International Journal of Particle Therapy最新文献

Purpose: Securing insurance authorization for proton therapy remains a challenge for many centers. When health insurance or employer-sponsored health plans deny coverage, Independent Review Organizations (IROs) can review proton therapy cases. However, despite providing an independent review pathway, IROs are often underutilized in securing approvals for care following a denial.

Materials and methods: We analyzed trends in IRO approvals, strategies, and legal procedures using publicly available data from California (CA), Washington (WA), and New York (NY).

Results: The aggregate analysis of the 3 states revealed an IRO average approval rate for proton therapy of 42.1%, with varying trends across states. All 3 states showed increases in IRO approval rates over time, averaging annual increases of +5.0%, +2.3%, and +7.2% for CA, WA, and NY, respectively. Sarcoma showed the highest IRO approval rate at 84.6%, followed by GYN cancers at 55.6% and breast cancer at 51.4%. CNS tumors and lymphomas had moderate approval rates at 44.7% and 40.0% respectively. Head and neck cancers had a 33.3% approval rate, while thoracic malignancies were at 36.8%. The lowest IRO approval rate was seen in prostate cancer at 16.5%. Qualitative analysis revealed that referencing guidelines, discussing published studies, citing trial inclusion, and submitting personalized letters were associated with higher IRO approval rates.

Conclusion: IRO reviews provide a more objective remedy for patients denied care through internal appeals, particularly for plans with historically unfavorable proton policies. Our study demonstrates that IRO appeals provide a valuable pathway to proton therapy access with higher overturn rates improving significantly in recent years. Nearly half of initially denied patients eventually received approval through this process. Proton centers should strategically utilize IRO reviews to increase patient access and improve approval chances.

Purpose: Robustness evaluation is critical for proton beam therapy (PBT) planning, but ideal robustness criteria are not clearly defined. Here, we compared robustness of PBT plans to published intensity-modulated radiation therapy (IMRT)-derived clinical target volume (CTV) robustness benchmarks and assessed the dosimetric impact of meeting IMRT-derived benchmarks on adjacent organs at risk.

Patients and methods: Patients receiving PBT to 70 GyE in 28 fractions to the prostate alone from 2021 to 2022 at our institution were evaluated. PBT plan robustness was evaluated in nominal and worst-case data scenarios for CTV V100%, CTV V95%, rectum V70 Gy, and bladder V60 Gy. Clinically delivered ("Clinical") plans were compared to IMRT-derived worst-case CTV benchmarks. If benchmarks were not met, PBT plans were modified to meet both CTV V100% and V95% goals ("Benchmark" plans). Dosimetric comparisons between Clinical and Benchmark plans used a Wilcoxon signed-rank test with alpha set at 0.05.

Results: Among 32 patients, median age and PSA at diagnosis were 71 years and 6.84 ng/mL, respectively. Most patients had favorable-intermediate risk disease (56.3%). Only 31% of clinical PBT met both worst-case CTV V100% > 90% and CTV V95% > 99% IMRT benchmarks. Plan renormalization (16 patients) or reoptimization (6 patients) resulted in all Benchmark plans meeting worst-case CTV thresholds. For Benchmark plans, nominal rectum V70 Gy increased from 0.72 to 0.92 cm³, and nominal bladder V60 Gy increased from 5.9% to 6.0% (P < .05 for each). Overall plan hot spot between Clinical and Benchmark plans increased from 104.5 to 105.5% (P < .05).

Conclusion: When compared to an IMRT-derived benchmark for robustness coverage, Clinical PBT plans were less robust. However, all PBT plans were successfully modified to meet worst-case CTV benchmark with limited clinically expected impact on organ at risk dosimetry. Consideration should be made to adopt these benchmark criteria for prostate PBT.

Purpose: We aim to assess the magnetic resonance imaging (MRI)-to-CT deformable image registration (DIR) quality of our treatment planning system in the pelvic region as the first step of an online MRI-guided particle therapy clinical workflow.

