tbuckley/cabot-search huggingface dataset:
Antitumor effect of whole body hyperthermia combined with alpha-galactosylceramide in subcutaneous tumor model of colon cancer
Authors: Takeshi Hattori, Satoshi Kokura, Toshimitu Okuda, Tetsuya Okayama, Satoko Adachi, Naoyuki Sakamoto, Yuji Naito, Norimasa Yosida, Haruki Kato, Toshikazu Yoshikawa
Journal: Cancer Research (2006)

4424  Aim: Whole body hyperthermia (WBH) has been used clinically as an adjunct to radio-/chemotherapy in patients with various cancers. Recently, it has been reported that an activation of the immune system might contribute to the therapeutic effect of WBH. On the other hand, it has been established that alpha-galactosylceramide (alpha-GalCer), a glycolipid, is recognized by natural killer T (NKT) cells together with the monomorphic MHC-like antigen, CD1d, in mice and humans. In this study, we investigated the antitumor effect of WBH combined with alpha-GalCer in mouse subcutaneous tumor model of colon cancer. Methods: Colon26 cells were inoculated subcutaneously in male BALB/c mice to establish subcutaneous tumor. Colon26-bearing mice were treated with whole body hyperthermia by using far infrared rays 3 times a week. Rectal temperature was maintained for 60 min at 41 degrees Celsius. In some experimental groups, alpha-GalCer was intraperitoneally injected before WBH. We investigated the therapeutic effect of WBH, alpha-GalCer, and the combined therapy. Furthermore, we also investigated the mechanism of antitumor effect by monitoring the change of IFN-gamma, NK activity, CTL activity. Results: (1) Compared with control group, whole body hyperthermia alone showed a tendency to inhibit tumor growth and to prolong survival rate. (2) Alpha-GalCer did not show the inhibitory effect to tumor growth. (3) The combination of whole body hyperthermia and alpha-GalCer showed significant inhibitory effect of tumor growth and prolongation of survival rate. (4) Serum IFN-gamma increased after 3 hours and returned to its basal level after 24hours of alpha-GalCer administration. (5) Both NK activity and CTL activity were enhanced on the group of combination therapy with whole body hyperthermia and alpha-GalCer. Conclusion: (1) Whole body hyperthermia showed the antitumor effect on mouse subcutaneous tumor model of colon cancer. (2) The combination with alpha-GalCer increased the efficacy of whole body hyperthermia probably via the enhancement of both NK activity and CTL activity.
Development of cancer care episodes to measure costs for breast, colorectal, and non-small cell lung cancer.
Authors: Catherine R. Fedorenko, Karma L. Kreizenbeck, Laura Panattoni, Julia Rose Walker, Cara L. McDermott, Mikael Anne Greenwood-Hickman, Gary H. Lyman, Ted Conklin, Bruce Smith, Sarah Barger, Scott David Ramsey
Journal: Journal of Clinical Oncology (2017)

29 Background: Cancer care costs are rising, creating concerns about affordability. As a result, delivery systems are creating alternative payment structures to lower costs while maintaining or improving quality. As cancer care delivery often involves multiple provider systems, measuring cost may be difficult. In response, using commercial insurance claims linked to cancer registry records, we constructed broadly applicable, reproducible, clinically relevant episodes to measure costs. Methods: Cancer registry records for patients diagnosed in Western Washington from January 2007-June 2016 were linked with claims from two regional commercial insurers. Patients are age 18+, diagnosed with breast, colorectal (CRC), or non-small cell lung cancer (NSCLC) and enrolled with a single insurance plan. With oncologist input, we constructed three care phases: diagnosis (30 days before diagnosis to first treatment), initial treatment (first treatment through first 4 month treatment gap), and end of life (last 30 days). Costs include all claims paid within the phase (2016 inflation adjusted). Supportive care includes colony-stimulating factors, blood transfusions, antibiotics, antivirals, antifungals, and antiemetics. Results: This study included 8,727 patients at diagnosis, 7,686 during treatment, and 1,736 at end of life. Diagnosis phase averaged 54 days and cost $6,936 (SD $11,761, median $4,021). Treatment averaged 126 days, with costs of $61,148 (SD $75,432, median $35,750). Average end-of-life costs were $15,829 (SD $30,222, median $2,347). The table below provides an example of the variation in costs during the treatment phase using local-stage tumors. Conclusions: Clinically relevant episodes of care and cost measures can be constructed using claims-registry data. This allows for identification of high-cost care categories and areas with large-cost variability, which may be helpful when designing value-based reimbursement programs or identifying areas for potential cost-reduction.[Table: see text]
Detecting lower in addition to the highest Gleason score prostate cancer on core biopsy and the odds of upgrading at radical prostatectomy.
