Intensity-modulated proton radiotherapy spares musculoskeletal structures in regional nodal irradiation for breast cancer: a dosimetric comparison.

BACKGROUND AND PURPOSE: Regional nodal irradiation (RNI) for breast cancer delivers radiation in proximity to the shoulder and torso, and radiation exposure may contribute to long-term upper extremity and postural morbidity. To date, no studies have assessed the differential dosimetric impact of proton versus photon radiation on shoulder and torso anatomy. This study examined clinically relevant musculoskeletal (MSK) structures and assessed the dose delivered with each modality. PATIENTS/MATERIAL AND METHODS: Ten MSK structures were contoured on IMPT (intensity-modulated proton therapy) and VMAT (volumetric modulated arc therapy) plans for 30 patients receiving RNI. Relevant dose metrics were compared for each of the structures. Intensity-modulated proton therapy dose was calculated using the relative biological effective value of 1.1. Hypo-fractionated plans were scaled to the equivalent dose in 2 Gy fractions (EQD2) using an alpha/beta ratio of four. Wilcoxon signed rank sum tests compared doses. Select three-dimensional and optimised VMAT plans were also informally compared. RESULTS AND INTERPRETATION: Each of the 10 structures received a statistically significantly lower dose with the use of IMPT compared with VMAT. Differences were greatest for posterior structures, including the trapezius, latissimus dorsi and glenohumeral joint. Mean absolute differences were as great as 23 Gy (supraspinatus D5cc) and up to 30-fold dose reductions were observed (deltoid D50cc). An average 3.7-fold relative dose reduction existed across all structures. Measures of low/intermediate dose (V15Gy and D50cc) showed the largest differences. Intensity-modulated proton therapy results in statistically lower radiation exposure to relevant shoulder and torso anatomy compared to photon radiation for patients requiring RNI. Prospective study is needed to correlate functional outcomes with radiation dose.

Superior antitumor immune response achieved with proton over photon immunoradiotherapy is amplified by the nanoradioenhancer NBTXR3.

Recent findings suggest that immunoradiotherapy (IRT), combining photon radiotherapy (XRT) or proton radiotherapy (PRT) with immune checkpoint blockade, can enhance systemic tumor control. However, the comparative efficacy of XRT and PRT in IRT remains understudied. To address this, we compared outcomes between XRT + αPD1 and PRT + αPD1 in murine αPD1-resistant lung cancer (344SQR). We also assessed the impact of the nanoparticle radioenhancer NBTXR3 on both XRT + αPD1 and PRT + αPD1 for tumor control and examined the tumor immune microenvironment using single-cell RNA sequencing (scRNAseq). Additionally, mice cured by NBTXR3 + PRT + αPD1 were rechallenged with three lung cancer cell lines to evaluate memory antitumor immunity. PRT + αPD1 showed superior local tumor control and abscopal effects compared to XRT + αPD1. NBTXR3 + PRT + αPD1 significantly outperformed NBTXR3 + XRT + αPD1 in tumor control, promoting greater infiltration of antitumor lymphocytes into irradiated tumors. Unirradiated tumors treated with NBTXR3 + PRT + αPD1 had more NKT cells, CD4 T cells, and B cells, with fewer Tregs, than those treated with NBTXR3 + XRT + αPD1. NBTXR3 + PRT + αPD1 also stimulated higher expression of IFN-γ, GzmB, and Nkg7 in lymphocytes, reduced the TGF-ß pathway, and increased tumor necrosis factor alpha expression compared to NBTXR3 + XRT + αPD1. Moreover, NBTXR3 + PRT + αPD1 resulted in greater M1 macrophage polarization in both irradiated and unirradiated tumors. Mice achieving remission through NBTXR3 + PRT + αPD1 exhibited a robust memory immune response, effectively inhibiting growth of subsequent tumors from three distinct lung cancer cell lines. Proton IRT combined with NBTXR3 offers enhanced tumor control and survival rates over photon-based treatments in managing αPD1-resistant lung cancer, indicating its potential as a potent systemic therapy.

