Particle tracking, recognition and LET evaluation of out-of-field proton therapy delivered to a phantom with implants.

OBJECTIVE: This study aims to assess the composition of scattered particles generated in proton therapy for tumors situated proximal to titanium dental implants. The investigation involves decomposing the mixed field and recording Linear Energy Transfer (LET) spectra to quantify the influence of metallic dental inserts located behind the tumor. Approach: A therapeutic conformal proton beam was used to deliver the treatment plan to an anthropomorphic head phantom with two types of implants inserted in the target volume (made of titanium and plastic, respectively). The scattered radiation resulted during the irradiation was detected by a hybrid semiconductor pixel detector MiniPIX Timepix3 that was placed distal to the Spread-out Bragg peak. Visualization and field decomposition of stray radiation were generated using algorithms trained in particle recognition based on artificial intelligence convolution neural networks (AI CNN). Spectral sensitive aspects of the scattered radiation were collected using two angular positions of the detector relative to the beam direction: 0° and 60°. Results: Using AI CNN, 3 classes of particles were identified: protons, electrons & photons, and ions & fast neutrons. Placing a Titanium implant in the beam's path resulted in predominantly electrons and photons, contributing 52.2%, whereas for plastic implants, the contribution was 65.4%. Scattered protons comprised 45.5% and 31.9% with and without metal inserts, respectively. The LET spectra was derived for each group of particles identified, with values ranging from 0.01 to 7.5 keV·µm-1 for Titanium implants/plastic implants. The low-LET component was primarily composed of electrons and photons, while the high-LET component corresponded to protons and ions. Significance: This method, complemented by directional maps, holds potential for evaluating and validating treatment plans involving stray radiation near organs at risk, offering precise discrimination of the mixt field, enhancing in this way the LET calculation. .

Proton beam therapy and dentofacial development in paediatric cancer patients: A scoping review.

Purpose: It is known that radiation to dentofacial structures during childhood can lead to developmental disturbances. However, this appears to be a relatively subordinated research subject. For this reason, this review aims to establish the current evidence base on the effect of PBT on dentofacial development in paediatric patients treated for cancer in the head and neck region. Materials and methods: A comprehensive search was undertaken to identify both published and unpublished studies or reports. A single reviewer completed initial screening of abstracts; 2 independent reviewers completed secondary screening and data extraction. A narrative synthesis was then conducted. Results: 82 records were screened in total, resulting in 11 included articles. These articles varied in terms of study design and reporting quality. Owing to both poor study reporting and limited patient numbers, it is not possible to determine the effect of cancer diagnosis, chronological age at treatment, radiation dose or treatment modality on the incidence of facial deformation or dental development anomalies. Conclusion: Disturbances in dentofacial development are an under-reported toxicity in paediatric cancer survivors treated with PBT to the head and neck. There is a need for more research on dentofacial toxicity reporting, focused on the impact of treatment age, radiation dose, concurrent therapies, and the subsequent impact on quality of life.

Using diffusion MRI to understand white matter damage and the link between brain microstructure and cognitive deficits in paediatric medulloblastoma patients.

PURPOSE: Survivors of medulloblastoma face a range of challenges after treatment, involving behavioural, cognitive, language and motor skills. Post-treatment outcomes are associated with structural changes within the brain resulting from both the tumour and the treatment. Diffusion magnetic resonance imaging (MRI) has been used to investigate the microstructure of the brain. In this review, we aim to summarise the literature on diffusion MRI in patients treated for medulloblastoma and discuss future directions on how diffusion imaging can be used to improve patient quality. METHOD: This review summarises the current literature on medulloblastoma in children, focusing on the impact of both the tumour and its treatment on brain microstructure. We review studies where diffusion MRI has been correlated with either treatment characteristics or cognitive outcomes. We discuss the role diffusion MRI has taken in understanding the relationship between microstructural damage and cognitive and behavioural deficits. RESULTS: We identified 35 studies that analysed diffusion MRI changes in patients treated for medulloblastoma. The majority of these studies found significant group differences in measures of brain microstructure between patients and controls, and some of these studies showed associations between microstructure and neurocognitive outcomes, which could be influenced by patient characteristics (e.g. age), treatment, radiation dose and treatment type. CONCLUSIONS: In future, studies would benefit from being able to separate microstructural white matter damage caused by the tumour, tumour-related complications and treatment. Additionally, advanced diffusion modelling methods can be explored to understand and describe microstructural changes to white matter.

