Predicted Secondary Malignancies following Proton versus Photon Radiation for Oropharyngeal Cancers.

PURPOSE: There has been a recent epidemic of human papillomavirus (HPV)-positive oropharyngeal cancer, accounting for 70% to 80% of diagnosed cases. These patients have an overall favorable prognosis and are typically treated with a combination of surgery, chemotherapy, and radiation. Because these patients live longer, they are at risk of secondary malignant neoplasms (SMNs) associated with radiation therapy. Therefore, we assessed the predicted risk of SMNs after adjuvant radiation therapy with intensity-modulated proton therapy (IMPT) compared with intensity modulated photon radiation therapy (IMRT) in patients with HPV- positive oropharyngeal cancers after complete resection. MATERIALS AND METHODS: Thirteen consecutive patients with HPV-positive oropharyngeal cancers treated with postoperative radiation alone were selected. All patients were treated with pencil beam scanning IMPT to a total dose of 60 Gy in 2 Gy fractions. The IMRT plans were generated for clinical backup and were used for comparative purposes. The SMN risk was calculated based on an organ equivalent dose model for the linear-exponential dose-response curve. RESULTS: Median age of the patient cohort was 63 years (range, 47-73 years). There was no difference in target coverage between IMPT and IMRT plans. We noted significant reductions in mean mandible, contralateral parotid, lung and skin organ equivalent doses with IMPT compared with IMRT plans (P < .001). Additionally, a significant decrease in the risk of SMNs with IMPT was observed for all the evaluated organs. Per our analysis, for patients with oropharyngeal cancers diagnosed at a national median age of 54 years with an average life expectancy of 27 years (per national Social Security data), 4 excess SMNs per 100 patients could be avoided by treating them with IMPT versus IMRT. CONCLUSIONS: Treatment with IMPT can achieve comparable target dose coverage while significantly reducing the dose to healthy organs, which can lead to fewer predicted SMNs compared with IMRT.

Verification of representative data for output factors of SRS cones utilizing IAEA TRS 483 recommendations.

Measurements of small fields continue to be a clinical challenge despite the recent work done to identify their characteristics. Due to this challenge, many physicists use representative data supplied by their vendors to verify their own measurements for small field output factors. However, with recent guidelines being released in IAEA TRS 483, the question remains if this representative data provides an accurate representation for small field dosimetry. A Sun Nuclear EDGE detector, PTW 60012 stereotactic diode, and GafChromic EBT3 films were used to measure the output factor for a set of Varian SRS cones (4 mm-17.5 mm diameters) on a TrueBeam linear accelerator. The measured output factors were then compared to the Varian provided SRS representative data. IAEA TRS 483 recommendations for measuring small field output factors were applied and the impact of those recommendations were examined. The EDGE detector showed good agreement with the representative data when correction factors were not applied (0.01%-1.64% difference) but the PTW 60012 diode showed larger deviation (0.61%-3.35% difference). The EBT3 film showed the largest difference with the representative data (0.66%-9.19%). After application of IAEA TRS 483 detector specific correction factors the output factors measured by the diodes showed good agreement with the EBT3 film for 6MV (<1.8% difference) but showed a large deviation with the representative data (up to 9% difference). The 6FFF energy output factors agreed between the EDGE, the PTW 60012, and EBT3 Film. This work shows that the use of uncorrected representative data on the Truebeam can lead to a significant over estimation of the SRS cone output factors.

Design and commissioning of an image-guided small animal radiation platform and quality assurance protocol for integrated proton and x-ray radiobiology research.