Materials and methods: Using 2 different DIR algorithms, ANAtomically CONstrained Deformation Algorithm (ANACONDA), the DIR algorithm incorporated in RayStation, and Elastix, an open-source registration software, we retrospectively assessed the quality of the deformed CT (dCT) generation in the pelvic region for 5 patients. T1- and T2-weighted daily control MRI acquired prior to treatment delivery were used for the DIR. We compared the contours automatically mapped on the dCT against the manual contours on the MRI (ground truth) by calculating the Dice similarity coefficients and mean distances to the agreement for organs at risk, targets, and outer contour. We assessed the dosimetric impact of the DIR on the clinical treatment plans, comparing the dose-volume histograms and the value of the clinical goals achieved for each dCT. The water equivalent path lengths and dose range 80% (R80%) maps were compared by casting on the beams' eye view.

Results: The T1 sequences performed better for the DIR with ANACONDA compared against the T2. ANACONDA's performance agreed with Elastix. The bladder and rectum led to the worst agreement. For the remaining structures analyzed, Dice similarity coefficients above 0.80 were obtained. Maximum median deviations of 7.1 and 2.1 mm were observed for water equivalent path lengths and R80%, respectively, on the PTV.

Conclusion: This work shows a good agreement on the DIR quality achieved with ANACONDA for the structures in the beams' path. By comparing the R80% generated with ANACONDA and Elastix, we give a first quantification of the uncertainties to be considered in an online MRI-guided particle therapy workflow for pelvic treatment.

Purpose: To compare intensity-modulated proton therapy with CyberKnife (CK) therapy for hypo-fractionated treatments of prostate with focal boost, as a first planning study for prostate with dose escalation to a dominant intraprostatic lesion (DIL).

Materials and methods: Ten patients who possess one DIL in their prostate and their CK plans that were used to treat the planning target volume of prostate were chosen. Six of the plans were further escalated to DIL. Intensity-modulated proton therapy plans were created for the patients with robust optimization, accounting for setup and range uncertainties for the clinical target volume (CTV) of prostate. The CK plans were then compared with the proton plans.

Results: In the worst scenario of the robust evaluation, the proton plans reasonably met all objectives and constraints used in CK planning for both CTV coverage and organs-at-risk (OAR) sparing. Under the nominal scenario of the robust optimization, the proton plans produced dosimetric values comparable to those by the CK plans for both CTV and DIL coverage. The average dose to CTV, outside DIL and urethra, was found lower in the proton plans than in the CK plans due to the uncertainties. A similar trend was observed for the dose conformity to CTV. These two findings, however, were not planning objectives. Regarding organs-at-risk sparing, the proton plans in the nominal scenario were comparable to the CK plans for doses >18.125 Gy; for doses below it, the proton performed better. This study offers a basis for a clinical trial of treatment of prostate cancer by proton that may be transferred from the CK system in our center.

Conclusion: The dosimetric objectives and constraints used in the CK plans were achieved with the proton plans.

Purpose: The purpose of this work was to reduce the severity of radiation dermatitis for breast cancer patients receiving pencil beam scanning proton therapy. The hypothesis was that eliminating proton spots (SpotDelete) in the 0.5 cm skin rind would reduce the potentially higher relative biological effectiveness (RBE) known to occur at the Bragg Peak.

Patients and methods: Our center has been using an in-house developed Python script in RayStation since 2021 to remove spots from the skin rind of breast patients. In this work, we retrospectively reviewed the on-treatment visit data from a cohort of breast patients treated with hypofractionation (16 fractions) before this technique (MinDepth) and after (SpotDelete) to acquire the physician-reported radiation dermatitis scores. We evaluated the delivered treatment plans, calculating the linear energy transfer (LET) and applying 3 variable RBE models, Carabe-Fernandez, Wedenberg, and McNamara. An α/β of 10 was assumed for the skin.

