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Full-Text Articles in Medicine and Health Sciences
Estimating The Probability Of Clonal Relatedness Of Pairs Of Tumors In Cancer Patients, Audrey Mauguen, Venkatraman E. Seshan, Irina Ostrovnaya, Colin B. Begg
Estimating The Probability Of Clonal Relatedness Of Pairs Of Tumors In Cancer Patients, Audrey Mauguen, Venkatraman E. Seshan, Irina Ostrovnaya, Colin B. Begg
Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series
Next generation sequencing panels are being used increasingly in cancer research to study tumor evolution. A specific statistical challenge is to compare the mutational profiles in different tumors from a patient to determine the strength of evidence that the tumors are clonally related, i.e. derived from a single, founder clonal cell. The presence of identical mutations in each tumor provides evidence of clonal relatedness, although the strength of evidence from a match is related to how commonly the mutation is seen in the tumor type under investigation. This evidence must be weighed against the evidence in favor of independent tumors …
An Efficient Basket Trial Design, Kristen Cunanan, Alexia Iasonos, Ronglai Shen, Colin B. Begg, Mithat Gonen
An Efficient Basket Trial Design, Kristen Cunanan, Alexia Iasonos, Ronglai Shen, Colin B. Begg, Mithat Gonen
Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series
The landscape for early phase cancer clinical trials is changing dramatically due to the advent of targeted therapy. Increasingly, new drugs are designed to work against a target such as the presence of a specific tumor mutation. Since typically only a small proportion of cancer patients will possess the mutational target, but the mutation is present in many different cancers, a new class of basket trials is emerging, whereby the drug is tested simultaneously in different baskets, i.e., sub-groups of different tumor types. Investigators not only desire to test whether the drug works, but also to determine which types of …
Dose Expansion Cohorts In Phase I Trials, Alexia Iasonos, John O'Quigley
Dose Expansion Cohorts In Phase I Trials, Alexia Iasonos, John O'Quigley
Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series
A rapidly increasing number of Phase I dose-finding studies, and in particular those based on the standard 3+3 design, frequently prolong the study and include dose expansion cohorts (DEC) with the goal to better characterize the toxicity profiles of experimental agents and to study disease specific cohorts. These trials consist of two phases: the usual dose escalation phase that aims to establish the maximum tolerated dose (MTD) and the dose expansion phase that accrues additional patients, often with different eligibility criteria, and where additional information is being collected. Current protocols typically do not specify whether the MTD will be updated …
A Systematic Selection Method For The Development Of Cancer Staging Systems, Yunzhi Lin, Richard Chappell, Mithat Gonen
A Systematic Selection Method For The Development Of Cancer Staging Systems, Yunzhi Lin, Richard Chappell, Mithat Gonen
Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series
The tumor-node-metastasis (TNM) staging system has been the anchor of cancer diagnosis, treatment, and prognosis for many years. For meaningful clinical use, an orderly, progressive condensation of the T and N categories into an overall staging system needs to be defined, usually with respect to a time-to-event outcome. This can be considered as a cutpoint selection problem for a censored response partitioned with respect to two ordered categorical covariates and their interaction. The aim is to select the best grouping of the TN categories. A novel bootstrap cutpoint/model selection method is proposed for this task by maximizing bootstrap estimates of …