Purpose To determine the efficacy and late toxicities of moderate (2.5–4 Gy) hypofractionated radiotherapy (H-RT) in localized prostate cancer, a meta-analysis of published randomized clinical trials comparing moderate H-RT with conventional fractionated RT (C-RT) was performed. Materials and methods Systematic search on published randomized clinical trials in English according to Cochrane review guidelines in databases of Pubmed, Embase, Cochrane, web of science, and Wiley Online Library was carried out. Outcomes of interests were biochemical and clinical disease failure (BCDF), biochemical failure (BF), overall survival (OS), and late toxicities. Results Seven of the 365 studies fulfilled inclusion criteria with 8,156 participants. Compared with C-RT, moderate H-RT showed a lower BF rate (risk ratio [RR] =0.80, 95% CI: 0.68–0.95, P =0.009), while did not improve OS (RR =0.68, 95% CI: 0.78–1.02, P =0.10). There was no significant difference in BCDF rates between H-RT and C-RT (RR =0.92, 95% CI: 0.82–1.02, P =0.12). The H-RT was deeply grouped into dose-escalated H-RT (with a higher biologically effective dose [BED 1.5 ] than C-RT) and no dose-escalated H-RT; dose-escalated H-RT significantly decreased BCDF rate compared with C-RT (RR =0.84, 95% CI: 0.73–0.96, P =0.01). Regarding late toxicities, there is no significant difference in late gastrointestinal (GI; RR =0.97, 95% CI: 0.71–1.33, P =0.85) and genitourinary (GU) toxicities (RR =1.04, 95% CI: 0.87–1.24, P =0.69). When subgrouped into dose-escalated H-RT (with a higher BED 5 compared with C-RT) and no dose-escalated H-RT, dose-escalated H-RT increased GI toxicity (RR =1.62, 95% CI: 1.26–2.09, P =0.0002) and GU toxicity (RR =1.28, 95% CI: 1.05–1.55, P =0.01), while no dose-escalated H-RT significantly lowered GI toxicity (RR =0.81, 95% CI: 0.70–0.94, P =0.005) and placed no influence on GU toxicity (RR =1.02, 95% CI: 0.88–1.20, P =0.77). Conclusion This meta-analysis provides reliable evidence that moderate H-RT decreases BF rate, while does not improve OS. Compared with C-RT, H-RT with an increase in BED 1.5 improved BCDF rates significantly, and accordingly, an increase in BED 5 will result in elevated late GI and GU toxicities.

Backgrounds: With the excellent local control in T1 to T3 nasopharyngeal carcinoma (NPC) treated with intensity modulated radiotherapy (IMRT), the importance of toxicities is increasingly being recognised. This retrospective propensity score analysis sought to assess whether moderate dose reduction compromised long-term outcome compared with standard dose in T1-3 NPCs.Materials and Methods: A total of 266 patients (67 female, 199 male) with a median age of 50 years between June 2011 and June 2015 were analysed. All were treated with IMRT, with or without systemic chemotherapy. The prescription radiation dose to gross tumor is 70Gy/2.12Gy/33F in our institution.Results: With a median follow-up time of 50 months, the 5-year loco-regional failure-free survival (LRFS) and overall survival (OS) were 93.5% and 81.8%, respectively. 32 patients received radiation dose less than prescription dose, with a median dose of 63.6Gy (53-67Gy). Another 234 patients received exactly the prescription dose of 70Gy. Propensity scores were computed (32 patients treated with de-escalated dose and 64 patients with standard dose), there was no significant difference in 5-year LRFS and 5-year OS between the two groups (92.5% and 91.7% with standard dose; 82.1% and 85.7% with de-escalation dose; p=0.863 for LRFS and 0.869 for OS). No independent prognostic factor was associated with loco-regional failure in univariate analysis.Conclusions: T1-3 nasopharyngeal carcinoma presenting with superior locoregional control, a moderately reduced dose (about 10%) delivered with IMRT resulted in comparable prognosis to those with prescription dose of 70Gy.

