Secondary analysis of RTOG 9508, a phase 3 randomized trial of whole-brain radiation therapy versus WBRT plus stereotactic radiosurgery in patients with 1-3 brain metastases; poststratified by the graded prognostic assessment (GPA)
PubMed | University of Minnesota, Thomas Jefferson University, University of Maryland, Baltimore, Metro Minnesota CCOP and Minneapolis Radiation Oncology and 4 more.
Type: Clinical Trial, Phase III | Journal: International journal of radiation oncology, biology, physics | Year: 2014
Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary.In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPA are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool (brainmetgpa.com) simplified GPA use.The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P=.05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively.This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted.
PubMed | McGill Montreal General Hospital, CHUQ Pavillon Hotel Dieu de Quebec and CHUM Hospital Notre Dame
Type: Journal Article | Journal: Medical physics | Year: 2017
To study Cherenkov light emission in plastic scintillation detectors (PSDs) from a theoretical point of view to identify situations that may arise where the calibration coefficient obtained in one condition is not applicable to another condition. By identifying problematic situations, we hope to provide guidance on how to confidently use PSDs.Cherenkov light emission in PSD was modelled using basic physical principles. In particular, changes in refractive index as a function of wavelength were accounted for using the Sellmeier empirical equation. Both electron and photon beams were considered. For photons, realistic distributions of secondary charged particles were calculated using Klein-Nishinas formula. Cherenkov production and collection in PSDs were studied for a range of parameters including beam energy, charged particle momentum distribution, detector orientation and material composition. Finally, experimental validation was made using a commercial plastic scintillation detector.In specific situations, results show that the Cherenkov spectrum coupled in the PSD can deviate from its expected behaviour (i.e. one over the square of the wavelength). In these cases were the model is realistic it is possible to see a peak wavelength instead of a monotonically decreasing function. Consequences of this phenomenon are negligible when the momentum of charged particle is distributed randomly, but in some clinically relevant cases, such as an electron beam at depth close to R50 or for photon beams with minimal scatter component, the value of the calibration coefficient can be altered. Experimental tests with electron beams showed changes in the Cherenkov light ratio, the parameter used in the calibration of PSDs, up to 2-3% depending on the PSD orientation.This work is the first providing a physical explanation for apparent change in PSD calibration coefficient. With this new information at hand, it will be possible to better guide the clinical use of PSDs.
Mak R.H.,Harvard University |
Hunt D.,Data Management |
Efstathiou J.A.,Harvard University |
Heney N.M.,Harvard University |
And 13 more authors.
Urologic Oncology: Seminars and Original Investigations | Year: 2016
Introduction To estimate the contribution of the prostate gland and prostatic urethral inflammation to urinary symptoms after radiation therapy for prostate cancer, we performed a secondary analysis of urinary toxicity after primary radiation to an intact prostate vs. postprostatectomy radiation to the prostatic fossa in protocols RTOG 94-08 and 96-01, respectively. Materials and methods Patients randomized to the radiation-alone arms (without hormone therapy) of the 2 trials were evaluated, including 104 men receiving primary prostate radiation to 68.4 Gy on RTOG 94-08 and 371 men receiving 64.8 Gy to the prostatic fossa on RTOG 96-01. Acute and late urinary toxicity were scored prospectively by RTOG scales. Chi-square test/logistic regression and cumulative incidence approach/Fine-Gray regression model were used for analyses of acute and late toxicity, respectively. Results Grade≥2 acute urinary toxicity was significantly higher after primary prostatic radiation compared with postprostatectomy radiation (30.8% vs. 14.0%; P<0.001), but acute grade≥3 toxicity did not differ (3.8% vs. 2.7%; P = 0.54). After adjusting for age, primary radiation resulted in significantly higher grade≥2 acute urinary toxicity (odds ratio = 3.72; 95% CI: 1.65–8.37; P = 0.02). With median follow-up of 7.1 years, late urinary toxicity was not significantly different with primary vs. postprostatectomy radiation (5-year grade≥2: 16.7% vs. 18.3%; P = 0.65; grade≥3: 6.0% vs. 3.3%; P = 0.24). Conclusions Primary radiation to an intact prostate resulted in higher grade≥2 acute urinary toxicity than radiation to the prostatic fossa, with no difference in late urinary toxicity. Thus, a proportion of acute urinary toxicity in men with an intact prostate may be attributable to inflammation of the prostatic gland or urethra. © 2016 Elsevier Inc.