To become part of the team-patient experiences of participating in decision-making for a new treatment (proton beam therapy).

PURPOSE: The aim of this study was to explore patients' experience of participation in the treatment decision of proton beam therapy versus conventional radiotherapy. BACKGROUND: Proton beam therapy (PBT) has become a treatment option for some cancer patients receiving radiotherapy. The decision to give PBT instead of conventional radiotherapy (CRT) needs to be carefully planned together with the patient to ensure that the degree of participation is based on individuals' preferences. There is a knowledge gap of successful approaches to support patients' participation in the decision-making process, which is particularly important when it comes to the situation of having to choose between two treatment options such as PBT and CRT, with similar expected outcomes. METHOD: We conducted a secondary analysis of qualitative data collected from interviews with patients who received PBT for their brain tumor. Transcribed verbatims from interviews with 22 patients were analyzed regarding experiences of participation in the decision-making process leading to PBT. FINDINGS: Participants experienced their participation in the decision-making process to a varying degree, and with individual preferences. Four themes emerged from data: to be a voice that matters, to get control over what will happen, being in the hand of doctors' choice, and feeling selected for treatment. CONCLUSION: A decision for treatment with PBT can be experienced as a privilege but can also cause stress as it might entail practical issues affecting everyday life in a considerable way. For the patient to have confidence in the decision-making process, patients' preferences, expectations, and experiences must be included by the healthcare team. Including the patient in the healthcare team as an equal partner by confirming the person enables and facilitates for patients' voice to be heard and reckoned with. Person-centered care building on a partnership between patients and healthcare professionals should provide the right basis for the decision-making process.

Proton Beam Therapy for Treating Patients with Hepatocellular Carcinoma with Major Portal Vein Tumor Invasion: A Single Center Retrospective Study.

Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) has a poor prognosis and is generally not indicated for surgery. Proton beam therapy (PBT) may offer an alternative treatment. In this study, long-term outcomes were examined in 116 patients (median age 66 years, 100 males) with HCC with advanced PVTT (Vp3 or Vp4) who received PBT from April 2008 to March 2018. Of these patients, 63 received PBT as definitive treatment and 53 as palliative treatment. The representative dose was 72.6 Gy (RBE) in 22 fractions. Eight patients died in follow-up, including 72 due to tumor progression. The 5-year overall survival (OS) rate was 18.0% (95% CI 9.8-26.2%) and the 5-year local control (LC) rate was 86.1% (74.9-97.3%). In multivariate analyses, performance status and treatment strategy were significantly associated with OS. The median follow-up period for survivors with definitive treatment was 33.5 (2-129) months, and the 5-year OS rate was 25.1% (12.9-37.3%) in these cases. The median survival time after definitive irradiation was >20 months. The 5-year OS rate was 9.1% (0-19.7%) for palliative irradiation. These results compare favorably with those of other therapies and suggest that PBT is a useful option for cases of HCC with advanced PVTT that cannot undergo surgery, with an expected survival benefit and good local control. Determining the optimal indication for this treatment is a future challenge.

Comparison of proton-based definitive chemoradiotherapy and surgery-based therapy for esophageals cell carcinoma: a multi-center retrospective Japanese cohort study.

