed to determine which factors were independently associated with CAM use. Results: The study is ongoing and the data collected thus far is from 130 surveyed patients. The study population had a median age of 61 (22-87) years. More than half (51.5%) were immigrants, 62.3% were female and 46.1% did not have English as their primary language. The most common cancer was breast (34%), followed by lung (14%). Most patients had advanced cancer stage III/IV (65.3%). Eighty six (66%) of patients reported using some modality of CAM: the most common were prayers and spirituality (53.4%), followed by dietary medicine (38.3%) and herbal medicine (29%). The highest predictor of CAM use was female gender (75.3% vs. 51.0% in males; p = 0.002).Patients who had lived in the United States for > 20 years were more inclined to use CAM compared to those who had lived < 20 years (69.2% vs. 52.2%) (p= 0.0007). There was a trend for higher use of CAM in educated patients and those with metastatic cancer. Patients who used CAM had lower anxiety level scores. Conclusions: The preliminary results from this multi-cultural study suggest that some factors may increase likelihood of CAM use in cancer patients, such as female gender, longer United States residency, higher education, and metastatic disease. More data is needed from our ongoing accrual of patients to confirm those preliminary findings. If they were corroborated, they could indicate that those with better access to resources and/or those with non-curable conditions may be more likely to use CAM.
Outcomes for matched patients with metastatic colitis-associated cancers versus sporadic colorectal cancer receiving chemotherapy.
Authors: Rona Yaeger, Jonathan Hersch, David Bates, Viktoriya Paroder, Joanne F. Chou, Laura H. Tang, Marc Jeffrey Gollub, Marinela Capanu, David Paul Kelsen
Journal: Journal of Clinical Oncology (2018)

e15534 Background: Colitis-associated cancers (CAC) develop in the setting of inflammatory bowel disease (IBD) and have a distinct pathogenesis and genomic features compared to sporadic colorectal cancer (CRC). Despite these differences, CAC are treated the same as CRC. We analyzed a matched series of patients with metastatic CAC and CRC to compare outcomes. Methods: We queried the electronic medical record of Memorial Sloan Kettering Cancer Center and identified 18 patients with metastatic CAC (7 with ulcerative colitis, 11 with Crohn’s disease). Each case was matched to a CRC case based on location of primary tumor, metachronous or synchronous metastatic disease, and regimen of first line metastatic treatment. The MSK-IMPACT next generation sequencing assay was used to identify genomic alterations (GA) in all cases. All cases were studied for survival. Tumor response to first line metastatic chemotherapy was evaluated by independent radiology review blinded to history of IBD, using RECIST 1.1 in 14 matched patient pairs with measurable disease. Results: Median overall survival was 15 months for CAC patients versus 34 months for CRC patients, and there was a trend towards shorter survival for CAC patients in the matched survival analysis (HR 2.02, 95% CI: 0.92-4.45, p = 0.08). Response rate to first line chemotherapy did not differ significantly (57% CAC, 64% CRC). Six month progression free survival (PFS) was 38% for CAC and 72% for CRC (p = 0.11); in the matched analysis, accounting for resection after chemotherapy, CAC was associated with a hazard ratio of 1.98 for PFS (p = 0.085). KRAS alterations, BRAF V600E, and TP53 mutations did not vary significantly between the paired groups, while APC mutations were significantly less common in CAC. Unique GA seen in CAC included IDH1 R132C and FGFR2-INA fusion. Conclusions: While objective response rates were similar, metastatic CAC patients appear to have shorter survival than patients with metastatic CRC. Our data suggest that patients with CAC may be less likely to benefit from standard chemotherapies, but differences did not reach statistical significance. New therapies focusing on the distinct tumor genomics of this group should be studied.
Adjuvant androgen deprivation (AD) +/- mitoxantrone + prednisone (MP) in patients with high-risk prostate cancer (PC) post radical prostatectomy (RP): Phase III intergroup trial S9921.