Small animal x-ray irradiation platforms are expanding the capabilities and future pathways for radiobiology research. Meanwhile, proton radiotherapy is transitioning to a standard treatment modality in the clinician's precision radiotherapy toolbox, highlighting a gap between state-of-the-art clinical radiotherapy and small animal radiobiology research. Comparative research of the biological differences between proton and x-ray beams could benefit from an integrated small animal irradiation system for in vivo experiments and corresponding quality assurance (QA) protocols to ensure rigor and reproducibility. The objective of this study is to incorporate a proton beam into a small animal radiotherapy platform while implementing QA modelled after clinical protocols. A 225 kV x-ray small animal radiation research platform (SARRP) was installed on rails to align with a modified proton experimental beamline from a 230 MeV cyclotron-based clinical system. Collimated spread out Bragg peaks (SOBP) were produced with beam parameters compatible with small animal irradiation. Proton beam characteristics were measured and alignment reproducibility with the x-ray system isocenter was evaluated. A QA protocol was designed to ensure consistent proton beam quality and alignment. As a preliminary study, cellular damage via γ-H2AX immunofluorescence staining in an irradiated mouse tumor model was used to verify the beam range in vivo. The beam line was commissioned to deliver Bragg peaks with range 4-30 mm in water at 2 Gy min-1. SOBPs were delivered with width up to 25 mm. Proton beam alignment with the x-ray system agreed within 0.5 mm. A QA phantom was created to ensure reproducible alignment of the platform and verify beam delivery. γ-H2AX staining verified expected proton range in vivo. An image-guided small animal proton/x-ray research system was developed to enable in vivo investigations of radiobiological effects of proton beams, comparative studies between proton and x-ray beams, and investigations into novel proton treatment methods.

Dosimetric Performance and Planning/Delivery Efficiency of a Dual-Layer Stacked and Staggered MLC on Treating Multiple Small Targets: A Planning Study Based on Single-Isocenter Multi-Target Stereotactic Radiosurgery (SRS) to Brain Metastases.

Purpose: To evaluate the dosimetric performance and planning/delivery efficiency of a dual-layer MLC system for treating multiple brain metastases with a single isocenter. Materials and Methods: 10 patients each with 6-10 targets with volumes from 0.11 to 8.57 cc, and prescription doses from 15 to 24 Gy, were retrospectively studied. Halcyon has only coplanar delivery mode. Halcyon V1 MLC modulates only with the lower layer at 1 cm resolution, whereas V2 MLC modulates with both layers at an effective resolution of 0.5 cm. For each patient five plans were compared varying MLC and beam arrangements: the clinical plan using multi-aperture dynamic conformal arc (DCA) and non-coplanar arcs, Halcyon-V1 using coplanar-VMAT, Halcyon-V2 using coplanar-VMAT, HDMLC-0.25 cm using coplanar-VMAT, and HDMLC-0.25 cm using non-coplanar-VMAT. All same-case plans were generated following the same planning protocol and normalization. Conformity index (CI), gradient index (GI), V12Gy, V6Gy, V3Gy, and brain mean dose were compared. Results: All VMAT plans met clinical constraints for critical structures. For targets with diameter < 1 cm, Halcyon plans showed inferior CI among all techniques. For targets with diameter >1 cm, Halcyon VMAT plans had CI similar to non-coplanar VMAT plans, and better than non-coplanar clinical DCA plans. For GI, Halcyon MLC plans performed similarly to coplanar HDMLC plans and inferiorly compared to non-coplanar HDMLC plans. All coplanar VMAT plans (Halcyon MLC and HDMLC) and clinical DCA plans had similar V12Gy, but were inferior compared to non-coplanar VMAT plans. Halcyon plans had slightly reduced V3Gy and mean brain dose compared to HDMLC plans. The difference between Halcyon V1 and V2 is only significant in CI of tumors less than 1cm in diameter. Halcyon plans required longer optimization than Truebeam VMAT plans, but had similar delivery efficiency. Conclusion: For targets with diameter >1 cm, Halcyon's dual-layer stacked and staggered MLC is capable of producing similar dose conformity compared to HDMLC while reducing low dose spill to normal brain tissue. GI and V12Gy of Halcyon MLC plans were, in general, inferior to non-coplanar DCA or VMAT plans using HDMLC, likely due to coplanar geometry and wider MLC leaves. HDMLC maintained its advantage in CI for smaller targets with diameter <1 cm.