Daniel Sargent

..We present our method in terms of a Bayesian hierarchical model. We fit the model to the data using Markov chain Monte Carlo methods. Finally, we illustrate the approach with several examples...

..We discuss the advantages and disadvantages of the two trial designs and their appropriateness to specific clinical situations to assist investigators seeking to design rigorous, marker-based clinical trials...

..A shorter-term end point providing convincing evidence to allow treatment comparisons could significantly speed the translation of advances into practice...

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..In the genomic age, in which targeted therapies with or without specific biomarkers are emerging in cancer care, new approaches are necessary to generate the evidence required for decision making...

..Clinical trials typically enroll less than 10% of patients with a PS of 2 (PS2); thus, the benefit of systemic chemotherapy in PS2 patients is uncertain...

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..Limited data are available on the time course of treatment failures (recurrence and/or death), the nature and duration of adjuvant treatment benefit, and long-term recurrence rates in patients with resected stage II and III colon cancer...

..We also include a discussion of situations where flexibility may be required, relative to the ideal rigorous evaluation, to accommodate inevitable real-world feasibility constraints...

..We examined MMR status as a predictor of adjuvant therapy benefit in patients with stages II and III colon cancer...

..The goal of this design is to mirror clinical practice, where a treatment's success probability is often only one of many considerations in determining a treatment recommendation for a particular patient...

..The relationship between end-points in trials with oral fluoropyrimidines, oxaliplatin and irinotecan is unknown...

..We report a planned analysis performed on 241 patients...

..We previously validated disease-free survival (DFS) after 3-year follow-up as an excellent predictor of 5-year OS results. Here we explore shorter term DFS and OS end points, as well as stage dependency...

..We describe the theoretical properties of this design and illustrate it with several examples. We focus on the clinical implications of the three-outcome design. Control Clin Trials 2001;22:117-125..

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..Its judicious use should be considered without regard to patient age, although scant data are available among patients older than 80 years...

..We examined disease-free survival (DFS), overall survival (OS), recurrence-free interval (RFI), and grade 3+ adverse events (AEs) in younger patients in the 33,574 patient Adjuvant Colon Cancer Endpoints Group data set...

..However, the importance of the availability of all three active cytotoxic agents, FU-LV, irinotecan, and oxaliplatin, on overall survival (OS) has not yet been evaluated...

..v.) without dose-limiting toxicity. CONCLUSION: Gemcitabine 30 mg/m(2) i.v. twice weekly and cisplatin 10 mg/m(2) i.v. twice weekly may be given concurrently with radiation therapy (50.4 Gy in 28 fractions) with acceptable toxicity...

..We hypothesized that stage I and IIA colon cancer patients would experience similar benefits...

..Efficacy and toxicity of oxaliplatin (Eloxatin; Sanofi-Aventis, Paris, France) combined with irinotecan (IROX) were examined in 383 patients enrolled on the IROX arm of Intergroup Study N9741...

..Therefore, the authors recommend the use of more tolerable infusional 5-FU-based regimens in the treatment of metastatic CRC...

..1 months was reported. The association between various pre- and post-treatment factors (including the use of bevacizumab beyond first progression [BBP]) and survival was examined...

..This risk does not appear to persist during chemotherapy after completion of pelvic RT...

..This will be followed by explicit consideration of study design, specifically the trial randomization schema for both prognostic and predictive factor studies...

..Additional research is clearly warranted to achieve the goal of 'predictive oncology'...

..3-100%). CONCLUSIONS: The results of this study suggest that concurrent intraarterial cisplatin chemotherapy at a dose of 150 mg/m(2) with concomitant boost accelerated radiation therapy is not feasible...

..Long-term survival can be achieved, especially for patients with no symptoms and minimal fixation of the recurrence in the pelvis, provided no gross residual disease remains...

..Older age, however, is associated with proximal tumor site independent of MSI status...

