Phase I Trial of MRI-Guided Prostate Cancer Lattice Extreme Ablative Dose (LEAD) Boost Radiation Therapy.

PURPOSE: A phase I clinical trial was designed to test the feasibility and toxicity of administering high-dose spatially fractionated radiation therapy to magnetic resonance imaging (MRI)-defined prostate tumor volumes, in addition to standard treatment. METHODS AND MATERIALS: We enrolled 25 men with favorable to high-risk prostate cancer and 1 to 3 suspicious multiparametric MRI (mpMRI) gross tumor volumes (GTVs). The mpMRI-GTVs were treated on day 1 with 12 to 14 Gy via dose cylinders using a lattice extreme ablative dose technique. The entire prostate, along with the proximal seminal vesicles, was then treated to 76 Gy at 2 Gy/fraction. For some high-risk patients, the distal seminal vesicles and pelvic lymph nodes received 56 Gy at 1.47 Gy/fraction concurrently in 38 fractions. The total dose to the lattice extreme ablative dose cylinder volume(s) was 88 to 90 Gy (112-123 Gy in 2.0 Gy equivalents, assuming an α-to-β ratio of 3).
RESULTS: Dosimetric parameters were satisfactorily met. Median follow-up was 66 months. There were no grade 3 acute/subacute genitourinary or gastrointestinal adverse events. Maximum late genitourinary toxicity was grade 1 in 15 (60%), grade 2 in 4 (16%), and grade 4 in 1 (4%; sepsis after a posttreatment transurethral resection). Maximum late gastrointestinal toxicity was grade 1 in 11 (44%) and grade 2 in 4 (16%). Two patients experienced biochemical failure.
CONCLUSIONS: External beam radiation therapy delivered with an upfront spatially fractionated, stereotactic high-dose mpMRI-GTV boost is feasible and was not associated with any unexpected events. The technique is now part of a follow-up phase II randomized trial.

RCT Entities:   Population Interventions Outcomes