BACKGROUND: Proton-based, definitive chemoradiotherapy (P-CRT) for esophageal squamous cell carcinoma (ESCC) previously showed comparable survival outcomes with the surgery-based therapy, i.e., neoadjuvant chemotherapy followed by esophagectomy (NAC-S), in a single-institutional study. This study aimed to validate this message in a Japanese multicenter study. METHODS: Eleven Japanese esophageal cancer specialty hospitals have participated. A total of 518 cases with clinical Stage I-IVA ESCC between 2010 and 2019, including 168 P-CRT and 350 NAC-S patients, were enrolled and long-term outcomes were evaluated. Propensity-score weighting analyses with overlap weighting for confounding adjustment were used. RESULTS: The 3-year overall survival (OS) of the P-CRT group was equivalent to the NAC-S group (74.8% vs. 72.7%, hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.61-1.25). Although, the 3-year P-CRT group progression-free survival (PFS) was inferior to the NAC-S group (51.4% vs. 59.6%, HR 1.39, 95% CI 1.04-1.85), the progression P-CRT group cases showed better survival than the NAC-S group (HR 0.58, 95% CI 0.38-0.88), largely because of salvage surgery or endoscopic submucosal dissection for local progression. The survival advantage of P-CRT over NAC-S was more pronounced in the cT1-2 (HR 0.61, 95% CI 0.29-1.26) and cStage I-II (HR 0.50, 95% CI 0.24-1.07) subgroups, although this trend was not evident in other populations, such as cT3-4 and cStage III-IVA. CONCLUSIONS: Proton-based CRT for ESCC showed equivalent OS to surgery-based therapy. Especially for patients with cT1-2 and cStage I-II disease, proton-based CRT has the potential to serve as a first-line treatment.

Investigation of intra-fractionated range guided adaptive proton therapy (RGAPT): (Part II) range-shift compensated on-line treatment adaptation and verification.

We previously proposed range-guided adaptive proton therapy (RGAPT) that uses mid-range treatment beams as probing beams and intra-fractionated range measurements for online adaptation. In this work, we demonstrated experimental verification and reported the dosimetric accuracy for RGAPT. A STEEV phantom was used for the experiments, and a 3x3x3 cm3 cube inside the phantom was assigned to be the treatment target. We simulated three online range shift scenarios: reference, overshoot, and undershoot, by placing upstream Lucite sheets, 4, 0, and 8 that corresponded to changes of 0, 6.8, and -6.8 mm, respectively, in water-equivalent path length (WEPL). The reference treatment plan was to deliver single-field uniform target doses in pencil beam scanning mode and generated on the Eclipse treatment planning system. Different numbers of mid-range layers, including single, three, and five layers, were selected as probing beams to evaluate beam range measurement accuracy in Positron Emission Tomography (PET). Online plans were modified to adapt to beam range shifts and compensate for probing beam doses. In contrast, non-adaptive plans were also delivered and compared to adaptive plans by film measurements. The mid-range probing beams of three (5.55MU) and five layers (8.71MU) yielded accurate range shift measurements in 60 seconds of PET acquisition with uncertainty of 0.5mm while the single-layer probing (1.65MU) was not sufficient for measurements. The adaptive plans achieved an average gamma (2%/2mm) passing rate of 95%. In contrast, the non-adaptive plans only had an average passing rate of 69%. RGAPT planning and delivery are feasible and verified by the experiments. The probing beam delivery, range measurements, and adaptive planning and delivery added a small increase in treatment delivery workflow time but resulted in substantial dose improvement. The three-layer mid-range probing was most suitable considering the balance of high range measurement accuracy and the low number of probing beam layers.

Investigation of intra-fractionated range guided adaptive proton therapy: (Part I) on-line PET imaging and range measurement.

OBJECTIVE: Develop a prototype on-line PET scanner and evaluate its capability of on-line imaging and intra-fractionated proton-induced radioactivity range measurement. Approach: Each detector consists of 32×32 array of 2×2×30 mm3 Lutetium-Yttrium Oxyorthosilicate scintillators with single-scintillator-end readout through a 20×20 array of 3×3 mm2 Silicon Photomultipliers. The PET can be configurated with a full-ring of 20 detectors for conventional PET imaging or a partial-ring of 18 detectors for on-line imaging and range measurement. All detector-level readout and processing electronics are attached to the backside of the system gantry and their output signals are transferred to a Field-Programable-Gate-Array based system electronics and data acquisition that can be placed 2 meters away from the gantry. The PET imaging performance and radioactivity range measurement capability were evaluated by both the offline study that placed a radioactive source with known intensity and distribution within a phantom and the online study that irradiated a phantom with proton beams under different radiation and imaging conditions. Main results: The PET has 32 cm diameter and 6.5 cm axial length field-of-view (FOV), ~2.3 to 5.0 mm spatial resolution within FOV, 3% sensitivity at the FOV center, 18% to 30% energy resolution, and ~9 ns coincidence time resolution. The offline study shows the PET can determine the shift of distal falloff edge position of a known radioactivity distribution with the accuracy of 0.30.3 mm even without attenuation and scatter corrections, and online study shows the PET can measure the shift of proton-induced positron radioactive range with the accuracy of 0.60.3 mm from the data acquired with a short-acquisition (60 second) and low-dose (5 MU) proton radiation to a human head phantom. Significance: This study demonstrated the capability of intra-fractionated PET imaging and radioactivity range measurement and will enable the investigation on the feasibility of intra-fractionated, range-shift compensated adaptive proton therapy.