Exploring dual energy CT synthesis in CBCT-based adaptive radiotherapy and proton therapy: application of denoising diffusion probabilistic models.

Background.Adaptive radiotherapy (ART) requires precise tissue characterization to optimize treatment plans and enhance the efficacy of radiation delivery while minimizing exposure to organs at risk. Traditional imaging techniques such as cone beam computed tomography (CBCT) used in ART settings often lack the resolution and detail necessary for accurate dosimetry, especially in proton therapy.Purpose.This study aims to enhance ART by introducing an innovative approach that synthesizes dual-energy computed tomography (DECT) images from CBCT scans using a novel 3D conditional denoising diffusion probabilistic model (DDPM) multi-decoder. This method seeks to improve dose calculations in ART planning, enhancing tissue characterization.Methods.We utilized a paired CBCT-DECT dataset from 54 head and neck cancer patients to train and validate our DDPM model. The model employs a multi-decoder Swin-UNET architecture that synthesizes high-resolution DECT images by progressively reducing noise and artifacts in CBCT scans through a controlled diffusion process.Results.The proposed method demonstrated superior performance in synthesizing DECT images (High DECT MAE 39.582 ± 0.855 and Low DECT MAE 48.540± 1.833) with significantly enhanced signal-to-noise ratio and reduced artifacts compared to traditional GAN-based methods. It showed marked improvements in tissue characterization and anatomical structure similarity, critical for precise proton and radiation therapy planning.Conclusions.This research has opened a new avenue in CBCT-CT synthesis for ART/APT by generating DECT images using an enhanced DDPM approach. The demonstrated similarity between the synthesized DECT images and ground truth images suggests that these synthetic volumes can be used for accurate dose calculations, leading to better adaptation in treatment planning.

Impact of Proton Irradiation Depending on Breast Cancer Subtype in Patient-Derived Cell Lines.

Research on different types of ionizing radiation's effects has been ongoing for years, revealing its efficacy in damaging cancer cells. Solid tumors comprise diverse cell types, each being able to respond differently to radiation. This study evaluated the radiobiological response of established (MDA-MB-231 (Triple negative breast cancer, TNBC), MCF-7 (Luminal A)) and patient-derived malignant cell lines, cancer-associated fibroblasts, and skin fibroblasts following proton IRR. All cell line types were irradiated with the proton dose of 2, 4, and 6 Gy. The radiobiological response was assessed using clonogenic assay, γH2AX, and p53 staining. It was noticeable that breast cancer lines of different molecular subtypes displayed no significant variations in their response to proton IRR. In terms of cancer-associated fibroblasts extracted from the tumor tissue, the line derived from a TNBC subtype tumor demonstrated higher resistance to ionizing radiation compared to lines isolated from luminal A tumors. Fibroblasts extracted from patients' skin responded identically to all doses of proton radiation. This study emphasizes that tumor response is not exclusively determined by the elimination of breast cancer cells, but also takes into account tumor microenvironmental variables and skin reactions.

CYRAD: a translational study assessing immune response to radiotherapy by photons or protons in postoperative head and neck cancer patients through circulating leukocyte subpopulations and cytokine levels.

