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.

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.

Comparison of Estimated Late Toxicities between IMPT and IMRT Based on Multivariable NTCP Models for High-Risk Prostate Cancers Treated with Pelvic Nodal Radiation.

Purpose: To compare the late gastrointestinal (GI) and genitourinary toxicities (GU) estimated using multivariable normal tissue complication probability (NTCP) models, between pencil-beam scanning proton beam therapy (PBT) and helical tomotherapy (HT) in patients of high-risk prostate cancers requiring pelvic nodal irradiation (PNI) using moderately hypofractionated regimen. Materials and Methods: Twelve consecutive patients treated with PBT at our center were replanned with HT using the same planning goals. Six late GI and GU toxicity domains (stool frequency, rectal bleeding, fecal incontinence, dysuria, urinary incontinence, and hematuria) were estimated based on the published multivariable NTCP models. The ΔNTCP (difference in absolute NTCP between HT and PBT plans) for each of the toxicity domains was calculated. A one-sample Kolmogorov-Smirnov test was used to analyze distribution of data, and either a paired t test or a Wilcoxon matched-pair signed rank test was used to test statistical significance. Results: Proton beam therapy and HT plans achieved adequate target coverage. Proton beam therapy plans led to significantly better sparing of bladder, rectum, and bowel bag especially in the intermediate range of 15 to 40 Gy, whereas doses to penile bulb and femoral heads were higher with PBT plans. The average ΔNTCP for grade (G)2 rectal bleeding, fecal incontinence, stool frequency, dysuria, urinary incontinence, and G1 hematuria was 12.17%, 1.67%, 2%, 5.83%, 2.42%, and 3.91%, respectively, favoring PBT plans. The average cumulative ΔNTCP for GI and GU toxicities (ΣΔNTCP) was 16.58% and 11.41%, respectively, favoring PBT. Using a model-based selection threshold of any G2 ΔNTCP >10%, 67% (8 patients) would be eligible for PBT. Conclusion: Proton beam therapy plans led to superior sparing of organs at risk compared with HT, which translated to lower NTCP for late moderate GI and GU toxicities in patients of prostate cancer treated with PNI. For two-thirds of our patients, the difference in estimated absolute NTCP values between PBT and HT crossed the accepted threshold for minimal clinically important difference.

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.

Development and Validation of a MATLAB Software Program for Decoding the Treatment Errors in Real-time Position Management™ Gating-generated Breathing Trace.

INTRODUCTION: The Real-time Position Management™ (RPM) is used as a motion management tool to reduce normal tissue complication. However, no commercial software is available to quantify the "beam-on" errors in RPM-generated breathing traces. This study aimed to develop and validate an in-house-coded MATLAB program to quantify the "beam-on" errors in the breathing trace. MATERIALS AND METHODS: A graphical user interface (GUI) was developed using MATLAB (Matrix Laboratory Ra2016) software. The GUI was validated using two phantoms (Varian-gated phantom and Brainlab ET gating phantom) with three regular motion profiles. Treatment time delay was calculated using regular sinusoidal motion profile. Ten patient's irregular breathing profiles were also analyzed using this GUI. RESULTS: The beam-on comparison between the recorded reference trace and irradiated trace profile was done in two ways: (1) beam-on time error and (2) beam-on displacement error. These errors were ≤1.5% with no statistical difference for phase- and amplitude-based treatments. The predicated amplitude levels of reference phase-based profiles, and the actual amplitude levels of amplitude-based irradiated profiles were almost equal. The average treatment time delay was 47 ± 0.003 ms. The irregular breathing profile analysis showed that the amplitude-based gating treatment was more accurate than phase based. CONCLUSION: The developed GUI gave the same and acceptable results for all regular profiles. These errors were due to the lag time of the linear accelerator with gating treatment. This program can be used as to quantifying the intrafraction "beam-on" errors in breathing trace with both mode of gating techniques for irregular breathing trace, and in addition, it is capable to convert phase-based gating parameters to amplitude-based gating parameters for treatment.

Ambient neutron and photon dose equivalent H*(10) around a pencil beam scanning proton therapy facility.

OBJECTIVES: To measure leakage ambient dose equivalent H*(10) from stray secondary neutron and photon radiation around proton therapy (PT) facility and evaluate adequacy of shielding design. METHODS AND MATERIALS: H*(10) measurement were carried out at 149 locations around cyclotron vault (CV), beam transport system (BTS) and first treatment room (GTR3) of a multiroom PT facility using WENDI-II and SmartIon survey meter. Measurement were performed under extreme case scenarios wherein maximum secondary neutrons and photons were produced around CV, BTS and GTR3 by stopping 230MeV proton of 300nA on beam degrader, end of BTS and isocenter of GTR3. Weekly time average dose rate (TADR) were calculated from H*(10) value measured at selective hot spots by irradiating actual treatment plans of mix clinical sites. RESULTS: The maximum total H*(10) were within 2 µSv/hr around CV, 5 µSv/hr around outer wall of BTS which increases up to 62 µSv/hr at the end of inside BTS corridor. Maximum H*(10) of 20.8 µSv/hr in treatment control console (P125), 23.4 µSv/hr behind the common wall between GTR3 and GTR2 (P132) and 25.7 µSv/hr above isocenter (P99) were observed around GTR3. Reduction of beam current from 6 to 3 nA and 1 nA at nozzle exit lead to decrease in total H*(10) at P125 from 20.8 to 11.35 and 4.62 µSv/hr. In comparison to extreme case scenario, H*(10) value at P125, P132 and P99 from clinically relevant irradiation parameters were reduce by a factor ranging from 8.6 for high range cube to 46.4 for brain clinical plan. The maximum weekly TADR per fraction was highest for large volume, sacral chordoma patient at 8.5 µSv/hr compare to 0.3 µSv/hr for brain patient. The calculated weekly TADR for 30 mix clinical cases and 15 fractions of 1 L cube resulted total weekly TADR of 83-84 µSv/hr at P125, P132 and P99. The maximum annual dose level at these hot spots were estimated at 4.37 mSv/Yr. CONCLUSION: We have carried out an extensive measurement of H*(10) under different conditions. The shielding thickness of our PT facility is adequate to limit the dose to occupational worker and general public within the permissible stipulated limit. The data reported here can bridge the knowledge gap in ambient dose around PT facility and can also be used as a reference for any new and existing proton facility for intercomparison and validation. ADVANCES IN KNOWLEDGE: First extensive investigation of neutron and photon H*(10) around PT facility and can bridge the knowledge gap on ambient dose.