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Purpose/Objective(s) Randomized trials have shown improved local control (LC) but no overall survival (OS) benefit with the addition of non-ablative radiation therapy (RT) dose compared to chemotherapy (CT) alone for pancreas cancer (PCa). Emerging data suggest that dose-escalated RT may improve LC and OS. A few studies suggest that stereotactic magnetic resonance-guided adaptive RT (SMART) can facilitate the safe delivery of ablative dose for inoperable PCa, although long-term outcomes are not well understood. Materials/Methods Inoperable PCa patients who received SMART were identified from the RSSearch Registry. Patients with Results A total of 148 PCa patients were treated on a 0.35T MR LINAC across 3 institutions between 2018-2020. Median age was 68 years (range 47-91), and 73.6% had ECOG 0-1 performance status. Patients had locally advanced (57.4%), borderline resectable (29.1%), or medically inoperable (13.5%) disease. Median CA19-9 at diagnosis was 202.1 U/mL (range 0.9-21,281). Induction CT was delivered to 89.2% for a median 3.9 mo (range 0.2-11.3); FOLFIRINOX (52.7%) or gemcitabine/nab-paclitaxel (23.4%) were common. Median prescribed RT dose was 50 Gy (range 40-50) in 5 fractions, mostly in consecutive days (96.6%) and in breath hold (95.3%). Median biologically effective dose (BED10) was 100 Gy10. All patients were treated with real-time tissue tracking and automated beam gating without fiducial markers. An elective target volume was rarely used (25%). Pancreaticoduodenectomy was performed in 23% at a median 46 days (range 34-304) after SMART. Median follow-up was 16 mo. from diagnosis for all patients (range, 4-39). Median, 1-year, and 2-year LC was not reached (NR), 94.6%, and 83%, respectively. Median, 1-year, and 2-year PFS was 18 mo., 72%, and 35.9%, respectively. Median, 1-year, and 2-year OS was 26 mo., 82%, and 52.7%, respectively. Acute and late grade 3 toxicity possibly related to SMART occurred in 4.1% and 12.8%, respectively. There was no reported grade 4+ toxicity. Conclusion To our knowledge, this is the largest reported analysis of 5-fraction SMART for inoperable PCa. These data add to the evidence that ablative radiation dose may improve long-term outcomes including OS. Prospective evaluation of this novel approach is warranted with attention directed at optimizing patient selection, understanding the clinical significance of cumulative dose delivered across all adapted fractions, and assessing treatment response after the delivery of ablative dose.

Purpose To describe and evaluate a method for generating synthetic computed tomography (synCT) images from magnetic resonance simulation (MR-SIM) data for accurate digitally reconstructed radiograph (DRR) generation and dose calculations in prostate cancer radiation therapy. Methods and Materials A retrospective evaluation was performed in 9 prostate cancer patients who had undergone MR-SIM in addition to CT simulation (CT-SIM). MR-SIM data were used to generate synCT images by using a novel, voxel-based weighted summation approach. A subset of patients was used for weight optimization, and the number of patients to use during optimization was determined. Hounsfield unit (HU) differences between CT-SIM and synCT images were analyzed via mean absolute error (MAE). Original, CT-based treatment plans were mapped onto synCTs. DRRs were generated, and agreement between CT and synCT-generated DRRs was evaluated via Dice similarity coefficient (DSC). Dose was recalculated, and dose-volume metrics and gamma analysis were used to evaluate resulting treatment plans. Results Full field-of-view synCT MAE across all patients was 74.3 ± 10.9 HU with differences from CTs of 2.0 ± 8.1 HU and 11.9 ± 46.7 HU for soft tissue structures (prostate, bladder, and rectum) and femoral bones, respectively. Calculated DSCs for anterior-posterior and lateral DRRs were 0.90 ± 0.04 and 0.92 ± 0.05, respectively. Differences in D99%, mean dose, and maximum dose to the clinical target volume from CT-SIM dose calculations were 0.75% ± 0.35%, 0.63% ± 0.34%, and 0.54% ± 0.33%, respectively, for synCT-generated plans. Gamma analysis (2%/2 mm dose difference/distance to agreement) revealed pass rates of 99.9% ± 0.1% (range, 99.7%-100%). Conclusion Generated synCTs enabled accurate DRR generation and dose computation for prostate MR-only simulation. Dose recalculated on synCTs agreed well with original planning distributions. Further validation using a larger patient cohort is warranted.

Purpose To report on a prospective clinical trial of the use of daily kilovoltage cone-beam computed tomography (CBCT) to evaluate the interfraction and residual error motion of patients undergoing intensity-modulated radiotherapy for head-and-neck cancer. Methods and Materials Patients were treated with intensity-modulated radiotherapy with an Elekta linear accelerator using a mounted CBCT scanner. CBCT was performed before every treatment, and translational (but not rotational) corrections were performed. At least once per week, a CBCT scan was obtained after intensity-modulated radiotherapy. Variations were measured in the medial–lateral, superoinferior, and anteroposterior dimensions, as well as in the rotation around these axes. Results A total of 28 consecutive patients (1,013 CBCT scans) were studied. The average interfraction shift was 1.4 ± 1.4, 1.7 ± 1.9, and 1.8 ± 2.1 mm in the medial–lateral, superoinferior, and anteroposterior dimensions, respectively. The corresponding average residual error shifts were 0.7 ± 0.8, 0.9 ± 0.9, and 0.9 ± 0.9 mm. These data indicate that in the absence of daily CBCT image-guided radiotherapy, a clinical target volume to planning target volume margin of 3.9, 4.1, and 4.9 mm is needed in the medial–lateral, superoinferior, and anteroposterior dimensions, respectively. With daily CBCT, corresponding margins of 1.6, 2.5, and 1.9 mm should be acceptable. Subgroup analyses showed that larynx cancers and/or intratreatment weight loss indicate a need for slightly larger clinical target volume to planning target volume margins. Conclusion The results of our study have shown that image-guided radiotherapy using CBCT for head-and-neck cancer is effective. These data suggest it allows a reduction in the clinical target volume to planning target volume margins by about 50%, which could facilitate future studies of dose escalation and/or improved toxicity reduction. Caution is particularly warranted for cases in which the targets are mobile ( e.g., the tongue).