Cobalt Gray Equivalent Research Articles

Impact of Dosimetric Compromises on Early Outcomes of Chordomas and Chondrosarcomas Treated With Image-guided Pencil Beam Scanning Proton Beam Therapy

PurposeTo critically review the clinical factors, dosimetry, and their correlation with early outcomes in patients with chordomas and chondrosarcomas treated with pencil beam scanning proton beam therapy (PBS-PBT). MethodsConsecutive 64 patients diagnosed with chordoma, or chondrosarcoma treated at our centre were studied. Patient, tumor and treatment-related factors including dosimetry were captured. Early and late toxicities and early outcomes were evaluated and correlated with clinical and dosimetric factors using standard statistical tools. ResultsThe median age of patients was 39(4-74 years) and most common site was skullbase (47%) followed by sacrum(31%) and mobile spine(22%). The median prescription dose to the high-risk CTV for chordoma and chondrosarcoma was 70.4CGE(Cobalt Gray equivalent) and 66CGE at 2.2CGE per fraction respectively. At presentation to our centre, 55% presented after a recurrence/progression of which 17% received prior radiation and 32% had a significant neural compression. At the time of PBT, 25% of patients had suboptimal neural separation. Three-fourths of patients had at least an acceptable target coverage. While 11% had a tier-1 compromise (GTVD98<90%), 14% had a tier-2 compromise (GTVD98<59CGE). With a median follow-up of 27.5 months, 2-year local control and PFS was 86.7% and 81.8% for chordomas and 87.5% and 77.1% for chondrosarcomas respectively. Residual GTV>25cc and a tier-2 compromise were associated with inferior local control (HR-0.19,p=0.019; HR-0.061,p=0.022 respectively) and progression-free survival (HR-0.128,p=0.014; HR-0.194,p=0.025 respectively) on multivariate analysis. Despite multiple surgeries, a majority with recurrent disease and prior radiations, grade-3 acute and late toxicities were limited and comparable to others in the literature. ConclusionDespite multiple surgeries, adequate neural separation was challenging to achieve. Severe dosimetric compromise(GTVD98<59CGE) led to inferior early outcomes. Adequate neural separation is key to avoiding dosimetric compromise and achieving optimal local control.

RADT-30. PROTON THERAPY FOR RE-IRRADIATION OF RECURRENT GLIOMA

Abstract BACKGROUND Proton therapy may improve the side effect profile of re-irradiation for recurrent glioma by limiting the overlap with previous radiation dose received by the brain. Limited data exist regarding the outcomes or side effects after proton re-irradiation. METHODS We retrospectively reviewed the charts of 43 consecutive adult patients with glioma treated with uniform scanning or pencil beam scanning proton re-irradiation from June 2014-June 2022. Outcomes were estimated utilizing Kaplan-Meier analysis. RESULTS Median age of the cohort was 45 years (range 19-74). Initial histologic diagnosis was glioblastoma for 18 (42%), astrocytoma for 16 (37%), oligodendroglioma for 8 (19%) and diffuse glioma NOS for 1 (2%) patient. The median initial prescription dose was 60 Gy (range 54-61.2 Gy) with 86% receiving concurrent temozolomide. The median interval between initial radiation therapy (RT) and re-irradiation was 51 months (range 6-185 months). The median re-irradiation dose delivered was 37.5 cobalt gray equivalent (CGE) in 15 fractions (range 6-50.4 CGE in 2-28 fractions) with 34 patients receiving this dose fractionation. Concurrent systemic therapy included bevacizumab (8), chemotherapy (5), immunotherapy (2) or none (28). Overall, 40 (93%) finished the planned course and three stopped early given progression. Median survival was 11.5 months for the full cohort (95% confidence interval: 6.8-13.6 months). For patients with glioblastoma, median survival was 6.4 months (95%CI 5.0-13.5 months). For patients without glioblastoma, median survival was 11.6 months (95%CI 9.2-34.3 months). Twelve patients (28%) developed symptomatic pseudoprogression/radiation necrosis, with ten requiring increased steroids and four requiring bevacizumab. CONCLUSIONS Proton re-irradiation was well tolerated in patients with recurrent glioma, with 6.4 and 11.6 month median survival estimates for glioblastoma and non-glioblastoma histologies, respectively. Symptomatic pseudoprogression/radiation necrosis was common. Further study is needed to determine whether proton re-irradiation has improved tolerability compared to photons.