Results: In the MinDepth cohort (n = 28), grade 1, 2, and 3 dermatitis accounted for 57%, 36%, and 7% of the cases, respectively. For SpotDelete (n = 27), the incidence rate of grade 1 and 2 acute radiation dermatitis was 67% and 37%, respectively. There were 0 instances of grade 3 dermatitis observed in the SpotDelete cohort. The onset of radiation dermatitis in the SpotDelete cohort was delayed compared to MinDepth, occurring 1 week later in the course of treatment. There was no significant difference in LET or in any of the variable RBE models when analyzing the 0.5 cm skin rind between the cohorts.

Conclusion: Despite the lack of correlation in LET or RBE, SpotDelete has been shown to reduce the severity and onset of radiation dermatitis. Possibly, more research into the α/β for skin and RBE models based on skin cell lines could provide insight into the efficacy of the SpotDelete technique.

Purpose: Previous studies have shown that external beam radiation therapy is associated with an increased risk of second primary cancer (SPC) among prostate cancer (PCa) patients, but the relative risks associated with newer and advanced radiation modalities such as proton beam therapy (PBT) and stereotactic body radiation therapy (SBRT) are unclear. This study aimed to assess the relative probability of SPC among patients treated with these newer modalities compared to intensity-modulated radiation therapy (IMRT).

Patients and methods: Using the National Cancer Database (NCDB), N0M0 PCa cases diagnosed between 2004 and 2018 were identified. Second primary cancer probabilities were compared among those treated with curative-intent PBT, SBRT, and IMRT. Multivariable logistic regression and inverse probability of treatment weighting were used to generate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).

Results: In total, 133 898 patients were included, with a median age of 69 years and median follow-up of 6.4 years. As their first course of treatment, 3420 (2.6%) received PBT, 121 211 (90.5%) received IMRT, and 9267 (6.9%) received SBRT. Compared with IMRT, PBT and SBRT were associated with lower SPC risk (aORs and 95% CIs, PBT: 0.49 [0.40-0.60], SBRT: 0.57 (0.51-0.63), P < .001). Inverse probability of treatment weighting analyses corroborated these results.

Conclusion: In this large national cohort, PBT and SBRT performed similarly and were associated with reduced SPC risk compared to IMRT when used as the first course of treatment.

Particle therapy (PT) represents a significant advancement in cancer treatment, precisely targeting tumor cells while sparing surrounding healthy tissues thanks to the unique depth-dose profiles of the charged particles. Furthermore, their linear energy transfer and relative biological effectiveness enhance their capability to treat radioresistant tumors, including hypoxic ones. Over the years, extensive research has paved the way for PT's clinical application, and current efforts aim to refine its efficacy and precision, minimizing the toxicities. In this regard, radiobiology research is evolving toward integrating biotechnology to advance drug discovery and radiation therapy optimization. This shift from basic radiobiology to understanding the molecular mechanisms of PT aims to expand the therapeutic window through innovative dose delivery regimens and combined therapy approaches. This review, written by over 30 contributors from various countries, provides a comprehensive look at key research areas and new developments in PT radiobiology, emphasizing the innovations and techniques transforming the field, ranging from the radiobiology of new irradiation modalities to multimodal radiation therapy and modeling efforts. We highlight both advancements and knowledge gaps, with the aim of improving the understanding and application of PT in oncology.

Purpose: Radiation-induced lymphopenia is a common immune toxicity that adversely impacts treatment outcomes. We report here our approach to translate a deep-learning (DL) model developed to predict severe lymphopenia risk among esophageal cancer into a strategy for incorporating the immune system as an organ-at-risk (iOAR) to mitigate the risk.

Materials and methods: We conducted "virtual clinical trials" utilizing retrospective data for 10 intensity-modulated radiation therapy (IMRT) and 10 passively-scattered proton therapy (PSPT) esophageal cancer patients. For each patient, additional treatment plans of the modality other than the original were created employing standard-of-care (SOC) dose constraints. Predicted values of absolute lymphocyte count (ALC) nadir for all plans were estimated using a previously-developed DL model. The model also yielded the relative magnitudes of contributions of iOARs dosimetric factors to ALC nadir, which were used to compute iOARs dose-volume constraints, which were incorporated into optimization criteria to produce "IMRT-enhanced" and "intensity-modulated proton therapy (IMPT)-enhanced" plans.