BACKGROUND: Radiotherapy has both immunostimulant and immunosuppressive effects, particularly in radiation-induced lymphopenia. Proton therapy has demonstrated potential in mitigating this lymphopenia, yet the mechanisms by which different types of radiation affect the immune system function are not fully characterized. The Circulating Immunes Cells, Cytokines and Brain Radiotherapy (CYRAD) trial aims to compare the effects of postoperative X-ray and proton radiotherapy on circulating leukocyte subpopulations and cytokine levels in patients with head and neck (CNS and ear nose throat) cancer. METHODS: CYRAD is a prospective, non-randomized, single-center non interventional study assessing changes in the circulating leukocyte subpopulations and cytokine levels in head and neck cancer patients receiving X-ray or proton radiotherapy following tumor resection. Dosimetry parameters, including dose deposited to organs-at-risk such as the blood and cervical lymph nodes, are computed. Participants undergo 29 to 35 radiotherapy sessions over 40 to 50 days, followed by a 3-month follow-up. Blood samples are collected before starting radiotherapy (baseline), before the 11th (D15) and 30th sessions (D40), and three months after completing radiotherapy. The study will be conducted with 40 patients, in 2 groups of 20 patients per modality of radiotherapy (proton therapy and photon therapy). Statistical analyses will assess the absolute and relative relationship between variations (depletion, recovery) in immune cells, biomarkers, dosimetry parameters and early outcomes. DISCUSSION: Previous research has primarily focused on radiation-induced lymphopenia, paying less attention to the specific impacts of radiation on different lymphoid and myeloid cell types. Early studies indicate that X-ray and proton irradiation may lead to divergent outcomes in leukocyte subpopulations within the bloodstream. Based on these preliminary findings, this study aims to refine our understanding of how proton therapy can better preserve immune function in postoperative (macroscopic tumor-free) head and neck cancer patients, potentially improving treatment outcomes. PROTOCOL VERSION: Version 2.1 dated from January 18, 2023. TRIAL REGISTRATION: The CYRAD trial is registered from October 19, 2021, at the US National Library of Medicine, ClinicalTrials.gov ID NCT05082961.

Proton beam therapy in a patient with secondary glioblastoma (32 years after postoperative irradiation of medulloblastoma): case report and literature review.

OBJECTIVE: This report details the experience of a patient who developed a second primary glioblastoma (GB), offering insights into the treatment process and reviewing relevant literature. CASE PRESENTATION: A male patient, who was diagnosed with medulloblastoma at age 9, received treatment with cobalt-60 craniospinal irradiation (CSI) (36 Gy/20 fractions) and a tumor bed boost (total of 56 Gy). After 32 years, at age 41, an MRI revealed a space-occupying mass in the left cerebellar hemisphere. Surgical resection was performed, and postoperative pathology confirmed a diagnosis of radiation-induced glioblastoma (RIGB). Given the history of irradiation and the current tolerability of brainstem doses, proton beam therapy (PBT) combined with Temozolomide (75 mg/m2) was chosen. The treatment plan included 60 Gy on the gross tumor bed and 54 Gy on the clinical target volume, delivered in 30 fractions. The patient underwent regular follow-up and achieved a complete response. CLINICAL DISCUSSION: For childhood cancer survivors, the development of a second primary tumor significantly impacts prognosis. RIGB is a rare form of secondary tumor with distinct molecular characteristics compared to primary GB and recurrent secondary GB. Molecular markers such as IDH and MGMT status can help differentiate between primary GB, recurrent secondary GB, and radiation-induced secondary GB in patients with a history of prior radiation therapy. Surgical resection remains a primary treatment option, while PBT is preferred for postoperative treatment due to its superior protection of normal tissues and the ability to deliver high-dose irradiation. CONCLUSION: RIGB is a rare second primary tumor that requires strategic molecular profiling and individualized management. Proton beam therapy provides effective high-dose irradiation in the postoperative phase and is the preferred treatment option for such cases.

Cost-utility analysis of proton beam therapy for locally advanced esophageal cancer in Japan.

