Double Scattering Proton Therapy Research Articles

Proton Radiation Therapy After Chemotherapy in the Management of Aggressive Mediastinal Non-Hodgkin Lymphomas: A Particle Therapy Cooperative Group Lymphoma Subcommittee Collaboration

PurposeCombined modality therapy with multiagent chemotherapy and radiation therapy is a standard treatment option for aggressive mediastinal non-Hodgkin lymphomas (AMNHLs); however, concerns regarding acute and late radiation toxicities have fueled an effort to use systemic therapy alone. The use of proton therapy (PT) is a promising treatment option, but there are still limited data regarding clinical outcomes with this treatment modality. In this Particle Therapy Cooperative Group lymphoma subcommittee collaboration, we report outcomes of patients with AMNHL treated with pencil-beam scanning PT or double-scatter PT after chemotherapy. Methods and MaterialsThis was a multi-institutional retrospective observational cohort study of patients with AMNHL treated with PT following chemotherapy between 2011 and 2021. Progression-free survival (PFS), local recurrence–free survival (LRFS), and overall survival (OS) rates were estimated with the Kaplan-Meier method. PT toxicity was graded by the Common Terminology Criteria for Adverse Events version 5.0. A 2-tailed paired t test was used for dosimetric comparisons. ResultsTwenty-nine patients were identified. With a median follow-up time of 4.2 years (range, 0.2-8.9 years), the estimated 5-year PFS for all patients was 93%, 5-year LRFS was 96%, and estimated 5-year OS was 87%. Maximum acute grade 1 (G1) toxicities occurred in 18 patients, and 7 patients had maximum G2 toxicities. No G3+ radiation-related toxicities were observed. Average mean lung dose and lung V20 Gy were lower for patients treated with pencil-beam scanning PT compared with double-scatter PT (P = .016 and .006, respectively), while patients with lower mediastinal disease had higher doses for all evaluated dosimetric heart parameters. ConclusionsPT after chemotherapy for patients with AMNHL resulted in excellent outcomes with respect to 5-year PFS, LRFS, and OS without high-grade toxicities. Future work with larger sample sizes is warranted to further elucidate the role of PT in the treatment of AMNHL.

Postoperative or Salvage Proton Radiotherapy for Prostate Cancer After Radical Prostatectomy.

PurposePostprostatectomy radiation improves disease control, but limited data exist regarding outcomes, toxicities, and patient-reported quality of life with proton therapy.Method and MaterialsThe first 102 patients who were enrolled on an outcome tracking protocol between 2006 and 2017 and treated with double-scattered proton therapy after prostatectomy were retrospectively reviewed. Eleven (11%) received adjuvant radiation, while 91 (89%) received salvage radiation. Seventy-four received double-scattered proton therapy to the prostate bed only. Twenty-eight received a double-scattered proton therapy prostate-bed boost after prostate-bed and pelvic-node treatment. Eleven adjuvant patients received a median dose of 66.6 GyRBE (range, 66.0-70.2). Ninety-one salvage patients received a median dose of 70.2 GyRBE (range, 66.0-78.0). Forty-five patients received androgen deprivation therapy for a median 9 months (range, 1-30). Toxicities were scored using Common Terminology Criteria for Adverse Events v4.0 criteria, and patient-reported quality-of-life data were reviewed.ResultsThe median follow-up was 5.5 years (range, 0.8-11.4 years). Five-year biochemical relapse-free and distant metastases-free survival rates were 72% and 91% for adjuvant patients, 57% and 97% for salvage patients, and 57% and 97% overall. Acute and late grade 3 or higher genitourinary toxicity rates were 1% and 7%. No patients had grade 3 or higher gastrointestinal toxicity. Acute and late grade 2 gastrointestinal toxicities were 5% and 2%. The mean values and SDs of the International Prostate Symptom Score, International Index of Erectile Function, and Expanded Prostate Cancer Index Composite bowel function and bother were 7.5 (SD = 5.9), 10.2 (SD = 8.3), 92.8 (SD = 11.1), and 91.2 (SD = 6.4), respectively, at baseline, and 12.1 (SD = 9.1), 10.1 (SD = 6.7), 87.3 (SD = 18), and 86.7 (SD = 13.8) at the 5-year follow-up.ConclusionHigh-dose postprostatectomy proton therapy provides effective long-term biochemical control and freedom from metastasis, with low acute and long-term gastrointestinal and genitourinary toxicity.

Second tumor risk in children treated with proton therapy.