Results: Model-predicted ALC nadir for the original IMRT (IMRT-SOC) and PSPT plans agreed well with actual values. IMPT-SOC showed greater immune sparing vs IMRT and PSPT. The average mean body doses were 13.10 Gy vs 7.62 Gy for IMRT-SOC vs IMPT-SOC for patients treated with IMRT-SOC; and 8.08 Gy vs 6.68 Gy for PSPT vs IMPT-SOC for patients treated with PSPT. For IMRT patients, the average predicted ALC nadir of IMRT-SOC, IMRT-enhanced, IMPT-SOC, and IMPT-enhanced was 281, 327, 351, and 392 cells/µL, respectively. For PSPT patients, the average predicted ALC nadir of PSPT, IMPT-SOC, and IMPT-enhanced was 258, 316, and 350 cells/µL, respectively. Enhanced plans achieved higher predicted ALC nadir, with an average improvement of 40.8 cells/µL (20.6%).

Conclusion: The proposed DL model-guided strategy to incorporate the immune system as iOAR in IMRT and IMPT optimization has the potential for radiation-induced lymphopenia mitigation. A prospective clinical trial is planned.

Purpose: Periodic quality assurance CTs (QACTs) are routine in proton beam therapy. In this study, we tested whether the necessity for a QACT could be determined by evaluating the change in beam path length (BPL) on daily cone-beam CT (CBCT).

Patients and methods: In this Institutional Review Board-approved study, we retrospectively analyzed 959 CBCT images from 78 patients with sarcomas treated with proton pencil-beam scanning. Plans on 17 QACTs out of a total of 243 were clinically determined to be replanned for various reasons. Daily CBCTs were retrospectively analyzed by automatic ray-tracing of each beam from the isocenter to the skin surface along the central axis. A script was developed for this purpose. Patterns of change in BPL on CBCT images were compared to those from adaptive planning using weekly QACTs.

Results: Sixteen of the 17 adaptive replans showed BPL changes ≥4 mm for at least 1 of the beams on 3 consecutive CBCT sessions. Similarly, 43 of 63 nonadaptively planned patients had BPL changes <4 mm for all of the beams. A new QACT criterium of a BPL change of any beam ≥4 mm on 3 consecutive CBCT sessions resulted in a sensitivity of 94.1% and a specificity of 68.3%. Had the BPL change been used as the QACT predictor, a total of 37 QACTs would have been performed rather than 243 QACTs in clinical practice.

Conclusion: The use of BPL changes on CBCT images represented a significant reduction (85%) in total QACT burden while maintaining treatment quality and accuracy. QACT can be performed only when it is needed, but not in a periodic manner. The benefits of reducing QACT frequency include reducing imaging dose and optimizing patient time and staff resources.

Purpose: Radiotherapy delivery in the definitive management of lower gastrointestinal (LGI) tract malignancies is associated with substantial risk of acute and late gastrointestinal (GI), genitourinary, dermatologic, and hematologic toxicities. Advanced radiation therapy techniques such as proton beam therapy (PBT) offer optimal dosimetric sparing of critical organs at risk, achieving a more favorable therapeutic ratio compared with photon therapy.

Materials and methods: The international Particle Therapy Cooperative Group GI Subcommittee conducted a systematic literature review, from which consensus recommendations were developed on the application of PBT for LGI malignancies.

Results: Eleven recommendations on clinical indications for which PBT should be considered are presented with supporting literature, and each recommendation was assessed for level of evidence and strength of recommendation. Detailed technical guidelines pertaining to simulation, treatment planning and delivery, and image guidance are also provided.

Conclusion: PBT may be of significant value in select patients with LGI malignancies. Additional clinical data are needed to further elucidate the potential benefits of PBT for patients with anal cancer and rectal cancer.