Elective nodal irradiation with simultaneous integrated boost stereotactic body radiotherapy for pancreatic cancer: Analyses of planning feasibility and geometrically driven DVH prediction model.

PURPOSE: We evaluate the feasibility of the elective nodal irradiation strategy in stereotactic body radiotherapy (SBRT) for pancreatic cancer. METHODS: Three simultaneous integrated boost (SIB)-SBRT plans (Boost1, Boost2, and Boost3) were retrospectively generated for each of 20 different patients. Boost1 delivered 33 and 25 Gy to PTV1 and PTV2, respectively. Boost2 delivered 40, 33, and 25 Gy to boostCTV, PTV1, and PTV2, respectively. Boost3 delivered 33 and 25 Gy to PTV1 and PTV3, respectively. PTV1 covered the initial standard SBRT plan (InitPlan) gross tumor volume (GTV). PTV2 covered CTVgeom which was created by a 10-mm expansion (15 mm posterior) of GTV. PTV3 covered CTVprop which included elective nodal regions. The boostCTV included GTV as well as involved vasculature. The planning feasibility in each scenario and dose-volume histograms (DVHs) were analyzed and compared with the InitPlan (delivered 33 Gy only to PTV1) by paired t-test. Next, a novel DVH prediction model was developed and its performance was evaluated according to the prediction accuracy (AC) of planning violations. Then, the model was used to simulate the impacts of GTV-to-organs at risk (OAR) distance and gastrointestinal (GI) OAR volume variations on planning feasibility. RESULTS: Significant dose increases were observed in GI-OARs in SIB-SBRT plans when compared with InitPlan. All dose constraints were met in 63% of cases in InitPlan, Boost1, and Boost2, whereas Boost3 developed DVH violations in all cases. Utilizing previous patient anatomy, the novel DVH prediction model achieved a high AC in the prediction of violations for GI-OARs; the positive predictive value, negative predictive value, and AC were 66%, 90%, and 84%, respectively. Experiments with the model demonstrated that the larger proximity volume of GI-OAR at the shorter distance substantially impacted on planning violations. CONCLUSIONS: SIB-SBRT plan with geometrically defined prophylactic areas can be dosimetrically feasible, but including all nodal areas with 25 Gy in five fractions appears to be unrealistic.

Gallbladder toxicity and high-dose ablative-intent radiation for liver tumors: Should we constrain the dose?

PURPOSE: Little is known about the risk of gallbladder toxicity from hypofractionated (HFXRT) and stereotactic body radiation therapy (SBRT). We report on gallbladder toxicity and attribution to treatment in a prospective series of patients with primary and metastatic liver tumors receiving ablative-intent HFXRT and SBRT with protons. METHODS AND MATERIALS: We evaluated 93 patients with intact gallbladders enrolled in either of 2 trials investigating proton HFXRT and SBRT for primary and metastatic liver tumors from 2009 to 2014. Patients received 45 to 67.5 GyE in 15 fractions for primary liver tumors (n = 45) and 30 to 50 GyE in 5 fractions for metastatic tumors (n = 48). No gallbladder dose constraints were used at treatment, and gallbladder volumes and dose-volume histograms were created retrospectively. Attributable toxicity was defined as cholecystitis or perforation without preexisting gallbladder disease. Baseline factors were evaluated using Fisher exact test and the nonparametric K-sample test. RESULTS: At baseline, 25 patients had preexisting cholelithiasis and 15 underwent biliary stenting before or after RT. Median follow-up after treatment was 11.8 months (range, 0.1-59.2 months). Despite maximum gallbladder doses >70 GyE in 41%, >80 GyE in 31%, and >90 GyE in 13% (equieffective dose at 2 Gy [EQD2], α/ß = 3), there were no attributable cases of gallbladder toxicity. Two patients developed grade 3 and 4 cholecystitis 16 and 2 months after treatment, respectively, and both had a strong history of preexisting cholelithiasis and biliary stenting. These patients received relatively low gallbladder doses with mean doses of 0.02 GyE and 5.1 GyE (EQD2, α/ß = 3), well below the 17.1 GyE mean for the remaining cohort (range, 0-81.1 GyE, EQD2). CONCLUSIONS: We identified no relationship between gallbladder dose and toxicity and did not reach the maximum tolerated gallbladder dose in this cohort treated with high-dose radiation. We recommend not constraining dose to the gross tumor volume to protect the gallbladder during ablative HFXRT and SBRT.

Randomized trial comparing two fractionation schedules for patients with localized prostate cancer.

PURPOSE: The optimal radiation dose fractionation schedule for localized prostate cancer is unclear. This study was designed to compare two dose fractionation schemes (a shorter 4-week radiation schedule v a longer 6.5-week schedule). PATIENTS AND METHODS: Patients with early-stage (T1 or T2) prostate cancer were randomly assigned to 66 Gy in 33 fractions over 45 days (long arm) or 52.5 Gy in 20 fractions over 28 days (short arm). The study was designed as a noninferiority investigation with a predefined tolerance of -7.5%. The primary outcome was a composite of biochemical or clinical failure (BCF). Secondary outcomes included presence of tumor on prostate biopsy at 2 years, survival, and toxicity. RESULTS: From March 1995 to December 1998, 936 men were randomly assigned to treatment; 470 were assigned to the long arm, and 466 were assigned to the short arm. The median follow-up time was 5.7 years. At 5 years, the BCF probability was 52.95% in the long arm and 59.95% in the short arm (difference = -7.0%; 90% CI, -12.6% to -1.4%), favoring the long arm. No difference in 2-year postradiotherapy biopsy or in overall survival was detected between the arms. Acute toxicity was found to be slightly higher in the short arm (11.4%) compared with the long arm (7%; difference = -4.4%; 95% CI, -8.1% to -0.6%); however, late toxicity was similarly low in both arms (3.2%). CONCLUSION: Given the results, we cannot exclude the possibility that the chosen hypofractionated radiation regimen may be inferior to the standard regimen. Further evaluation involving higher dose hypofractionated radiation regimens in contemporary radiation settings is necessary.