Proton therapy and oral mucositis in oral & oropharyngeal cancers: outcomes, dosimetric and NTCP benefit.

INTRODUCTION: Radiation-induced oral mucositis (RIOM), is a common, debilitating, acute side effect of radiotherapy for oral cavity (OC) and oropharyngeal (OPx) cancers; technical innovations for reducing it are seldom discussed. Intensity-modulated-proton-therapy (IMPT) has been reported extensively for treating OPx cancers, and less frequently for OC cancers. We aim to quantify the reduction in the likelihood of RIOM in treating these 2 subsites with IMPT compared to Helical Tomotherapy. MATERIAL AND METHODS: We report acute toxicities and early outcomes of 22 consecutive patients with OC and OPx cancers treated with IMPT, and compare the dosimetry and normal tissue complication probability (NTCP) of ≥ grade 3 mucositis for IMPT and HT. RESULTS: Twenty two patients, 77% males, 41% elderly and 73% OC subsite, were reviewed. With comparable target coverage, IMPT significantly reduced the mean dose and D32, D39, D45, and D50, for both the oral mucosa (OM) and spared oral mucosa (sOM). With IMPT, there was a 7% absolute and 16.5% relative reduction in NTCP for grade 3 mucositis for OM, compared to HT. IMPT further reduced NTCP for sOM, and the benefit was maintained in OC, OPx subsites and elderly subgroup. Acute toxicities, grade III dermatitis and mucositis, were noted in 50% and 45.5% patients, respectively, while 22.7% patients had grade 3 dysphagia. Compared with published data, the hospital admission rate, median weight loss, feeding tube insertion, unplanned treatment gaps were lower with IMPT. At a median follow-up of 15 months, 81.8% were alive; 72.7%, alive without disease and 9%, alive with disease. CONCLUSION: The dosimetric benefit of IMPT translates into NTCP reduction for grade 3 mucositis compared to Helical Tomotherapy for OPx and OC cancers and encourages the use of IMPT in their management.

Proton therapy for reducing heart and cardiac substructure doses in Indian breast cancer patients.

PURPOSE: Indians have a higher incidence of cardiovascular diseases, often at a younger age, than other ethnic groups. This higher baseline risk requires consideration when assessing additional cardiac morbidity of breast cancer treatment. Superior cardiac sparing is a critical dosimetric advantage of proton therapy in breast cancer radiotherapy. We report here the heart and cardiac-substructure doses and early toxicities in breast cancer patients treated post-operatively with proton therapy in India's first proton therapy center. MATERIALS AND METHODS: We treated twenty breast cancer patients with intensity-modulated proton therapy (IMPT) from October 2019 to September 2022, eleven after breast conservation, nine following mastectomy, and appropriate systemic therapy, when indicated. The most prescribed dose was 40 GyE to the whole breast/chest wall and 48 GyE by simultaneous integrated boost to the tumor bed and 37.5 GyE to appropriate nodal volumes, delivered in 15 fractions. RESULTS: Adequate coverage was achieved for clinical target volume (breast/chest wall), i.e., CTV40, and regional nodes, with 99% of the targets receiving 95% of the prescribed dose (V95% > 99%). The mean heart dose was 0.78 GyE and 0.87 GyE for all and left breast cancer patients, respectively. The mean left anterior descending artery (LAD) dose, LAD D0.02cc, and left ventricle dose were 2.76, 6.46, and 0.2 GyE, respectively. Mean ipsilateral lung dose, V20Gy, V5Gy, and contralateral breast dose (Dmean) were 6.87 GyE, 14.6%, 36.4%, and 0.38 GyE, respectively. CONCLUSION: The dose to heart and cardiac substructures is lower with IMPT than published photon therapy data. Despite the limited access to proton therapy at present, given the higher cardiovascular risk and coronary artery disease prevalence in India, the cardiac sparing achieved using this technique merits consideration for wider adoption in breast cancer treatment.

Standard Operating Procedure (SOP) for mould room practices and simulation of head neck cancer patients undergoing proton therapy.