Clinical Trials Radiographers identifying priority challenges associated with implementing a national programme of clinical trials in the United Kingdom's first proton beam therapy centre.

Objectives: This article is an evaluation of the current trial processes within a national proton beam therapy (PBT) clinical trial service in the United Kingdom. The work within the article identifies priority challenges associated with the implementation of PBT trials with a view to improving patient trial processes. Methods: The nominal group technique (NGT) was used. Five Clinical Trials Radiographers were asked the target question "what are the major challenges when implementing PBT clinical trials and facilitating PBT trial-related activities?" Participants individually and silently listed their challenges to the target question. Following this, group discussion clarified and refined responses. Participants then individually selected five challenges that they deemed most pertinent to the target question, giving a weighted score (out of 10). Individual scores were combined to provide a ranked, weighted order of challenges. Further group discussion identified improvement strategies to the highest scored challenges. Results: After combining lists generated by participants, 59 challenges were identified. Group discussion eliminated 27 responses. Eighteen were merged, resulting in 14 challenges. The two challenges that ranked highest were: (i) lack of initial understanding of the responsibilities of teams and who the relevant stakeholders were, and (ii) that a national PBT service requires the provision of shared care across multi-disciplinary teams and sites. Improvement areas include the development of shared protocols, clarifying stakeholder responsibilities and improving communication between centres to streamline PBT trial processes. Conclusions: This work has identified priority areas requiring development to improve the conduct of a national PBT clinical trials programme. Advances in knowledge: This is the first publication to evaluate current clinical trial processes for the United Kingdom's PBT service.

Proton-beam Therapy for Locally Advanced Hepatocellular Carcinoma With Inferior Vena Cava Tumor Thrombus: Case Report.

BACKGROUND/AIM: We report on a case of locally advanced hepatocellular carcinoma (HCC) accompanied by an inferior vena cava tumor thrombus (IVCTT), treated successfully with proton-beam therapy (PBT). CASE REPORT: A 63-year-old male presented with a primary, single HCC with IVCTT, without metastasis to the intrahepatic region, lymph nodes, or distant organs. The clinical staging was identified as T4N0M0 Stage IIIB. The patient's liver function was classified as Child-Pugh class A (score: 6), with a modified albumin-bilirubin (mALBI) grade of 2a. The patient had liver cirrhosis due to non-alcoholic steatohepatitis. Magnetic resonance imaging revealed a nodular tumor measuring 13.2×8.9×9.8 cm across segments 1, 6, 7, and 8, along with IVCTT. The patient received PBT, with a total dose of 72.6 Gy (relative biological effectiveness) delivered in 22 fractions. Throughout the PBT treatment, the patient experienced no acute toxicities and completed the therapy as planned. Twelve months following PBT, the patient was alive without evidence of local recurrence, lymph node involvement, or distant organ metastasis. The only late toxicity observed was a mild worsening of the mALBI grade. CONCLUSION: We observed a favorable local response with manageable toxicities in a patient with locally advanced HCC and IVCTT treated with PBT. While this is a single case report, our findings suggest that PBT could be considered a viable treatment option for HCC with IVCTT.

Assessing alimentary tract radiation in liver cancer treatment with proton beam therapy: a PET/CT imaging study.