Evaluation of Proton Therapy Reirradiation for Patients With Recurrent Head and Neck Squamous Cell Carcinoma

Use of proton therapy reirradiation (PT-ReRT) for head and neck cancer is increasing; however, reports are heterogenous and outcomes can be difficult to interpret. To evaluate outcomes and toxic effects following PT-ReRT in a uniform and consecutive cohort of patients with head and neck squamous cell carcinoma. This retrospective cohort study included patients with recurrent primary head and neck squamous cell carcinoma who were treated with PT-ReRT from January 1, 2013, to December 31, 2020, at a single institution. Patient, clinical, and treatment characteristics were obtained, and multidisciplinary review was performed to record and grade early and late toxic effects. Proton therapy reirradiation. Follow-up was defined from the start of PT-ReRT. The Kaplan-Meier method was used for outcomes of interest, including local control (LC), locoregional control, distant metastatic control, progression-free survival, and overall survival (OS). Cox proportional hazards regression modeling was used to assess associations of covariates with OS. A total of 242 patients (median [range] age, 63 [21-96] years; 183 [75.6%] male) were included. Of these patients, 231 (95.9%) had a Karnofsky performance status score of 70 or higher, and 145 (59.9%) had at least a 10-pack-year smoking history. Median (range) follow-up was 12.0 (5.8-26.0) months for all patients and 24.5 (13.8-37.8) months for living patients. A total of 206 patients (85.1%) had recurrent disease vs second primary or residual disease. The median (range) interval between radiation courses was 22 (1-669) months. Median PT-ReRT dose was 70 cobalt gray equivalents (CGE) for the fractionated cohort and 44.4 CGE for the quad shot cohort. For the fractionated cohort, the 1-year LC was 71.8% (95% CI, 62.8%-79.0%) and the 1-year OS was 66.6% (95% CI, 58.1%-73.8%). For the quad shot cohort, the 1-year LC was 61.6% (95% CI, 46.4%-73.6%) and the 1-year OS was 28.5% (95% CI, 19.4%-38.3%). Higher Karnofsky performance status scores (hazard ratio [HR], 0.50; 95% CI, 0.25-0.99; P = .046) and receipt of salvage surgery prior to PT-ReRT (HR, 0.57; 95% CI, 0.39-0.84; P = .005) were associated with improved OS, whereas receipt of quad shot (HR, 1.97; 95% CI, 1.36-2.86; P < .001) was associated with worse OS. There were a total of 73 grade 3 and 6 grade 4 early toxic effects. There were 79 potential grade 3, 4 grade 4, and 5 grade 5 late toxic effects. The findings of this cohort study suggest that, compared with previous reports with photon-based reirradiation, patients are living longer with aggressive PT-ReRT; however, surviving patients remain at risk of early and late complications.

Proton Beam Therapy versus Photon Radiotherapy for Stage I Non-Small Cell Lung Cancer

Simple SummaryStereotactic body radiotherapy (SABR) is accepted as a standard of care for patients who are not candidates for surgery in stage I non-small cell lung cancer (NSCLC). SABR has shown encouraging disease control and acceptable toxicity in peripherally located stage I NSCLC. However, for centrally located tumors around the proximal bronchial tree or for tumors located close to the chest wall, toxicities by SABR are not negligible. Therefore, proton beam therapy (PBT), which provides better organ at risk (OAR) sparing than photon radiotherapy by the Bragg peak, was tested and investigated to reduce radiation-induced toxicities in stage I NSCLC. Here, we compared 112 and 117 stage I NSCLC patients who underwent PBT and photon radiotherapy, respectively. PBT showed significantly lower lung and heart radiation exposure than photon radiotherapy without worsening disease control. PBT could be an effective treatment to reduce long-term toxicities of the lung and heart.Proton beam therapy (PBT) and photon radiotherapy for stage I non-small cell lung cancer (NSCLC) were compared in terms of clinical outcomes and dosimetry. Data were obtained from patients who underwent PBT or photon radiotherapy at two institutions—the only two facilities where PBT is available in the Republic of Korea. Multivariate Cox proportional hazards models and propensity score-matched analyses were used to compare local progression-free survival (PFS) and overall survival (OS). Survival and radiation exposure to the lungs were compared in the matched population. Of 289 patients included in the analyses, 112 and 177 underwent PBT and photon radiotherapy, respectively. With a median follow-up duration of 27 months, the 2-year local PFS and OS rates were 94.0% and 83.0%, respectively. In the multivariate analysis, a biologically effective dose (BED10, using α/β = 10 Gy) of ≥125 cobalt gray equivalents was significantly associated with improved local PFS and OS. In the matched analyses, the local PFS and OS did not differ between groups. However, PBT showed significantly lower lung and heart radiation exposure in the mean dose, V5, and V10 than photon radiotherapy. PBT significantly reduced radiation exposure to the heart and lungs without worsening disease control in stage I NSCLC patients.

Dosimetric Parameters Related to Acute Radiation Dermatitis of Patients with Nasopharyngeal Carcinoma Treated by Intensity-Modulated Proton Therapy.

