tbuckley/cabot-search huggingface dataset:
Transitions in House Staff Care and Patient Mortality
Authors: Justin S. Sadhu
Journal: JAMA (2017)

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8 Gy TBI/cyclophosphamide (TBI8/CY) as conditioning regimen for allogeneic transplantation in patients with advanced multiple myeloma.
Authors: Thomas Schmitt, Stefan Schoenland, Andrea Bondong, Hartmut Goldschmidt, Kai Neben, Klaus K Herfarth, Anthony D Ho, Peter Dreger, Ute Hegenbart
Journal: Journal of Clinical Oncology (2014)

e19562 Background: Multiple myeloma (MM) is still considered an incurable disease by standard chemotherapy and autologous stem cell transplantation (autoSCT). Outcome for patients (pts) with adverse disease characteristics is dismal. Therefore we investigated allogeneic stem cell transplantation (alloSCT) after conditioning with TBI8/CY. Methods: We included in this retrospective analysis pts with advanced MM who were considered to have poor prognostic factors and were allografted after TBI8/CY between 09/09 and 06/13. Pts received 2x2 Gy TBI days –5 and –4, cyclophosphamide 40 mg/kg BW days –3 and –2, and ATG in case of unrelated donors (10 mg/kg BW in matched unrelated donors, MUD, and 20 mg/kg BW in mismatch donors, MMD) days -3 to -1. Ciclosporine combined with mycophenolat mofetil was used for GVHD prophylaxis. Results: We identified 24 pts (early relapse after autoSCT, n=16; adverse karyotype, n=12; chemotherapy refractory disease, n=4). Median age and follow-up were 53 years [range 38 – 65] and 24 months, respectively. Remission status prior to alloSCT was VGPR or better in 8 pts, PR in 11 pts and non-response in 5 pts. Donors were matched siblings (n=9), MUD (n=11), and MMD (n=4). Median time to leukocyte and platelet engraftment was 14 days. Major toxicities (CTC grade ≥3) included FUO (n=22), nausea (n=7), pneumonia (n=5), catheter/soft tissue infections (n=7) and mucositis (n=4). Acute GVHD (grade II – IV) and chronic GVHD occurred in 10 and 12 subjects, respectively. 2-year overall (OS), progression-free (PFS) and event-free survival rates (EFS) were 55%, 18% and 16%, respectively. Treatment-related mortality (TRM) occurred in 2 pts after 2.2 and 11.0 months, due to acute GVHD grade IV and their complications. Pts with chronic GVHD had a significantly prolonged PFS (median 12 vs 4 months, p<0.01), and a trend to an improved OS (median 37 vs. 8 months, p=0.1) in comparison to pts without cGVHD (n=9). 5 pts received donor lymphocyte infusions (2 pts prophylactically, 3 after myeloma relapse). Conclusions: TBI8/CY is a feasible new conditioning regimen for advanced myeloma pts with a low TRM and no undue toxicities. However, myeloma disease control has to be improved in further studies.
Combined IHC4 score and local recurrence in breast cancer.
Authors: Roopa Lakhanpal, Bruce Shadbolt, Genevieve M Bennett, Michael Brown, Tessa Phillips, Amanda Bullman, Angela Rezo
Journal: Journal of Clinical Oncology (2014)

549 Background: The immunohistochemical 4 (IHC4) score is a pathological prognostic score that is a quantative measurement of estrogen and progesterone receptor status, the her2 status and the Ki-67 score. Cuzick et al. created a prognostic model that integrates IHC4 with clinical parameters of nodal status, tumour size, grade and age that may be as useful prognostically as multiple gene expression profiling assays (Cuzick et al J Clin Oncol. 2011 Nov 10;29(32):4273-8.). The role of the IHC4 score in predicting local recurrence is evolving. This study explores the role of the combined IHC4 score and loco-regional recurrence in women who have had breast conservation surgery without radiotherapy. Methods: Women with invasive breast cancer treated with breast conservation surgery and no radiotherapy were selected from a prospective cohort of breast cancer patients enrolled in the Australian Capital Territory and South East New South Wales Breast Cancer Treatment Group (ACT&SE NSW BCTG) Quality Assurance Project from 1997-2010.The IHC4 parameters were scored using pathology reports, slide review, and conducting further IHC testing when data was missing. Clinical information was obtained from the database and combined scores were calculated using the formula described by Cuzick. A Cox regression model was used to assess the association between the combined score and the risk of loco-regional recurrence. Results: Fifty-nine women in whom all the IHC4 variables were quantified and who had breast conservation surgery, were ER positive and who did not have adjuvant radiotherapy or chemotherapy were used to test the model. Using the same cut-off points and patient selection criteria for the combined IHC4 score described by Cuzick for low, intermediate and high risk groups, the loco-regional recurrence rates were zero for the low risk group(n=34), 23.5% in the intermediate group (n=17), and 37.5% in the high-risk group (n=8). Local recurrence tended to occur within 5 years for the high-risk group and beyond 5 years in the intermediate group. Conclusions: The combined IHC4 clinical effectively defined a sub-group of women with breast cancer treated with breast conservation surgery without radiotherapy that had negligible local recurrence rates.
Place of readmission and outcomes after major cancer surgery.
Authors: Karyn Beth Stitzenberg, YunKyung Chang, Angela Smith, Matthew Edward Nielsen
Journal: Journal of Clinical Oncology (2014)