Authors: Maha Hussain, Catherine M. Tangen, Ian Murchie Thompson, Gregory P. Swanson, David Peter Wood, Wael Sakr, Nancy Ann Dawson, Naomi B. Haas, Thomas W. Flaig, Tanya B. Dorff, Daniel W. Lin, E. David Crawford, David I. Quinn, Nicholas J. Vogelzang, L. Michael Glode
Journal: Journal of Clinical Oncology (2017)

5019 Background: Patients (pts) with high-risk PC post RP are at risk of systemic relapse with related morbidity/mortality. Adjuvant AD can reduce this risk. In 1999, based on available data, we hypothesized that adjuvant MP + 2 years (ys) of AD can further reduce mortality. Methods: Eligible pts had cT1-T3, N0 PC with post RP &gt; = 1 high risk factors defined as Gleason sum (GS) ≥ 8, pT3b, pT4, pN+, GS 7 + positive margin or any of these preoperative findings (in pts with neoadjuvant AD): preoperative PSA of &gt; 15 ng/ml, bx GS score &gt; 7, or PSA of &gt; 10 ng/ml + bx GS &gt; 6. Pts had to have post RP PSA = &lt; 0.2 ng/ml, were stratified by T, N, GS, and adjuvant radiation plan and randomized: Arm 1 AD (bicalutamide + goserelin for 2 ys) or Arm 2 AD + 6 cycles m 12 mg/m 2 + P 5mg BID. Primary endpoint: overall survival (OS). Median OS was estimated to be 10 ys in AD arm requiring 680 pts/arm to detect a hazard ratio (HR) of 1.30 with 92% power and one-sided α = 0.05. Results: 983 pts (961 eligible intent to treat) with median age 60 ys and median PSA 7.6 ng/ml were randomized to AD or AD + MP from 10/99 -1/07 when the DSMC recommended stopping accrual due to higher leukemia rate in Arm 2. 16% had N1 (Group “Gr” 1), 61% GS ≥8 or pT3b (Gr 2),23% other risk factors (Gr 3). Median time to testosterone recovery was 9.5 months. Median follow-up (f/u) 11.2 ys. Conclusions: OS was higher than anticipated in both arms; MP did not improve OS and increased other malignancy risk. These data illustrate that systemic therapy benefit cannot be extrapolated from different disease stages and the importance of adequate f/u in adjuvant PCa trials. The remarkable DFS and 10 y OS, irrespective of risk extent, may be result of risk definition, and/or 2 ys AD. Pending definitive data 2 ys adjuvant AD for high-risk PCa post RP is a reasonable option to consider. Clinical trial information: NCT00004124. [Table: see text]
S-1 maintenance therapy following induction therapy with carboplatin plus S-1 in advanced squamous cell lung cancer.
