tbuckley/cabot-search huggingface dataset:
Long-term outcomes among patients who achieve complete or near-complete responses after the induction phase of bladder-preserving combined modality therapy for muscle-invasive bladder cancer: A pooled analysis of RTOG 9906 and 0233.
Authors: Timur Mitin, Asha George, Anthony L. Zietman, Donald S. Kaufman, Robert G. Uzzo, Robert Dreicer, Niall M. Heney, H. James Wallace, Luis Souhami, M. Chris Dobelbower, Howard Mark Sandler, William U. Shipley
Journal: Journal of Clinical Oncology (2014)

284 Background: Bladder preserving combined-modality therapy for muscle-invasive bladder cancer (MIBC) includes transurethral resection and concurrent chemo-RT given in two phases. After the induction phase with chemo-RT to 40 Gy the tumor response is assessed by cystoscopic biopsies and urine cytology. Early salvage cystectomy is promptly offered in case of persistent disease, otherwise patients proceed to consolidation chemo-RT to 64 Gy. The two most recent RTOG protocols 9906 and 0233 allowed patients with near-complete response (Ta or Tis) after the induction phase to proceed to consolidation. Methods: We performed a pooled analysis of 119 eligible patients with MIBC enrolled on RTOG trials 9906 and 0233, who were classified as having a complete (T0) or near-complete (Ta or Tis) response after induction chemo-RT and completed consolidation with a total RT dose of at least 60 Gy. We estimated bladder recurrence, salvage cystectomy rates and disease-specific survival by the cumulative incidence method and bladder-intact and overall survivals by the Kaplan-Meier method. Results: Among 119 eligible patients, 101 (85%) achieved T0 and 18 (15%) achieved Ta or Tis after induction chemo-RT and proceeded to consolidation. After a median follow-up of 5.9 years, 36/101 (36%) T0 patients vs. 5/18 (28%) Ta or Tis patients experienced bladder recurrence (p=0.52). Fourteen patients among complete responders eventually required late salvage cystectomy for tumor recurrence, in comparison to one patient among near-complete responders (p=0.47). Disease-specific, bladder-intact, and overall survivals were not significantly different. Conclusions: There is no apparent difference in the bladder recurrence and salvage cystectomy rates between complete and near-complete responders as judged at the time of cystoscopic evaluation after induction phase of bladder preserving CMT. It is appropriate to recommend that patients with Ta or Tis after induction chemo-RT continue with bladder-sparing therapy. This project was supported by RTOG grant U10 CA21661 and CCOP grant U10 CA37422 from the NCI.
Efficacy of interferon alpha 2a in 18 versus 60 months of treatment in patients with primary melanoma of ≥ 1.5 mm tumor thickness: A randomized phase III DeCOG trial
Authors: A. Hauschild, M. Volkenandt, W. Tilgen, R. Linse, J. Böttjer, T. Vogt, K. Spieth, T. Eigentler, N. H. Brockmeyer, M. Weichenthal
Journal: Journal of Clinical Oncology (2008)

9032 Background: Low-dose Interferon alpha 2a (IFNa2a) is approved for the adjuvant treatment of high-risk malignant melanoma (MM) in Europe. Controversy exists as to the impact of the duration of IFN treatment, which prompted us to study the potential efficacy of a long term IFN treatment in comparison to the standard schedule. Methods: Patients with resected cutaneous MM of ≥1.5mm tumor thickness were included in the trial. Patients had to be lymph-node negative either clinically or by sentinel lymph node biopsy (SLNB). After informed consent they were randomized to receive 3 MU IFNa2a 3x/wk s.c. for either 18 (Arm A) or 60 months (Arm B). Results: Of 850 pts. randomized, 840 were eligible for intent-to-treat evaluation, median follow-up was 4.3 years. All relevant prognostic parameters were well balanced between both groups. In particular, mean tumor thickness was 3.06 mm in Arm A versus 3.01 mm in Arm B. SLNB was performed in 635 pts. (75.6%) with 113 (26.7%; Arm A) and 91 (21.7% Arm B) positive. The clinical outcome is shown in the Table. Cumulative toxicity was significantly different with toxicity or patient related treatment discontinuations in 75 (17.8%; Arm A) and 159 (37.9%; Arm B) cases (p<0.001). Conclusions: In this study comparing conventional 18 months with extended 60 months IFNa2a treatment showed no clinical benefit in the outcome parameters. The fact that 5-year survival rates were even slightly lower in the experimental arm makes any relevant positive effect with larger patient numbers highly unlikely. Furthermore, the high rate of treatment terminations does not support the long-term use of low-dose IFNa2a. RFS DMFS OS 18mon (A) 60mon (B) 18mon (A) 60mon (B) 18mon (A) 60mon (B) Events (n) 98 104 70 76 54 56 5 year survival 75.6 % 72.6 % 81.9 % 79.7 % 85.9 % 84.9 % P-value 0.72 0.56 0.86 HR (95%-CI) 1.05 (0.80-1.39) 1.10 (0.80-1.52) 1.03 (0.71-1.50) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche Pharma Roche Pharma Roche Pharma
Clinicopathologic features and survival outcomes of primary signet ring cell carcinoma of colon: Retrospective analysis of VACCR database.
Authors: R. Thota, S. Birdsong, T. Tashi, W. Gonsalves, J. Tiwana, A. R. Sama, J. Krishnamurthy, X. Fang, P. M. Townley, P. T. Silberstein, S. Subbiah
Journal: Journal of Clinical Oncology (2011)