BACKGROUND: Proton beams deposit energy along their path, abruptly stopping and generating various radioactive particles, including positrons, along their trajectory. In comparison with traditional proton beam therapy, scanning proton beam therapy is effective in delivering proton beams to irregularly shaped tumors, reducing excessive radiation exposure to the alimentary tract during the treatment of liver cancer. METHODS: In this study, we utilized positron emission tomography/computed tomography (PET/CT) imaging to assess the total amount of radiation to the alimentary tract during liver cancer treatment with proton beam therapy, involving the administration of complex irradiation in 13 patients. RESULTS: This approach resulted in the prevention of excess radiation. The planned radiation restraint doses for the colon exhibited a significant correlation with the PET values of the colon (correlation coefficient 0.8384, P = .0003). Likewise, the scheduled radiation restraint doses for the gastroduodenum were correlated with the PET values of the gastroduodenum (correlation coefficient 0.5397, P = .0569). CONCLUSIONS: PET/CT conducted after proton beam therapy is useful for evaluating excess radiation in the alimentary tract. Proton beam therapy in liver cancer, assessed via PET/CT, effectively reduced alimentary tract radiation, which is vital for optimizing treatments and preventing excess exposure.

Feasibility study for the development of multilayered solar cells for proton linear energy transfer depth profile measurement.

BACKGROUND: Previous study proposed a method to measure linear energy transfer (LET) at specific points using the quenching magnitude of thin film solar cells. This study was conducted to propose a more advanced method for measuring the LET distribution. PURPOSE: This study focuses on evaluating the feasibility of estimating the proton LET distribution in proton therapy. The feasibility of measuring the proton LET and dose distribution simultaneously using a single-channel configuration comprising two solar cells with distinct quenching constants is investigated with the objective of paving the way for enhanced proton therapy dosimetry. METHODS: Two solar cells with different quenching constants were used to estimate the proton LET distribution. Detector characteristics (e.g., dose linearity and dose-rate dependency) of the solar cells were evaluated to assess their suitability for dosimetry applications. First, using a reference beam condition, the quenching constants of the two solar cells were determined according to the modified Birks equation. The signal ratios of the two solar cells were then evaluated according to proton LET in relation to the estimated quenching constants. The proton LET distributions of six test beams were obtained by measuring the signal ratios of the two solar cells at each depth, and the ratios were evaluated by comparing them with those calculated by Monte Carlo simulation. RESULTS: The detector characterization of the two solar cells including dose linearity and dose-rate dependence affirmed their suitability for use in dosimetry applications. The maximum difference between the LET measured using the two solar cells and that calculated by Monte Carlo simulation was 2.34 keV/µm. In the case of the dose distribution measured using the method proposed in this study, the maximum difference between range measured using the proposed method and that measured using a multilayered ionization chamber was 0.7 mm. The expected accuracy of simultaneous LET and dose distribution measurement using the method proposed in this study were estimated to be 3.82%. The signal ratios of the two solar cells, which are related to quenching constants, demonstrated the feasibility of measuring LET and dose distribution simultaneously. CONCLUSION: The feasibility of measuring proton LET and dose distribution simultaneously using two solar cells with different quenching constants was demonstrated. Although the method proposed in this study was evaluated using a single channel by varying the measuring depth, the results suggest that the proton LET and dose distribution can be simultaneously measured if the detector is configured in a multichannel form. We believe that the results presented in this study provide the envisioned transition to a multichannel configuration, with the promise of substantially advancing proton therapy's accuracy and efficacy in cancer treatment.

Analytical parameterization of Bragg curves for proton beams in muscle, bone, and polymethylmethacrylate.

Proton dose calculation in media other than water may be of interest for either research purposes or clinical practice. Current study aims to quantify the required parameters for analytical proton dosimetry in muscle, bone, and PMMA. Required analytical dosimetry parameters were extracted from ICRU-49 report and Janni study. Geant4 Toolkit was also used for Bragg curve simulation inside the investigated media at different proton energies. Calculated and simulated dosimetry data were compared using gamma analysis. Simulated and calculated Bragg curves are consistent, a fact that confirms the validity of reported parameters for analytical proton dosimetry inside considered media. Furthermore, derived analytical parameters for these media are different from those of water. Listed parameters can be reliably utilized for analytical proton dosimetry inside muscle, bone, and PMMA. Furthermore, accurate proton dosimetry inside each medium demands dedicated analytical parameters and one is not allowed to use the water coefficients for non-water media.

