International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationA Phase II Trial of Arc-Based Hypofractionated Intensity-Modulated Radiotherapy in Localized Prostate Cancer
Introduction
Prostate cancer is the most commonly diagnosed male cancer, and radical external beam radiotherapy is an accepted treatment modality (1). However, the biochemical failure-free rate with conventional non–dose-escalated external beam radiotherapy remains below 50% 2, 3, 4, 5. Research to improve biochemical control has included the addition of adjuvant hormones and dose escalation. Dose escalation trials with conventional (1.8–2 Gy/day) fractionation to doses in excess of 75 Gy are associated with prolonged treatment times of more than 2 months 3, 6, 7, 8, 9, 10. These trials have shown reduced biochemical and distant failures 1, 11, 12, 13, 14, 15, 16, 17. The associated prolonged treatment time of more than 2 months 3, 6, 7, 8, 9, 10 has raised the issues of patient convenience, image guidance, and resource management (18). In addition, despite these escalated doses, failure rates of up to 33% for patients treated to 78 Gy have been reported (8).
Recent studies have examined the use of hypofractionated treatment using fractional doses greater than 2 Gy based on the rationale that the predicted α/β for prostate cancer is approximately two 3, 4, 19, 20, 21, 22, 23, 24, 25, 26. Early data from hypofractionation studies suggest that hypofractionated radiotherapy up to 60 Gy in 20 fractions is safe, is effective, and holds similar long-term bowel and bladder sequelae compared to conventional treatment while permitting the treatment to be delivered over a shorter time 27, 28, 29.
Arc radiotherapy techniques such as intensity-modulated arc therapy, helical tomotherapy, and volumetric arc therapy have been proposed as alternatives to existing intensity-modulated radiotherapy (IMRT) delivery techniques 30, 31. One advantage of arc therapy is the ability to optimize the beam delivery over a large number of beam angles for better conformality. In the first intensity-modulate arc therapy proposal, a beam fluence pattern using inverse treatment planning is generated (32). The fluence pattern is decomposed into a series of conformally shaped arcs (moving beam) treatments. Wong et al. have proposed a simplification of this technique: simplified intensity modulated arc therapy (SIMAT) (11). The SIMAT technique involves a series of dynamically shaped arcs that are used to treat the target volume with the option of dynamic shielding of critical organs as the gantry rotates. By varying the relative importance (weights) of the arcs, an optimal plan with concave dose distributions can be obtained, satisfying the desired treatment dose prescriptions and normal tissue constraints. We have shown that SIMAT is similar to other IMRT techniques and produces better dose distributions than three-dimensional (3D) conformal therapy 33, 34.
In this article we report on a Phase I/II trial of image-guided, hypofractionated radiotherapy for localized prostate cancer with an emphasis on acute and late toxicities and early biochemical control rates.
Section snippets
Study design
This was a Phase II, single-institution, prospective clinical trial carried out at the London Regional Cancer Program for patients with biopsy-proven localized adenocarcinoma of the prostate. Pretreatment evaluation included baseline history, physical examination, determination of prostate-specific antigen (PSA), and pathology review. A negative bone scan before treatment was required for PSA values greater than 10, a Gleason score greater than 7, or staging of T2B or greater. Estimated nodal
Results
The trial was conducted between October 2003 and July 2006, during which 66 patients were enrolled. All patients were treated according to protocol, with no observed target or normal tissue dose–volume histogram deviations. Toxicity data were analyzed as of August 2009 on all 66 patients. Two patients were lost to follow-up. One received all posttreatment follow-up at a separate center; another was followed up by his family physician after his 3-month posttreatment follow-up. These 2 patients
Discussion
We previously reported on a study of SIMAT for conventionally fractionated radiotherapy with toxicity comparable to that of reported 3D and intensity-modulated techniques 34, 38. The present study, which enrolled 66 patients with a median follow-up of 36 months, gave 63 Gy in 3.16-Gy fractions (biologically effective dose2Gy of 81.5Gy). The acute GU Grade 2 toxicity observed (33.8%) was within the findings of previous IMRT-based hypofractionated studies (9–48%) (Table 7). For acute Grade 3 GU
Conclusions
Hypofractionation using daily localization with fiducial markers or ultrasound and arc-based SIMAT delivery in this Phase II trial was associated with acute Grade 2 and late Grade 3 toxicity similar to previously reported IMRT-based hypofractionated trials. However, the acute Grade 3 and late Grade 2 toxicity was higher than previously published hypofractionation and dose escalation trials, suggesting this method may require caution with its use. Randomized trials of hypofractionation (RTOG
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Conflict of interest: none.