6531 Background: Readmission rates after major cancer surgery are high (20-45%). Many patients are readmitted to a hospital different than where surgery was performed. We hypothesize that readmission to a different hospital is associated with poorer outcomes and higher costs. Methods: We used SEER-Medicare to examine 2001-6 incident cases of bladder, esophagus, lung and pancreas cancer. Claims data were used to identify any hospital readmissions during the 90-days post-discharge from the surgical admission (index hospitalization). Pearson chi-square and multiple logistic regression were used for all tumor sites together and individually to compare location of readmission based on various patient and hospital factors. Cox proportional hazard models were constructed to examine the association between the location of readmission and survival. Results: Of the 24,412 patients who had surgery, 6,552 (27%) were readmitted at least once, and 2,133 (33%) were initially readmitted to a hospital other than the index hospital. There were no significant differences in demographics between patients readmitted to the index vs. different hospital. Patients who had surgery at the highest volume centers were the most likely to be readmitted to a different hospital (p<.001 for all). Patients readmitted to a different hospital lived farther from the index hospital than those readmitted to index hospital (median 24-33 vs. 6-11 miles, p< .001 for all). The association with volume persisted after accounting for distance. Patients readmitted to a different hospital were more likely to be transferred to another hospital (9-10% vs. 2-3%, p<0.05 for all). Total 90 day costs of care differed significantly only for esophagus cancer (index $69K vs. different hosp $62K, p=0.005). Survival was associated with location of readmission only for bladder cancer (index hosp HR=1.22; 95% CI=1.067-1.401). Conclusions: From a broad perspective, initial readmission to a hospital other than the index hospital after major cancer surgery is not associated with substantially poorer long-term survival or higher costs for Medicare patients. However, more detailed studies are needed to determine the impact on fragmentation of care and other patient-level outcomes.
Does the dose and type of nonselective beta‐blocker really matter?
Authors: Pramod Kumar, Sunil Taneja, Virendra Singh
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. TO THE EDITOR: Nonselective beta‐blockers (NSBBs) are the only drugs recommended for the prophylaxis of variceal hemorrhage, and they are also considered the hepatologist's aspirin. In the recently updated guidelines for the management of portal hypertension by Garcia‐Tsao et al.,1 lower maximal doses of NSBBs (namely, propranolol and nadolol) are advocated for patients with ascites. However, the original studies published on NSBBs included fewer than 50% of patients with mild to moderate ascites, and the efficacy in this subgroup has not been fully assessed. In several recent studies, there have been conflicting results regarding the impact of NSBBs on survival in ascites patients, and the poor survival has been explained by the effect of high doses of NSBBs on cardiac output. The studies that have shown a safety/survival benefit in patients with ascites used a low median dose of propranolol (∼80 mg/day). There is also lack of real‐life data on NSBB use, and the higher doses are rarely used in routine clinical practice. A recent study showed that the use of propranolol beyond 6 months in Child‐Turcotte‐Pugh (CTP) class C patients was associated with increased mortality,2 and a lower dose of 80 mg/day appears safe even in severe liver disease without affecting efficacy.3 Similar to the dose recommendations on carvedilol, a fixed dose of propranolol between 40 and 80 mg/day based on individual tolerability without any heart rate titration appears more realistic until further evidence is available. Another dosing schedule for propranolol can be based on CTP class, similar to the recent pharmacokinetic study of carvedilol that showed a low optimal dose of carvedilol in different stages of cirrhosis (CTP class A, 9.375 mg; CTP class B, 4.68 mg; CTP class C, 2.34 mg versus 25 mg in healthy subjects) for best results.4 Interestingly, a recently published meta‐analysis by Njei et al.5 demonstrated that carvedilol, but not propranolol or nadolol, increased overall mortality in patients with ascites, adding to the confusion regarding the use of beta‐blockers in patients with cirrhosis and ascites. As such, a fixed low dose of NSBBs appears much safer and beneficial in all patients with cirrhosis requiring prophylaxis to achieve clinically meaningful outcomes.
Relation of antioxidant capacity of diet and markers of oxidative status with C-reactive protein and adipocytokines: a prospective study
Authors: Najada Stringa, Adela Brahimaj, Asija Zaciragic, Abbas Dehghan, Mohammad Arfan Ikram, Albert Hofman, Taulant Muka, Jessica C. Kiefte-de Jong, Oscar H. Franco
Journal: Metabolism (2017)
Treatability of patients with metastatic breast cancer after treatment by ixabepilone in first-line
Authors: E. Thivat, F. Dalenc, X. Durando, L. Gladieff, M. Mouret-Reynier, F. Kwiatkowski, M. Deslandres, P. Chollet, H. Roché
Journal: Journal of Clinical Oncology (2009)