Head Neck cancer patients treated with modern proton therapy need special attention during mould room procedures. In addition to usual mould room practices, patients undergoing Intensity Modulated Proton Therapy (IMPT) require attention to the special characteristics of protons viz., sensitivity to beam path and its alteration, sharp dose fall off and end of range. In this article, we discuss the Standard Operating Procedure (SOP) for HNC immobilization and simulation for IMPT, developed and practiced at our centre. The SOP details each step during the immobilization and simulation process, with nuances specific to IMPT.

Proton therapy for skull-base adenoid cystic carcinomas: A case series and review of literature.

Purpose: An indolent nature, with a high risk of local recurrence along with the potential for distant metastases, makes the relatively rare adenoid cystic carcinomas (ACCs) of the head-and-neck region, a unique entity. In the base of skull (BOS) region, these cancers require radiation doses as high as 70-72 GyE in proximity to critical structures. Proton therapy (PT) confers physical and radiobiological advantages and local control at 2-5 years exceeding 80% in most series, compared with below 60% with photon-based techniques. We report a case series of ACCs of the BOS, treated with image-guided, intensity-modulated PT (IMPT). Materials and Methods: During 2019-2020, we treated six patients with skull-base ACC IMPT with on-board, cross-sectional image guidance. Dosimetric data, toxicity, and early outcomes were studied, and a comparative review of literature was done. Results: Three patients underwent PT/proton-photon treatment for residual/inoperable lesions and three patients underwent reirradiation for recurrent lesions. The prescription was 70 GyE in 31-35 fractions, and 95% of the clinical target volume (CTV) received 98% of the prescribed dose in five of the six patients. Grade 3 mucositis and skin reactions were noted in two patients and one patient, respectively. Five of the six patients were controlled locally at a median follow-up of 15 months. Conclusion: The radiobiological and physical characteristics of PT help to deliver high doses with excellent CTV coverage in skull-base ACCs, adjacent to critical neurological structures.

Encouraging early outcomes with image guided pencil beam proton therapy for cranio-spinal irradiation: first report from India.

BACKGROUND: To report our experience with image guided pencil beam proton beam therapy (PBT) for craniospinal irradiation (CSI). MATERIALS AND METHODS: Between January 2019 and December 2021, we carried out a detailed audit of the first forty patients treated with PBT. We had recorded acute toxicities, reporting early outcomes and discuss limitations of current contouring guidelines during CSI PBT planning. RESULTS: Median age of the patient cohort was 8 years, and histologies include 20 medulloblastoma, 7 recurrent ependymoma, 3 pineoblastoma, 3 were germ cell tumors and remaining 7 constituted other diagnoses. Forty percent patients received concurrent chemotherapy. Median CSI dose was 23.4 Gy (Gray; range 21.6-35 Gy). Thirty-five patients (87.5%) completed their CSI without interruption, 5 required hospital admission. No patient had grade 2/ > weight loss during the treatment. Forty-five percent (18) developed grade 1 haematological toxicities and 20% (8) developed grade 2 or 3 toxicities; none had grade 4 toxicities. At median follow up of 12 months, 90% patients are alive of whom 88.9% are having local control. Special consideration with modification in standard contouring used at our institute helped in limiting acute toxicities in paediatric CSI patients. CONCLUSION: Our preliminary experience with modern contemporary PBT using pencil beam technology and daily image guidance in a range of tumours suitable for CSI is encouraging. Patients tolerated the treatment well with acceptable acute toxicity and expected short-term survival outcome. In paediatric CSI patients, modification in standard contouring guidelines required to achieve better results with PBT.

Leaf open time sinogram (LOTS): a novel approach for patient specific quality assurance of total marrow irradiation.