Authors: John G Phillips, Ayal A. Aizer, Ming-Hui Chen, Michelle S. Hirsch, Jerome P. Richie, Clare M. Tempany, John Hegde, Marian Loffredo, Anthony Victor D'Amico
Journal: Journal of Clinical Oncology (2013)

e16026 Background: We evaluated the odds of upgrading at radical prostatectomy when a biopsy core with a lower Gleason score (GS) compared to the core with the highest GS was present (ComboGS) versus not at diagnosis and in a concurrent submission, test ComboGS in a validation data set on the endpoint of prostate cancer-specific mortality. Methods: The study cohort consisted of 134 men with clinically localized PC diagnosed between 4/08 and 9/11 using a 12-core prostate needle biopsy. GS at biopsy and RP were assigned by an expert genitourinary pathologist. Logistic regression multivariable analysis (Table) was performed to assess the impact that ComboGShad on the odds of upgrading at RP adjusting for known predictors of upgrading. Results: Of 134 patients, 46 (34%) were upgraded. Both increasing percent positive biopsies (ppb) (p &lt; 0.001) and PSA level (p=0.001) were associated with an increased odds of upgrading, whereas ComboGSwas associated with a decreased odds of upgrading (0.18 [95% CI: 0.04-0.76); p = 0.02). Men whose ppb was ≥ 33% (median) were upgraded in 47% (28 of 60) versus 14% (3 of 21) of cases (p = 0.009) when ComboGSwas absent versus present. These respective estimates in men with a PSA ≥ 5.2 ng/ml (median) were 43% and 12% (p = 0.019). Conclusions: In men with clinical factors associated with upgrading namely, increasing ppb and PSA, ComboGSis a favorable prognostic factor associated with a high rate of downgrading (&gt; 40%) and a low rate (&lt; 15%) of upgrading. Adjusted odds ratios and associated 95% confidence intervals and p values representing the impact of clinical factors at diagnosis on upgrading at radical prostatectomy. [Table: see text]
Phase I trial of pemetrexed plus paclitaxel administered every 21 days in patients with advanced solid tumors
Authors: A. Awada, R. Clark, H. Dumez, T. Gil, A. Hanauske, M. Piccart, A. Suri, A. Van Oosterom
Journal: Journal of Clinical Oncology (2004)

2053 Background: Pemetrexed (a novel multitargeted antifolate) and paclitaxel are active in various solid tumors. The primary objective was maximum tolerated dose (MTD) determination. Secondary objectives included: dose-limiting toxicities (DLTs) in cycle 1, recommended phase II dose, antitumor activity, and pharmacokinetics (PK) assessments. Methods: Patients (pts) with advanced cancer received on d1 pemetrexed (10 min iv) followed by paclitaxel (3h) q21d. Protocol was amended requiring vitamin supplementation (VS): folic acid (0.4 mg po) and B12 (1 mg im q9 weeks). Serial plasma samples were drawn for PK. Results: Prior to VS, 17 pts were enrolled into 3 dose levels (mg/m2): 7 pts 400/135 (one DLT: febrile neutropenia, FN); 6 pts 400/175 (one DLT: G4 diarrhea); 4 pts 500/135 (two DLTs: neutropenic sepsis, G4 neurotoxicity). Toxicities included (all grades/G3/G4): anemia (17/7/0 pts), neutropenia (15/3/8), thrombocytopenia (7/2/0), mucositis (12/0/0), diarrhea (7/1/1), and rash (10/0/0). Post VS amendment, 12 pts [8 M, 4 F; median age 49; prior chemotherapy (11 pts)] were enrolled at 500/135. 