Out-of-field neutron dissemination during double-scattered proton therapy has raised concerns of increased second malignancies, disproportionally affecting pediatric patients due to the proportion of body exposed to scatter dose and inherent radiosensitivity of developing tissue. We sought to provide empiric data on the incidence of early second tumors. Between 2006 and 2019, 1713 consecutive children underwent double-scattered proton therapy. Median age at treatment was 9.1years; 371 were ≤3years old. Thirty-seven patients (2.2%) had tumor predisposition syndromes. Median prescription dose was 54Gy (range 15-75.6). Median follow-up was 3.3years (range 0.1-12.8), including 6587 total person-years. Five hundred forty-nine patients had ≥5years of follow-up. A second tumor was defined as any solid neoplasm throughout the body. Eleven patients developed second tumors; the 5- and 10-year cumulative incidences were 0.8% (95% CI, 0.4-1.9%) and 3.1% (95% CI, 1.5-6.2%), respectively. Using age- and gender-specific data from the Surveillance, Epidemiology, and End Results (SEER) program, the standardized incidence ratio was 13.5; the absolute excess risk was 1.5/1000 person-years. All but one patient who developed second tumors were irradiated at ≤5years old (p<.0005). There was also a statistically significant correlation between patients with tumor predisposition syndromes and second tumors (p<.0001). Excluding patients with tumor predisposition syndromes, 5- and 10-year rates were 0.6% (95% CI, 0.2-1.7%) and 1.7% (95% CI, 0.7-4.0%), respectively, with all five malignant second tumors occurring in the high-dose region. Second tumors are rare within the decade following double-scattered proton therapy, particularly among children irradiated at >5years old and those without tumor predisposition syndrome.

RONC-22. SECOND TUMORS IN PEDIATRIC PATIENTS TREATED WITH PROTON THERAPY TO THE CENTRAL NERVOUS SYSTEM

BACKGROUNDPrevious institutional data suggests the 10-year cumulative incidence of second tumors is 3% in children treated with photon radiation for central nervous system (CNS) malignancy, with 90% of these tumors occurring in areas receiving ≤36 Gy. Comparative figures for children treated with proton therapy (PT) does not exist.METHODS1056 consecutive pediatric patients with a median follow-up of 5.0 years were treated between 2006–2019 with double-scattered PT to a site within the craniospinal axis. 230 patients were ≤3 years old and 14 had neurofibromatosis. A second tumor was defined as any solid neoplasm with histologic features different from the original tumor that had arisen within the irradiated volume.RESULTSFive patients developed second tumors resulting in a 5- and 10-year cumulative incidence of 0.2% (95% CI: 0–1.2%) and 1.6% (95% CI: 0.6%-3.9%), respectively. Of those who developed second tumors, median age at radiation was 4.3 years old (range, 2.1 to 5.1 years old) and diagnoses consisted of medulloblastoma (n=2), ependymoma (n=2), and craniopharyngioma (n=1). The second tumors included high grade gliomas (n=3) and high grade sarcoma (n=1) that occurred in regions receiving at least 54 Gy. One patient with neurofibromatosis developed both a low-grade glioma and choroidal melanoma in craniospinal irradiation regions receiving 36 Gy. Four of five patients with second tumors are alive.CONCLUSIONThe reduction in moderate-to-low dose radiation exposure from proton therapy may be associated with a decreased incidence of second tumors in children treated for CNS neoplasms. More follow-up is needed to confirm these findings.

Second Tumors in Pediatric Patients Treated with Double-Scattered Proton Therapy

We hypothesize that double-scattered proton therapy results in neutron dissemination far beyond the treatment field, resulting in an increased risk of second malignancies that disproportionally affect pediatric patients. Between 2006 and 2019, 1708 consecutive children ≤ 21 years old were treated with double-scattered proton therapy at a single institution. Most common indications included CNS tumors (60%), sarcomas (28%), and head/neck tumors (5%). The median age at treatment was 9.2 years, and 370 children were ≤ 3 years. Thirty-five patients (2%) had tumor predisposition syndromes: 18 with neurofibromatosis (NF), 11 with retinoblastoma, and 6 with Li-Fraumeni (LF). Across the cohort, the median prescription dose was 54 Gy (range, 15 - 75.6 Gy). The median follow-up duration was 3.5 years (range, 0.1 - 12.8 years) and includes 6886 total person-years in follow-up. Four hundred patients have ≥ 5 years of follow-up. Seven patients (0.4%) were lost to follow-up. A second tumor was defined as any solid neoplasm throughout the body. The Kaplan-Meier product limit method estimated freedom from second tumor and the log-rank test statistic estimated the level of statistical significance between strata of patients with tumor predisposition syndromes and those patients without. Standardized incidence ratio (SIR) was assessed as the ratio of the observed/expected cases for second solid tumor development using general pediatric incidence rates from the Surveillance, Epidemiology, and End Results (SEER) Program. Seven patients overall developed second tumors resulting in a 5- and 10-year cumulative incidence of 0.4% (95% CI: 0.1-1.1%) and 1.9% (95% CI: 0.8%-4.4%), respectively. The SIR was 7.9. All patients who developed second tumors were irradiated at ≤ 5 years old. There was a statistically significant correlation between patients with NF or LF and second tumors (p < 0.0001). Excluding these patients, 5- and 10-year rates were 0.2% (95% CI: 0-1.1%) and 1.1% (95% CI: 0.4- 3.6%), respectively, and no second tumors developed in regions receiving < 50 Gy. Two patients overall developed hematologic second malignancies < 12 months following chemotherapy and radiation. Second tumors are rare within the decade following double-scattered proton therapy, particularly among children irradiated at > 5 years of age and those without tumor predisposition syndrome. Longer follow-up is needed to empirically validate claims that proton therapy results in less overall second tumors in children, but it is unlikely that neutrons from double-scattered proton therapy in children result in an increased rate of “out-of-field” second tumors.