Background: Growing patients with nasopharyngeal carcinoma (NPC) were treated with intensity-modulated proton therapy (IMPT). However, a high probability of severe acute radiation dermatitis (ARD) was observed. The objective of the study is to investigate the dosimetric parameters related to ARD for NPC patients treated with IMPT. Methods: Sixty-two patients with newly diagnosed NPC were analyzed. The ARD was recorded based on the criteria of Common Terminology Criteria for Adverse Events version 4.0. Logistic regression model was performed to identify the clinical and dosimetric parameters related to ARD. Receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) were used to evaluate the performance of the models. Results: The maximum ARD grade was 1, 2, and 3 in 27 (43.5%), 26 (42.0%), and 9 (14.5%) of the patients, respectively. Statistically significant differences (p < 0.01) in average volume to skin 5 mm with the respective doses were observed in the range 54–62 Cobalt Gray Equivalent (CGE) for grade 2 and 3 versus grade 1 ARD. Smoking habit and N2-N3 status were identified as significant predictors to develop grade 2 and 3 ARD in clinical model, and V58CGE to skin 5 mm as an independent predictor in dosimetric model. After adding the variable of V58CGE to the metric incorporating two parameters of smoking habit and N status, the AUC value of the metric increases from 0.78 (0.66–0.90) to 0.82 (0.72–0.93). The most appropriate cut-off value of V58CGE to skin 5 mm as determined by ROC curve was 5.0 cm3, with a predicted probability of 54% to develop grade 2 and 3 ARD. Conclusion: The dosimetric parameter of V58CGE to skin 5 mm < 5.0 cm3 could be used as a constraint in treatment planning for NPC patients treated by IMPT.

A Comparative Analysis of Photon versus Proton Beam Therapy in Neoadjuvant Concurrent Chemoradiotherapy for Intrathoracic Squamous Cell Carcinoma of the Esophagus at a Single Institute

Simple SummaryRadiotherapy for an esophageal malignancy results in undesired radiation exposure to nearby critical organs such as the heart, lungs, and spinal cord, leading to unfavorable clinical outcomes. Although only utilized at a few centers, proton beam radiotherapy spares adjacent organs from radiation exposure more effectively than conventional photon radiotherapy. We confirmed that, in terms of sparing adjacent organs from radiation, proton beam radiotherapy, as a modality of neoadjuvant chemoradiotherapy, was significantly superior to conventional photon radiotherapy for locally advanced esophageal squamous cell carcinoma with an even distribution of intrathoracic locations, and may lead to improved clinical outcomes.Background: Proton beam therapy (PBT), as a neoadjuvant chemoradiotherapy (nCRT) modality, is expected to result in better outcomes than photon-based radiotherapy (RT) for esophageal cancer, particularly adenocarcinoma. This study reports the results of nCRT for locally advanced esophageal squamous cell carcinoma (ESCC) using both modalities. Methods: We retrospectively reviewed the records of patients who underwent nCRT for ESCC between 2001 and 2020. A median of 41.4 Gy or cobalt gray equivalents of radiation was delivered using either photons or protons, with concurrent chemotherapy. Dosimetric and clinical parameters were compared between the two groups. Results: Of the 31 patients, the lungs and heart of the proton group (n = 15) were exposed to significantly less radiation compared to the photon group (n = 16). No significant differences in short-term postoperative outcomes or lymphocyte count were observed between the groups, and there were no significant differences between the photon and proton groups in 2-year overall survival (67.8% vs. 68.6%, p = 0.867) or 2-year disease-free survival (33.3% vs. 34.5%, p = 0.749), with a median follow-up of 17 months. Conclusions: PBT provided a significant dosimetric benefit over photon-based RT during nCRT for ESCC; however, it did not improve clinical outcomes.

Treatment outcomes of passive scattering proton beam therapy\xa0for stage I non-small cell lung cancer

IntroductionTo investigate the treatment outcomes of passive scattering proton beam therapy using stereotactic ablative radiotherapy (SABR) or hypofractionated radiation therapy (RT) for inoperable patients or those who refused surgery for stage I non-small cell lung cancer (NSCLC).MethodsFrom January 2016 to December 2019, we retrospectively analyzed 42 patients with stage I NSCLC treated with proton beam therapy. The initially intended dose regimen was 60 cobalt Gray equivalents (CGE) in 4 fractions; however, sequentially modified dose regimens were used when the dose-volume constraints could not be met. The median total dose was 50 CGE (range 50–70 CGE), while the corresponding median biologically effective dose using alpha{/}beta= 10 (BED10) was 112.5 CGE (range 96–150 CGE).ResultsThe median follow-up time was 40 months (interquartile range 32–48 months). Among the 42 treated patients, 33 had pathologically proven cancers of which most were adenocarcinoma (n = 21, 64%). The 3-year overall survival rate was 71.8%. The estimated rates of local control and progression free survival at 3 years were 91.5% and 66.9%, respectively. Thirteen patients experienced disease progression consisting of three local, six regional, and nine distant failures. No grade 4 or 5 toxicities were observed.ConclusionPassive scattering proton beam therapy for stage I NSCLC using SABR or hypofractionated RT was safe and showed high LC rates.

Photon Versus Proton Beam Therapy for T1-3 Squamous Cell Carcinoma of the Thoracic Esophagus Without Lymph Node Metastasis.

