(P 559) PROSPECTIVE PHASE II TRIAL OF PREOPERATIVE HYPOFRACTIONATED PROTON THERAPY FOR EXTREMITY AND TRUNCAL AND TRUNCAL SOFT TISSUE SARCOMA: THE PRONTO STUDY RATIONALE AND DESIGN

Objective: Oncologic surgical resection is the standard of care for extremity and truncal soft tissue sarcoma (STS), often accompanied by the addition of pre- or postoperative radiation therapy (RT). Preoperative (preop) RT may decrease the risk of joint stiffness and fibrosis at the cost of higher wound complication rates, occurring in 20-40% of patients. Late toxicity is also a common complication which affects quality of life, occurring in 10-35% of patients. Hypofractionated, preop RT has been shown to provide acceptable outcomes. A summary of prospective trials studying preop RT is provided in Table 1.

Proton beam therapy (PBT) provides the means to decrease dose to surrounding organs at risk and has not yet been studied in patients with extremity and truncal STS. We conducted an analysis comparing identical hypofractionated regimens of photon and proton RT as those used in this trial, showing significantly lower doses to skin, femur, and joint with PBT, as shown in Figure 1. Thus, PBT has the potential to provide lower rates of toxicity and wound complications than those associated with photon RT.

Our study titled “PROspective phase II trial of preoperative hypofractionated protoN therapy for extremity and Truncal soft tissue sarcOma (PRONTO)” represents the first trial evaluating the use of hypofractionated PBT for STS. We aim to prove the safety and efficacy of this approach and to compare our results to historical outcomes established by previous trials. Given the limited availability to proton centers, the short course of PBT may enable treatment for patients who would otherwise be limited when treating with several weeks of daily RT. We hope this trial will lead to increased referral patterns, offer benefits towards patient convenience and clinic workflow efficiency, and provide evidence supporting the use of PBT in this setting.

Methods: PRONTO is a non-randomized, prospective phase II trial evaluating the safety and efficacy of preop, hypofractionated PBT for patients with extremity and truncal STS. Patients who meet all inclusion and no exclusion criteria, as outlined in Table 2, will be enrolled.

A flow chart outlining the trial schema is provided in Figure 2. Treatment will consist of 5 fractions of PBT delivered every other weekday to a total dose of 30 Gy radiobiological equivalent. Clinical target volumes include gross tumor with a 3 cm margin longitudinally and 1.5 cm margin radially excluding natural barriers of spread, in addition to any surrounding edema seen on T2 weighted MRI, cropped 0.3 cm from skin. Oncologic surgical resection occurs within 2-12 weeks of completing PBT. Patients will be followed in the postoperative setting according to standard of care surveillance for STS.

The primary outcome is the rate of major wound complications within 90 days after surgery, as defined according to the National Cancer Institute of Canada Sarcoma2 (NCIC-SR2) Multicenter Trial. Secondary objectives include safety and tolerability (acute grade ≥3 adverse events), 1- and 2-year local recurrence- and distant metastasis-free survival rates, incidence of late grade ≥2 radiation toxicity (fibrosis, lymphedema, or joint stiffness), functional outcomes using the Musculoskeletal Tumor Rating Scale and the Toronto Extremity Salvage Score, quality of life assessed via Functional Assessment of Cancer Therapy-General forms, and pathologic response (complete response, positive margins, and percentage necrosis in comparison with pre-treatment biopsy).

A sample size of 36 evaluable patients will allow us to obtain a two-sided 90% exact confidence interval with a width less than 0.3 if the incidence is between 30% and 60%, based on those reported in previous prospective trials. Guarding against the potential that 10% of patients may be not evaluable, we plan to accrue 40 patients in total to provide 36 evaluable patients. Patients will be considered evaluable if they have received 1 fraction of PBT and completed surgery.

Results: N/A (Trial)

Conclusion: N/A (Trial)