Image-guided hypofractionated double-scattering proton therapy in the management of centrally-located early-stage non-small cell lung cancer

Background The treatment of centrally-located early-stage non-small cell lung cancer (NSCLC) with image-guided stereotactic body radiotherapy (SBRT) is challenging due to the proximity of critical normal structures to the tumor target. The purpose of this study was to report the results of our experience in treating centrally-located early-stage NSCLC with hypofractionated proton therapy (PT). Material and methods Between 2009 and 2018, 23 patients with T1–T2N0M0 NSCLC (T1, 46%; T2, 54%) were treated with image-guided hypofractionated double-scattering PT. The median age at the time of treatment was 74 years (range, 58–88). Patients underwent 4-dimensional computed tomography (CT) simulation following fiducial marker placement, and daily image guidance was performed. All patients were treated with 60 GyRBE in 10 fractions. Patients were assessed for CTCAEv4 toxicities weekly during treatment, and at regular follow-up intervals with CT imaging for tumor assessment. Overall survival, cause-specific survival, local control, regional control, and metastases-free survival were evaluated using cumulative incidence with competing risks. Results Median follow-up for all patients was 3.2 years (range, 0.2–9.2 years). Overall survival rates at 3 and 5 years were 81% and 50% (95% CI, 27–79%), respectively. Cause-specific survival rates at 3 and 5 years were 81% and 71% (95% CI, 46–92%). The 3-year local, regional, and distant control rates were 90%, 81%, and 87%, respectively. Three patients (13%) experienced local recurrences as their first recurrence, at a median time of 28 months from completion of radiation (range, 18–61 months). Two patients (9%) experienced late grade 3 toxicities, including 1 patient who developed a bronchial stricture that required stent placement. Conclusion Image-guided hypofractionated PT for centrally-located early-stage NSCLC provides excellent local control with low rates of grade ≥3 toxicities. For tumors in sensitive locations, PT may provide safer treatment than photon-based treatments due to its dosimetric advantages.

Simulation study of proton arc therapy with the compact single-room MEVION-S250 proton therapy system

AbstractAim:The purpose of this study is to investigate the feasibility of proton arc therapy (PAT) using the double-scattering MEVION-S250 proton system. The treatment planning and dose delivery parameters from PAT were compared with conventional treatment planning techniques.Materials and methods:PAT was simulated with multiple conformal and fixed-aperture beams (5–15) using the MEVION-S250-double-scattering proton system. Conformal apertures were simulated with the Eclipse-treatment-planning system: (a) using a static single aperture that provides the best average conformal circular or rectangular apertures to cover the tumour from different angular views (SPAT), and (b) dynamic conformal apertures of the tumour shape at each irradiation angle that can be obtained from a multi-leaf-collimator system (DPAT).Results:The DPAT and SPAT plans provided superior dose coverage and sparing of normal tissues in comparison with conventional plans (CPT). The entrance normal tissue and skin doses (&lt;40%) were lowered significantly by delivering dose from different directions over a wider angular view compared to conventional plans that have large entrance dose from only two fields. While the mean and minimum doses from PAT and CPT were comparable, the maximum doses from arc plans were lower than the maximum doses in conventional plans. The SPAT and DPAT plans had comparable dose parameters for regularly shaped targets. The heterogeneity index (HI) was superior in PAT plans which improved with increasing number of beams in arc plans for the different treatment sites. The conformality index (CI) depends on the treatment site and complexity of the shape of the planning target volume where for brain, pancreatic and lung tumours, PAT plans conformality was comparable and sometimes superior to CPT; and HI and CI were generally better in DPAT compared to SPAT.Conclusions:PAT plans have superior dose coverage and sparing of normal tissues compared to CPT plans using the MEVION double-scattering system as shown in this simulation study. Ideally, conformal proton arcs require beam shaping and dose delivery with the gantry moving; however, the MEVION double-scattering system lacks a multi-leaf collimator system and cannot deliver dose during gantry rotation. The single aperture conformal proton therapy technique is more time and cost effective compared with conventional techniques that are used currently with the MEVION proton therapy system because of the elimination of the need for patient-specific compensators. In present study, PAT was simulated with the MEVION double-scattering proton therapy system; however, it can be performed also with other proton therapy systems.