The impact of the titanium cranial hardware in proton single-field uniform dose plans.

BACKGROUND: Neurosurgical cranial titanium mesh and screws are commonly encountered in postoperative radiation therapy. However, only a limited number of reports are available in the context of proton therapy, resulting in a lack of consensus among the proton centers regarding the protocol for handling the hardware. PURPOSE: This study is to examine the impact of the hardware in proton plans. The results serve as evidence for proton centers to generate standard operating procedures to manage the hardware in proton treatment. METHODS: Plans with different gantry angles and material overrides are generated on the CT images of a phantom made of the hardware. The dose distributions of the plans with and without material override, at different depths are compared. Films and ionization chambers are used to measure the plans and the measurements are compared to the treatment planning system (TPS) calculations by gamma analysis. RESULTS: There are some overdose and underdose regions downstream of the hardware. The overdose and underdose values are within a few percent of the prescribed dose when multiple fields with large hinge angles are used. The gamma analysis results show that the measurements agree with the TPS calculations within limits that are clinically relevant. CONCLUSION: The study has demonstrated the influence of the hardware on proton plans. Based on the result of this study, a standard operating procedure of managing the hardware has been implemented in our clinic.

Preliminary Investigation of the Efficacy and Indications of Proton Beam Therapy for Stage IV Pancreatic Adenocarcinoma.

BACKGROUND: The present study aimed to evaluate proton beam therapy (PBT) for stage IV pancreatic adenocarcinoma and its metastases and define the criteria for eligibility. Materials and methods: We retrospectively evaluated the patients who had a histopathological diagnosis of pancreatic adenocarcinoma, had progressed to stage IV, and underwent PBT for both the primary and some metastatic lesions between 2017 and 2022. PBT was performed using the passive scattering technique. RESULTS: Sixteen patients (median age, 72 years; range, 55-85 years) were enrolled. All patients had stage IV pancreatic cancer at the initiation of PBT. The median duration from the date of stage IV diagnosis to the initiation of PBT was 5.8 (range, 0.4-13.5) months. Three patients had been diagnosed as having recurrent stage IV cancer at other institutions before their referral to our hospital because they had local recurrence and distant metastases after the resection of the primary tumor. Chemotherapy was as follows: pre-PBT, 0, 1, 2, and 3 lines in 4, 7, 4, and 1 patients, respectively; concurrent with PBT, 0 and 1 line in 11 and 5 patients, respectively; post-PBT, 0 and 1 line in 5 and 5 patients, respectively; and unknown, 6 patients. The median survival times (MSTs) from the date of stage IV diagnosis for the with or without non-irradiated active metastatic tumor were 11.4 and 20.1 months, respectively. Univariate analysis revealed that the performance status (PS) levels (p < 0.01), the carbohydrate antigen (CA) 19-9 tumor marker levels (p < 0.01), active tumors not treated with irradiation (p = 0.02), and with or without post-PBT chemotherapy (p < 0.01) were statistically significant factors. Multivariate analysis revealed that the CA 19-9 tumor marker levels (p= 0.04), the number of metastatic lesions (p = 0.049), and with or without non-irradiated active metastatic tumors (p = 0.02) were significant factors. CONCLUSION: PBT is indicated when the number of metastases is limited to ≤ 4 lesions and all tumors can be irradiated within the smallest possible number of irradiation fields that can be performed within the patient's tolerable time, which is a subjective duration that depends on the patient's reaction during each session. It may be a viable treatment option for patients with oligometastatic pancreatic cancer.

Moderately hypofractionated proton beam therapy for localized prostate cancer: 5-year outcomes of a phase II trial.