Background and PurposeWe compared treatment outcomes and toxicities of photon radiotherapy versus proton beam therapy (PBT) and evaluated radiation field effects for T1–3 squamous cell carcinoma of the thoracic esophagus (EC) without lymph node metastasis.MethodsMedical records of 77 patients with T1–3N0M0 thoracic EC treated with radiotherapy between 2011 and 2019 were retrospectively analyzed. Among these patients, 61 (79.2%) individuals had T1 EC. The initial clinical target volume encompassed the whole esophagus with or without supraclavicular and/or abdominal lymph nodes (extended-field radiotherapy; 67 patients, 87.0%) or the area 3–5 cm craniocaudally and 1–2 cm radially from the gross tumor volume (involved-field radiotherapy; 10 patients, 13.0%). The final clinical target volume included margins of at least 1 cm from the gross tumor volume, with total radiation doses of 50–66 (median, 66) cobalt gray equivalent. Three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and PBT were used in twenty-four, five, and forty-eight patients, respectively. Concurrent chemotherapy was administered to 17 (22.0%) patients overall and only five (8.0%) T1 patients.ResultsPBT showed significantly lower lung and heart radiation exposure in mean dose, V5, V10, V20, and V30 than photon radiotherapy. The median follow-up for all patients was 46 (interquartile range, 22–72) months. The 5-year progression-free survival and overall survival rates were 56.5 and 64.9%, respectively, with no significant survival difference between photon radiotherapy and PBT. In patients with T1 EC, 5-year progression-free survival and overall survival rates were 62.6 and 73.5%, respectively.ConclusionsExtended-field radiotherapy using modern radiotherapy techniques without chemotherapy showed satisfactory clinical outcomes for lymph node-negative T1 EC.

Proton Therapy for Skull-Base Chordomas and Chondrosarcomas: Initial Results From the Beaumont Proton Therapy Center.

Background:Skull-base chordomas and chondrosarcomas are rare tumors that arise directly adjacent to important critical structures. Appropriate management consists of maximal safe resection followed by postoperative dose-escalated radiation therapy. Proton beam therapy is often employed in this context to maximize the sparing of organs at risk, such as the brainstem and optic apparatus.Methods: This is a single-institutional experience treating skull-base chordomas and chondrosarcomas with postoperative pencil beam scanning proton therapy. We employed a simultaneous integrated boost to the gross tumor volume (GTV) for increased conformality. Demographic, clinicopathologic, toxicity, and dosimetry information were collected. Toxicity was assessed according to Common Terminology Criteria for Adverse Events (CTCAE), v. 4.0.Results: Between 2017 and 2020, 13 patients were treated with postoperative proton therapy. There were 10 patients with chordoma (77%) and three with chondrosarcoma (23%). A gross total resection was achieved in six (60%) patients with chordoma and one patient with chondrosarcoma (33%). Nine patients (69%) received postoperative therapy, whereas four (31%) received treatment at recurrence/progression following re-excision. The median dose to the GTV was 72.4 cobalt-Gray equivalents (range, 70.0 to 75.8). The mean GTV was 3.4 cc (range, 0.2-38.7). There were no grade 3 or greater toxicities. One patient developed grade 2 temporal lobe necrosis. At 10.7 months' median follow-up (range, 2.1-30.6), the rates of local control and overall survival were 100%.Conclusions: Proton beam therapy with pencil beam scanning and simultaneous integrated boost to the GTV affords excellent early local control with the suggestion of low morbidity. This method deserves consideration as an optimal method for limiting dose to adjacent organs at risk and delivering clinically effective doses to the treatment volume.

Salvage proton beam therapy for locoregional recurrence of non-small cell lung cancer.

PurposeThis study aimed to evaluate the clinical outcomes and toxicities of salvage proton beam therapy (PBT) in patients with locoregional recurrent non-small cell lung cancer (NSCLC).Materials and MethodsWe retrospectively reviewed 53 patients who received salvage PBT for locoregionally recurrent NSCLC between January 2016 and December 2019. The median clinical target volume (CTV) was 71.2 cm3 (range, 13.3 to 1,200.7 cm3). The median prescribed dose was 64.0 cobalt gray equivalent (CGE) (range, 45.0 to 70.0 CGE). One-third of the patients (32.1%) received concurrent chemoradiotherapy (CCRT).ResultsThe patients’ median age was 67 years (range, 44 to 86 years). The initial treatments were surgery in 31 (58.5%), definitive CCRT in 12 (22.6%), and definitive radiotherapy in 10 (18.9%) patients. The median disease-free interval (DFI) was 14 months (range, 3 to 112 months). Thirty-seven patients (69.8%) had a previous radiotherapy history. Among them, 18 patients (48.7%) had in-field recurrence. The median follow-up time after salvage PBT was 15.0 months (range, 3.5 to 49.3 months). During the follow-up period, 26 patients (49.1%) experienced disease progression: local in 13 (24.5%), regional in 14 (26.5%), and distant metastases in 15 (26.5%). The 2-year overall survival (OS) rate, local control rate, and progression-free survival rate were 79.2%, 68.2%, and 37.1%, respectively. Shorter DFI (≤12 months; p = 0.015) and larger CTV (>80 mL; p = 0.014) were associated with poor OS. Grade 3 toxicities occurred in 8 patients (15.1%): esophagitis in 2, dermatitis in 3, and pulmonary toxicities in 4.ConclusionSalvage PBT for locoregionally recurrent NSCLC was effective, and treatment-related toxicities were tolerable.

Using patient-specific bolus for pencil beam scanning proton treatment of periorbital disease.