40 total cycles (range 1–7) with a median 3 cycles were given. No dose reductions, omissions, or drug-related deaths reported. Of the first 6 pts, 1 experienced FN (DLT). Dose level expanded to evaluate 3 pts treated with ≤1 prior systemic regimen; 1 pt experienced G4 neutropenia (DLT). Dose level was expanded to evaluate 3 pts with PS=0 and treated with ≤1 prior systemic regimen; 1 pt experienced G4 FN (DLT). Toxicities included: neutropenia (7/2/3), anemia (11/1/0), thrombocytopenia (3/0/0), mucositis (2/0/0); diarrhea (0/0/0), and rash (2/0/0). Stable disease reported in 5 pts: head/neck (2), mesothelioma (2), stomach (1). PK evaluation indicates no paclitaxel effect on pemetrexed PK. Conclusions: : The MTD of pemetrexed with VS and paclitaxel q21d is 500/135. VS appears to decrease mucositis, diarrhea, rash, and myelosuppresion. There was no significant change in exposure of either drug when given concomitantly. In a phase 2 study of this combination, pts should have vitamin supplementation, good PS and bone marrow reserve, and minimal prior chemotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly & Co. Eli Lilly & Co.; Novartis; Pfizer; Aventis; Lilly; Roche; Pharmamar Eli Lilly & Co. Eli Lilly Eli Lilly & Co.
Phase I study of VNP40101M (101M) and AraC in patients (pts) with refractory leukemia
Authors: F. J. Giles, S. Verstovsek, J. Cortes, S. Faderl, G. Garcia-Manero, F. Ravandi-Kashani, S. Kornblau, S. Gerson, M. Sznol, H. Kantarjian
Journal: Journal of Clinical Oncology (2004)

6617 Background: 101M is a new alkylating agent with broad activity in murine tumor models, including alkylator-resistant L1210 leukemia. In a phase I single agent study of relapsed/refractory (R/R) leukemias, the MTD was 600 mg/m2, the DLT was prolonged myelosuppression, and 2/38 pts achieved a complete remission (CR). The current phase I trial will determine the MTD of 101M with high dose araC (HDAC). Because alkylguanine transferase (AGT) mediates resistance to 101M in vitro studies, pt leukemia cells are collected for analysis of AGT expression and possible correlation with outcome. Methods: AraC is given by IV continuous infusion at a dose of 1.5gm/m2/day on D1–3 in pts ≥ 65 y/o and D1–4 in pts < 65 y/o. 101M is given IV on D2 over 15–90 min. The 101M dose is escalated in cohorts of 3–6 pts. Results: Six, 3, 4, and 3 pts have been enrolled to the following dose levels (DL): 200, 300, 400, 500 mg/m2. Fourteen pts had R/R AML, and 2 had R/R ALL. Median age is 52 (range 22–74); 8 pts. are male; and 15 had ECOG PS of 0–1. Two early deaths were observed on the first DL; one prior to the 101M infusion, and a second from sepsis on day 6. Gr 3 toxicities included: diarrhea in 1 pt at DL 400mg (VRE+) and 1 at DL 500mg (C. diff +); reversible hepatotoxicity in 2 pts at DL 200mg and 2 pts at DL 500mg; and fatigue in 2 pts at DL 500 mg. Other gr 1–2 toxicities included nausea and/or vomiting, conjunctivitis, mucositis, rash, and infusion-related hypotension and/or lightheadedness. Eleven pts (4, 3, 4 at DL 1–3, respectively) are evaluable for response. A CR in a HDAC resistant AML pt was observed at the 400mg DL, and a second primary refractory and HDAC resistant patient at DL 400mg had reduction in marrow blasts (97% baseline to 3% at day 45) with recovery of peripheral ANC. In leukemia cells from 7 patients in DL 1–2, AGT levels exceeded 500 fmol/mg protein. Conclusions: 101M + HDAC shows activity and a good safety profile in R/R AML. Phase II trials are warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Vion Pharmaceuticals, Inc. Vion Pharmaceuticals, Inc. Vion Pharmaceuticals, Inc. Vion Pharmaceuticals, Inc. Vion Pharmaceuticals, Inc.
Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T cell repertoire
Authors: Ryan O Emerson, William S DeWitt, Marissa Vignali, Jenna Gravley, Joyce K Hu, Edward J Osborne, Cindy Desmarais, Mark Klinger, Christopher S Carlson, John A Hansen, Mark Rieder, Harlan S Robins
Journal: Nature Genetics (2017)
Renal safety evaluation of zoledronic acid and thalidomide when used as post-stem cell transplant maintenance therapy in multiple myeloma
Authors: A. Spencer, A. Roberts, T. Neeman, H. Schran, K. Lynch
Journal: Journal of Clinical Oncology (2004)

6655 Background: Anecdotal reports suggest that combination therapy with zoledronic acid (ZA) and thalidomide (T) in multiple myeloma (MM) patients may increase the risk of renal dysfunction compared to ZA alone. As part of a multicentre Phase III trial of post autologous stem cell transplant (ASCT) T maintenance therapy we have compared renal function in MM patients receiving ZA with or without concomitant T. Methods: A multicentre, open label, randomised trial of T 200mg p.o daily for 12 months post-ASCT in patients with non-progressive MM. All patients also received ZA 4mg IV over 15 minutes every 28 days and alternate day prednisolone 50mg. A subset of patients underwent ZA Cmax and AUC (0–48) determinations for the first two ZA doses. Univariate analysis was conducted using student t-tests and chi-square tests for equal proportion. Multivariate analysis was conducted using a repeat measures analysis of variance. Differences in creatinine (Cr) between arms over time were determined by fitting an interaction between dose and arm, with dose and arm treated as linear predictors. Results: To-date 83 patients have commenced maintenance therapy (T=40), received a median of 9 (T) or 8 (no T) ZA doses and 15 patients have completed the PK study (T=8). The arms were well matched for gender, age, pre-ASCT B2microglobulin and baseline Cr. Four patients have had ZA withheld because of a rise in Cr (T = 1, no T=3). No ZA-related serious adverse events have occurred. Multivariate analysis demonstrated that higher Cr levels were associated with male gender and pre-ASCT B2M >4mg/L (both p<0.001). The relationship between Cr and cumulative ZA dose demonstrated no significant difference between the two arms (p =.12, for T vs no T). Peak drug concentrations (Cmax) and overall drug exposure (AUC 0–48) were similar between the two arms, both at day 1 and day 29 (p = ns, student t-test), and there was no suggestion of accumulation or changed PK profile after the second ZA dose. Conclusions: There is no evidence for a PK interaction by T on ZA. ZA was found to be safe in this previously treated MM population irrespective of concomitant T administration. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals; Novartis Pharmaceuticals Australia Pty Ltd. Novartis Pharmaceuticals Novartis Pharmaceuticals Pharmion Pty Ltd. Novartis Pharma; Amgen Australia Pty Ltd.; Pharmion Pty Ltd.
UN SISTEMA DE ACCESO Y LIBERACION DE UNA PROTESIS METÁLICA DE APOSICIÓN LUMINAL DISMINUYE EL COSTE DEL DRENAJE DE COLECCIONES PANCREATICAS CON NECROSIS
Authors: A Sanchez-Yague, A Gonzalez-Canoniga, C Lopez-Muñoz, A Sanchez-Cantos
Journal: Endoscopy (2015)

Introducción: El drenaje de colecciones pancreaticas sintomáticas guiado por ecoendosocopia ha reemplazado otras opciones. La estrategia clásica (EC) requiere varios pasos: acceso con aguja, dilatación y colocación de prótesis. Una nueva estrategia (NE) utiliza un dispositivo de acceso y liberación de una prótesis metálica recubierta de aposición luminal (PMC-AL) en un solo paso. La PMC-AL mantiene el orificio abierto facilitando la necrosectomia.
