scholarly journals Variability of α/β Ratios for Prostate Cancer With the Fractionation Schedule: Caution Against Using the Linear-Quadratic Model for Hypofractionated Radiotherapy

2021 ◽  
Author(s):  
Ming Cui ◽  
Xianshu Gao ◽  
Xiaoying Li ◽  
Mingwei Ma ◽  
Xin Qi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hypofractionated Radiotherapy ◽  
Target Cells ◽  
Linear Quadratic ◽  
Fractionated Radiotherapy ◽  
Fractionation Schedule ◽  
High Doses ◽  
Fractionation Schedules ◽  
Conventionally Fractionated ◽  
Dose Per Fraction

Abstract Background: Prostate cancer (PCa) is known to be suitable for hypofractionated radiotherapy due to the very low α/β ratio (about 1.5-3 Gy). However, several randomized controlled trials have not shown the superiority of hypofractionated radiotherapy over conventionally fractionated radiotherapy. Besides, in vivo and in vitro experimental results show that the linear-quadratic (LQ) model may not be appropriate for hypofractionated radiotherapy, and we guess it may be due to the influence of fractionation schedules on the α/β ratio. Therefore, this study attempted to estimate the α/β ratio in different fractionation schedules and evaluate the applicability of the LQ model in hypofractionated radiotherapy. Methods: The maximum likelihood principle in mathematical statistics was used to fit the parameters: k, α and β values in the tumor control probability (TCP) formula derived from the LQ model. In addition, the fitting results were substituted into the original TCP formula to calculate 5-year biochemical relapse-free survival for further verification.Results: Information necessary for fitting could be extracted from a total of 23,281 PCa patients. A total of 16,442 PCa patients were grouped according to fractionation schedules. We found that, for patients who received conventionally fractionated radiotherapy, moderately hypofractionated radiotherapy, and stereotactic body radiotherapy, the average α/β ratios were 1.78 Gy (95% CI: 1.59-1.98, P < 0.001), 3.46 Gy (95% CI: 3.08-3.83, P < 0.001), and 4.24 Gy (95% CI: 4.10-4.39, P < 0.001), respectively. Hence, the calculated α/β ratios for PCa tended to become higher when the dose per fraction increased. Among all PCa patients, 14,641 could be grouped according to the risks of PCa in patients receiving radiotherapy with different fractionation schedules. The results showed that as the risk increased, the k and α values decreased, indicating that the number of effective target cells decreased and the radioresistance increased.Conclusions: The LQ model appeared to be inappropriate for high doses per fraction owing to α/β ratios tending to become higher when the dose per fraction increased. Therefore, to convert the conventionally fractionated radiation doses to equivalent high doses per fraction using the standard LQ model, a higher α/β ratio should be used for calculation.

scholarly journals Salvage hypofractionated accelerated versus standard radiotherapy for the treatment of biochemical recurrence after radical prostatectomy (SHARE): the protocol of a prospective, randomized, open-label, superiority, multi-institutional trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Geumju Park ◽  
Yeon Joo Kim ◽  
Hanjong Ahn ◽  
Won Park ◽  
Ji sung Lee ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Biochemical Recurrence ◽  
Hypofractionated Radiotherapy ◽  
Biochemical Control ◽  
Fractionated Radiotherapy ◽  
Prostate Bed ◽  
Conventionally Fractionated

Abstract Background While several phase III trials have investigated the role of hypofractionated radiotherapy in the definitive treatment of localized prostate cancer, prospective data reporting the outcomes of hypofractionated radiotherapy in the postoperative treatment setting are sparse. Therefore, this study is designed to assess the efficacy and treatment-related toxicity of hypofractionated salvage radiotherapy for the treatment of biochemical recurrence in men who underwent radical prostatectomy. The primary objective of this trial is to investigate whether hypofractionated radiotherapy improves biochemical control compared with conventionally fractionated radiotherapy. In addition, treatment-related toxicity, quality of life, and survival will be evaluated as secondary endpoints. Methods In this prospective, randomized, multi-institutional trial (the SHARE study), patients with intermediate- or high-risk prostate cancer will be randomized to receive either hypofractionated radiotherapy (65 Gy in 2.5-Gy fractions) or conventionally fractionated radiotherapy (66 Gy in 2-Gy fractions). Prostate bed irradiation or elective pelvic nodal irradiation including the prostate bed will be performed using intensity-modulated radiotherapy and daily image guidance. Treatment efficacy will be assessed using the serum tumor marker prostate-specific antigen, and toxicity will be evaluated through both physician- and patient-reported outcomes. Quality of life will also be investigated. Discussion This study is designed to demonstrate whether hypofractionated radiotherapy is beneficial in terms of biochemical control and toxicity compared with standard salvage radiotherapy. If hypofractionated radiotherapy is shown to be superior to conventionally fractionated radiotherapy, it will mean that improved biochemical control can be achieved, accompanied by greater patient convenience and more efficient use of medical resources. Trial registration ClinicalTrials.gov NCT03920033. Registered on 18 April 2019

Comparison of conventionally fractionated and hypofractionated schedule for post-prostatectomy salvage radiotherapy: Early results from non-randomized observational study.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e551-e551
Author(s):  
Jure Murgic ◽  
Blanka Jaksic ◽  
Ivan Kruljac ◽  
Marin Prpic ◽  
Mirjana Budanec ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Side Effects ◽  
Hormonal Therapy ◽  
Cox Proportional Hazards Model ◽  
Hypofractionated Radiotherapy ◽  
Definitive Treatment ◽  
Early Results ◽  
Significant Difference ◽  
Conventionally Fractionated

e551 Background: Data on hypofractionated radiotherapy in definitive treatment of prostate cancer are maturing; however, limited information is available for hypofractionated radiotherapy after prostatectomy. We aimed to compare hypofractionated and conventionally fractionated radiotherapy in salvage setting for biochemically recurrent prostate cancer. Methods: A retrospective analysis was performed in 106 patients with proven PSA recurrence treated to the prostate bed. Patients were non-randomly, in a alternating fashion, subjected to either 52.5 Gy in 20 fractions of 2.625 Gy over 4 weeks (N = 57, hypofractionated group) or 66 Gy in 33 fractions of 2 Gy over 6.5 weeks (N = 49, conventionally fractionated group). There was no statistically significant difference in pathologic T-stage and Gleason score distribution between the groups. In the conventionally fractionated group there were more patients with positive margins (p = 0.01), more prevalent concomitant hormonal therapy (50.9% vs 61.2%, p = 0.001), but less long-term hormonal therapy (21.4% vs 81%, p < 0.001), compared to hypofractionated group. Median follow-up was 20 months (range 6-36 months). Failure (PSA nadir+0.2) rates between the groups were compared using Cox proportional hazards model. Radiation-related side-effects were assessed using RTOG scoring scale. Results: At this early point, 13 patients (22.8%), and 6 patients (12.2%) experienced treatment failure in the hypofractionated group and conventionally fractionated group, respectively (HR 3.1, 95%CI (1.5-6.3)). More late grade 2 gastrointestinal and genitourinary side-effects were observed in conventionally fractionated group (4.1% vs 1.8%, and 2% vs 0%, p = 0.01, respectively). No grade 3 toxicities were observed. Conclusions: More initial biochemical failures were observed in hypofractionated group compared to conventionally fractionated group. However, baseline heterogeneity between the groups and short follow-up preclude any causal observation of differential efficacy between these two schedules. Randomized phase II trial is planned to prospectively compare these two regimens.

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