Authors: Seiichiro Suzuki, Masato Karayama, Naoki Inui, Tomoyuki Fujisawa, Noriyuki Enomoto, Yutaro Nakamura, Shigeki Kuroishi, Hiroyuki Matsuda, Koshi Yokomura, Naoki Koshimizu, Mikio Toyoshima, Toshihiro Shirai, Masafumi Masuda, Takashi Yamada, Shiro Imokawa, Takafumi Suda
Journal: Journal of Clinical Oncology (2016)

e20554 Background: Maintenance therapy has been widely accepted as a standard therapy in non-squamous non-small-cell lung cancer (NSCLC). However, the clinical benefit of maintenance therapy for squamous-cell lung cancer (SQCLC) remains unclear. We evaluated the efficacy and safety of maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with SQCLC. Methods: In this phase II trial, chemotherapy-naïve patients with SQCLC received induction therapy with carboplatin (AUC 5 on day 1) and S-1 (80mg/m2 on day 1 to 14) of a 28-day cycle. Patients achieving disease control after four cycles of induction therapy received maintenance therapy with S-1 (80mg/m2 on days 1 to 14) of a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) from the start of maintenance therapy. In addition, the efficacy in elderly patients was evaluated. Results: Fifty-one SQCLC patients were enrolled in the study. Thirty-six patients (70.6%) completed four cycle of the induction therapy. Eighteen (35.3%) patients received maintenance therapy. The median PFS from the start of the maintenance therapy was 3.0 months (95% CI, 2.5-3.5 months).The median overall survival (OS) from the start of the maintenance therapy was 9.2 months (95% CI, 6.2-12.3 months). The most common grade ≥ 3 toxicities were thrombocytopenia (16.7%), anemia (16.7%), fatigue (16.7%), neutropenia (5.6%) and nausea (5.6%) throughout the study. In 30 elderly patients (aged > 70 years), 11 (36.7%) received maintenance therapy and demonstrated the median PFS of 3.2 month (95% CI: 0.5-5.8 months) and the median OS of 9.2 months (95% CI: 2.5-16.0 months). The most common grade ≥ 3 toxicities in elderly patients were thrombocytopenia (18.2%), anemia (18.2%), fatigue (16.7%), neutropenia (9.1%), and nausea (9.1%). Conclusions: Maintenance therapy with S-1 after induction therapy with carboplatin and S-1 might be a feasible treatment in SQCLC patients. This was the case for elderly patients. Clinical trial information: UMIN000006983.
Decision-making in the older patient with diagnosis of cancer: Sarcopenia and frailty as predictors of toxicity to chemotherapy—ONCOSARCO project.
Authors: Carmen Guillen, Borja M Fernandez-Felix, Mar Munoz Sanchez, JA Santiago Crespo, Amaya Olaverri, Maria-Carmen Soriano-RodrÃ Âguez, MJ Molina-Garrido
Journal: Journal of Clinical Oncology (2016)

e21525 Background: Given the high risk of toxicity to chemotherapy (CT) in elderly, decision making in this population is complex. In this sense, the project ONCOSARCO aims: 1) To know what (frailty [F] or sarcopenia) is the best predictor of toxicity to CT; 2) To identify new predictors of toxicity (To) between variables related to muscle mass (MM), muscle strength (MS) or physical function (PF). Methods: Between 12/2012 and 12/2014, 103 patients (≥ 70 years) were included. MM (muscle mass index), MS (handgrip, spherical strength, pinch-gauge, knee-extension strength, hip-flexion strength) and PF (gait speed and 5-to sit chair test) were recorded before starting CT. European Working Group on Sarcopenia in Older People (EWGSOP)’s criteria were used to define sarcopenia and Linda Fried’s criteria were used to detect frailty. Toxicities of grade 3-4 were used as final event, and mortality without severe To was used as a competitive event. It was used a multinomial logistic regression analysis to predictors of severe To. Results: Severe toxicity appeared in 44 patients (42.7%); 30 patients had no To (29.1%); 29 patients died without toxicity of CT (28.2%).Frail patients had no a higher risk of making To (p = 0.220) than prefrail patients. After adjusting by full doses of CT and tumoral stage, F was associated with more severe toxicity from CT, but not significantly (RR = 2.4; 95% CI 0.9 to 6.9; p = 0.090). Sarcopenia was not good predictor of To to CT in older patients with cancer (p = 0.59).It was built a predictive model of To by using variables related to MM, MS and PF. In the analysis, the only variable that was significantly associated with To was the strength of knee extension (RRR 0.7, 95% CI: 0.5-0.9; p = 0.031).1 Conclusions: In the field of Oncogeriatry, frail patients showed 2.4 times higher risk of developing To to CT (p = 0.090) than prefrail patients. Sarcopenia was not associated with To, unlike the force of knee extension (p = 0.031). Further studies should confirm the new role of this variable as a predictor of To in the elderly; if confirmed, the knee-extension strength could be a new tool in the decision-making process in the consultations of older patients with cancer.