The usefulness of moderately hypofractionated radiotherapy for localized prostate cancer has been extensively reported, but there are limited studies on proton beam therapy (PBT) using similar hypofractionation schedules. The aim of this prospective phase II study is to confirm the safety of a shortened PBT course using 70 Gy relative biological effectiveness (RBE) in 28 fractions. From May 2013 to June 2015, 102 men with localized prostate cancer were enrolled. Androgen deprivation therapy was administered according to risk classification. Toxicity was assessed using Common Terminology Criteria for Adverse Events version 4.0. Of the 100 patients ultimately evaluated, 15 were classified as low risk, 43 as intermediate risk, and 42 as high risk. The median follow-up time of the surviving patients was 96 months (range: 60-119 months). The 5-year cumulative incidences of grade 2 gastrointestinal/genitourinary adverse events were 1% (95% CI: 0.1-6.9) and 4% (95% CI: 1.5-10.3), respectively; no grade ≥ 3 gastrointestinal/genitourinary adverse events were observed. The current study revealed a low incidence of late adverse events in prostate cancer patients treated with moderately hypofractionated PBT of 70 Gy (RBE) in 28 fractions, indicating the safety of this schedule.

Comparing 90-Day Postoperative Mortality After Neoadjuvant Proton-Based Versus Photon-Based Chemoradiotherapy for Esophageal Cancer.

Purpose: Evidence suggests that proton-beam therapy (PBT) results in less toxicity and postoperative complications compared to photon-based radiotherapy in patients who receive chemoradiotherapy followed by esophagectomy for cancer. Ninety-day mortality (90DM) is an important measure of the postoperative (nononcologic) outcome as proxy of quality-of-care. We hypothesize that PBT could reduce 90DM compared to photon-based radiotherapy. Materials and Methods: From a single-center retrospective database patients treated with chemoradiotherapy before esophagectomy for cancer were selected (1998-2022). Univariable logistic regression was used to study the association of radiotherapy modality with 90DM. Three separate methods were applied to adjust for confounding bias, including multivariable logistic regression, propensity score matching, and inverse probability of treatment weighting. Stratified analysis for the age threshold that maximized the difference in 90DM (ie, ≥67 vs <67 years) was performed. Results: A total of 894 eligible patients were included and 90DM was 5/202 (2.5%) in the PBT versus 29/692 (4.2%) in the photon-based radiotherapy group (P = .262). After adjustment for age and tumor location, PBT versus photon-based radiotherapy was not significantly associated with 90DM (P = .491). The 90DM was not significantly different for PBT versus photon-based radiotherapy in the propensity score matching (P = .379) and inverse probability of treatment weighting cohort (P = .426). The stratified analysis revealed that in patients aged ≥67 years, PBT was associated with decreased 90DM (1.3% vs 8.8%; P = .026). Higher age significantly increased 90DM risk within the photon-based radiotherapy (8.8% vs 2.7%; P = .001), but not within the PBT group (1.3% vs 3.2%; P = .651). Conclusion: No statistically significant difference was observed in postoperative 90DM after esophagectomy for cancer between PBT and photon-based neoadjuvant chemoradiotherapy. However, among older patients a signal was observed that PBT may reduce 90DM risk.

Proton Beam Therapy for Intrahepatic Cholangiocarcinoma: A Multicenter Prospective Registry Study in Japan.

Introduction: Intrahepatic cholangiocarcinoma (ICC) can be treated with chemotherapy in unresectable cases, but outcomes are poor. Proton beam therapy (PBT) may provide an alternative treatment and has good dose concentration that may improve local control. Methods: Fifty-nine patients who received initial PBT for ICC from May 2016 to June 2018 at nine centers were included in the study. The treatment protocol was based on the policy of the Japanese Society for Radiation Oncology. Forty patients received 72.6-76 Gy (RBE) in 20-22 fr, 13 received 74.0-76.0 Gy (RBE) in 37-38 fr, and 6 received 60-70.2 Gy (RBE) in 20-30 fr. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. Results: The 59 patients (35 men, 24 women; median age: 71 years; range: 41-91 years) had PS of 0 (n = 47), 1 (n = 10), and 2 (n = 2). Nine patients had hepatitis and all 59 cases were considered inoperable. The Child-Pugh class was A (n = 46), B (n = 7), and unknown (n = 6); the median maximum tumor diameter was 5.0 cm (range 2.0-15.2 cm); and the clinical stage was I (n = 12), II (n = 19), III (n = 10), and IV (n = 18). At the last follow-up, 17 patients were alive (median follow-up: 36.7 months; range: 24.1-49.9 months) and 42 had died. The median OS was 21.7 months (95% CI: 14.8-34.4 months). At the last follow-up, 37 cases had recurrence, including 10 with local recurrence. The median PFS was 7.5 months (95% CI: 6.1-11.3 months). In multivariable analyses, Child-Pugh class was significantly associated with OS and PFS, and Child-Pugh class and hepatitis were significantly associated with local recurrence. Four patients (6.8%) had late adverse events of grade 3 or higher. Conclusion: PBT gives favorable treatment outcomes for unresectable ICC without distant metastasis and may be particularly effective in cases with large tumors.