Photons or protons for reirradiation in (non-)small cell lung cancer: Results of the multicentric ROCOCO in silico study.

Locally recurrent disease is of increasing concern in (non-)small cell lung cancer [(N)SCLC] patients. Local reirradiation with photons or particles may be of benefit to these patients. In this multicentre in silico trial performed within the Radiation Oncology Collaborative Comparison (ROCOCO) consortium, the doses to the target volumes and organs at risk (OARs) were compared when using several photon and proton techniques in patients with recurrent localised lung cancer scheduled to undergo reirradiation. 24 consecutive patients with a second primary (N)SCLC or recurrent disease after curative-intent, standard fractionated radio(chemo)therapy were included in this study. The target volumes and OARs were centrally contoured and distributed to the participating ROCOCO sites. Remaining doses to the OARs were calculated on an individual patient's basis. Treatment planning was performed by the participating site using the clinical treatment planning system and associated beam characteristics. Treatment plans for all modalities (five photon and two proton plans per patient) were available for 22 patients (N = 154 plans). 3D-conformal photon therapy and double-scattered proton therapy delivered significantly lower doses to the target volumes. The highly conformal techniques, i.e., intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), CyberKnife, TomoTherapy and intensity-modulated proton therapy (IMPT), reached the highest doses in the target volumes. Of these, IMPT was able to statistically significantly decrease the radiation doses to the OARs. Highly conformal photon and proton beam techniques enable high-dose reirradiation of the target volume. They, however, significantly differ in the dose deposited in the OARs. The therapeutic options, i.e., reirradiation or systemic therapy, need to be carefully weighed and discussed with the patients. Highly conformal photon and proton beam techniques enable high-dose reirradiation of the target volume. In light of the abilities of the various highly conformal techniques to spare specific OARs, the therapeutic options need to be carefully weighed and patients included in the decision-making process.

Proceedings to the 6th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA): 14-16 October 2019, Hosted by Miami Cancer Institute, part of Baptist Health South Florida, Miami, FL, USA.

Proceedings to the 6th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA): 14-16 October 2019, Hosted by Miami Cancer Institute, part of Baptist Health South Florida, Miami, FL, USA.

Proton therapy following induction chemotherapy for pediatric and adolescent nasopharyngeal carcinoma.

In children treated for nasopharyngeal carcinoma, proton therapy and postchemotherapy target volumes can reduce the radiation dose to developing tissue in the brain and the skull base region. We analyzed outcomes in children with nasopharyngeal carcinoma treated with induction chemotherapy followed by moderate-dose proton therapy. Seventeen patients with nonmetastatic nonkeratinizing undifferentiated/poorly differentiated nasopharyngeal carcinoma underwent double-scattered proton therapy between 2011 and 2017. Median age was 15.3 years (range, 7-21). The American Joint Committee on Cancer T and N stage distribution included the following: T1, one patient; T2, five patients; T3, two patients; and T4, nine patients; and N1, six patients; N2, nine patients; and N3, two patients. Median radiation dose to the primary target volume and enlarged lymph nodes was 61.2Gy (range, 59.4-61.2). Uninvolved cervical nodes received 45Gy (range, 45-46.8). All radiation was delivered at 1.8Gy/fraction daily using sequential plans. In 11 patients, photon-based intensity-modulated radiotherapy was used for elective neck irradiation to optimize dose homogeneity and improve target conformity. All patients received induction chemotherapy; all but one received concurrent chemotherapy. Five received adjuvant beta-interferon therapy. Median follow-up was 3.0 years (range, 1.6-7.9). No patients were lost to follow-up. Overall survival, progression-free survival, and local control rates were 100%. Fifteen patients developed mucositis requiring enteral feeding (n=14) or total parenteral nutrition (n=1) during radiotherapy. Serious late side effects included cataract (n=1), esophageal stenosis requiring dilation (n=1), sensorineural hearing loss requiring aids (n=1), and hormone deficiency (n=5, including three with isolated hypothyroidism). Following induction chemotherapy, moderate-dose proton therapy can potentially reduce toxicity in the brain and skull base region without compromising disease control. However, further follow-up is needed to fully characterize and evaluate any reduction in long-term complications.

An Integrated Framework Based on Full Monte Carlo Simulations for Double-Scattering Proton Therapy.