PURPOSE: Proton beam therapy (PBT) has recently been included in Japan's health insurance benefit package for certain cancer types. This study aimed to determine the cost-effectiveness of PBT as a replacement for conventional three-dimensional conformal radiotherapy (3D-CRT) for locally advanced esophageal cancer (LAEC) that is not covered by social insurance. METHODS: We estimated the incremental cost-effectiveness ratio (ICER) of PBT as a replacement for 3D-CRT, using clinical evidence from the literature and expert opinions. We used an economic model, decision tree, and Markov model to illustrate the courses followed by patients with LAEC. Effectiveness was estimated as quality-adjusted life years (QALY) using utility weights for the health state. Social insurance fees were calculated as costs. We assumed two base cases depending on the two existing levels of fees for PBT in social insurance: 2,735,000 Japanese yen (US$20,652) or 1,600,000 yen (US$13,913). The stability of the ICER against these assumptions was appraised using sensitivity analysis. RESULTS: The effectiveness of PBT and 3D-CRT was 2.62 and 2.51 QALY, respectively. The estimated ICER was 14,025,268 yen (US$121,958) per QALY for the higher fee level and 7,026,402 yen (US$61,099) for the lower fee level. According to the Japanese threshold for cost-effectiveness of anticancer therapy of 7,500,000 yen (US$65,217) per QALY gain, the inclusion of PBT for LAEC in the benefit package of social insurance is cost-effective if a lower fee is applied. CONCLUSION: PBT is a cost-effective alternative to 3D-CRT for LAEC and making it available to patients under social insurance could be justifiable.

Sparing Effect on Cell Survival Under Normoxia Using Ultra-high Dose Rate Proton Beams from a Compact Superconducting AVF Cyclotron.

BACKGROUND/AIM: The purpose of this study was to evaluate whether the sparing effect on cell survival is observed under normoxia. MATERIALS AND METHODS: A superconducting spiral sector-type azimuthally varying field (AVF) cyclotron produced 230 MeV proton beams at 250 Gy/s as ultra-high dose rate (uHDR) and 1 Gy/s as normal dose rate (NDR) to irradiate tumor and normal cell lines (HSGc-c5 and HDF up to 24 Gy at the center of spread-out Bragg peak (SOBP). The Advanced Markus chamber and Gafchromic film were used to measure the examined absolute dose and field sizes. Colony formation assay and immunofluorescence staining were conducted to evaluate the sparing effect. RESULTS: A homogeneous field was achieved at the center of the SOBP for both uHDR and NDR scanned proton beams, and dose reproducibility and linearity were adequate for experiments. There were significant differences in cell surviving fractions of HSGc-C5 and HDF cells irradiated at uHDRs compared to NDRs at 20 Gy and 24 Gy. Increasing γ-H2AX foci were observed for both cell lines at NDR. CONCLUSION: The sparing effect on cell survival was first observed under normoxic conditions for tumor and normal cells with doses exceeding 20 Gy, using proton irradiation at 250 Gy/s extracted from a superconducting AVF cyclotron. This study marks a significant milestone in advancing our understanding of the underlying mechanism behind the sparing effect.

Impact of interplay effects on spot scanning proton therapy with motion mitigation techniques for lung cancer: SFUD versus robustly optimized IMPT plans utilizing a four-dimensional dynamic dose simulation tool.

BACKGROUND: The interaction between breathing motion and scanning beams causes interplay effects in spot-scanning proton therapy for lung cancer, resulting in compromised treatment quality. This study investigated the effects and clinical robustness of two types of spot-scanning proton therapy with motion-mitigation techniques for locally advanced non-small cell lung cancer (NSCLC) using a new simulation tool (4DCT-based dose reconstruction). METHODS: Three-field single-field uniform dose (SFUD) and robustly optimized intensity-modulated proton therapy (IMPT) plans combined with gating and re-scanning techniques were created using a VQA treatment planning system for 15 patients with locally advanced NSCLC (70 GyRBE/35 fractions). In addition, gating windows of three or five phases around the end-of-expiration phase and two internal gross tumor volumes (iGTVs) were created, and a re-scanning number of four was used. First, the static dose (SD) was calculated using the end-of-expiration computed tomography (CT) images. The four-dimensional dynamic dose (4DDD) was then calculated using the SD plans, 4D-CT images, and the deformable image registration technique on end-of-expiration CT. The target coverage (V98%, V100%), homogeneity index (HI), and conformation number (CN) for the iGTVs and organ-at-risk (OAR) doses were calculated for the SD and 4DDD groups and statistically compared between the SD, 4DDD, SFUD, and IMPT treatment plans using paired t-test. RESULTS: In the 3- and 5-phase SFUD, statistically significant differences between the SD and 4DDD groups were observed for V100%, HI, and CN. In addition, statistically significant differences were observed for V98%, V100%, and HI in phases 3 and 5 of IMPT. The mean V98% and V100% in both 3-phase plans were within clinical limits (> 95%) when interplay effects were considered; however, V100% decreased to 89.3% and 94.0% for the 5-phase SFUD and IMPT, respectively. Regarding the significant differences in the deterioration rates of the dose volume histogram (DVH) indices, the 3-phase SFUD plans had lower V98% and CN values and higher V100% values than the IMPT plans. In the 5-phase plans, SFUD had higher deterioration rates for V100% and HI than IMPT. CONCLUSIONS: Interplay effects minimally impacted target coverage and OAR doses in SFUD and robustly optimized IMPT with 3-phase gating and re-scanning for locally advanced NSCLC. However, target coverage significantly declined with an increased gating window. Robustly optimized IMPT showed superior resilience to interplay effects, ensuring better target coverage, prescription dose adherence, and homogeneity than SFUD. TRIAL REGISTRATION: None.