e14097 Background: Signet ring cell carcinoma accounts for less than 1% of all colon cancers. We examined the clinical pathological features and prognosis of signet ring cell carcinoma of colon Methods: A total of 206 patients diagnosed with signet ring cell carcinoma from 1995 to 2009 were identified from the VA Central Cancer Registry (VACCR) database. Age, race, histology, grade, lymph node status, stage and type of treatment received data were collected. Results: Out of 206 patients, 173 (83.9%) were white, 31 (15%) were black, and 2 patients were listed as unknown. Median age of diagnosis was 67 years as compared to 70 years for both mucinous and non-mucinous adenocarcinoma of colon. Pathological T-stages were as follows: T1 = 2.9%, T2=5.3%, T3=33.9%, T4= 25.7%, and unknown 32%. Of the total, 22.3% were located in caecum, 21.8% in ascending colon, 15.5% in sigmoid colon, 7.7% in appendix and hepatic flexure of colon, 11.1% in transverse colon, 2.9% in splenic flexure and 4.4% in descending colon. 33.5% were lymph node positive, 34.6% were lymph node negative, and 31.8% were unknown. Histological grade 3-(55.4%) was most commonly reported followed by grade 2 (7.3%), grade1 (2.5%), grade 4 (1.9%) and in 33% grade was unknown. 41.3% patients received only surgery while 34% received surgery with adjuvant chemotherapy, 7.3% received chemotherapy alone, 7.8% received radiation alone and 9% did not receive any therapy. 1 yr, 3 yr and 5 yr survivals for signet ring cell cancer compared to adeno carcinoma was 60% vs 80%, 33% vs 60%, and 24% vs 47% respectively. Median survival of signet ring cell carcinoma compared to mucinous and non mucinous adenocarcinoma was 19 mos, 48 mos and 67 mos respectively. Conclusions: Signet ring cell carcinoma of colon has poor survival rates than other histological subtypes. Signet ring cell carcinoma presents at an earlier age, has higher tumor grade and advanced stage at diagnosis when compared to mucinous and non-mucinous adeno carcinoma of colon. Due to rarity of this disease further multi-institute studies are required for in-depth understanding of this disease.
Randomized trial of early integrated palliative and oncology care.
Authors: Jennifer S. Temel, Areej El-Jawahri, Joseph A. Greer, William F. Pirl, Vicki A. Jackson, Elyse R. Park, Anthony Back, Alona Muzikansky, Mihir M. Kamdar, Simone Rinaldi, Juliet Jacobsen, Risa Wong, Ryan David Nipp, Emily R. Gallagher, Joel Fishbein, Justin Eusebio, Harry VanDusen, David P. Ryan
Journal: Journal of Clinical Oncology (2016)

