Exploratory study of seed spots analysis to characterize dose and linear‐energy‐transfer effect in adverse event initialization of pencil‐beam‐scanning proton therapy

Abstract

Background: Both dose and linear energy transfer (LET) could play a substantial role in adverse event (AE) initialization of cancer patients treated with pencil-beam-scanning (PBS) proton therapy. However, not all the voxels within the AE regions are directly induced from the dose and LET effect. It is important to study the synergistic effect of dose and LET in AE initialization by only including a subset of voxels that are dosimetrically important. Purpose: To perform exploratory investigation of the dose and LET effects upon AE initialization in PBS using seed spots analysis. Methods: A total of 113 head-and-neck (H&N) cancer patients receiving curative PBS were included. Among them, 20 patients experienced unanticipated CTCAEv4.0 grade ≥3 AEs (AE group) and 93 patients did not (control group). Within the AE group, 13 AE patients were included in the seed spot analysis to derive the descriptive features of AE initialization and the remaining 7 mandible osteoradionecrosis patients and 93 control patients were used to derive the feature-based volume constraint of mandible osteoradionecrosis. The AE regions were contoured and the corresponding dose-LET volume histograms of AE regions were generated for all patients in the AE group. We selected high LET voxels (the highest 5% of each dose bin) with a range of moderate-to-high dose (≥∼40-Gy relative biological effectiveness) as critical voxels. Critical voxels that were contiguous with each other were grouped into clusters. Each cluster was considered a potential independent seed spot for AE initialization. Seed spots were displayed in a 2D dose-LET plane based on their mean dose and LET to derive the descriptive features of AE initialization. A volume constraint of mandible osteoradionecrosis was then established based on the extracted features using a receiver operating characteristic curve. Results: The product of dose and LET (xBD) was found to be a descriptive feature of seed spots leading to AE initialization in this preliminary study. The derived xBD volume constraint for mandible osteoradionecrosis showed good performance with an area under curve of 0.87 (sensitivity of 0.714 and specificity of 0.807 in the leave-one-out cross-validation) for the very limited patient data included in this study. Conclusion: Our exploratory study showed that both dose and LET were observed to be important in AE initializations. The derived xBD volume

Rotating Gantries Provide Individualized Beam Arrangements for Charged Particle Therapy

“…In the iterative treatment planning process between the dosimetrist, physicist and physician, the beam angles were modified and the number of beams increased to optimize target coverage, minimize organ at risk dose including lowering biological dose and improve plan robustness by adding beams and adjusting beam angles, as is done with CIRT treatment planning. The plans included in this study represent what the treating physician determined to be the best clinical plan for the patient for optimal target coverage and sparing of organs at risk considering physical and biological dose [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Using fewer beams or more standard beam angles resulted in inferior treatment plans which were not accepted by the treating physician.…”

Collimating individual beamlets in pencil beam scanning proton therapy, a dosimetric investigation

“…The opensource fast MC code, MCsquare (2,17,18,20,43) has been thoroughly validated against other MC codes and measurements in both phantoms and patient geometries (2,18,(43)(44)(45)(46)(47)(48)(49). In addition, MCsquare has been fully commissioned and has been incorporated into our in-house treatment planning system, Shiva (6,19,(50)(51)(52)(53)(54)(55), and has been clinically used as the second monitor unit (MU) check system at our proton center for years (2,18) and other proton centers (56). Therefore, we chose MCsquare in this study as a fast Monte Carlo dose and linear energy transfer (LET) calculation engine.…”

Technical note: Investigation of dose and LETd effect to rectum and bladder by using non‐straight laterals in prostate cancer receiving proton therapy

“…The adverse events after PBT are more complex than photon therapy due to the unique non-linear characteristic of the relationship of RBE with dose and LET d in PBT. 6,8,[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] A newly developed tool, dose-LET d volume histogram (DLVH), was developed and was able to correlate high LET d and high dose with rectal adverse events. 26,28 It was reported that high LET d (≥2.5 keV/µm) volume in the rectum might result in a higher incidence rate of grade≥2 (CACTE V4.0) rectal bleeding in prostate cancer patients treated with proton therapy, even though the corresponding dose volume was moderate.…”

“…Dose averaged LET (LET d ) is relevant in planning study because it is a physical parameter that can be scored through Monte Carlo methods. The adverse events after PBT are more complex than photon therapy due to the unique non‐linear characteristic of the relationship of RBE with dose and LET d in PBT 6,8,10–27 . A newly developed tool, dose‐LET d volume histogram (DLVH), was developed and was able to correlate high LET d and high dose with rectal adverse events 26,28 .…”