We developed an integrated framework that employs a full Monte Carlo (MC) model for treatment-plan simulations of a passive double-scattering proton system. We have previously validated a virtual machine source model for full MC proton-dose calculations by comparing the percentage of depth-dose curves, spread-out Bragg peaks, and lateral profiles against measured commissioning data. This study further expanded our previous work by developing an integrate framework that facilitates its clinical use. Specifically, we have (1) constructed patient-specific applicator and compensator numerically from the plan data and incorporated them into the beamline, (2) created the patient anatomy from the computed tomography image and established the transformation between patient and machine coordinate systems, and (3) developed a graphical user interface to ease the whole process from importing the treatment plan in the Digital Imaging and Communications in Medicine format to parallelization of the MC calculations. End-to-end tests were performed to validate the functionality, and 3 clinical cases were used to demonstrate clinical utility of the framework. The end-to-end tests demonstrated that the framework functioned correctly for all tested functionality. Comparisons between the treatment planning system calculations and MC results in 3 clinical cases revealed large dose difference up to 17%, especially in the beam penumbra and near the end of beam range. The discrepancy likely originates from a variety of sources, such as the dose algorithms, modeling of the beamline, and the dose metric. The agreement for other regions was acceptable. An integrated framework was developed for full MC simulations of double-scattering proton therapy. It can be a valuable tool for dose verification and plan evaluation.

Temporal lobe sparing radiotherapy with photons or protons for cognitive function preservation in paediatric craniopharyngioma

Background and purposeReducing radiation exposure to the temporal lobes could be beneficial to preserve cognitive function in paediatric brain tumour patients. The distribution of doses to brain substructures associated with cognition (BSCs) both within and outside of the temporal lobe have not been reported. The aim of this study was therefore to investigate temporal lobe sparing photon vs. proton therapy for paediatric suprasellar tumours. Material and methodsData from ten anonymized craniopharyngioma patients were used in this study. Temporal lobe sparing volumetric modulated arc therapy (VMAT) and pencil beam scanning (PBS) proton therapy plans were optimized to maintain consistent target metrics as in the delivered double scattering proton therapy (DSPT) plans. Thirty BSCs were delineated, including temporal lobe substructures (i.e. amygdala, hippocampus, entorhinal cortex). The dose/volume fractions to each BSC were analysed, and intelligence quotient (IQ) as well as memory scores were estimated to compare the different modalities. ResultsThe exposed volumes of the temporal lobes and their substructures were consistently reduced with PBS compared to DSPT and VMAT, e.g. the left hippocampus V10Gy from 100% (VMAT) or 41% (DSPT) to 5% with PBS (p = 0.002). Some of the ventricular substructures were better spared with VMAT compared to both proton modalities. The reduced doses to the temporal lobes achieved with PBS translated into improved predicted memory outcomes, but not for the estimated IQ. ConclusionThe irradiated volumes of temporal lobe BSCs were consistently the lowest with PBS, whereas the model-based estimates of cognitive outcomes were less consistent.

Dosimetric comparisons of different hypofractionated stereotactic radiotherapy techniques in treating intracranial tumors > 3 cm in longest diameter.

The authors sought to compare the dosimetric quality of hypofractionated stereotactic radiosurgery in treating sizeable brain tumors across the following treatment platforms: GammaKnife (GK) Icon, CyberKnife (CK) G4, volumetric modulated arc therapy (VMAT) on the Varian TrueBeam STx, double scattering proton therapy (DSPT) on the Mevion S250, and intensity modulated proton therapy (IMPT) on the Varian ProBeam. In this retrospective study, stereotactic radiotherapy treatment plans were generated for 10 patients with sizeable brain tumors (> 3 cm in longest diameter) who had been treated with VMAT. Six treatment plans, 20-30 Gy in 5 fractions, were generated for each patient using the same constraints for each of the following radiosurgical methods: 1) GK, 2) CK, 3) coplanar arc VMAT (VMAT-C), 4) noncoplanar arc VMAT (VMAT-NC), 5) DSPT, and 6) IMPT. The coverage; conformity index; gradient index (GI); homogeneity index; mean and maximum point dose of organs at risk; total dose volume (V) in Gy to the normal brain for 2 Gy (V2), 5 Gy (V5), and 12 Gy (V12); and integral dose were compared across all platforms. Among the 6 techniques, GK consistently produced a sharper dose falloff despite a greater central target dose. GK gave the lowest GI, with a mean of 2.7 ± 0.1, followed by CK (2.9 ± 0.1), VMAT-NC (3.1 ± 0.3), and VMAT-C (3.5 ± 0.3). The highest mean GIs for the proton beam treatments were 3.8 ± 0.4 for DSPT and 3.9 ± 0.4 for IMPT. The GK consistently targeted the lowest normal brain volume, delivering 5 to 12 Gy when treating relatively smaller- to intermediate-sized lesions (less than 15-20 cm3). Yet, the differences across the 6 modalities relative to GK decreased with the increase of target volume. In particular, the proton treatments delivered the lowest V5 to the normal brain when the target size was over 15-20 cm3 and also produced the lowest integral dose to the normal brain regardless of the target size. This study provides an insightful understanding of dosimetric quality from both photon and proton treatment across the most advanced stereotactic radiotherapy platforms.

