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Purpose: Reirradiation (re-RT) using external beam radiation therapy (EBRT) is a novel salvage strategy for local failure in prostate cancer. We performed a systematic review describing oncologic and toxicity outcomes for salvage EBRT/stereotactic radiation therapy (SBRT) re-RT. Methods and Materials: A International Prospective Register of Systematic Reviews registered (#141466) systematic review, meta-analysis, and meta-regression was conducted using preferred reporting items for systematic reviews and meta-analyses guidelines. PubMed and EMBASE were searched from inception through September 2019. Outcome measures included local control (LC), biochemical relapse free survival (BRFS), and ≥grade 3 genitourinary (GU)/gastrointestinal (GI) toxicity. EBRT and SBRT data were collected separately. Meta-regression explored disease and toxicity outcomes as a function of equivalent dose in 2 Gy fractions (EQD2), length of follow-up, and partial versus whole prostate reirradiation. Results: Nineteen studies representing 13 cohorts were included (428 patients). Weighted mean follow-up was 26.1 months. Median re-RT EQD2 was 77.1 Gy (α/β = 1.5), with 92% of patients receiving SBRT, 52.1% of patients receiving partial prostate re-RT, and 30.1% of patients receiving androgen deprivation therapy with re-RT. LC was 83.2% (95% confidence interval [CI], 75.5%-90.9%) and BRFS was 59.3% (47.9%-70.7%). Reported late toxicity ≥grade 3 was 3.4% (95% CI, 1.0%-5.8%) for GU and 2.0% (95% CI, 0.1%-4.0%) for GI. Meta-regression found higher LC, BRFS, and reported GU/GI toxicity with increasing EQD2, with partial prostate re-RT associated with less reported GU/GI toxicity and no detriment to LC and BRFS. Conclusions: Salvage re-RT using EBRT, particularly with SBRT, is an emerging technique to treat isolated local failure of prostate cancer. With short-term follow-up, LC, BRFS, and reported toxicities appear reasonable, although further follow-up is required before definitive statements on late toxicities can be made. Our review is limited by incomplete reporting of androgen deprivation therapy use in the primary literature. Further prospective studies and longer follow-up are needed before considering re-RT as standard practice.

Purpose: Phase 2 randomized trials suggest that stereotactic ablative radiation therapy improves progression-free and overall survival in patients with oligometastatic cancer, with phase 3 trials currently testing stereotactic ablative radiation therapy in up to 10 metastases. Whether stereotactic radiation therapy could provide similar benefits in polymetastatic disease (>10 metastases) is unknown. We sought to evaluate the dosimetric feasibility of using stereotactic radiation therapy in polymetastatic disease in preparation for a phase 1 trial. Methods and Materials: Five craniospinal computed tomography simulations were used to simulate 24 metastatic targets (n = 2 patients), 30 targets (n = 2 patients), and 50 targets (n = 1 patient) that were not present on the initial scan. Creation of radiation therapy plans was attempted for doses up to 30 Gy in 5 fractions, with de-escalation to 24 Gy/4, 18 Gy/3, 12 Gy/2, or 6 Gy/1 if not feasible based on standardized dose constraints. Plans were created using Raystation for delivery on linear accelerators using volumetric modulated arc therapy and validated using Mobius 3D. Results: A stereotactic radiation therapy treatment plan was generated for each simulated patient. Dose constraints were met to a dose of 30 Gy in 5 fractions for the patients with 24 and 30 lesions. For the patient with 50 targets, dose de-escalation to 12 Gy in 2 fractions was required to meet lung constraints. Estimated beam-on time varied between 18 and 29 minutes per fraction of 6 Gy. Median D95 planning target volume dosimetry ranged from 96.6% to 97.7% of the prescription dose. The conformity index (R100) range was 0.89 to 0.95, and R50 range was 6.84 to 8.72. Conclusions: Stereotactic radiation therapy treatment plans meeting standardized dose constraints could be created in the setting of 24 to 50 metastatic lesions using volumetric modulated arc therapy. This safety of this approach is being evaluated in a phase 1 trial (NCT04530513).

Purpose: Accurate contouring in head and neck cancer (HNC) is critical. International consensus guidelines recommend the 5 + 5 mm rule for expansions around the primary tumor, wherein high- and low-dose clinical target volumes (CTV-P1 and CTV-P2, respectively) are created using successive 5 mm expansions on the gross tumor volume. To our knowledge, the necessity of a low-dose CTV-P2 has never been assessed; therefore, we evaluated the dosimetric impact of adding a CTV-P2 expansion using the 5 + 5 mm rule compared with contouring with a high-dose CTV-P1 alone. Methods and materials: A retrospective study of clinically delivered (chemo)radiation therapy treatment plans for HNC was conducted. All patients were treated with 70 Gy in 35 fractions using volumetric modulated arc therapy in a single phase. CTV-P2 was retrospectively contoured per guidelines as a 5 mm expansion on CTV-P1 from the clinical plan, carving off specified barriers to spread. We used a 5 mm planning target volume (PTV) expansion. Our primary outcome was whether 95% of the volume of the PTV for the CTV-P2 contour (ie, PTV-P2) received at least 56 Gy. To assess dose falloff, the coverage of a PTV ring structure was created by subtracting PTV-P1 from PTV-P2. Results: Twenty-seven patients from 4 HNC subsites (base of tongue, tonsil, hypopharynx, and supraglottic larynx) were included. In all 108 treatment plans, at least 95% of the PTV-P2 structure received at least 56 Gy. The minimum volume of the PTV-P2 structure receiving at least 56 Gy was 97.4%. Eight of 108 treatment plans had borderline coverage of the PTV ring substructure alone. Conclusions: Adding a CTV-P2 structure using the 5 + 5 mm rule had no dosimetric impact, adds contouring time, adds treatment planning complexity, and could potentially introduce errors. The 5 + 5 mm rule may have value in other settings, such as when smaller PTV margins are used, and warrants further evaluation with prospective or randomized studies.