Microdosimetric Simulation of Gold-Nanoparticle-Enhanced Radiotherapy.

Conventional X-ray therapy (XRT) is commonly applied to suppress cancerous tumors; however, it often inflicts collateral damage to nearby healthy tissue. In order to provide a better conformity of the dose distribution in the irradiated tumor, proton therapy (PT) is increasingly being used to treat solid tumors. Furthermore, radiosensitization with gold nanoparticles (GNPs) has been extensively studied to increase the therapeutic ratio. The mechanism of radiosensitization is assumed to be connected to an enhancement of the absorbed dose due to huge photoelectric cross-sections with gold. Nevertheless, numerous theoretical studies, mostly based on Monte Carlo (MC) simulations, did not provide a consistent and thorough picture of dose enhancement and, therefore, the radiosensitization effect. Radiosensitization by nanoparticles in PT is even less studied than in XRT. Therefore, we investigate the physics picture of GNP-enhanced RT using an MC simulation with Geant4 equipped with the most recent physics models, taking into account a wide range of physics processes relevant for realistic PT and XRT. Namely, we measured dose enhancement factors in the vicinity of GNP, with diameters ranging from 10 nm to 80 nm. The dose enhancement in the vicinity of GNP reaches high values for XRT, while it is very modest for PT. The macroscopic dose enhancement factors for realistic therapeutic GNP concentrations are rather low for all RT scenarios; therefore, other physico-chemical and biological mechanisms should be additionally invoked for an explanation of the radiosensitization effect observed in many experiments.

Deep learning-based statistical robustness evaluation of intensity-modulated proton therapy for head and neck cancer.

Objective. Previous methods for robustness evaluation rely on dose calculation for a number of uncertainty scenarios, which either fails to provide statistical meaning when the number is too small (e.g., ∼8) or becomes unfeasible in daily clinical practice when the number is sufficiently large (e.g., >100). Our proposed deep learning (DL)-based method addressed this issue by avoiding the intermediate dose calculation step and instead directly predicting the percentile dose distribution from the nominal dose distribution using a DL model. In this study, we sought to validate this DL-based statistical robustness evaluation method for efficient and accurate robustness quantification in head and neck (H&N) intensity-modulated proton therapy with diverse beam configurations and multifield optimization.Approach. A dense, dilated 3D U-net was trained to predict the 5th and 95th percentile dose distributions of uncertainty scenarios using the nominal dose and planning CT images. The data set comprised proton therapy plans for 582 H&N cancer patients. Ground truth percentile values were estimated for each patient through 600 dose recalculations, representing randomly sampled uncertainty scenarios. The comprehensive comparisons of different models were conducted for H&N cancer patients, considering those with and without a beam mask and diverse beam configurations, including varying beam angles, couch angles, and beam numbers. The performance of our model trained based on a mixture of patients with H&N and prostate cancer was also assessed in contrast with models trained based on data specific for patients with cancer at either site.Results. The DL-based model's predictions of percentile dose distributions exhibited excellent agreement with the ground truth dose distributions. The average gamma index with 2 mm/2%, consistently exceeded 97% for both 5th and 95th percentile dose volumes. Mean dose-volume histogram error analysis revealed that predictions from the combined training set yielded mean errors and standard deviations that were generally similar to those in the specific patient training data sets.Significance. Our proposed DL-based method for evaluation of the robustness of proton therapy plans provides precise, rapid predictions of percentile dose for a given confidence level regardless of the beam arrangement and cancer site. This versatility positions our model as a valuable tool for evaluating the robustness of proton therapy across various cancer sites.