PurposeA unique mantle cell lymphoma case with bilateral periorbital disease unresponsive to chemotherapy and with dosimetry not conducive to electron therapy was treated with pencil beam scanning (PBS) proton therapy. This patient presented treatment planning challenges due to the thin target, immediately adjacent organs at risk (OAR), and nonconformal orbital surface anatomy. Therefore, we developed a patient‐specific bolus and hypothesized that it would provide superior setup robustness, dose uniformity and dose conformity.Materials/MethodsA blue‐wax patient‐specific bolus was generated from the patient's face contour to conform to his face and eliminate air gaps. A relative stopping power ratio (RSP) of 0.972 was measured for the blue‐wax, and the HUs were overridden accordingly in the treatment planning system (TPS). Orthogonal kV images were used for bony alignment and then to ensure positioning of the bolus through fiducial markers attached to the bolus and their contours in TPS. Daily CBCT was used to confirm the position of the bolus in relation to the patient's surface. Dosimetric characteristics were compared between (a) nonbolus, (b) conventional gel bolus and (c) patient‐specific bolus plans. An in‐house developed workflow for assessment of daily treatment dose based on CBCT images was used to evaluate inter‐fraction dose accumulation.ResultsThe patient was treated to 24 cobalt gray equivalent (CGE) in 2 CGE daily fractions to the bilateral periorbital skin, constraining at least 50% of each lacrimal gland to under 20 Gy. The bolus increased proton beam range by adding 2–3 energy layers of different fields to help achieve better dose uniformity and adequate dose coverage. In contrast to the plan with conventional gel bolus, dose uniformity was significantly improved with patient‐specific bolus. The global maximum dose was reduced by 7% (from 116% to 109%). The max and mean doses were reduced by 6.0% and 7.7%, respectively, for bilateral retinas, and 3.0% and 13.9% for bilateral lacrimal glands. The max dose of the lens was reduced by 2.1%. The rigid shape, along with lightweight, and smooth fit to the patient face was well tolerated and reported as “very comfortable” by the patient. The daily position accuracy of the bolus was within 1 mm based on IGRT marker alignment. The daily dose accumulation indicates that the target coverage and OAR doses were highly consistent with the planning intention.ConclusionOur patient‐specific blue‐wax bolus significantly increased dose uniformity, reduced OAR doses, and maintained consistent setup accuracy compared to conventional bolus. Quality PBS proton treatment for periorbital tumors and similar challenging thin and shallow targets can be achieved using such patient‐specific bolus with robustness on both setup and dosimetry.

Visual outcomes of proton beam therapy for choroidal melanoma at a single institute in the Republic of Korea.

We evaluate the ocular effects of proton beam therapy (PBT) in a single institution, in Korea, and identify factors contributing to decreasing visual acuity (VA) after PBT. A total of 40 patients who received PBT for choroidal melanoma (2009‒2016) were reviewed. Dose fractionation was 60‒70 cobalt gray equivalents (CGEs) over five fractions. Complete ophthalmic examinations including funduscopy and ultrasonography were performed at baseline and at 3, 6, and 12 months after PBT, then annually thereafter. Only patients with at least 12 months follow-up were included. During the follow-up, consecutive best-corrected visual acuity (BCVA) changes were determined, and univariate and multivariate logistic regression analyses were performed to identify predictors for VA loss. The median follow-up duration was 32 months (range: 12‒82 months). The final BCVA of nine patients was > 20/40. The main cause of vision loss was intraocular bleeding, such as neovascular glaucoma or retinal hemorrhage. Vision loss was correlated with the tumor size, tumor distance to the optic disc or fovea, maculae receiving 30 CGEs, optic discs receiving 30 CGEs, and retinas receiving 30 CGEs. Approximately one-third of PBT-treated choroidal melanoma patients with good pretreatment BCVA maintained their VA. The patients who finally lost vision (VA < count fingers) usually experienced rapid declines in VA from 6‒12 months after PBT. Tumor size, tumor distance to the optic disc or fovea, volume of the macula, and optic discs or retinas receiving 30 CGEs affected the final VA.

Preliminary Experience of Treating Children and Young Adults With Image-Guided Proton Beam Therapy in India.