10003 Background: Early palliative care (PC) improves outcomes in patients with newly diagnosed metastatic non-small cell lung cancer (NSCLC) and in patients identified by clinicians as having poor prognosis, advanced cancer. We evaluated the impact of early, integrated palliative and oncology care in patients with newly diagnosed lung and gastrointestinal (GI) cancer. Methods: We randomly assigned patients with newly diagnosed incurable lung (NSCLC, small cell, mesothelioma) or GI (pancreas, hepatobiliary, gastric, esophageal) cancer to PC integrated with oncology care (at least monthly visits with PC) or usual oncology care. We used the Functional Assessment of Cancer Therapy-General (FACT-G) to assess quality of life (QOL) and the Patient Health Questionniare-9 (PHQ-9) and Hospital Anxiety and Depression Scale (HADS) for mood at baseline, weeks 12 and 24. We assessed patients’ perception of their likelihood of cure and their communication about their end of life (EOL) preferences. WΒe used linear regression controlling for baseline values and clinical characteristics to evaluate the impact of group assignment on QOL and mood and chi-square to evaluate report of treatment intent and communication about EOL. Results: Between 5/2/11 and 7/20/15, we randomized 350 patients (175 per group), including 191 lung and 159 GI cancer patients. Patients assigned to early PC had higher QOL (β=4.98, 95%CI: 1.58 to 8.38, p=0.004) and less depression on the PHQ-9 (β=-1.22, 95% CI: -2.40 to -0.02, p=0.047) at 24 weeks, but not at 12 weeks. There were no between-group differences in HADS at either time point. At 24 weeks, similar proportions of patients reported that their cancer was unlikely to be cured (36/105 [33.6%] in PC and 43/115 [37.4%] in usual care) but more patients assigned to early PC reported they discussed their EOL preferences (31/116 [30.2%] versus 71/117 [14.5%], p=0.005). Patterns of change in QOL over time differed between lung and GI patients. Conclusions: Early PC improved QOL, decreased depression, and increased the frequency of EOL discussions in patients with newly diagnosed lung and GI cancer. The benefits of the integrated care model extend to other populations with newly diagnosed disease and include improved communication about EOL care. Clinical trial information: NCT01401907.
Open-label phase II study of S-1 as second-line therapy for patients with advanced non-small cell lung cancer (NSCLC).
Authors: R. Govindan, C. Zergebel, K. Saito, J. H. Schiller
Journal: Journal of Clinical Oncology (2010)

7580 Background: S-1 is an oral, fixed-dose combination product comprised of tegafur (FT), a prodrug of 5-FU, and 2 modulators of 5-FU metabolism: gimeracil (CDHP) and oteracil (Oxo). S-1 is designed to provide oral delivery of 5-FU while reducing the rate of degradation of 5-FU and its conversion in the gastrointestinal tract to its toxic phosphorylated metabolite. Studies conducted in Japan have demonstrated antitumor activity of S-1 in patients with NSCLC. Methods: Patients with advanced NSCLC (stage IIIB/IV) who had received prior first-line combination chemotherapy and had measurable disease received S-1 30 mg/m2 orally bid for 2 weeks followed by a 7-day recovery period, repeated every 3 weeks. The trial had a 3-stage design: 30 patients evaluable for efficacy in stage 1; an additional 20 patients in stage 2 if ≥ 3/30 (10%) patients had a confirmed response (RECIST) in stage 1; and progression to stage 3 if ≥ 8/50 (16%) patients had a confirmed response in stage 2. Results: A total of 57 patients were enrolled in 2 stages at 21 sites and received a median of 3.0 cycles of therapy. Baseline characteristics were: 61.4% men; mean age = 63.2 years (range: 44-85); 22.8% ECOG = 0, 77.2% ECOG = 1; 45.6% adenocarcinoma, 31.6% squamous cell, 12.3% large cell, 14.0% other. Prior first-line regimens were primarily platinum-based (93%). Among 50 evaluable patients, 4 (8.0%) patients had confirmed PR and 27 (54.0%) had SD (independent assessment). Median duration of response was 6.0 months (95% CI: 3.8, 18.8). Median PFS was 2.9 months (95% CI: 1.7, 4.1). MST was 7.3 months (95% CI: 6.0, 9.7). At least 1 grade 3 or higher adverse drug reaction (ADR) occurred in 49.1% of patients. The most frequent grade 3 ADRs (occurring in > 10% of patients) were diarrhea (21.1%) and fatigue (12.3%). ADRs resulting in treatment discontinuation included fatigue (5.3%), rash/dermatitis (5.3%), and decreased creatinine clearance (3.5%). Conclusions: Although this study did not meet the predefined tumor response target to proceed to stage 3, median PFS and overall survival estimates were comparable to those observed with pemetrexed and docetaxel when used as second-line treatment of patients with NSCLC. Its effectiveness should be evaluated in a larger study. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Taiho Pharmaceutical Taiho Pharmaceutical
Modelling TKI258 exposure and biomarker response in support of phase I dosing schedule finding
Authors: X. Wang, J. Saro, Z. Wei, M. M. Shi, J. Xia, G. Jones, K. Bruckmann, L. Wisniewski, H. F. Schran
Journal: Journal of Clinical Oncology (2008)