Skull Base Chordoma and Chondrosarcoma: Neuroradiologist's Guide to Diagnosis, Surgical Management, and Proton Beam Therapy.

Skull base chordomas and chondrosarcomas are distinct types of rare, locally aggressive mesenchymal tumors that share key principles of imaging investigation and multidisciplinary care. Maximal safe surgical resection is the treatment choice for each, often via an expanded endoscopic endonasal approach, with or without multilayer skull base repair. Postoperative adjuvant radiation therapy is frequently administered, usually with particle therapy such as proton beam therapy (PBT). Compared with photon therapy, PBT enables dose escalation while limiting damage to dose-limiting neurologic structures, particularly the brainstem and optic apparatus, due to energy deposition being delivered at a high maximum with a rapid decrease at the end of the penetration range (Bragg peak phenomenon). Essential requirements for PBT following gross total or maximal safe resection are tissue diagnosis, minimal residual tumor after resection, and adequate clearance from PBT dose-limiting structures. The radiologist should understand surgical approaches and surgical techniques, including multilayer skull base repair, and be aware of evolution of postsurgical imaging appearances over time. Accurate radiologic review of all relevant preoperative imaging examinations and of intraoperative and postoperative MRI examinations plays a key role in management. The radiology report should reflect what the skull base surgeon and radiation oncologist need to know, including distance between the tumor and PBT dose-limiting structures, tumor sites that may be difficult to access via the endoscopic endonasal route, the relationship between intradural tumor and neurovascular structures, and tumor sites with implications for postresection stability. ©RSNA, 2024 Supplemental material is available for this article.

Proton- compared to X-irradiation leads to more acinar atrophy and greater hyposalivation accompanied by a differential cytokine response.

Proton therapy gives less dose to healthy tissue compared to conventional X-ray therapy, but systematic comparisons of normal tissue responses are lacking. The aim of this study was to investigate late tissue responses in the salivary glands following proton- or X-irradiation of the head and neck in mice. Moreover, we aimed at investigating molecular responses by monitoring the cytokine levels in serum and saliva. Female C57BL/6J mice underwent local fractionated irradiation with protons or X-rays to the maximally tolerated acute level. Saliva and serum were collected before and at different time points after irradiation to assess salivary gland function and cytokine expression. To study late responses in the major salivary glands, histological analyses were performed on tissues collected at day 105 after onset of irradiation. Saliva volume after proton and X-irradiation was significantly lower than for controls and remained reduced at all time points after irradiation. Protons caused reduced saliva production and fewer acinar cells in the submandibular glands compared to X-rays at day 105. X-rays induced a stronger inflammatory cytokine response in saliva compared to protons. This work supports previous preclinical findings and indicate that the relative biological effectiveness of protons in normal tissue might be higher than the commonly used value of 1.1.

Geometric target margin strategy of proton craniospinal irradiation for pediatric medulloblastoma.