PURPOSEProton beam therapy (PBT) has been a preferred modality in pediatric malignancies requiring radiotherapy. We report our preliminary experience of treating consecutive patients younger than 25 years with image-guided pencil beam scanning PBT from the first and only center on the Indian subcontinent.METHODSPatients were selected for PBT on the basis of a multidisciplinary tumor board decision. Patient demographic data, as well as tumor and treatment-related characteristics of the cohort, were captured. Patient and treatment-related factors and their association with acute toxicities were analyzed using univariable and multivariable analyses.RESULTSForty-seven patients (27 with CNS and 20 with non-CNS tumors) with a median age of 9 years (range, 2-25 years) were evaluated. Most common diagnoses were ependymoma, rhabdomyosarcoma, and glioma. Seventy-seven percent of patients traveled more than 500 km, and 70% of them lived in metropolitan cities. Forty-nine percent of patients had recurrent disease at presentation, and 15% had received a previous course of radiation. The median dose delivered was 54.8 cobalt gray equivalents (range, 40.0-70.4 cobalt gray equivalents) to a median clinical target volume of 175 mL (range, 18.7-3,083.0 mL), with 34% of patients requiring concurrent chemotherapy (CCT). Acute grade 2 and grade 3 dermatitis, mucositis, and hematologic toxicity was noted in 45% and 2%, 34% and 0%, and 38% and 30% of patients, respectively. Grade 2 fatigue was noted in 26% of patients. On multivariable analysis, for CNS tumors, both CCT and craniospinal irradiation were independently associated with ≥ 2 grade hematologic toxicity, whereas among non-CNS tumors, a clinical target volume > 150 mL was associated with ≥ 2 grade fatigue, head and neck irradiation was associated with ≥ 2 grade mucositis, and CCT was associated with grade ≥ 2 hematologic toxicity.CONCLUSIONThis study demonstrates safe implementation of a PBT program for children and young adults on the Indian subcontinent. Image-guided pencil beam scanning PBT in judiciously selected patients is feasible and can be delivered with acceptable acute toxicities.

Brainstem Toxicity in Pediatric Patients Receiving Cranial Radiotherapy with Protons: A Single Institution Experience

Asymptomatic post-radiation brainstem imaging changes (CTCAE version 5 Grade I toxicity) following proton beam therapy (PBT) have been reported as high as 20-30% incidence in some series while symptomatic brainstem injury is rarer, with an incidence of 2-7% in the literature. These findings have led to consensus statements and recommendations for brainstem dosimetric goals for patients receiving PBT. We retrospectively reviewed the incidence of post-PBT brainstem imaging changes and injury following cranial PBT utilizing a gantry-mounted synchrocyclotron single vault system. Patients ≤ 21 years of age who received a minimum 0.1cc max brainstem dose of 50 cobalt-Gray equivalents (CGE) were eligible for analysis. Patients were assessed for “central nervous system necrosis” in the brainstem per CTCAE v5.0 criteria. All patients were followed clinically and radiographically for ≥ 1 year after completing PBT. Analysis included brainstem doses exceeding University of Florida brainstem goal and max constraints. Between 2013 and 2018, 58 patients with a median age of 10.3 years (range 1–21.9 years) were included for analysis. The median radiation dose was 54 CGE (50.4–60 CGE). 36.2% of patients were treated with craniospinal radiation, 71.4% received 23.4 CGE and 23.4% received 36 CGE. 22.4% received pre-radiation chemotherapy, 32.8% received concurrent chemotherapy, and 34% received adjuvant chemotherapy. 3.4% received myeloablative chemotherapy with stem cell rescue. The percentage of patients exceeding the University of Florida goal and max brainstem constraints are presented in Table I. Two patients (3.4%) demonstrated evidence of radiographic changes consistent with CTCAE Version 5.0 Grade 1 toxicity. Both of these patients received pre-PBT myeloablative chemotherapy with stem cell rescue. There were no patients with CTCAE Version 5.0 Grade ≥ 2 brainstem injury. No symptomatic brainstem injury observed in pediatric patients treated using a gantry-mounted synchrocyclotron proton system despite exceeding previously recommended dose constraints. The incidence of post-radiation asymptomatic radiographic changes in the brainstem was lower than previous publications of grade I toxicity. While goal and max D50% were commonly exceeded, no patients exceeded the 0.1cc max constraint suggesting this may be more predictive of brainstem toxicity.Abstract 2532; TableGOAL 0.1cc Max > 56.6MAX 0.1cc Max > 58GOAL D10% > 55.4MAX D10% > 56GOAL D50% > 52.4MAX D50% > 54% Exceeded8.6%013.8%1.7%39.7%15.5% Open table in a new tab

Side effects of proton beam therapy of choroidal melanoma in dependence of the dose to the optic disc and the irradiated length of the optic nerve.

To analyze the impact of the dose to the optic disc and the irradiated length of the optic nerve on radiation-induced optic neuropathy, radiation-induced retinopathy, iris neovascularization, secondary glaucoma, enucleation, and local tumor control after proton beam therapy (PBT) of choroidal melanoma. Retrospective analysis of 1129 patients, who received primary PBT for the treatment of choroidal melanoma with a dose of 60 cobalt gray equivalents (CGE) between 1998 and 2013 at the Helmholtz-Zentrum Berlin, Germany. Kaplan-Meier curves and logrank test have been used for time-to-event analyses. Adjustment for potential confounders was done using multiple Cox regression models with forward and backward selection. We found a significant correlation between the irradiated length of the optic nerve and the dose to the optic disc (correlation coefficient, 0.93). Multivariate Cox regression revealed the dose to the optic disc as an independent predictive risk factor for the development of radiation-induced optic neuropathy (p < 0.001, HR 1.023, 95 CI 1.016-1.029), iris neovascularization (p < 0.001, HR 1.013, 95% CI 1.008-1.019), secondary glaucoma (p < 0.001, HR 1.017, 95% CI: 1.011-1.023) and enucleation (p < 0.001, HR 1.037, 95% CI 1.020-1.053). The irradiated length of the optic nerve was not a statistically independent predictive risk factor in multivariate analysis. Our data implicate the predominance of the dose to the optic disc over the irradiated length of the optic nerve regarding radiation-induced optic neuropathy, iris neovascularization, secondary glaucoma, and enucleation.