Investigating associations between health-related quality of life and endocrine therapy under-utilization in women with early-stage breast cancer.
Authors: Laura C Pinheiro, Stephanie B. Wheeler, Katherine Elizabeth Reeder-Hayes, Cleo A. Samuel, Andrew F Olshan, Bryce B. Reeve
Journal: Journal of Clinical Oncology (2017)

170 Background: Endocrine therapy under-utilization puts women at increased risk for breast cancer recurrence. The objective of this study was to determine if health-related quality of life (HRQOL) was significantly associated with under-utilization. Methods: Data came from the third phase of the population-based Carolina Breast Cancer Study. We included 1,599 women with hormone receptor positive disease aged 20-74 years. HRQOL was measured using the Functional Assessment of Cancer Therapy for Breast Cancer, on average, 5-months post-diagnosis. HRQOL domains included physical, functional, social, emotional, and spiritual well-being and breast cancer concerns. HRQOL subgroups were derived using latent profile analysis. Under-utilization was defined as not initiating or adhering to endocrine therapy by 36-months post-diagnosis. Multivariable logit models estimated adjusted odds ratios (aOR) between HRQOL subgroups and under-utilization. The subgroup with the best HRQOL scores across domains was the reference category. Chemotherapy and race-stratified models were estimated, separately. Results: Initiation analyses included 953 women with hormone receptor positive breast cancer who had not begun endocrine therapy by their 5-month survey, of whom 154 never initiated. Adherence analyses included 1,114 initiators, of whom 211 were non-adherent. HRQOL was not significantly associated with non-initiation except among non-chemotherapy users, with membership in the poorest subgroup associated with an increased odds of non-initiation (aOR 5.5; 1.7-17.4). Membership the two poorest HRQOL subgroups was associated with non-adherence (aOR 2.2; 1.2-4.0 and aOR1.9; 1.1-3.6), respectively. Membership in the poorest HRQOL subgroup was associated with non-adherence among non-chemotherapy users (aOR 2.1; 1.2-5.1). Conclusions: Our results suggest that women with poor HRQOL during active treatment may be at increased risk for under-utilization. Focusing on HRQOL, a modifiable factor, may improve targeting of future interventions early in the breast cancer continuum to improve endocrine therapy initiation, adherence, and breast cancer recurrence.
Weekly high-dose 5-FU as 24h-infusion and folinic acid (AIO regimen) plus Irinotecan in patients with advanced non-resectable adenocarcinoma or squamous epithelial carcinoma of the oesophagus: Interim analysis of a phase II trial
Authors: F. Boxberger, K. Wolff, V. Brueckl, W. M. Brueckl, C. Meier, G. Maennlein, T. Horbach, W. Hohenberger, E. G. Hahn, A. Wein
Journal: Journal of Clinical Oncology (2006)

14109 Background: At the moment of establishing the diagnosis, in approximately 50–60% of the patients with esophageal carcinoma only palliative treatment is possible due to either a locally advanced tumour growth or due to distant metastases. While adenocarcinomas of the esophagogastric junction are increasingly treated like gastric carcinomas, no palliative standard regimen is established for advanced squamous carcinomas of the oesophagus. The question should be answered whether the AIO regimen plus Irinotecan may achieve similarly positive results in esophageal carcinomas as in gastric carcinomas. Methods: Prospective phase II trial, patients: n=20, trial start: 03/2003, chemotherapeutic regimen: Irinotecan (80 mg/m 2 i.v. as 1h-infusion; d 1, 8, 15, 22, 29, 36, qd 57) as well as folinic acid (500 mg/m 2 i.v.) together with 5-Fluorouracil (2000 mg/m 2 i.v.; d 1, 8, 15, 22, 29, 36, qd 57) as 24h-infusion via port catheter. Results: n=16 (adenocarcinomas: n=8, squamous epithelial carcinomas: n=8); median age: 59,3 (44–72) years; men/women: 13/3; ECOG 0/1/2: 4/11/1; chemotherapeutic applications: 314. Evaluable in terms of toxicity: n=16. Higher grade toxicity: grade III diarrhea: n=2, grade III hyponatremia: n=1, thrombosis of the vena subclavia: n=1, grade III stomatitis: n=1, ischemic lesion of the brain stem: n=1. Two patients died after 2 chemotherapeutic applications with known peritoneal carcinomatosis and high tumour burden. Evaluable in terms of response: n=13. PR: n=7 (54%), SD: n=4 (31%), PD: n=2 (15%). Conclusion: The AIO regimen plus Irinotecan is excellently manageable on an outpatient basis in a multimorbid patient group and shows high efficacy in both adenocarcinomas and squamous epithelial carcinomas of the oesophagus. Final results, however, particularly in terms of median survival, still remain to be seen. No significant financial relationships to disclose.
Is rituximab sub-optimally dosed in indolent B cell lymphoma?
Authors: Yazeed Sawalha, Basel Rouphail, Xuefei Jia, Robert M. Dean, Brian Thomas Hill, Deepa Jagadeesh, Brad L. Pohlman, Paul Elson, Mitchell Reed Smith
Journal: Journal of Clinical Oncology (2015)

8567 Background: Rituximab (R) pharmacokinetics (PK) are affected by gender, age and weight (Wt) and can affect outcomes in aggressive B cell lymphoma (Pfreundschuh JCO 2014). Less is known about PK of R in indolent B cell lymphoma (iNHL). Methods: We analyzed effects of gender, age, Wt, BSA and BMI on outcomes for 303 consecutive patients (pts) at the Cleveland Clinic treated with 1st line R-based regimens for iNHL from 1997-2014. We divided pts into 3 treatment cohorts: R only (N = 119), R + Chemotherapy (CTX) (N = 120) and R-CTX followed by R maintenance (Rm) (N = 64); and by follicular (FL) (N = 184) or non-FL (N = 119) histology. Event-free survival (EFS) was based on date of relapse, progression, transformation, loss of follow-up, initiation of 2nd therapy or death. Characteristics among the 3 cohorts were compared using ANOVA, Chi-square and Fisher’s exact tests. Time to event data was summarized using proportional hazards models. Recursive partitioning survival trees were used to find the cut points for continuous variables. Results: Characteristics for the entire group were (mean ± SD): age 62 ± 12 yrs, Wt 83 ± 20 kg, BSA 2.0 ± 0.3 m2, BMI 24.3 ± 5.2, and 49% were male. There were no significant differences in baseline characteristics among the 3 cohorts. An event has occurred in 52%. Cut points determined were Wt ≥ 81.8 kg, BSA ≥ 2m2 and age ≥ 70. For all pts combined, higher Wt was significantly associated with inferior EFS (HR = 1.75, p = .007) with or without adjustment for gender and age. Univariable analysis by cohort revealed outcome differences only in the R-CTX cohort, with higher Wt associated with lower EFS (HR = 2, p = .008). For FL within the R-CTX cohort, Wt (HR 2.54, p = .003) and BSA (HR 2.02, p = .024) were associated with worse EFS. Elderly females in this group had better EFS (HR = 0.32) though this did not reach statistical significance (p = .098). Conclusions: Our results concur with DLBCL studies in which higher Wt was associated with faster R clearance and worse outcomes for R-CTX. As this is not observed in pts after R alone or R-CTX followed by Rm, we hypothesize that higher levels of weekly R and/or prolonged R exposure exceed therapeutic threshold despite more rapid clearance. Pts with iNHL, and FL specifically, treated with R-CTX may be sub-optimally dosed with R.