Fetal dose from proton pencil beam scanning craniospinal irradiation during pregnancy: a Monte Carlo study

Objective: We conducted a Monte Carlo study to comprehensively investigate the fetal dose resulting from proton pencil beam scanning (PBS) craniospinal irradiation (CSI) during pregnancy. Approach: The gestational-age dependent pregnant phantom series developed at the University of Florida (UF) were converted into DICOM-RT format (CT images and structures) and imported into a treatment planning system (TPS) (Eclipse v15.6) commissioned to a IBA PBS nozzle. A proton PBS CSI plan (prescribed dose: 36 Gy) was created on the phantoms. The TOPAS MC code was used to simulate the proton PBS CSI on the phantoms, for which MC beam properties at the nozzle exit (spot size, spot divergence, mean energy, and energy spread) were matched to IBA PBS nozzle beam measurement data. We calculated mean absorbed doses for 28 organs and tissues and whole body of the fetus at eight gestational ages (8, 10, 15, 20, 25, 30, 35, and 38 weeks). For contextual purposes, the fetal organ/tissue doses from the treatment planning CT scan of the mother’s head and torso were estimated using the National Cancer Institute dosimetry system for CT (NCICT, Version 3) considering a low-dose CT protocol (CTDIvol: 8.97 mGy). Main Results: The majority of the fetal organ/tissue doses from the proton PBS CSI treatment fell within a range of 3 to 6 mGy. The fetal organ/tissue doses for the 38-week phantom showed the largest variation with the doses ranging from 2.9 mGy (adrenals) to 8.2 mGy (eye lenses) while the smallest variation ranging from 3.2 mGy (oesophagus) to 4.4 mGy (brain) was observed for the doses for the 20-week phantom. The fetal whole-body dose ranged from 3.7 mGy (25 weeks) to 5.8 mGy (8 weeks). Most of the fetal doses from the planning CT scan fell within a range of 7 to 13 mGy, approximately 2-to-9 times lower than the fetal dose equivalents of the proton PBS CSI treatment (assuming a quality factor of 7). Significance: The fetal organ/tissue doses observed in the present work will be useful for one of the first clinically informative predictions on the magnitude of fetal dose during proton PBS CSI during pregnancy.

Pencil Beam Scanning (PBS) Intensity-Modulated Proton Therapy (IMPT) Chemoradiotherapy for Anal Canal Cancer—Single Institution Experience

Background: A favourable dose distribution has been described for proton beam therapy (PBT) of anal cancer in dosimetric studies. The relationship between dosimetric parameters in bone marrow and haematologic toxicity, treatment interruptions, and treatment efficacy has also been documented. There are only few references on clinical results of PBT for anal cancer. The primary objective of the retrospective study was to assess the efficacy of pencil beam scanning intensity-modulated proton therapy (PBS IMPT) in the definitive chemoradiotherapy of anal cancer. Secondary objectives were established to identify the risks of acute chronic toxicity risks and to assess colostomy rates. Materials and methods: Patients were treated for biopsy-proven squamous cell cancer (SCC) of the anus at initial or advanced stages. Eligible patients received PBS IMPT at a single institution. Treatment was administered in two volumes: 1—tumour with margins plus involved lymph nodes; 2—regional lymph node groups: perirectal (mesorectal), obturatory, inguinal, internal, external, and common iliac. The total doses of 57.5 GyE and 45 GyE, respectively, were administered in volumes 1 and 2 in 25 fractions, 5 fractions per week, respectively (a simultaneous integrated boost). Concomitant chemotherapy cisplatinum (CDDP) plus 5-FU or CDDP plus capecitabine was administered as per protocol. The treatment effect was assessed using DRE (digital rectal examination) and MRI (magnetic resonance imaging) within the follow-up period. Toxicity was scaled using CTCAE version 4.0 criteria. Results: 39 of 41 patients treated during the period of February 2014–August 2021 were eligible for analysis. All patients completed treatment, 76.9% without interruption. The median treatment time was 35 days (32–35). The median follow-up period was 30 months, 34 patients are alive to-date, 5 patients died prior to the date of analysis, and 2 deaths were unrelated to the primary disease. The 2-year overall survival, relapse-free survival, and colostomy-free survival were 94.2%, 93.8%, and 91.0%, respectively. Complete regression was achieved in 36 patients (92.3%), partial regression was achieved in 2 (5.1%), and immediate progression at end of treatment occurred in 1 patient (2.6%). Salvage resection was indicated for two patients in partial regression and due to severe chronic dermatologic toxicity. The grade 3 and 4 haematological toxicity rates were 7.7% and 5.1%, respectively. The most frequent non-haematological acute toxicities of grade 3–4 observed were dermatitis (23.1%), diarrhoea (7.7%), and dehydration (7.7%). Chronic toxicity emerged predominantly as skin atrophy/ulceration grade 2 (26.5%) and grade 3–4 (5.8%), and radiation proctitis grade 2 (38.2%) and grade 3 (2.9%). Discussion, conclusions: This single-institution study showed the high efficacy of PBS IMPT, achieving a high rate of complete regression. The haematological acute toxicity of grade 3–4 remained low; however, the impact of altered chemotherapy (CDDP instead of mitomycin C) remains unclear. The incidence of other acute toxicities shares similarity with photon therapy investigated in large studies. The acute toxicity completely resolved in all patients, had no lethal outcomes, and never resulted in the necessity for colostomy. By contrast, it was chronic toxicity, skin ulceration, perirectal fistulation, and fibrosis that resulted in salvage surgery and/or the need for a colostomy. A challenging question remains: to what extent can PBT prevent chronic toxicity? Longer follow-up remains necessary.

Silicon 3D Microdosimeters for Advanced Quality Assurance in Particle Therapy

The Centre for Medical Radiation Physics introduced the concept of Silicon On Insulator (SOI) microdosimeters with 3-Dimensional (3D) cylindrical sensitive volumes (SVs) mimicking the dimensions of cells in an array. Several designs of high-definition 3D SVs fabricated using 3D MEMS technology were implemented. 3D SVs were fabricated in different sizes and configurations with diameters between 18 and 30 µm, thicknesses of 2–50 µm and at a pitch of 50 µm in matrices with volumes of 20 × 20 and 50 × 50. SVs were segmented into sub-arrays to reduce capacitance and avoid pile up in high-dose rate pencil beam scanning applications. Detailed TCAD simulations and charge collection studies in individual SVs have been performed. The microdosimetry probe (MicroPlus) is composed of the silicon microdosimeter and low-noise front–end readout electronics housed in a PMMA waterproof sheath that allows measurements of lineal energies as low as 0.4 keV/µm in water or PMMA. Microdosimetric quantities measured with SOI microdosimeters and the MicroPlus probe were used to evaluate the relative biological effectiveness (RBE) of heavy ions and protons delivered by pencil-beam scanning and passive scattering systems in different particle therapy centres. The 3D detectors and MicroPlus probe developed for microdosimetry have the potential to provide confidence in the delivery of RBE optimized particle therapy when introduced into routine clinical practice.