There is no ideal detector-phantom combination to perform patient specific quality assurance (PSQA) for Total Marrow (TMI) and Lymphoid (TMLI) Irradiation plan. In this study, 3D dose reconstruction using mega voltage computed tomography detectors measured Leaf Open Time Sinogram (LOTS) was investigated for PSQA of TMI/TMLI patients in helical tomotherapy. The feasibility of this method was first validated for ten non-TMI/TMLI patients, by comparing reconstructed dose with (a) ion-chamber (IC) and helical detector array (ArcCheck) measurement and (b) planned dose distribution using 3Dγ analysis for 3%@3mm and dose to 98% (D98%) and 2% (D2%) of PTVs. Same comparison was extended for ten treatment plans from five TMI/TMLI patients. In all non-TMI/TMLI patients, reconstructed absolute dose was within ± 1.80% of planned and IC measurement. The planned dose distribution agreed with reconstructed and ArcCheck measured dose with mean (SD) 3Dγ of 98.70% (1.57%) and 2Dγ of 99.48% (0.81%). The deviation in D98% and D2% were within 1.71% and 4.10% respectively. In all 25 measurement locations from TMI/TMLI patients, planned and IC measured absolute dose agreed within ± 1.20%. Although sectorial fluence verification using ArcCHECK measurement for PTVs chest from the five upper body TMI/TMLI plans showed mean ± SD 2Dγ of 97.82% ± 1.27%, the reconstruction method resulted poor mean (SD) 3Dγ of 92.00% (± 5.83%), 64.80% (± 28.28%), 69.20% (± 30.46%), 60.80% (± 19.37%) and 73.2% (± 20.36%) for PTVs brain, chest, torso, limb and upper body respectively. The corresponding deviation in median D98% and D2% of all PTVs were < 3.80% and 9.50%. Re-optimization of all upper body TMI/TMLI plans with new pitch and modulation factor of 0.3 and 3 leads significant improvement with 3Dγ of 100% for all PTVs and median D98% and D2% < 1.6%. LOTS based PSQA for TMI/TMLI is accurate, robust and efficient. A field width, pitch and modulation factor of 5 cm, 0.3 and 3 for upper body TMI/TMLI plan is suggested for better dosimetric outcome and PSQA results.

Characterization and Performance Evaluation of the First-Proton Therapy Facility in India.

PURPOSE: The purpose of this study is to evaluate the performance characteristic of volumetric image-guided dedicated-nozzle pencil beam-scanning proton therapy (PT) system. MATERIALS AND METHODS: PT system was characterized for electromechanical, image quality, and registration accuracy. Proton beam of 70.2-226.2 MeV was characterized for short- and long-term reproducibility in integrated depth dose; spot profile characteristics at different air gap and gantry angle; positioning accuracy of single and pattern of spot; dose linearity, reproducibility and consistency. All measurements were carried out using various X-ray and proton-beam specific detectors following standard protocols. RESULTS: All electro-mechanical, imaging, and safety parameters performed well within the specified tolerance limit. The image registration errors along three translation and three rotational axes were ≤0.5 mm and ≤0.2° for both point-based and intensity-based auto-registration. Distal range (R90) and distal dose fall-off (DDF) of 70.2-226.2 MeV proton beams were within 1 mm of calculated values based on the international commission on radiation units and measurements 49 and 0.0156× R90, respectively. The R90 and DDF were reproducible within a standard deviation of 0.05 g/cm2 during the first 8 months. Dose were linear from 18.5 (0.011 MU/spot) to 8405 (5 MU/spot) MU, reproducible within 0.5% in 5 consecutive days and consistent within 0.8% for full rotation. The cGy/MU for 70.2-226.2MeV was consistent within 0.5%. In-air X(Y) spot-sigma at isocenter varies from 2.96 (3.00) mm to 6.68 (6.52) mm for 70.2-226.2 MeV. Maximum variation of spot-sigma with air-gap of ±20 cm was ±0.36 mm (5.28%) and ±0.82 mm (±12.5%) along X- and Y-direction and 3.56% for full rotation. Relative spot positions were accurate within ±0.6 mm. The planned and delivered spot pattern of known complex geometry agreed with (γ%≤1) for 1% @ 1 mm >98% for representative five-proton energies at four gantry angle. CONCLUSION: The PT-system performed well within the expected accuracy level and consistent over a period of 8 months. The methodology and data presented here may help upcoming modern PT center during their crucial phase of commissioning.

India's First Proton Beam Therapy Pediatric Patient.

We recently started India's first proton beam therapy facility. Proton beam therapy because of its unique physical characteristics of minimal exit dose has an unequivocal dosimetric superiority over high-end photon/standard X-ray beam therapy and is particularly advantageous in growing children with curable cancers in view of their very high probability of long-term cures. We hereby report a case of a 7-year-old boy with a craniopharyngioma which had been subtotally resected and was subsequently treated with modern pencil beam proton therapy under high-precision image guidance. This is the first ever child ever to be treated with proton therapy in India.