In proton craniospinal irradiation (CSI) for skeletally immature pediatric patients, a treatment plan should be developed to ensure that the dose is uniformly delivered to all vertebrae, considering the effects on bone growth balance. The technical (t) clinical target volume (CTV) is conventionally set by manually expanding the CTV from the entire intracranial space and thecal sac, based on the physician's experience. However, there are differences in contouring methods among physicians. Therefore, we aimed to propose a new geometric target margin strategy. Nine pediatric patients with medulloblastoma who underwent proton CSI were enrolled. We measured the following water equivalent lengths for each vertebra in each patient: body surface to the dorsal spinal canal, vertebral limbus, ventral spinal canal and spinous processes. A simulated tCTV (stCTV) was created by assigning geometric margins to the spinal canal using the measurement results such that the vertebral limb and dose distribution coincided with a margin assigned to account for the uncertainty of the proton beam range. The stCTV with a growth factor (correlation between body surface area and age) and tCTV were compared and evaluated. The median values of each index for cervical, thoracic and lumber spine were: the Hausdorff distance, 9.14, 9.84 and 9.77 mm; mean distance-to-agreement, 3.26, 2.65 and 2.64 mm; Dice coefficient, 0.84, 0.81 and 0.82 and Jaccard coefficient, 0.50, 0.60 and 0.62, respectively. The geometric target margin setting method used in this study was useful for creating an stCTV to ensure consistent and uniform planning.

Clinical implementation of deep learning robust IMPT planning in oropharyngeal cancer patients: A blinded clinical study.

BACKGROUND AND PURPOSE: This study aimed to evaluate the plan quality of our deep learning-based automated treatment planning method for robustly optimized intensity-modulated proton therapy (IMPT) plans in patients with oropharyngeal carcinoma (OPC). The assessment was conducted through a retrospective and prospective study, blindly comparing manual plans with deep learning plans. MATERIALS AND METHODS: A set of 95 OPC patients was split into training (n = 60), configuration (n = 10), test retrospective study (n = 10), and test prospective study (n = 15). Our deep learning optimization (DLO) method combines IMPT dose prediction using a deep learning model with a robust mimicking optimization algorithm. Dosimetrists manually adjusted the DLO plan for individual patients. In both studies, manual plans and manually adjusted deep learning (mDLO) plans were blindly assessed by a radiation oncologist, a dosimetrist, and a physicist, through visual inspection, clinical goal evaluation, and comparison of normal tissue complication probability values. mDLO plans were completed within an average time of 2.5 h. In comparison, the manual planning process typically took around 2 days. RESULTS: In the retrospective study, in 10/10 (100%) patients, the mDLO plans were preferred, while in the prospective study, 9 out of 15 (60%) mDLO plans were preferred. In 4 out of the remaining 6 cases, the manual and mDLO plans were considered comparable in quality. Differences between manual and mDLO plans were limited. CONCLUSION: This study showed a high preference for mDLO plans over manual IMPT plans, with 92% of cases considering mDLO plans comparable or superior in quality for OPC patients.

Role of Proton Beam Therapy in Spinal Chordomas: A Narrative Review of The Literature.

Chordomas are rare malignant neoplasms arising from vestigial remnants of the embryonic notochord. Approximately 55-70% of chordomas develop within the vertebral column. Their affinity to develop within the bones of the axial skeleton and propensity to locally invade and recur makes them challenging candidates for complete surgical excision. Adjuvant therapies are hence necessary to improve outcomes; for which chemotherapy has been observed to be largely ineffective, owing to the tumour being resistant to it. Radiotherapy is the current adjuvant therapy of choice for chordoma management. Over the years, proton beam therapy (PBT) has been the subject of medical attention, given the dosimetric benefits it confers over traditional radiotherapy, allowing more concentrated radiation to be given to the target of interest and reducing damage to surrounding normal tissue. A review of the current literature reveals PBT offers significantly better outcomes when used as an adjuvant to maximal surgical resection rather than as a definitive therapy.

Investigate potential clinical benefits and linear energy transfer sparing utilizing proton arc therapy for hepatocellular carcinoma.