Abstract P3-12-16: Five year outcomes of a prospective study of proton radiotherapy for breast cancer regional nodal irradiation

Abstract Purpose: Through improved nodal coverage and decreased dose to the heart and lung, proton therapy (PT) may improve the therapeutic ratio for treatment of breast cancer requiring regional nodal irradiation (RNI). The purpose of this study is to report 5 year disease control and toxicity. Methods: From May 2012 to February 2014, 18 women (stage IIA-IIIB) prospectively enrolled on a pilot study. Median age was 52 years (range, 42-73), with equal division between breast-conserving therapy (BCT) and mastectomy and right and left-sided cancers. Median number of positive nodes among the 16 node-positive patients was 2 (range, 1-14). Five patients had ≥ 10 nodes positive on axillary dissection (N3a). Treatment targets (CTVs for breast/chest wall, supraclavicular, axillary, internal mammary nodes (IMNs)) and organs at risk were delineated on CT scans. Double scatter PT alone was used for 10 patients (9 post-mastectomy, 1 after BCT) and combined proton-photon in 8 (all BCT). Toxicity was prospectively recorded using CTCAE v4.0. Results: Median follow-up was 4 years (range, 0.3 – 6). 5 year overall survival was 82% and locoregional control was 100%. 5 year distant metastases-free survival was 82%. No grade 4+ toxicity developed. Four patients developed grade 3 cellulitis, which was the only grade 3 toxicity. One patient had a reconstructive failure associated with a post-surgical cellulitis. A right-sided patient was diagnosed with CHF within 2 months of completion of PT, following diagnosis of a pulmonary embolus 1 month prior. She had an elevated BNP (1101) prior to PT following adriamycin-based chemotherapy. Mean heart dose was 0 Gy and cardiac V5 0%. Atrial fibrillation developed in two patients. One patient developed grade 2 pneumonitis (she received concurrent chemotherapy). One patient, with a history of rib fractures prior to PT, developed an ipsilateral rib fracture 7 months after PT. Conclusion: In a population of women with locally advanced breast cancer, PT for RNI has proven feasible after either mastectomy (with or without reconstruction) or BCT with excellent locoregional control. PT allows for highly conformal radiation delivery without compromise of target coverage or excess exposure of normal tissue. Documentation of the ultimate benefits of PT in this population, freedom from radiation induced cardiac disease and breast cancer recurrence will require prospective study of a larger numbers of patients. Citation Format: Bradley JA, Dagan R, Liang X, Ho MW, Rutenberg M, Mailhot R, Morris C, Mendenhall NP. Five year outcomes of a prospective study of proton radiotherapy for breast cancer regional nodal irradiation [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-16.

Efficient double-scattering proton therapy with a patient-specific bolus

PurposePassive scattering proton radiotherapy utilizes beam-specific compensators to shape the dose to the distal end of the tumor target. These compensators typically require therapists to enter the treatment room to mount between beams. This study investigates a novel approach that utilizes a single patient-specific bolus to accomplish the role of multi-field compensators to improve the efficiency of the treatment delivery. MethodsRay-tracing from the proton virtual source was used to convert the beam-specific compensators (mounted on the gantry nozzle) into an equivalent bolus thickness on the patient surface. The field bolus contours were combined to create a single bolus. A 3D acrylic bolus was milled for a head phantom. The dose distribution of the compensator plan was compared to the bolus plan using 3D Gamma analysis and film measurements. Boluses for two clinical patients were also designed. ResultsThe calculated phantom dose distribution of the original proton compensator plan was shown to be equivalent to the plan with the surface bolus. Film irradiations with the proton bolus also confirmed the dosimetric equivalence of the two techniques. The dose distribution equivalency of the bolus plans for the clinical patients were demonstrated. ConclusionsWe presented a novel approach that uses a single patient-specific bolus to replace patient compensators during passive scattering proton delivery. This approach has the potential to reduce the treatment time, the compensator manufacturing costs, the risk of potential collision between the compensator and the patient/couch, and the waste of compensator material.