e12030 Background: Ixabepilone (BMS-247550), an epothilone B analog, was an active drug in metastatic breast cancer (MBC) patients who were anthracycline pretreated. The main toxicity was mild to moderate neuropathy which was primarily sensory and mostly reversible. This study was performed to evaluate retrospectively the treatability of patients after discontinuation of ixabepilone given as first metastatic line in 2 institutions. Methods: From February 2001 to December 2002, 50 patients (median age 54 years) were enrolled in a phase II clinical trial evaluating ixabepilone as first line chemotherapy (CT) in MBC. Fifteen patients were treated by 50 mg/m2 (as a 1-hour infusion subsequently amended as a 3-hour infusion), and 34 received ixabepilone at 40 mg/m2 IV infusion during 3 hours every 3 weeks in response to the early safety findings. Neurotoxicity occurred in 38 patients (76%) leading to treatment discontinuation in 19 patients (38%). The description of subsequent treatments after ixabepilone was realized to detect eventual cross resistance and subsequent neurotoxicity. Results: Patients received a median number of 3 subsequent CT (range, 0–11) whatever the ixabepilone dosage. The median duration of subsequent CT lines after ixabepilone was of 3.6 months (range, 0–15.6 months). Patients who developed neurotoxicity received a median of 3 subsequents CT (range, 0–9), and those who did not, received a median of 1.5 subsequent lines. Forty-four patients received a second metastatic CT with different regimens stratified according the main cytotoxic agents, which were capecitabine in 54.5% of patients, taxane in 18.2%, and vinorelbine in 15.9%. At third line of metastatic CT (n = 37), taxane based regimen, capecitabine based regimen, and vinorelbine based regimen were administered respectively in 45.9%, 16.2%, and 13.5%. Median survival from first administration of ixabepilone was of 25.3 months (range, 0.2–89.2 months). After ixabepilone treatment, best response rate of subsequent CT was of 18.4%, and neurotoxicity was observed in 42.1%. Conclusions: In spite of neurotoxicity development with ixabepilone used as first metastatic line, the administration of subsequent lines of CT for treated MBC, especially with taxane based regimen, was normally possible. No significant financial relationships to disclose.
A genotype-directed study to optimize dosing of irinotecan according to the <i>UGT1A1</i> genotype.
Authors: Federico Innocenti, Ravi Salgia, Jacqueline Ramirez, Linda A. Janisch, Samir D. Undevia, Larry House, Soma Das, Kehua Wu, Michelle Turcich, Robert de Wilton Marsh, Theodore Karrison, Michael L. Maitland, Richard L. Schilsky, Mark J. Ratain
Journal: Journal of Clinical Oncology (2013)