Apatinib as a salvage treatment for refractory metastatic colorectal cancer.
Authors: Xiaofeng Chen, Ping Li, Jing Sun, Biao Wang, Peinan Lin, Xiaomin Cai, Xiao Han, Yanhong Gu
Journal: Journal of Clinical Oncology (2018)

3556 Background: Apatinib, an oral VEGFR2 inhibitor, has been approved as third line treatment for metastatic gastric cancer in China. The aim of this study was to evaluate the efficacy and safety of apatinib, in the treatment of refractory metastatic colorectal cancer patients who failed from two or more lines of chemotherapy. Methods: In this open-label, single-arm, phase II study, patients were treated with apatinib in daily dose of 500 mg, po, in the third - or more line setting. Capture sequencing was dynamically performed to identify somatic variants in circulating tumor DNA (ctDNA) with a panel of 1021 cancer related genes.The primary endpoint was progression-free-survival (PFS) and the tumor response was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Interim analyses was applied as predefined. Results: From June 01, 2016 to December 31, 2017, 26 patients were enrolled. The median PFS of the whole group was 3.9m (95% CI: 2.1-5.4). Patients with PS 0-1 had longer PFS than those with PS 2 (4.17m vs 1.93m, p = 0.0014). Patients without iver metastasis also had longer PFS than those who had live metastasis ( 5.87m vs 3.33m, p = 0.0274). Median overall survival was not reached. 10-month survival rate was 55%. The common side effects of apatinib were hypertension, hand-foot syndrome, proteinuria and diarrhea. The incidence for grade 3-4 hypertension, hand-foot syndrome, proteinuria and diarrhea were 76.92%, 11.54%, 73.08%, and23.08%, respectively. All of the patients received dose reduction due to adverse effect. Results of capture sequencing showed APC, TP53 and KRAS were most frequently mutant genes.Patients with high tumor mutation burden (TMB) in baseline blood had a trend of prolonged overall survival than those with low TMB (p = 0.077). The molecular tumor burden from ctDNA increased before the radiographic assessment in 10 patients. Conclusions: Apatinib monotherapy showed promising efficiency for refractory colorectal cancer patients, especially in patients with PS 0-1 or no liver metastasis. TMB is a potential prognostic biomarker. In addition, tumor molecular burden may be a predictor in serial monitoring of tumor load. Clinical trial information: NCT03190616.
Impact of <i>UGT1A1</i> genotype on prognosis in Japanese advanced colorectal cancer patients treated by irinotecan-based regimens.
Authors: Wataru Ichikawa, Keisuke Uehara, Keisuke Minamimura, Chihiro Tanaka, Yasumasa Takii, Hideaki Miyauchi, Sotaro Sadahiro, Katsunori Shinozaki, Kanehisa Fukumoto, Toshio Otsuji, Takeshi Kambara, Satoshi Morita, Yuichi Ando, Yukihiro Okutani, Masahiro Sugihara, Toru Sugiyama, Yasuo Ohashi, Yuh Sakata
Journal: Journal of Clinical Oncology (2015)

3525 Background: The influence of UGT1A1*6 and UGT1A1*28 on prognosis of irinotecan (IRI)-based regimens has been controversial, although UGT1A1 genotypes are risk factors for IRI-related toxicities in Asians. We conducted a prospective analysis to examine the correlation between UGT1A1 genotypes and safety/efficacy of IRI-based regimens in Japanese patients (pts) with advanced colorectal cancer (aCRC) (NCT 01039506). The validated nomogram for predicting the probability of severe neutropenia induced by IRI-based regimens was proposed based on safety analysis (ASCO 2014, Abst No. 3543). We analyzed the efficacy in terms of UGT1A1genotypes. Methods: 1,376 pts who had histologically confirmed aCRC and received IRI-based regimens were enrolled. UGT1A1 genotypes were categorized into three groups: wild (*1/*1), hetero (*1/*6, *1/*28), and homo (*6/*6, *6/*28, *28/*28). The primary objective was to