PURPOSE: To investigate the potential clinical benefits and dose-averaged Linear Energy Transfer (LETd) sparing, utilizing proton arc plan for hepatocellular carcinoma (HCC) patients in comparison with Intensity Modulated Proton Therapy (IMPT). METHODS: Ten HCC patients have been retrospectively selected. Two planning groups were created: Proton Arc plans using Monaco ver. 6 and the clinical IMPT plan. Both planning groups used the same robustness parameters. The prescription dose is 67.5 Gy (RBE) in 15 fractions of the Clinical Target Volume (CTV). Robustness evaluations were performed to ensure dose coverage. Normal Tissue Complicated Probability (NTCP) model was utilized to predict the possibility of Radiation-Induced Liver Disease (RILD) and evaluate the potential benefit of proton arc therapy. LETd calculation and evaluation were performed as well. RESULTS: Proton arc plan has shown better dosimetric improvements of most Organ-At-Risks (OARs). More specifically, the liver mean dose has been significantly reduced from 14.7 GyE to 10.62 GyE compared to the IMPT plan. The predicted possibility of RILD has also been significantly reduced for cases with a large and deep liver target where healthy liver tissue sparing is a challenge. Additionally, proton arc therapy could increase the average LETd in the target and reduce LETd in adjacent OARs. CONCLUSIONS: The potential clinical benefit of utilizing proton arc therapy HCC varies depending on the patient-specific geometry. With more freedom, proton arc therapy can offer a better dosimetric plan quality in the challenge cases, which might not be feasible using the current IMPT technique.

Excision of Giant Chronic Expanding Hematoma of the Thorax Caused by Rib Fractures after Proton Radiotherapy for Lung Cancer.

Chronic expanding hematoma (CEH) is defined as a hematoma that gradually expands over months to years. An 82-year-old female underwent proton radiotherapy for left upper lobe lung cancer 10 years previously. Two years after the therapy, a hematoma developed from the left 3rd to 5th dorsal rib fractures and gradually expanded, causing contraction of the left shoulder. Transcatheter arterial embolization was performed; however, the hematoma continued to expand with thrombocytopenia, and the platelet was decreased to 4.2 × 104/µL. Computed tomography showed a 17.2 × 14.0 × 10.0 cm mass between the left scapula and left dorsal ribs. The CEH of the thorax was completely excised with combined resection of the 3rd to 5th ribs, while the brachial plexus was preserved. Postoperatively, the platelet completely recovered and she could raise her left arm. A complete excision with surrounding organs preserved is the strategy used in the treatment of CEH of the thorax.

Evaluating the Effectiveness of Proton Beam Therapy Compared to Conventional Radiotherapy in Non-Metastatic Rectal Cancer: A Systematic Review of Clinical Outcomes.

Background and Objectives: Conventional radiotherapies used in the current management of rectal cancer commonly cause iatrogenic radiotoxicity. Proton beam therapy has emerged as an alternative to conventional radiotherapy with the aim of improving tumour control and reducing off-set radiation exposure to surrounding tissue. However, the real-world treatment and oncological outcomes associated with the use of proton beam therapy in rectal cancer remain poorly characterised. This systematic review seeks to evaluate the radiation dosages and safety of proton beam therapy compared to conventional radiotherapy in patients with non-metastatic rectal cancer. Materials and Methods: A computer-assisted search was performed on the Medline, Embase and Cochrane Central databases. Studies that evaluated the adverse effects and oncological outcomes of proton beam therapy and conventional radiotherapy in adult patients with non-metastatic rectal cancer were included. Results: Eight studies were included in this review. There was insufficient evidence to determine the adverse treatment outcomes of proton beam therapy versus conventional radiotherapy. No current studies assessed radiotoxicities nor oncological outcomes. Pooled dosimetric comparisons between proton beam therapy and various conventional radiotherapies were associated with reduced radiation exposure to the pelvis, bowel and bladder. Conclusions: This systematic review demonstrates a significant paucity of evidence in the current literature surrounding adverse effects and oncological outcomes related to proton beam therapy compared to conventional radiotherapy for non-metastatic rectal cancer. Pooled analyses of dosimetric studies highlight greater predicted radiation-sparing effects with proton beam therapy in this setting. This evidence, however, is based on evidence at a moderate risk of bias and clinical heterogeneity. Overall, more robust, prospective clinical trials are required.