Clinical Outcomes of Patients With Unresectable Cholangiocarcinoma Treated With Proton Beam Therapy.

To investigate the clinical outcomes and failure patterns of patients with unresectable cholangiocarcinoma (CC) who had been treated with proton beam therapy (PBT). The authors retrospectively examined 30 patients with unresectable CC who had undergone PBT between November 2015 and December 2017. Survival curves were plotted with the Kaplan-Meier method. Independent predictors of survival were identified by multivariate Cox proportional hazard regression analyses. Complications were assessed using the Common Terminology Criteria for Adverse Events v4.0. The median tumor size was 7 cm. Seventeen patients (56.7%) had regional lymph node metastases. The median radiation dose was 72.6 cobalt gray equivalents, and 23 patients (76.7%) received concurrent chemotherapy. The 1-year local control, regional control, and distant metastases-free rates were 88%, 86%, and 68%, respectively. The median overall survival and progression-free survival were 19.3 and 10.4 months, respectively. The median jaundice-free survival was 13 months, with a 1-year biliary tract infection (BTI)-free rate of 58%. Patients who received concurrent chemotherapy had a better median progression-free survival (12.1 vs. 4.7 mo). The most common form of acute toxicity from PBT was acute skin reactions which were rarely severe (grade III: 7% of patients). Three and 2 patients had grade III-IV toxicities and radiation-induced liver disease. There were no deaths caused by PBT or concurrent chemotherapy. PBT is clinically useful in patients with unresectable CC, even in the presence of large tumors or regional nodal metastases. Its use may induce durable symptom relief, without increasing acute or late toxicity.

Early clinical results of proton spatially fractionated GRID radiation therapy (SFGRT).

Approximately 70 patients with large and bulky tumors refractory to prior treatments were treated with photon spatially fractionated GRID radiation (SFGRT). We identified 10 additional patients who clinically needed GRID but could not be treated with photons due to adjacent critical organs. We developed a proton SFGRT technique, and we report treatment of these 10 patients. Subject data were reviewed for clinical results and dosimetric data. 50% of the patients were metastatic at the time of treatment and five had previous photon radiation to the local site but not via GRID. They were treated with 15-20 cobalt Gray equivalent using a single proton GRID field with an average beamlet count of 22.6 (range 7-51). 80% received an average adjuvant radiation dose to the GRID region of 40.8Gy (range 13.7-63.8Gy). Four received subsequent systemic therapy. The median follow-up time was 5.9 months (1.1-18.9). At last follow-up, seven patients were alive and three had died. Two patients who had died from metastatic disease had local shrinkage of tumor. Of those alive, four had complete or partial response, two had partial response but later progressed, and one had no response. For all patients, the tumor regression/local symptom improvement rate was 80%. 50% had acute side-effects of grade1/2 only and all were well-tolerated. In circumstances where patients cannot receive photon GRID, proton SFGRT is clinically feasible and effective, with a similar side-effect profile. Proton GRID should be considered as a treatment option earlier in the disease course for patients who cannot be treated by photon GRID.

Clinical outcomes and toxicity of proton beam radiation therapy for re-irradiation of locally recurrent breast cancer

PurposeRepeat radiation therapy (RT) using photons/X-rays for locally recurrent breast cancer results in increased short and long-term toxicity. Proton beam RT (PBRT) can minimize dose to surrounding organs, thereby potentially reducing toxicity. Here, we report the toxicity and clinical outcomes for women who underwent re-irradiation to the chest wall for locally recurrent breast cancer using PBRT. Materials and methodsThis was a retrospective study analyzing 16 consecutive patients between 2013 and 2018 with locally recurrent breast cancer who underwent re-irradiation to the chest wall with PBRT. For the recurrent disease, patients underwent maximal safe resection, including salvage mastectomy, wide local excision, or biopsy only per surgeons recommendations. Systemic therapy was used per the recommendation of the medical oncologist. Patients were treated with median dose of 50.4 Cobalt Gray Equivalent (CGyE) in 28 fractions at the time of re-irradiation. Follow-up was calculated from the start of second RT course. Acute toxicities were defined as those occurring during treatment or up to 8 weeks after treatment. Late toxicities were defined as those occurring more than 8 weeks after the completion of therapy. Toxicities were based on CTCAE 4.0. ResultsThe median age at original diagnosis and at recurrence was 49.8 years and 60.2 years, respectively. The median time between the two RT courses was 10.2 (0.7–20.2) years. The median follow-up time was 18.7 (2.5–35.2) months. No local failures were observed after re-irradiation. One patient developed distant metastasis and ultimately died. Grade 3–4 acute skin toxicity was observed in 5 (31.2%) patients. Four (25%) patients developed chest wall infections during or shortly (2 weeks) after re-irradiation. Late grade 3–4 fibrosis was observed in only 3 (18.8%) patients. Grade 5 toxicities were not observed. Hyperpigmentation was seen in 12 (75%) patients. Pneumonitis, telangiectasia, rib fracture, and lymphedema occurred in 2 (12.5%), 4 (25%), 1 (6.3%), and 1 (6.3%) patients, respectively. ConclusionsRe-irradiation with PBRT for recurrent breast cancer has acceptable toxicities. There was a high incidence of acute grade 3–4 skin toxicity and infections, which resolved, however, with skin care and antibiotics. Longer follow-up is needed to determine long-term clinical outcomes.