Dosimetric feasibility of 4DCT-ventilation imaging guided proton therapy for locally advanced non-small-cell lung cancer

BackgroundThe principle aim of this study is to incorporate 4DCT ventilation imaging into functional treatment planning that preserves high-functioning lung with both double scattering and scanning beam techniques in proton therapy.MethodsEight patients with locally advanced non-small-cell lung cancer were included in this study. Deformable image registration was performed for each patient on their planning 4DCTs and the resultant displacement vector field with Jacobian analysis was used to identify the high-, medium- and low-functional lung regions. Five plans were designed for each patient: a regular photon IMRT vs. anatomic proton plans without consideration of functional ventilation information using double scattering proton therapy (DSPT) and intensity modulated proton therapy (IMPT) vs. functional proton plans with avoidance of high-functional lung using both DSPT and IMPT. Dosimetric parameters were compared in terms of tumor coverage, plan heterogeneity, and avoidance of normal tissues.ResultsOur results showed that both DSPT and IMPT plans gave superior dose advantage to photon IMRTs in sparing low dose regions of the total lung in terms of V5 (volume receiving 5Gy). The functional DSPT only showed marginal benefit in sparing high-functioning lung in terms of V5 or V20 (volume receiving 20Gy) compared to anatomical plans. Yet, the functional planning in IMPT delivery, can further reduce the low dose in high-functioning lung without degrading the PTV dosimetric coverages, compared to anatomical proton planning. Although the doses to some critical organs might increase during functional planning, the necessary constraints were all met.ConclusionsIncorporating 4DCT ventilation imaging into functional proton therapy is feasible. The functional proton plans, in intensity modulated proton delivery, are effective to further preserve high-functioning lung regions without degrading the PTV coverage.

Commissioning an in-room mobile CT for adaptive proton therapy with a compact proton system.

PurposeTo describe the commissioning of AIRO mobile CT system (AIRO) for adaptive proton therapy on a compact double scattering proton therapy system.MethodsA Gammex phantom was scanned with varying plug patterns, table heights, and mAs on a CT simulator (CT Sim) and on the AIRO. AIRO‐specific CT‐stopping power ratio (SPR) curves were created with a commonly used stoichiometric method using the Gammex phantom. A RANDO anthropomorphic thorax, pelvis, and head phantom, and a CIRS thorax and head phantom were scanned on the CT Sim and AIRO. Clinically realistic treatment plans and nonclinical plans were generated on the CT Sim images and subsequently copied onto the AIRO CT scans for dose recalculation and comparison for various AIRO SPR curves. Gamma analysis was used to evaluate dosimetric deviation between both plans.Results AIRO CT values skewed toward solid water when plugs were scanned surrounded by other plugs in phantom. Low‐density materials demonstrated largest differences. Dose calculated on AIRO CT scans with stoichiometric‐based SPR curves produced over‐ranged proton beams when large volumes of low‐density material were in the path of the beam. To create equivalent dose distributions on both data sets, the AIRO SPR curve's low‐density data points were iteratively adjusted to yield better proton beam range agreement based on isodose lines. Comparison of the stoichiometric‐based AIRO SPR curve and the “dose‐adjusted” SPR curve showed slight improvement on gamma analysis between the treatment plan and the AIRO plan for single‐field plans at the 1%, 1 mm level, but did not affect clinical plans indicating that HU number differences between the CT Sim and AIRO did not affect dose calculations for robust clinical beam arrangements.ConclusionBased on this study, we believe the AIRO can be used offline for adaptive proton therapy on a compact double scattering proton therapy system.

Experimental Assessment of Proton Dose Calculation Accuracy in Small-Field Delivery Using a Mevion S250 Proton Therapy System.

Purpose:Dose calculation accuracy of the Varian Eclipse treatment planning system (TPS) is empirically assessed for small-aperture fields using a Mevion S250 double scattering proton therapy system.Materials and Methods:Five spherical pseudotumors were modeled in a RANDO head phantom. Plans were generated for the targets with apertures of 1, 2, 3, 4, or 5 cm diameter using one, two, and three beams. Depth-dose curves and lateral profiles of the beams were taken with the planned blocks and compared to Eclipse calculations. Dose distributions measured with EBT3 films in the phantom were also compared to Eclipse calculations. Film quenching effect was simulated and considered.Results:Depth-dose scans in water showed a range pullback (up to 2.0 mm), modulation widening (up to 9.5 mm), and dose escalation in proximal end and sub-peak region (up to 15.5%) when compared to the Eclipse calculations for small fields. Measured full width at half maximum and penumbrae for lateral profiles differed <1.0 mm from calculations for most comparisons. In the phantom study, Eclipse TPS underestimated sub-peak dose. Gamma passing rates improved with each beam added to the plans. Greater range pullback and modulation degradation versus water scans were observed due to film quenching, which became more noticeable as target size increased.Conclusions:Eclipse TPS generates acceptable target coverage for small targets with carefully arranged multiple beams despite relatively large dose discrepancy for each beam. Surface doses higher than Eclipse calculations can be mitigated with multiple beams. When using EBT3 film, the quenching effect should be considered.