..In March 1998, Common Toxicity Criteria (CTC) version 2.0 introduced the collection of attribution of adverse events (AEs) to study drug. We investigate whether attribution adds value to the interpretation of AE data...

..To test the hypothesis that surgeon volume would not predict short- and long-term outcomes when evaluated in the setting of technical credentialing...

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..Here, we highlight the impact of genomic advances on various aspects of clinical trial design...

..Stool DNA testing is a new approach to colorectal cancer detection. Few data are available from the screening setting...

..Expression of these proteins in colon cancer patients may account for differences in recurrence and survival rates...

..We determined if expression of these proteins in colon cancers may account for differences in patient survival...

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..Although the presence of dMMR seems to be a favorable prognostic marker, data suggest that these patients do not respond as well to adjuvant chemotherapy...

..CONCLUSION Based on these trials, the assessment of more than two lesions did not alter the conclusions regarding a treatment's efficacy as judged by response rate or TTP...

..We review and offer practical solutions to potentially overcome some of these challenges. The acceptance and integration of these designs in practice may be quicker and easier if they are developed in concert with a clinical paradigm...

..Biomarker validation has therefore become a central topic of discussion in the field of medicine, primarily due to the changing landscape of therapies for treatment of a disease and these therapies purported mechanism(s) of action...

..The objective of this study was to identify clinical predictors of severe rash in the hope of utilizing such factors in the design of future rash palliative and prevention trials...

..The AJCC Hindgut Taskforce sought population-based validation that depth of invasion and nodal status interact to affect survival...

..The AJCC Hindgut Taskforce sought population-based validation that depth of invasion interacts with nodal status to affect survival...

..We discuss and evaluate various clinical trial designs for the validation of biomarker-guided therapy...

..We investigated whether the intratumoral densities of FoxP3(+) and effector CD3(+) lymphocytes are associated with prognosis of patients with colon cancer...

..The authors developed models to predict MMR deficiency in sporadic colon cancer patients using routine clinical and pathological data...

..To review data demonstrating the prognostic and predictive impact of microsatellite instability (MSI) in human colon carcinomas...

..Given a large enough patient pool, the randomized phase II designs provide a more accurate decision for screening agents before phase III testing...

..Although age should not preclude trial entry, these adverse event rates suggest a need to develop more tolerable regimens for older patients with these malignancies...

..We also discuss several limitations of surrogate endpoints, including the critical issues that the extrapolation of the validity of a surrogate is always context-dependent and that such extrapolation should be exercised with caution...

..Obesity is associated with an increased risk of colon cancer. However, the influence of body mass index (BMI) on the prognosis of colon cancer survivors and its relationship to gender remains unknown...

..The review and evaluation of these designs represents an essential step toward the goal of personalized medicine because we explicitly seek to explore and evaluate the methodology for the clinical validation of biomarker guided therapy...

..Cross-over to the other treatment on disease progression was mandated...

..As these two superior therapies have differing mechanisms of action, we explored whether the improved survival associated with the superior therapy was dependent on tumor response...

..The proposed approach allowing the incorporation of both the toxicity and efficacy of each agent into the identification of an optimal dosing region for a combination is novel and warrants further consideration...

..To evaluate quality of life (QOL) and tumor response after administration of an oral chemotherapy regimen in patients with previously untreated metastatic colorectal cancer...

..Given that thymidylate synthase (TS) is inhibited by 5-FU, we studied the relationship between MSI and TS expression, and the prognostic effect of these and other markers (i.e., p53 and 17p allelic imbalance)...

..We believe the methods described present opportunities for improving patient safety in clinical research...

..We assessed the utility of the RAE data collected, relative to the volume...

..To compare operative morbidity, mortality, quality of life, and survival after pancreatoduodenectomy (PD) versus pancreatoduodenectomy with extended lymphadenectomy (PD/ELND) in patients with resectable pancreatic cancer...