14691 Background: TKI258 (dovitinib lactate), an inhibitor of type III-V receptor tyrosine kinases (RTK), is being evaluated in multiple Phase I trials, including acute myeloid leukemia (AML), multiple myeloma, and other tumor types. VEGF and PLGF have been identified as potential pharmacodynamic biomarkers of VEGFR inhibition by TKI258. A population pharmacokinetic-pharmacodynamic (PK/PD) model was developed to characterize TKI258 systemic exposure and effect on biomarkers in the ongoing Phase I trials, and to allow simulation of alternative dosing schedules for potential application in future studies. Methods: TKI258 plasma concentrations (measured by LC/MS/MS) from 87 patients were fitted to a one-compartmental PK model with first order oral absorption and Michaelis-Menten type elimination. The time-dependency of the drug’s kinetics was characterized by an indirect-response function. The PD data (VEGF, PLGF) were fitted to an indirect response model combining with the PK model. Results: The population PK model well described the TKI258 dose∼exposure relationship across the investigated range of 25 to 600 mg daily. Volume of distribution was 2440 L, suggesting extensive extravascular distribution of drug and was consistent with the >24 hour RTK inhibition observed after single dose treatment with TKI258. The baseline clearance of TKI258 was 56 L/h, whereas the maximum induced clearance could reach 3 times baseline value. Up to the 600mg/day dose, there was no saturation in the induction of VEGF and PLGF. The model-predicted TKI258 concentration for optimal effect on these biomarkers (e.g a 5-fold increase over baseline) was ∼ 200 ng/mL, a level not expected to be associated with dose limiting toxicities. Intermittent dosing (e.g. 700 mg on a 5-days on, 2-days off schedule, or 1200 mg on an every Monday, Wednesday, and Friday schedule) would be preferable over continuous daily dosing to ensure achievement of stable steady-state concentrations. Conclusions: PK/PD modelling and simulation has identified intermittent dosing schedules for controlling TKI258 exposure levels within a potentially pharmacodynamically active and safe range. No significant financial relationships to disclose.
Application of lean methodology to improve quality and efficiency of molecular diagnostic testing in non-small cell lung cancer (NSCLC).
Authors: Lawrence David Wagman, John Maurice, Peggy Crabtree, Ruslan Horblyuk
Journal: Journal of Clinical Oncology (2014)

220 Background: The advent of targeted cancer therapies has triggered an increase in the volume of molecular testing performed across multiple tumor types. This raises concern about the efficiency of associated operational and quality processes. This study’s objective was to apply lean methodology, using NSCLC as a pilot disease state, to evaluate current molecular testing processes, identify existing inefficiencies, design an improved process and assess scalability for application across other tumor sites at the pilot site. Methods: Modified Lean methodology was employed. Semi-structured 1:1 interviews with multidisciplinary team (MDT) stakeholders representing oncology, pathology, interventional radiology, pulmonology and administration were conducted. MDT-based value stream mapping workshops were carried out to describe the “current” and design the “future” state of molecular testing process in NSCLC. The goal was to identify existing inefficiencies and inform targeted process improvement efforts. Results: Interviews with 25 MDT stakeholders revealed substantial variability in the molecular diagnosis processes and a lack of coordinated communication across disciplinary silos. Specifically, the consensus-derived “current” state map identified appropriate biopsy tissue (quality and quantity) and inconsistent protocol utilization among the major inefficiencies resulting in repeat biopsies. Development and implementation of the MDT-based molecular testing protocol, including introduction of a tissue acquisition protocol, were identified as target areas for process variability improvement. Conclusions: Inefficiencies exist in molecular testing processes and need to be identified and minimized as the burden of molecular testing increases. This pilot successfully employed modified Lean methodology to identify areas of improvement in the molecular testing process in NSCLC and could be replicated in other relevant disease states. Program evaluation is underway to quantify the impact of this initiative on operational and patient care metrics.
A prospective study on behavioral symptoms’ impact to the quality of life in patients with early-stage cancer receiving radiotherapy.
Authors: Canhua Xiao, Jennifer Felger, Donna Mister, Tian Liu, Andrew H. Miller, Mylin Ann Torres
Journal: Journal of Clinical Oncology (2013)