A Prospective Outcomes Study of Proton Therapy for Skull-Base Chondrosarcomas

To evaluate the effectiveness of definitive or adjuvant external beam proton therapy on local control and survival in patients with base of skull chondrosarcoma. Between January 2007 and February 2016, 43 patients with a median age of 49 years (range, 23 - 80 years) with base of skull chondrosarcoma were treated with double-scattered proton therapy on an IRB-approved prospective outcomes protocol at our institution. The median total dose delivered was 73.8 Gy(RBE) [range, 64.5 - 74.4 Gy(RBE] with 33 patients treated with 1.8 Gy(RBE) daily fractionation and 10 patients treated with 1.2 Gy(RBE) twice daily fractionation. Primary site included skull base tumors involving the clivus, cavernous sinus, petrous bone, sella, and tumors involving the ethmoid or sphenoid sinuses. Surgical resection and biopsy alone were performed in 36 (83.7%) and 7 (16.3%) patients respectively. Tumor grade was as follows: 19 (44.2%) grade 1, 22 (51.1%) grade 2, and 2 (4.7%) grade 3. Forty patients had gross disease at the time of radiotherapy and 7 patients were treated for locally recurrent disease following initial surgery. Distant metastases, overall survival, cause-specific survival, local control, and disease-free survival were calculated. Proton therapy-related toxicities were scored using CTCAE v4.0. The median follow-up time was 3.7 years (range, 0.7 -10.1 years). The 3-year actuarial rate of overall survival was 95%; cause-specific survival was 100%, disease-free survival was 93%, local control was 93%, and freedom from distant metastases was 100%. Across all time points, 3 patients experienced local recurrence with no regional or distant recurrence observed. At the time of last follow-up, 38 patients were alive with no evidence of recurrent disease, 2 patients were alive with recurrent disease, 2 patients were dead from intercurrent disease, and 1 patient was dead of recurrent disease. The time to local progression was 2 years, 2.5 years, and 3 years (n = 3) following proton therapy. We did not observe any ≥ grade 3 acute toxicities. 9.3% (n=4) of patients experienced ≥ 3 grade late toxicity following proton therapy: grade 3 hearing loss (n = 3) and a grade 3 radiation-induced tumor consisting of a meningioma 9 years 9 months after treatment. We observed a grade 2 temporal lobe and brainstem radiation necrosis, both occurring in the same patient. High-dose, conformal proton therapy alone or following surgical resection for skull base chondrosarcoma is an effective treatment with a high rate of local control and with a relatively low toxicity profile. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.

Evaluation of Proton Arc Therapy Using a Double Scattering System with a Single, Pre-Cut Aperture with no Compensator

To simulate and quantitatively evaluate dose from proton arc therapy using a double scattering proton therapy system with a single aperture and no compensator. Proton arc therapy was simulated with 5, 10 and 15 fields using the Mevion S250 double scattering proton therapy system and the Eclipse treatment planning system (TPS). A single aperture that provided the best conformal circular or rectangular apertures covering the tumor from the different angular views was used. No compensator was used to modulate the intensity of the fields. TPS calculated for each field the most efficient range and modulation providing the most conformal dose coverage of the target. To account for dose delivery uncertainties without a compensator, a planning-target-volume (PTV) was defined as the target. The PTV dose coverage from the arc plans were compared with the conventional proton plans prepared with 2 fields using conformal aperture and compensator for each field. Several dosimetric parameters (Dmin, Dmax, Dmean, D95, D90, D50) were used to evaluate the dose coverage of the PTV and sparing of normal tissues. The proton arc plans for spherical or rectangular regular shape targets provided superior conformal plans with lower skin and critical structure doses compared to conventional proton plans. This was due to the use of multiple beams that delivered low doses at the entrance depths and paths through normal tissues. In contrast, conventional plans with only 2 beams had relatively larger entrance and path doses, while the PTV minimum, maximum and mean doses were nearly equal in both arc and conventional plans (Table 1). The patient setup and dose delivery times were comparable with both arc and conventional plans. This has been achievable by only having to position and image the patient once for setup. Furthermore, the use of no field-specific compensator and using of one aperture size eliminated the need to enter the room and replace these devices for each field. Although, this approach of using proton arc plans had several dosimetric and delivery advantages for regular-shaped targets, the advantages has been limited for PTV with complicated shapes. Simulation of proton arc therapy shows that regular shaped targets can be treated with superior dose coverage of the PTV and sparing of critical structures using a single aperture, no compensator proton arc plans compared to conventional 2 beam proton plans with patient specific apertures and compensators. This proton arc therapy approach is superior for regular spherical or rectangular shaped targets.Abstract 3511; Table 1Comparison of different dose parameters between 2 fields conventional beam plan and proton arc beam plans simulated with 5, 10 and 15 fields with a single circular aperture and no compensatorBeamsStructureMinMaxMeanD95D90D502PTV (%)92105103100101103591106104101104109310610310110415921061041011072Lt Femur (cGy)108131692977-29123026551264712171052121410532595128768912381549248713599671303 Open table in a new tab