International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationAcute and Late Toxicity After Dose Escalation to 82 GyE Using Conformal Proton Radiation for Localized Prostate Cancer: Initial Report of American College of Radiology Phase II Study 03-12
Introduction
Several randomized trials have shown a clear benefit of dose escalation to 78 to 79 Gy for men treated with conformal external radiation for localized prostate cancer 1, 2. Single-institution data suggest that further gains may be achieved with even further dose escalation to doses of greater than 80 Gy by use of intensity-modulated radiation therapy (IMRT) (3). This prompted exploration of the delivery of similar “ultrahigh” doses with conformal proton radiation alone.
American College of Radiology (ACR) 03-12 is a two-institution Phase II trial testing the late toxicity of 82 GyE (Gray equivalent) delivered with protons alone performed at both Massachusetts General Hospital and Loma Linda University Medical Center (LLUMC). This is a report of the acute and late toxicity for patients treated in this study.
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Patient population
Eligible patients had untreated localized prostate cancer, a Gleason score of 5 or greater, and Stages T1c–T2b based on the American Joint Committee on Cancer's sixth-edition criteria. A Gleason score of 8 to 10 was only permissible if the prostate-specific antigen (PSA) level was lower than 10 ng/ml and the T stage was T1c. Other eligibility criteria included demonstration of a PSA value of 15 ng/mL or less within 2 months prior to study entry and greater than 3 weeks after prostate biopsy,
Results
This study opened to accrual on May 18, 2003, and closed on March 3, 2006, with a total of 85 patients. One man withdrew consent, leaving a total of 84 evaluable men. This initial primary analysis includes all the information received by the RTOG headquarters as of April 2009. The median follow-up was 31.6 months (range, 1.9–51.1 months). Two patients were lost to follow-up within the first 2 months. All others had at least 1 year of follow-up. Patient characteristics are shown in Table 1. The
Discussion
This analysis of the ACR 03-12 shows an actuarial late Grade 3+ GU/GI toxicity rate of 6.08% at 18 months. This suggests that 82 GyE delivered by use of conformal proton radiation is not free of Grade 3+ GU/GI toxicity but is an acceptably tolerated dose with the use of current techniques. Although this level of toxicity is not low enough to support routine adoption of this dose of radiation, it does allow for further study of 82 GyE by use of these techniques in the context of a clinical
Conclusions
This report shows that 82 GyE can safely be delivered to the prostate by use of conformal proton radiation. Further follow-up is warranted to capture the late sequelae from prostate radiation that may appear many years after treatment, as well as to assess cancer control outcome. Dose escalation beyond this point, if clinically indicated, will require more advanced proton delivery techniques or altered fractionation.
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Rectal Hydrogel Spacer Improves Late Gastrointestinal Toxicity Compared to Rectal Balloon Immobilization After Proton Beam Radiation Therapy for Localized Prostate Cancer: A Retrospective Observational Study
2020, International Journal of Radiation Oncology Biology PhysicsSystematic review of methodology used in clinical studies evaluating the benefits of proton beam therapy
2019, Clinical and Translational Radiation OncologyCitation Excerpt :In one study, the authors noted that clinical benefits of improved dosimetry of PBT based on toxicity assessments may not be evident in the first few years after treatment, and further observation may show meaningful differences in clinician and patient reported toxicity over time [41]. In addition, authors emphasized the need for longer follow up to enable assessment of late radiation sequelae that may occur many years after treatment [42] and the need to assess long term QoL outcomes data [43]. Gardner et al [44] noted the potential for recall and selective biases in the long-term assessment of QoL in patients treated with high dose radiation techniques.
Finding Value for Protons: The Case of Prostate Cancer?
2018, Seminars in Radiation OncologyWhat is the best way to radiate the prostate in 2016?
2017, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :It is unclear if these dosimetric differences between proton and IMRT plans translate to differences in patient outcomes. Multiple single-arm phase II studies and retrospective analyses have shown that proton therapy for prostate cancer is safe (Table 3) and likely results in similar rates of urinary and bowel toxicity compared to IMRT (Table 4) [45–51]. In a case-matched study of toxicity outcomes after proton therapy and IMRT in 188 patients with localized prostate cancer, there was no difference in acute or late≥grade 2 GI or GU toxicity on multivariable analysis [49].
Conflict of interest: none.