investigate the non-inferiority of hetero or homo to wild in progression-free survival (PFS) under the non-inferiority margin of hazard ratio (HR) of 1.25, using propensity score weighting to adjust for baseline characteristics. Progression was evaluated by investigators according to the RECIST 1.1 criteria. The association of prognosis with IRI exposure was also examined. Results: The efficacy analysis was performed using 1,339 pts. The prevalence of UGT1A1 genotypes were 47% wild, 42% hetero, and 11% homo. The median PFSs according to UGT1A1genotypes were 6.0 (95% CI, 5.6–6.7) months (mo) in wild, 6.0 mo (5.4–6.6) in hetero, 5.6 mo (4.4–6.1) in homo. The HR of hetero to wild was 0.988 (0.864–1.130; non-inferiority p = 0.0006) and that of homo to wild was 1.202 (0.988–1.463, non-inferiority p = 0.6977). The HRs in the homo group with a starting dose not less than 80% to wild and with a dose less than 80% of the standard IRI dose were 1.037 (0.779–1.379, p = 0.8052) and 1.393 (1.106–1.754, p = 0.0049), respectively. Conclusions: This analysis revealed that PFS in the UGT1A1 hetero group were non-inferior to the wild group. However, the homo group had worse PFS as compared with the wild group. The excessive dose reduction of the starting IRI dose might account for the unfavorable results in the homo group.
Pharmacokinetics of midazolam and its metabolites in terminally ill adult patients.
Authors: Birgit Koch, Linda Franken, Anniek Masman, Brenda de Winter, Frans Baar, Dick Tibboel, Teun van Gelder, Ron Mathot
Journal: Journal of Clinical Oncology (2016)

e21506 Background: Midazolam is a commonly used sedative drug in terminally ill adult patients and is titrated to achieve the desired level of sedation. To support the patient it is of clinical importance to achieve adequate sedation as soon as possible. As terminally ill patients are a very heterogeneous population with severe co-morbidity (eg hepatic and renal impairment) patients could potentially benefit from an individualised dose that is determined beforehand. To find clinical relevant parameters for dose individualisation we performed a pharmacokinetic study on midazolam, 1OH-midazolam (1OH-M) and 1OH-midazolam-glucuronide (1OH-MG) in adult terminally ill patients. Methods: 192 from 47 patients who had received midazolam orally and subcutaneously were available. Population pharmacokinetic parameters were estimated using non-linear mixed effects modelling (NONMEM 7.2). The covariates analysed were patient characteristics, co-medication and blood chemistry levels. Results: The data were best described by a one-compartment model for midazolam, 1OH-M and 1OH-MG. Between-subject variability (BSV) was shown for the bioavailability of midazolam, clearance of midazolam, 1OH-M and 1OH-MG and for the volume of distribution of midazolam. The population mean estimates for midazolam, 1OH-M and 1OH-MG clearance were 9.1 L/h (BSV 46%), 48 L/h (BSV 58%) and 5.7L/h (BSV 49%) respectively. Low albumin levels corresponded with low midazolam clearance and explained 19 % of the BSV in midazolam clearance. 1OH-MG clearance was correlated with the estimated glomular filtration rate explaining 40% of the BSV in 1OH-MG clearance. Conclusions: The population pharmacokinetics of midazolam and its two major metabolites were accurately quantified. A decreased eGFR resulted in lower clearance of 1OH-MG and could therefore result in increased sedation. Low albumin levels were associated with decreased midazolam clearance, probably as a result of inflammatory response. CRP as a covariate had a similar effect as albumin yet less significant. eGFR and albumin might be useful clinical parameters to develop an individualized dosing regimen. Additional studies on the pharmacodynamic effects of midazolam in this population are recommended.