2570 Background: The risk of severe neutropenia from irinotecan (I) is in part related to UGT1A1*28, a polymorphism that reduces the elimination of SN-38, the active metabolite of I. We aimed to identify the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of I in advanced solid tumor patients (pts) stratified by*1/*1, *1/*28, and *28/*28 genotypes. We hypothesized that *1/*1 pts would tolerate a higher MTD than the standard 350 mg/m 2 dose and that *28/*28 pts would require dose reduction. Methods: 68 pts (30 lung, 30 gastrointestinal, 8 other cancers) received q3w, flat-dose I. Genotype frequencies were 46% (*1/*1), 41% (*1/*28), and 13% (*28/*28). Pts (66% males, median age 68 years) had 0-1 PS (only one pt had PS 2). 82% were Caucasians, 13% African Americans, and 4% Hispanics. The I starting dose was 700 mg in *1/*1 and *1/*28 pts, and 500 mg in *28/*28 pts. Pharmacokinetics was obtained at cycle 1. DLT at cycle 1 was defined as grade (G) 4 neutropenia (N) for ≥4 days, G≥3N on a treatment day, G≥3 febrile N, G4 anemia or thrombocytopenia, or G≥3 non-hematological toxicity. Results: In *1/*1 pts, the MTD was 850 mg (4 DLTs/16 pts), and 1000 mg was not tolerated (2 DLTs/6). In *1/*28 pts, the MTD was 700 mg (5 DLTs/22) and 850 mg was not tolerated (4 DLTs/6). In *28/*28 pts, the MTD was 400 mg (1 DLT/6) and 500 mg was not tolerated (3 DLTs/3). DLTs were mainly G4N, G≥3 febrile N, and G3 diarrhea. I clearance followed linear kinetics. I and SN-38 AUCs were associated with decreased log 10 ANC nadir (r 2 0.27 and 0.30, respectively, p&lt;0.0001). At the MTD, I AUC in *28/*28 pts was 50% and 62% lower than that of *1/*28 and *1/*1 pts (16.8±4.4, 33.4±11.9, 44.2±11.3 h*ug/ml [mean±SD], respectively). At the MTD, SN-38 AUC in *28/*28 pts was 30% and 26% lower than that of *1/*28 and *1/*1 pts (620±407, 881±715, 841±888 h*ng/ml). 3 PRs were observed (NSCLC-700 mg-*1/*28, gastric-850 mg-*1/*1, small bowel-850 mg-*1/*28). Conclusions: In a heavily pretreated population, UGT1A1*28 information can be used to individualize dosing of I. Additional studies should evaluate the effect of genotype-guided dosing on efficacy in pts receiving I. Clinical trial information: NCT00708773.
Impact of the Intermediate Oncotype DX Recurrence Score results on adjuvant treatment recommendations in hormone receptor-positive early breast cancer in a single center.
Authors: Borja Lopez De San Vicente, Patricia Novas, Elena Galve Calvo, Sara Fernandez, Virginia Arrazubi, María Ángeles Sala, Seila Fernandez, Alberto Arevalo, Juan Fernando Arango, Ane Zumarraga, Laura Sande, Maria Teresa Perez-Hoyos, Teresa Abad, Purificación Martínez del Prado
Journal: Journal of Clinical Oncology (2015)

e11560 Background: The Oncotype DX (ODX) Breast Cancer assay (Genomic Health NC., Redwood City, CA) has been validated as a predictor of the likelihood of chemotherapy benefit in hormone receptor positive (HR+) early stage breast cancer (ESBC). It classifies patients (pts) into 3 risk recurrence categories: low ( < 18), intermediate (18-30), and high ( > 30). For pts with high recurrence score (RS), the benefit from adjuvant chemotherapy is significant, while is minimal for pts with low RS. In the intermediate recurrence score (IRS) category, adjuvant chemotherapy is controversial. We evaluated the impact of IRS on our adjuvant treatment decisions pre and post-testing. Methods: We retrospectively analyzed a cohort of 37 pts with IRS by Oncotype DX assay at the Basurto University Hospital from September 2012 to December 2014. They were breast tumor surgical specimens, HR+, Her 2 negative, tumor size T1b (if at least two histological unfavorable characteristic: high histological grade, lymphatic invasion and Ki 67 ≥ 14), T1c (excluding those with low histological grade and Ki 67 < 14%) and T2 (excluding high histological grade), negative lymph nodes or pN1mi histologically verified. Physicians´ treatment recommendations were documented before and after the RS results. Results: Clinicopathology features in IRS group were: negative lymph nodes 27 pts (73%), positive progesterone receptors 31pts (83.8%), luminal B 25 pts (67.6%), lymphatic invasion 3 pts (8.1%) and histological grade G1 10 pts (27.8%), G2 23 pts (63.9%) and G3 3 pts (8.3%). Before testing, 28 pts (75.7%) were recommended hormonal therapy (HT) and 9 (24.3%) chemohormonal therapy (CHT). Post-testing, 2 pts (5.4%), one of each group, changed the treatment, one to HT and another to CHT (no significantly difference by McNemar´s test P = 1). Conclusions: The difference between treatment recommendations pre and post ODX testing in our IRS pts was 5.4% (lower than described in the literature). The final decision was elected by clinicopathology features and patient´s preference.
Factors associated with venous thromboembolism among pancreatic cancerpatients.
Authors: Ankit Mangla, Hussein Hamad, Muhammad Umair Mushtaq, Michael Russell Mullane
Journal: Journal of Clinical Oncology (2015)