Head and Neck Adenoid Cystic Carcinoma: Focus on Outcomes of Intensity Modulated Proton Therapy

In this study, we report cancer control outcomes and toxicity from intensity modulated proton therapy (IMPT) in patients treated for adenoid cystic carcinoma (ACC) of the head and neck. This study combines 2 prospective protocols evaluating IMPT in head and neck cancer. This analysis included patients with ACC, treated with IMPT in the adjuvant or definitive setting between December 2010 and June 2018. Patients with recurrent or metastatic disease were excluded. Locoregional control (LRC), disease free survival (DFS) and overall survival (OS) were estimated using the Kaplan Meier Method. Patterns of failure as well as toxicities were prospectively collected. Cox regression analysis was performed to determine prognostic factors. Toxicities were graded as per Common Terminology Criteria for Adverse Events version 4.01. 60 patients met the inclusion criteria for this analysis. Median follow-up was 2.9 years. Median age was 50 years (range 18-82) and 58% of patients were female. Primary treatment sites included: Peri-orbital (30%), oral cavity (17%), paranasal sinuses (17%), parotid gland (15%), nasopharynx (12%), oropharynx (7%), larynx (1 patient), and trachea (1 patient). As per AJCC 8th Ed, 22%, 18%, 17%, 44% of patients had T1, T2, T3 and T4 stage; only 1 patient had nodal involvement. Treatments involved surgery followed by chemo-IMPT, surgery followed by IMPT and definitive chemo-IMPT in 47%, 30%, and 23% of patients. Most frequent chemotherapy regimen included Cisplatin (63%) and Carboplatin (17%). Median dose was 64 Cobalt Gray Equivalent (range: 60-70 CGE). In patients treated with definitive chemo-IMPT, adjuvant chemo-IMPT and adjuvant RT alone, 3-year LRC was 83%, 92% and 90%, respectively (p=0.5); 3-year DFS was 44%, 87% and 90%, respectively (p=0.09); and 3-year OS was 80%, 85% and 100%, respectively (p=0.5). Acute toxicities included grade 3 dermatitis, mucositis, and dysphagia in 7%, 7%, and 1 patient; there was no grade 4 toxicity. There was a 7% rate of temporary feeding tubes and no permanent feeding tube. Chronic toxicities included 1 patient who developed optic neuropathy after treatment for a peri-orbital tumor. This is the largest cohort of head and neck ACC treated with IMPT. We report excellent cancer outcomes in patients treated with adjuvant IMPT +/- chemotherapy. In addition, Outcomes of patients treated with upfront chemo-IMPT were acceptable, despite typically high risk, more advanced disease. The acute and late toxicity profiles were highly favorable.

Long-term results of a phase II study of hypofractionated proton therapy for prostate cancer: moderate versus extreme hypofractionation

BackgroundWe performed a prospective phase II study to compare acute toxicity among five different hypofractionated schedules using proton therapy. This study was an exploratory analysis to investigate the secondary end-point of biochemical failure-free survival (BCFFS) of patients with long-term follow-up.MethodsEighty-two patients with T1-3bN0M0 prostate cancer who had not received androgen-deprivation therapy were randomized to one of five arms: Arm 1, 60 cobalt gray equivalent (CGE)/20 fractions/5 weeks; Arm 2, 54 CGE/15 fractions/5 weeks; Arm 3, 47 CGE/10 fractions/5 weeks; Arm 4, 35 CGE/5 fractions/2.5 weeks; and Arm 5, 35 CGE/5 fractions/4 weeks. In the current exploratory analysis, these ardms were categorized into the moderate hypofractionated (MHF) group (52 patients in Arms 1–3) and the extreme hypofractionated (EHF) group (30 patients in Arms 4–5).ResultsAt a median follow-up of 7.5 years (range, 1.3–9.6 years), 7-year BCFFS was 76.2% for the MHF group and 46.2% for the EHF group (p = 0.005). The 7-year BCFFS of the MHF and EHF groups were 90.5 and 57.1% in the low-risk group (p = 0.154); 83.5 and 42.9% in the intermediate risk group (p = 0.018); and 41.7 and 40.0% in the high risk group (p = 0.786), respectively. Biochemical failure tended to be a late event with a median time to occurrence of 5 years. Acute GU toxicities were more common in the MHF than the EHF group (85 vs. 57%, p = 0.009), but late GI and GU toxicities did not differ between groups.ConclusionsOur results suggest that the efficacy of EHF is potentially inferior to that of MHF and that further studies are warranted, therefore, to confirm these findings.Trial registrationThis study is registered at ClinicalTrials.gov, no. NCT01709253; registered October 18, 2012; retrospectively registered).