..The use of neoadjuvant chemotherapy to improve the likelihood of resection in disease that is not optimally resectable has not been as well studied...

..To compare microsatellite instability (MSI) testing with immunohistochemical (IHC) detection of hMLH1 and hMSH2 in colorectal cancer...

..To determine survival and relapse rates by T and N stage and treatment method in five randomized phase III North American rectal adjuvant studies...

..This study investigated the prognostic significance of TUNEL, bcl-2, p53, proliferation marker Ki-67 and DNA mismatch repair (MMR) status in patients with Dukes' stage B2 and C colorectal adenocarcinomas...

..Given that high-frequency MSI (MSI-H) and diploidy are correlated, we determined whether they are independent prognostic variables...

..We explore alternative options to customize the graphic representation for other data sets drawn from several NCCTG clinical trials...

..To evaluate the disease control, survival results, and tolerance of intraoperative electron beam radiotherapy (IOERT) as a component of treatment for retroperitoneal soft tissue sarcomas...

..To evaluate clinical characteristics and survival outcomes among patients with locally advanced or metastatic colorectal cancer who achieve a complete response (CR) to systemic treatment either alone or with multimodality approach...

..After these findings, an additional meta-analysis of the toxicity profiles on five NCCTG colorectal cancer treatment trials was undertaken...

..Some patients with colon cancer have a high risk of local recurrence postoperatively. This trial was undertaken to determine whether radiation therapy added to an adjuvant chemotherapy regimen improves outcome in high-risk patients...

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..In this article, we review the use and potential of several such designs in neurooncology trials in order to support the development of personalized treatment approaches for brain tumor patients...

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..New therapies have extended survival after recurrence from 1 to approximately 2 years. We examined the possible impact of this improvement on the DFS/OS association...

..5 Gy (cumulative dose 130.1 Gy). CONCLUSIONS: IORT at a dose of 12.5 Gy is safe and produces tumor control and survival for patients likely to have microscopic residual disease in sites difficult to resect such as the skull base...

..In this study, we compared the activity and toxicity of three different two-drug combinations in patients with metastatic colorectal cancer who had not been treated previously for advanced disease...

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..For future trial design, it may be preferable to perform separate studies, or a planned statistical analysis, for the "intermediate-risk" vs. the "moderately high" or "high-risk" subsets of patients...

..05). CONCLUSION: This retrospective investigation failed to demonstrate a significant association between TS, Ki-67, or p53 staining and clinical outcome...

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..In addition, we discuss the role of comorbidity and how it factors in treatment decisions. Finally, we discuss future research directions and funding for elders with cancer...

..To perform a meta-analysis of trials randomizing patients with colon cancer to laparoscopically assisted or open colectomy to enhance the power in determining whether laparoscopic colectomy for cancer is oncologically safe...

..We investigated whether progression-free survival (PFS) could be considered a valid surrogate for OS in advanced colorectal cancer...

..High rates of severe gastrointestinal and neurologic side effects were observed with the high-dose levamisole regimen...

..High rates of grade > or = 3 toxicity on IFL (resulting in some deaths) led us to reduce the starting doses of both irinotecan and FU by 20% (rIFL). This article compares rIFL with FOLFOX4...

..This study investigated morbidity, mortality, and long-term survival after multimodality management of locally recurrent rectal carcinoma involving the urinary tract...

..The trade-offs between costs and survival for these two regimens have not been explored...

..Rarely, there is selective loss of PMS2 expression. We sought to describe the frequency and clinical correlates of selective loss of expression of PMS2 with the MSI-H tumor phenotype...

..The insulin-like growth factor (IGF) family of proteins is associated with QOL in noncancer populations. We sought to study whether these proteins are associated with QOL in patients with colorectal cancer...

..Age alone should not be used to determine whether older patients are treated, because performance status is predictive of dose intensity, response rate, time to tumor progression, and overall survival...

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