Purpose/Objective(s)Radiation with concurrent chemotherapy is a treatment option for locally advanced vulvar cancer (LAVC), however toxicity often limits radiation dose. In this prospective trial, we aim to determine if FDG-PET/CT based adaptive radiotherapy (ART) improves dosimetry outcomes and toxicity for patients treated with definitive radiation for LAVC.Materials/MethodsWomen with LAVC were enrolled in two sequential IRB-approved prospective protocols for PET/CT ART from 2012-2020. Subjects were planned with pretreatment PET/CT to 45-56Gy in 1.8Gy/fx, followed by a boost to gross disease (nodal and/or primary) to a total of 64-66Gy. Intratreatment PET/CT was obtained at 30-36Gy, and all subjects were replanned to the same dose goals with revised OAR, GTV and PTV contours. Toxicity was graded by the CTCAE v5.0. Local control (LC), disease free survival (DFS), overall survival (OS), and time to toxicity were estimated using the Kaplan-Meier method. Dosimetry metrics for OARs were compared using the Wilcoxon signed rank test.Results22 patients were enrolled, and 20 were eligible for analysis. 10% of patients were FIGO stage IB, 35% II, 15% IIIA, 10% IIIB, 10% IIIC, and 20% IVA. 95% received concurrent chemotherapy (weekly cisplatin). Median follow up among surviving patients was 5.5 years. LC, DFS, and overall survival (OS) at 2 years were 63%, 43%, and 68%, respectively. ART significantly reduced the following OAR doses: bladder, max dose (dmax) (median reduction 1.1Gy (IQR 0.48 – 2.3 Gy), p<0.001) and D2cc (median reduction 1.5 Gy (IQR 0.51 – 2.1 Gy), p<0.001); bowel, dmax (median reduction 1.0 Gy (IQR 0.11 – 2.9 Gy), p<0.001), D2cc (median reduction 0.39 Gy (IQR 0.023 – 1.7 Gy), p<0.001), and D15cc (median reduction 0.19 Gy (IQR 0.026 – 0.47 Gy), p=0.002)); rectal, mean dose (median reduction 0.66 Gy (IQR 0.17 – 1.7 Gy) p=0.006) and D2cc (median reduction 0.46 Gy (IQR 0.17 – 0.80 Gy), p=0.006). 45% of patients experienced ≥grade 2 (G2) acute gastrointestinal (GI) toxicity, and 20% of patients experienced acute genitourinary (GU) toxicity. No patients experienced any grade 3 or higher acute toxicity. ≥G2 late GI toxicity at 2 years was 5% (95% CI, 0% – 15%). ≥G2 late GU toxicity at 2 years was 11% (95% CI, 0% - 26%). There were no reported late ≥G2 vaginal toxicities. Lymphedema at 2 years was 17% (95% CI, 0% - 34%).ConclusionIn this prospective study, doses to bladder, bowel, and rectum were statistically significant improved, though the median magnitudes were modest. Which subjects benefit most from adaptive treatment is a matter for future investigation. Treatment was overall well tolerated. Local control is similar to historical experiences, and efforts are indicated to improve on these results. PET/CT ART may be considered a reasonable option for the treatment of LAVC in future studies and may allow for dose escalation or the inclusion of novel radiation sensitizers, while limiting potential toxicities. Radiation with concurrent chemotherapy is a treatment option for locally advanced vulvar cancer (LAVC), however toxicity often limits radiation dose. In this prospective trial, we aim to determine if FDG-PET/CT based adaptive radiotherapy (ART) improves dosimetry outcomes and toxicity for patients treated with definitive radiation for LAVC. Women with LAVC were enrolled in two sequential IRB-approved prospective protocols for PET/CT ART from 2012-2020. Subjects were planned with pretreatment PET/CT to 45-56Gy in 1.8Gy/fx, followed by a boost to gross disease (nodal and/or primary) to a total of 64-66Gy. Intratreatment PET/CT was obtained at 30-36Gy, and all subjects were replanned to the same dose goals with revised OAR, GTV and PTV contours. Toxicity was graded by the CTCAE v5.0. Local control (LC), disease free survival (DFS), overall survival (OS), and time to toxicity were estimated using the Kaplan-Meier method. Dosimetry metrics for OARs were compared using the Wilcoxon signed rank test. 22 patients were enrolled, and 20 were eligible for analysis. 10% of patients were FIGO stage IB, 35% II, 15% IIIA, 10% IIIB, 10% IIIC, and 20% IVA. 95% received concurrent chemotherapy (weekly cisplatin). Median follow up among surviving patients was 5.5 years. LC, DFS, and overall survival (OS) at 2 years were 63%, 43%, and 68%, respectively. ART significantly reduced the following OAR doses: bladder, max dose (dmax) (median reduction 1.1Gy (IQR 0.48 – 2.3 Gy), p<0.001) and D2cc (median reduction 1.5 Gy (IQR 0.51 – 2.1 Gy), p<0.001); bowel, dmax (median reduction 1.0 Gy (IQR 0.11 – 2.9 Gy), p<0.001), D2cc (median reduction 0.39 Gy (IQR 0.023 – 1.7 Gy), p<0.001), and D15cc (median reduction 0.19 Gy (IQR 0.026 – 0.47 Gy), p=0.002)); rectal, mean dose (median reduction 0.66 Gy (IQR 0.17 – 1.7 Gy) p=0.006) and D2cc (median reduction 0.46 Gy (IQR 0.17 – 0.80 Gy), p=0.006). 45% of patients experienced ≥grade 2 (G2) acute gastrointestinal (GI) toxicity, and 20% of patients experienced acute genitourinary (GU) toxicity. No patients experienced any grade 3 or higher acute toxicity. ≥G2 late GI toxicity at 2 years was 5% (95% CI, 0% – 15%). ≥G2 late GU toxicity at 2 years was 11% (95% CI, 0% - 26%). There were no reported late ≥G2 vaginal toxicities. Lymphedema at 2 years was 17% (95% CI, 0% - 34%). In this prospective study, doses to bladder, bowel, and rectum were statistically significant improved, though the median magnitudes were modest. Which subjects benefit most from adaptive treatment is a matter for future investigation. Treatment was overall well tolerated. Local control is similar to historical experiences, and efforts are indicated to improve on these results. PET/CT ART may be considered a reasonable option for the treatment of LAVC in future studies and may allow for dose escalation or the inclusion of novel radiation sensitizers, while limiting potential toxicities.