Purpose: The passive scattering proton therapy (PSPT) technique is the commonly used radiotherapy technique for craniospinal irradiation (CSI). However, PSPT involves many numbers of junction shifts applied over the course of treatment to reduce the cold and hot regions caused by field mismatching. In this work, we introduced a robust planning approach to develop an optimal and clinical efficient techniques for CSI using intensity modulated proton therapy (IMPT) so that junction shifts can essentially be eliminated. Methods: The intra‐fractional uncertainty, in which two overlapping fields shift in the opposite directions along the craniospinal axis, are incorporated into the robust optimization algorithm. Treatment plans with junction sizes 3,5,10,15,20,25 cm were designed and compared with the plan designed using the non‐robust optimization. Robustness of the plans were evaluated based on dose profiles along the craniospinal axis for the plans applying 3 mm intra‐fractional shift. The dose intra‐fraction variations (DIV) at the junction are used to evaluate the robustness of the plans. Results: The DIVs are 7.9%, 6.3%, 5.0%, 3.8%, 2.8% and 2.2%, for the robustly optimized plans with junction sizes 3,5,10,15,20,25 cm. The DIV are 10% for the non‐robustly optimized plans with junction size 25 cm. The dose profiles along the craniospinal axis exhibit gradual and tapered dose distribution. Using DIVs less than 5% as maximum acceptable intrafractional variation, the overlapping region can be reduced to 10 cm, leading to potential reduced number of the fields. The DIVs are less than 5% for 5 mm intra‐fractional shifts with junction size 25 cm, leading to potential no‐junction‐shift for CSI using IMPT. Conclusion: This work is the first report of the robust optimization on CSI based on IMPT. We demonstrate that robust optimization can lead to much efficient carniospinal irradiation by eliminating the junction shifts.

Purpose: To determine whether a hybrid intensity-modulated proton therapy (IMPT) and passive scattered proton therapy (PSPT) technique, termed HimpsPT, could be adopted as an alternative delivery method for patients demanding scanning beam proton therapy. Patients and Methods: We identified 3 representative clinical cases-an oropharyngeal cancer, skull base chordoma, and stage III non-small-cell lung cancer-that had been treated with IMPT at our center. We retrospectively redesigned these cases using HimpsPT. The PSPT plans for all three cases were designed with the same prescriptions as those used in the IMPT plans. In this way, the whole treatment was delivered using alternating or sequential PSPT and IMPT. Results: All HimpsPT plans met the clinical dose criteria and were of similar quality as the IMPT plans. In the skull base case, the mixed plan was more effective at sparing the brain stem because the sharp penumbra of the aperture in the PSPT plans was not present in the IMPT plans. The HimpsPT plans were more robust than the clinical IMPT plans generated without robust optimization. Conclusion: The HimpsPT delivery technique can achieve a treatment-plan quality similar to that of IMPT, even in the most challenging clinical cases. In addition, at centers equipped with both scattering and scanning beam capabilities, the HimpsPT technique may allow more patients to benefit from scanning beam technology.

translational shifts were 0.12 AE 0.00, 0.16 AE 0.01 and 0.09 AE 0.00 mm, respectively. The average calculated distance shift for these patients was 0.26 AE 0.01 mm. The average absolute pitch, roll and yaw rotational shifts for these patients were 0.14 AE 0.01, 0.10 AE 0.00 and 0.13 AE 0.00 degrees, respectively. The two patient groups demonstrate no statistically significant difference in the translational or rotational intra-fractional shifts. Conclusion: Our analysis revealed no correlation between pain relief outcome and the amount of intra-fractional shift in all six dimensions during frameless IGRS. Our results indicate the less than 0.5 mm nominal mechanical deviation during frameless IGRS does not impact on TGN pain outcome.