Late Changes in Renal Volume and Function after Proton Beam Therapy in Pediatric and Adult Patients: Children Show Significant Renal Atrophy but Deterioration of Renal Function Is Minimal in the Long-Term in Both Groups.

To compare late renal effects in pediatric and adult patients with malignancies after PBT involving part of the kidney. A retrospective study was conducted to assess changes in renal volume and function in 24 patients, including 12 children (1-14 years old) and 12 adults (51-80 years old). Kidney volumes were measured from CT or MRI images during follow-up. Dose-volume histograms were calculated using a treatment planning system. In children, the median volume changes for the irradiated and control kidneys were -5.58 (-94.95 to +4.79) and +14.92 (-19.45 to +53.89) mL, respectively, with a relative volume change of -28.38 (-119.45 to -3.87) mL for the irradiated kidneys. For adults, these volume changes were -22.43 (-68.7 to -3.48) and -21.56 (-57.26 to -0.16) mL, respectively, with a relative volume change of -5.83 (-28.85 to +30.92) mL. Control kidneys in children exhibited a marked increase in size, while those in adults showed slight volumetric loss. The percentage of irradiated volume receiving 10 Gy (RBE) (V10) and 20 Gy (RBE) (V20) were significantly negatively associated with the relative volume change per year, especially in children. The CKD stage based on eGFR for all patients ranged from 1 to 3 and no cases with severe renal dysfunction were found before or after PBT. Late effects on the kidneys after PBT vary among age groups. Children are more susceptible than adults to significant renal atrophy after PBT. V10 and V20 might serve as predictors of the degree of renal atrophy after PBT, especially in children. PBT has a minimal impact on deterioration of renal function in both children and adults.

Proton Therapy in Non-Rhabdomyosarcoma Soft Tissue Sarcomas of Children and Adolescents.

This paper provides insights into the use of Proton Beam Therapy (PBT) in pediatric patients with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS). NRSTS are a heterogeneous group of rare and aggressive mesenchymal extraskeletal tumors, presenting complex and challenging clinical management scenarios. The overall survival rate for patients with NRSTS is around 70%, but the outcome is strictly related to the presence of various variables, such as the histological subtype, grade of malignancy and tumor stage at diagnosis. Multimodal therapy is typically considered the preferred treatment for high-grade NRSTS. Radiotherapy plays a key role in the treatment of children and adolescents with NRSTS. However, the potential for radiation-induced side effects partially limits its use. Therefore, PBT represents a very suitable therapeutic option for these patients. The unique depth-dose characteristics of protons can be leveraged to minimize doses to healthy tissue significantly, potentially allowing for increased tumor doses and enhanced preservation of surrounding tissues. These benefits suggest that PBT may improve local control while reducing toxicity and improving quality of life. While clear evidence of therapeutic superiority of PBT over other modern photon techniques in NRSTS is still lacking-partly due to the limited data available-PBT can be an excellent treatment option for young patients with these tumors. A dedicated international comprehensive collaborative approach is essential to better define its role within the multidisciplinary management of NRSTS. Shared guidelines for PBT indications-based on the patient's age, estimated outcome, and tumor location-and centralization in high-level referral centers are needed to optimize the use of resources, since access to PBT remains a challenge due to the limited number of available proton therapy facilities.