Journal of clinical oncology : official journal of the American Society of Clinical Oncology
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Comparative Study
Comparison of error rates in single-arm versus randomized phase II cancer clinical trials.
PURPOSE To improve the understanding of the appropriate design of phase II oncology clinical trials, we compared error rates in single-arm, historically controlled and randomized, concurrently controlled designs. PATIENTS AND METHODS We simulated error rates of both designs separately from individual patient data from a large colorectal cancer phase III trials and statistical models, which take into account random and systematic variation in historical control data. RESULTS In single-arm trials, false-positive error rates (type I error) were 2 to 4 times those projected when modest drift or patient selection effects (eg, 5% absolute shift in control response rate) were included in statistical models. ⋯ Randomized two-arm design conformed to planned error rates. CONCLUSION Variability in historical control success rates, outcome drifts in patient populations over time, and/or patient selection effects can result in inaccurate false-positive and false-negative error rates in single-arm designs, but leave performance of the randomized two-arm design largely unaffected at the cost of 2 to 4 times the sample size compared with single-arm designs. Given a large enough patient pool, the randomized phase II designs provide a more accurate decision for screening agents before phase III testing.
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PURPOSE Allogeneic hematopoietic cell transplantation (HCT) is curative therapy for chronic myeloid leukemia (CML), but its long-term outcomes are not well described. We studied the long-term outcomes of CML patients in first chronic phase who receive an allogeneic HCT. PATIENTS AND METHODS Our study included 2,444 patients who received myeloablative HCT for CML in first chronic phase between 1978 and 1998 and survived in continuous complete remission for at least 5 years (median follow-up, 11 years; range, 5 to 25 years). ⋯ In multivariable analyses, history of chronic graft-versus-host disease increased risks of late overall mortality and nonrelapse mortality but reduced risks of relapse. In comparison with age-, race-, and sex-adjusted normal populations, the mortality of HCT recipients was significantly higher until 14 years post-HCT; thereafter, mortality rates were similar to those of the general population (relative mortality ratio at 15 years, 2.3; 95% CI, 0 to 4.9). CONCLUSION Recipients of allogeneic HCT for CML in first chronic phase who remain in remission for at least 5 years have favorable subsequent long-term survival, and their mortality rates eventually approach those of the general population.
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Currently, the most widely used criteria for assessing response to therapy in high-grade gliomas are based on two-dimensional tumor measurements on computed tomography (CT) or magnetic resonance imaging (MRI), in conjunction with clinical assessment and corticosteroid dose (the Macdonald Criteria). It is increasingly apparent that there are significant limitations to these criteria, which only address the contrast-enhancing component of the tumor. For example, chemoradiotherapy for newly diagnosed glioblastomas results in transient increase in tumor enhancement (pseudoprogression) in 20% to 30% of patients, which is difficult to differentiate from true tumor progression. ⋯ The recognition that contrast enhancement is nonspecific and may not always be a true surrogate of tumor response and the need to account for the nonenhancing component of the tumor mandate that new criteria be developed and validated to permit accurate assessment of the efficacy of novel therapies. The Response Assessment in Neuro-Oncology Working Group is an international effort to develop new standardized response criteria for clinical trials in brain tumors. In this proposal, we present the recommendations for updated response criteria for high-grade gliomas.
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PURPOSE Standardized questionnaires for patient-reported outcomes are generally composed of specified predetermined items, although other areas may also cause patients distress. We therefore studied reports of what was most distressing for 343 patients with inoperable lung cancer (LC) at six time points during the first year postdiagnosis and how these concerns were assessed by three quality-of-life and symptom questionnaires. PATIENTS AND METHODS Qualitative analysis of patients' responses to the question "What do you find most distressing at present?" generated 20 categories, with 17 under the dimensions of "bodily distress," "life situation with LC," and "iatrogenic distress." Descriptive and inferential statistical analyses were conducted. ⋯ While 55% to 59% of concerns reported as most distressing were clearly assessed by the European Organisation for Research and Treatment for Cancer Quality of Life Questionnaire Core-30 and Lung Cancer Module instruments, the Memorial Symptom Assessment Scale, and the modified Distress Screening Tool, iatrogenic distress is not specifically targeted by any of the three instruments examined. CONCLUSION Using this approach, several distressing issues were found to be commonly reported by this patient group but were not assessed by standardized questionnaires. This highlights the need to carefully consider choice of instrument in relation to study objectives and characteristics of the sample investigated and to consider complementary means of assessment in clinical practice.
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Randomized Controlled Trial Multicenter Study
Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study.
PURPOSE To determine whether the Recurrence Score (RS) provided independent information on risk of distant recurrence (DR) in the tamoxifen and anastrozole arms of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trial. PATIENTS AND METHODS RNA was extracted from 1,372 tumor blocks from postmenopausal patients with hormone receptor-positive primary breast cancer in the monotherapy arms of ATAC. Twenty-one genes were assessed by quantitative reverse transcriptase polymerase chain reaction, and the RS was calculated. ⋯ Nine-year DR rates in low (RS < 18), intermediate (RS = 18 to 30), and high RS (RS > or = 31) groups were 4%, 12%, and 25%, respectively, in N0 patients and 17%, 28%, and 49%, respectively, in N+ patients. The prognostic value of RS was similar in anastrozole- and tamoxifen-treated patients. CONCLUSION This study confirmed the performance of RS in postmenopausal HR+ patients treated with tamoxifen in a large contemporary population and demonstrated that RS is an independent predictor of DR in N0 and N+ hormone receptor-positive patients treated with anastrozole, adding value to estimates with standard clinicopathologic features.