How will Comparative Effectiveness Research Influence Clinical Decision Making?

Most health care recommendations in the United States have come from trials designed to measure efficacy of medical interventions, with randomized controlled trials considered the gold standard for evidence-based medicine. Comparative effectiveness research has become an essential component of research to help define the benefits, risks, and effectiveness of different interventions for a particular illness. Comparative effectiveness research is informally defined as an assessment of all available options for a specific medical condition, with intent to estimate effectiveness in specific subpopulations. In this article, we contrast efficacy-based healthcare research and recommendations in the United States, under the model of evidencebased medicine, to the contemporary paradigm of comparative effectiveness research. We review the recent emphasis by the federal government on comparative effectiveness research. Finally, we review the limitations of effectiveness and efficiency

Radiation therapy after radical prostatectomy for prostate cancer: evaluation of complications and influence of radiation timing on outcomes in a large, population-based cohort.

PURPOSE: To evaluate the influence of timing of salvage and adjuvant radiation therapy on outcomes after prostatectomy for prostate cancer. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified prostate cancer patients diagnosed during 1995-2007 who had one or more adverse pathological features after prostatectomy. The final cohort of 6,137 eligible patients included men who received prostatectomy alone (n = 4,509) or with adjuvant (n = 894) or salvage (n = 734) radiation therapy. Primary outcomes were genitourinary, gastrointestinal, and erectile dysfunction events and survival after treatment(s). RESULTS: Radiation therapy after prostatectomy was associated with higher rates of gastrointestinal and genitourinary events, but not erectile dysfunction. In adjusted models, earlier treatment with adjuvant radiation therapy was not associated with increased rates of genitourinary or erectile dysfunction events compared to delayed salvage radiation therapy. Early adjuvant radiation therapy was associated with lower rates of gastrointestinal events that salvage radiation therapy, with hazard ratios of 0.80 (95% CI, 0.67-0.95) for procedure-defined and 0.70 (95% CI, 0.59, 0.83) for diagnosis-defined events. There was no significant difference between ART and non-ART groups (SRT or RP alone) for overall survival (HR = 1.13 95% CI = (0.96, 1.34) p = 0.148). CONCLUSIONS: Radiation therapy after prostatectomy is associated with increased rates of gastrointestinal and genitourinary events. However, earlier radiation therapy is not associated with higher rates of gastrointestinal, genitourinary or sexual events. These findings oppose the conventional belief that delaying radiation therapy reduces the risk of radiation-related complications

A Cone Beam CT-Based Study For Clinical Target Definition Using Pelvic Anatomy During Post-Prostatectomy Radiotherapy

Introduction: Radiation therapy (RT) is delivered after radical prostatectomy (RP) either as salvage treatment for an elevated prostate-specific antigen (PSA) level1-6 or as adjuvant therapy for patients with highrisk pathologic features7-8. Recent prospective data demonstrated a disease-free survival benefit of adjuvant RT for pathologic T3N0 prostate cancer9-10. Despite literature supporting the delivery of post-RP RT to the prostatic fossa (PF), no clear target definition guidelines exist for intensity modulated radiation therapy (IMRT) or image-guided RT (IGRT)11. Visualization of the PF is limited on standard CT images, with significant interobserver variability and uncertainty in CTV definition12. Efforts to incorporate complementary imaging modalities such as MRI for PF target volume definition have generated neither demonstrably more reliable PF delineation, nor practical contouring guidelines13. Regardless of the imaging modality, direct visualization and delineation of the PF clinical target volume (CTV) is fraught with uncertainty. On the other hand, it is possible to distinguish the borders of important nearby pelvic structures, namely the bladder and the rectum. The reliability of rectal volume definition on helical CT is supported by analysis of rectal contours defined in a prospective trial, suggesting the feasibility of rectal dose-volume data collection in a multicenter setting14. Fiorino et al have described a correlation between PF CTV shift and anterior rectal wall shift for the cranial half of the rectum in their report of rectal and bladder movement during post-RP RT using weekly CT images15. These studies support the reliability of CT-defined rectum contours and a limited correlation between PF CTV and anterior rectal wall, an important tenet in the current study. Int. J. Radiation Oncol. Biol. Physics, Volume 70, Issue 2, pages 431-436, Feb. 1, 2008

Does Intraoperative Radiation Therapy Improve Local Tumor Control in Patients Undergoing Pancreaticoduodenectomy for Pancreatic Adenocarcinoma? A Propensity Score Analysis

Background: Locoregional recurrence (LRR) is an important factor after pancreaticoduodenectomy (PD) for pancreatic cancer. IORT administered to the resection bed may improve local tumor control. Methods: We performed a retrospective analysis of patients who underwent PD at Thomas Jefferson University Hospital (TJUH) between 1995 and 2005 to identify patients who underwent resection with and without intraoperative radiation therapy (IORT). Data collected included age, gender, complications, margin status, stage, survival, and recurrence. Unadjusted analyses of the IORT and non-IORT groups were performed using Fisher’s chi-square method for discrete variables and Wilcoxon Rank Sum test for continuous variables. To account for biases in patient selection for IORT, a propensity score was calculated for each patient and adjusted statistical analyses were performed for survival and recurrence outcomes. Results: Between January 1995 and November 2005, 122 patients underwent PD for perimpullary tumors, including 99 pancreatic cancers. Of this group, 37 patients were treated with IORT, and there was adequate follow-up information for a group of 46 patients who underwent PD without IORT. The IORT group contained a higher percentage of Stage IIB or higher tumors (65%) than in the non-IORT group (39.1%), though differences in stage did not reach significance (p = 0.16). There was a non-significant decrease in the rate of LRR in patients who had IORT (39% non-IORT vs. 23% IORT, p = 0.19). The median survival time of patients who received IORT was 19.2 months, which was not significantly different than patients managed without IORT, 21.0 months (p=0.78). In the propensity analyses, IORT did not significantly influence survival or recurrence after PD. Conclusions: IORT can be safely added to management approaches for resectable pancreatic cancer, with acceptable morbidity and mortality. IORT did not improve loco-regional control and did not alter survival for patients with resected pancreatic cancer. IORT is an optional component of adjuvant chemoradiation for pancreatic cancer. In the future, IORT may be combined with novel therapeutic agents in the setting of a clinical trial in order to attempt to improve outcomes for patients with pancreatic cancer. Annals of Surgical Oncology, Volume 16, Edition 8, August, 2009, pages 2116-22, “Does intraoperative radiation therapy improve local tumor control in patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma? A propensity score analysis”. Authors: Showalter TN, Rao AS, Anné PR, Rosato FE, Rosato EL, Andrel J, Hyslop T, Xu X, Berger AC