46 Background: Fatigue, sleep problems, and depression are the most common behavioral symptoms experienced by breast cancer patients. The purpose of this study was to examine these behavioral symptoms’ impact on quality of life (QOL) for early stage breast cancer patients receiving radiotherapy (RT). Methods: This was a prospective study of 46 patients receiving whole breast RT (50 Gy plus a 10 Gy boost) following lumpectomy. Data were collected at pre-RT, week 6 of RT, and 6-weeks post-RT. QOL was measured by Short Form-36, fatigue by Multidimensional Fatigue Inventory, sleep by Pittsburgh Sleep Quality Index, depression by Inventory for Depressive Symptomatology-Self-Rated, and stress by Perceived Stress Scale. No patients were treated with chemotherapy. Demographic/clinical variables, including age, race, marriage, smoking history, hormone treatment, and cancer stage, were collected at the time of enrollment. Mixed effect modeling was utilized to observe behavioral symptoms’ impact on QOL over time. Results: Fatigue and depression, along with stress, had significant impact on QOL after controlling for body mass index (BMI; the only one significant demographic/clinical variable; see Table). Patients with more fatigue, depression, or stress were more likely to have worse QOL during and post-RT. Patients having a higher BMI at baseline also reported worse QOL over time. Sleep was significantly correlated with QOL in univariate analyses, while this effect disappeared in multivariate models. Conclusions: Behavioral symptoms, in particular fatigue and depression, along with stress, have significant impact on the QOL of early breast cancer patients’ receiving RT. Future research on the underlying biological mechanisms will improve our understanding of these symptoms and their relationships, which will help to find potential targets for multiple related symptoms and, ultimately, improve patients’ QOL. [Table: see text]
A randomized, double-blind, controlled trial of methylphenidate for fatigue in patients with advanced cancer.
Authors: E. Bruera, V. Valero, W. Breitbart, Y. Guo, J. L. Palmer, M. Z. Cohen, C. Scott, M. B. Lake
Journal: Journal of Clinical Oncology (2010)

TPS321 Background: Fatigue is the most common and one of the most distressing symptoms in patients with advanced cancer. Currently, there is no standard treatment for this multidimensional syndrome. Methylphenidate is found to be well-tolerated, with minimal side-effects, in both elderly and frail populations. Our objective through this ongoing trial is to determine the affect of methylphenidate on patients with fatigue, as well as investigate the role a nursing telephone intervention (NTI) plays in the improvement of fatigue. During an initial study, our group found that methylphenidate reduces opioid-induced sedation. More recent research by our group suggests that methylphenidate and a NTI are both capable of significantly reducing fatigue (Bruera et. al., JCO 2006). In order to better understand these preliminary results, we developed this clinical trial. Methods: Advanced cancer patients with fatigue ≥ 4/10 on the Edmonton Symptom Assessment Scale (ESAS), normal cognition evidenced by the Mini Mental State Examination (MMSE), no evidence of major depression and hemoglobin ≥ 8 are eligible. Following enrollment, patients are randomized twice. The first blinded randomization occurs to determine if eligible patients will receive methylphenidate or a placebo for their treatment of fatigue. The second randomization occurs to determine if patients will receive a NTI or not. This allows our group to isolate the affects both methylphenidate and a NTI play on improving patient fatigue. It also allows us to determine if there is a synergistic affect of receiving both methylphenidate and a NTI. The data will be analyzed in four groups: methylphenidate and a NTI, placebo and a NTI, methylphenidate and no specific phone call intervention (NSPCI) and finally, placebo and a NSPCI. The primary endpoint is fatigue, measured by the Functional Assessment of Chronic Illness–Fatigue (FACIT-F), administered at baseline and day 14. Following week 2, patients enter an open phase where all patients receive methylphenidate 5 mg every two hours, as needed, up to 20 mg/day through Day 36. The study blinding code will not be broken before entering this open phase. Total sample size is 250 patients; we have accrued 125 patients. No significant financial relationships to disclose.