e15285 Background: The study was designed to explore correlates of venous thromboembolism (VTE) among pancreatic cancer patients. Methods: A retrospective review of 168 patients diagnosed with pancreatic cancer (2005-2014) was performed at Cook County Hospital, Chicago. Socio-demographic, clinical and pathologic factors were recorded at the time of diagnosis. Chi-square test and t-test were used as the tests of trend. Multivariate linear and logistic regression models were used to quantify the independent predictors of VTE. Regression coefficients (Rco) and adjusted odds ratios (aOR) with 95% confidence intervals (CI) were obtained. Results: The study included 49% Afro-Americans, 22% Caucasians and 20% Hispanics. Median age was 58.5 years and 54% were males. Past history was significant for hypertension (48%), diabetes (37.5%), smoking (49%) and alcohol abuse (47%). Stage 4 cancer was seen in 60% patients and 63% had tumor located in the head of pancreas. Median neutrophil-lymphocyte ratio (NLR) was 3.1. Treatment modalities used were chemotherapy (55%), radiation therapy (33%), surgical resection (23%) and palliative reduction (15%). VTE after diagnosis of pancreatic cancer was seen in 19% patients (n = 32), primarily in stage 4 patients (84%, n = 27). Hypertension (69% vs 31%; P = 0.01), surgical resection (6% vs 94%; P = 0.01), NLR > 3.1 (69% vs 31%; P = 0.03), low platelets (Mean, SD: 250, 81 vs 298, 109; P = 0.02), higher globulin (Mean, SD: 3.3, 0.7 vs 3.0, 0.6; P = 0.033), low albumin-globulin ratio (Mean, SD: 1.2, 0.3 vs. 1.3, 0.3; P = 0.02) and higher AST-ALT ratio (Mean, SD: 1.4, 0.7 vs. 1.0, 0.5; P = 0.001) were related with incidence of VTE. Independent predictors of VTE were hypertension (aOR 3.17, 95% CI 1.35-7.44; P = 0.008), surgical resection (aOR 0.19, 95% CI 0.04-0.86, P = 0.031), NLR more than 3.1 (aOR 2.61, 95% CI 1.11-6.15; P = 0.029), low platelets (Rco -0.001, 95% CI -0.001 to < 0.001; P = 0.007) and higher AST-ALT ratio (Rco 0.137, 95% CI 0.034 to 0.240; P = 0.01). Conclusions: High NLR, high AST-ALT ratio, low platelet count at the time of diagnosis and hypertension independently predicted increased VTE incidence while surgical resection of tumor had independent association with decreased VTE incidence among pancreatic cancer patients.
The Charlson age comorbidity index to predict prognosis in patients with resected pancreatic cancer.
Authors: Tomonari Asano, Tsutomu Fujii, Suguru Yamada, Norimitsu Yabusaki, Go Ninomiya, Goro Nakayama, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera
Journal: Journal of Clinical Oncology (2017)

495 Background: The Charlson age comorbidity index (CACI) is a useful measure of comorbidity to standardize the evaluation of surgical patients and has been reported to predict postoperative mortality in various cancers. Methods: A total of 379 patients who underwent R0/R1 resection for pancreatic cancer between 2003 and 2014 were enrolled in this study. According to the CACI, the age-adjusted comorbidity index was calculated by weighting individual comorbidities; CACI &lt; 4 was considered the low-CACI group, whereas CACI ≥ 4 was considered the high-CACI group. The correlations between the CACI and clinicopathologic features and survival outcomes were statistically analyzed. Results: The patients with a high CACI were more likely to be old and had higher CA19-9 levels and lower incidences of portal vein resection and blood transfusion. The rate of patients who received chemotherapy was significantly higher in the low-CACI group than in the high-CACI group (87% vs. 69%, P&lt; 0.0001). There was no difference in relapse-free survival (RFS) between the low- and high-CACI groups; however, the overall survival (OS) rate was significantly higher in the low-CACI group than in the high-CACI group ( P= 0.047). Multivariable analysis showed that a high CACI was a predictor of poor survival. In the high-CACI group, patients with high relative dose intensity (RDI) for postoperative adjuvant chemotherapy had significantly better RFS and OS than those with low RDI (both P&lt; 0.0001). Conclusions: The CACI was a significant independent predictor of prognosis and compliance for postoperative adjuvant chemotherapy and could be clinically useful for decision-making in the treatment strategy for pancreatic cancer.