Proton Therapy Research Articles

1348: Clinical application of a probabilistic robustness evaluation tool for proton therapy treatments

1348: Clinical application of a probabilistic robustness evaluation tool for proton therapy treatments

1028: Is volumetric repainting needed to minimize interplay induced dose effects in lung proton therapy?

1028: Is volumetric repainting needed to minimize interplay induced dose effects in lung proton therapy?

777: Initial evaluation of real-time gated proton therapy for prostate cancer in Singapore

777: Initial evaluation of real-time gated proton therapy for prostate cancer in Singapore

936: Neutron doses to staff and comforters from clinical treatments in proton therapy centres

936: Neutron doses to staff and comforters from clinical treatments in proton therapy centres

1265: Comparison of total out-of-field dose in 6 MV VMAT and proton therapy for classical Hodgkin lymphoma

1265: Comparison of total out-of-field dose in 6 MV VMAT and proton therapy for classical Hodgkin lymphoma

548: Outcome of childhood-onset craniopharyngioma treated at the West German Proton Therapy Centre Essen

548: Outcome of childhood-onset craniopharyngioma treated at the West German Proton Therapy Centre Essen

753: MR-guided proton therapy: Influence of magnetic fields and air gaps on TLD response

753: MR-guided proton therapy: Influence of magnetic fields and air gaps on TLD response

2608: Rectal and bladder LET in patients with vs without morbidity after proton therapy of prostate cancer

2608: Rectal and bladder LET in patients with vs without morbidity after proton therapy of prostate cancer

831: Online-adaptive proton therapy: Feasibility of prompt-gamma verification for CBCT-based adapted plan

831: Online-adaptive proton therapy: Feasibility of prompt-gamma verification for CBCT-based adapted plan

Current state of proton therapy for tumors of the central nervous system in Spain: physical bases, indications, controversies and perspectives.

The unique biophysical properties of proton therapy (PT), regarding the precise dose distribution, a remarkable better sparing of surrounding normal tissues, and the decreasing costs have promoted the spread of this technique worldwide. In Spain, eleven new PT centers, added to the currently two in function, are expected to be available in the near future. Indications for PT are currently evolving. The suitability of PT in central nervous system tumors of the adult population has been extrapolated from the favorable experience in children and adolescents. Given the lack of appropriate randomized trials, controversies remain regarding its use in lower grade tumors, re-irradiation, and other clinical scenarios in which an a priori dose distribution benefit is expected compared to photon-based radiotherapy. PT is a reasonable option in many brain and spinal tumors associating long life expectancy, in which cognitive decline, and the appearance of radiation-induced neoplasms can be minimized.Estado actual de la terapia con protones en los tumores del sistema nervioso central en España: bases físicas, indicaciones, controversias y perspectivas.

Robust IMPT and follow-up toxicity in skull base chordoma and chondrosarcoma-asingle-institution clinical experience.

Chordomas and chondrosarcomas of the skull base are rare, slowly growing malignant bone neoplasms. Despite their radioresistant properties, proton therapy has been successfully used as an adjunct to resection or as adefinitive treatment. Herewith, we present our experience with robustly optimized intensity-modulated proton therapy (IMPT) and related toxicities in skull base chordoma and chondrosarcoma patients treated at HollandPTC, Delft, the Netherlands. Clinical data, treatment plans, and acute toxicities of patients treated between July 2019 and August 2021 were reviewed. CT and 3.0T MRI scans for treatment planning were performed in supine position in athermoplastic mold. In total, 21dose optimization and 28dose evaluation scenarios were simulated. Acute toxicity was scored weekly before and during the treatment according to the CTCAE v4.0. Median follow-up was 35months (range 12-36months). Overall, 9chordoma and 3chondrosarcoma patients with 1-3 resections prior to IMPT were included; 4patients had titanium implants. Brainstem core and surface and spinal cord core and surface were used for nominal plan robust optimization in 11, 10, 8, and 7patients, respectively. Middle ear inflammation, dry mouth, radiation dermatitis, taste disorder, and/or alopecia of grades 1-3 were noted at the end of treatment among 6patients without similar complaints at inclusion; symptoms disappeared 3months following the treatment. Robustly optimized IMPT is clinically feasible as apostoperative treatment for skull base chordoma and chondrosarcoma patients. We observed acceptable early toxicities (grade1-3) that disappeared within the first 3months after irradiation.

The Latest Developments and Applications in Radiation Therapy Equipment and Technology

This paper reviews the latest technological developments in contemporary radiation therapy equipment and their significance in clinical applications. It begins with an introduction to the basic principles and historical evolution of radiation therapy, followed by a detailed analysis of common types of radiation therapy equipment, including linear accelerators, Gamma Knives, proton therapy equipment, and heavy ion therapy equipment. For each type, the paper conducts an in-depth comparative analysis of their technical characteristics, covering aspects such as performance, accuracy, therapeutic efficacy, safety, side effects, cost, and maintenance. The paper then explores the latest trends in radiation therapy technology development, such as image-guided radiation therapy (IGRT), intensity-modulated radiation therapy (IMRT), stereotactic radiosurgery (SRS), and adaptive radiation therapy (ART), highlighting their clinical applications and potential through case studies. Finally, the paper looks forward to future development directions in radiation therapy technology, including the research and development of new equipment and technologies, trends in personalized treatment, and the prospects for artificial intelligence in radiation therapy. The aim of this paper is to provide comprehensive references and guidance for research and clinical practice in radiation therapy equipment.

Artificial intelligence-based motion tracking in cancer radiotherapy: A review.

Radiotherapy aims to deliver a prescribed dose to the tumor while sparing neighboring organs at risk (OARs). Increasingly complex treatment techniques such as volumetric modulated arc therapy (VMAT), stereotactic radiosurgery (SRS), stereotactic body radiotherapy (SBRT), and proton therapy have been developed to deliver doses more precisely to the target. While such technologies have improved dose delivery, the implementation of intra-fraction motion management to verify tumor position at the time of treatment has become increasingly relevant. Artificial intelligence (AI) has recently demonstrated great potential for real-time tracking of tumors during treatment. However, AI-based motion management faces several challenges, including bias in training data, poor transparency, difficult data collection, complex workflows and quality assurance, and limited sample sizes. This review presents the AI algorithms used for chest, abdomen, and pelvic tumor motion management/tracking for radiotherapy and provides a literature summary on the topic. We will also discuss the limitations of these AI-based studies and propose potential improvements.

Reducing Radiation Dermatitis for PBS Proton Therapy Breast Cancer Patients Using SpotDelete

PurposeThe purpose of this work was to reduce the severity of radiation dermatitis for breast cancer patients receiving pencil beam scanning proton therapy. The hypothesis was that eliminating proton spots (SpotDelete) in the 0.5 cm skin rind would reduce the potentially higher relative biological effectiveness (RBE) known to occur at the Bragg Peak. Patients and MethodsOur center has been using an in-house developed Python script in RayStation since 2021 to remove spots from the skin rind of breast patients. In this work, we retrospectively reviewed the on-treatment visit data from a cohort of breast patients treated with hypofractionation (16 fractions) before this technique (MinDepth) and after (SpotDelete) to acquire the physician-reported radiation dermatitis scores. We evaluated the delivered treatment plans, calculating the linear energy transfer (LET) and applying 3 variable RBE models, Carabe-Fernandez, Wedenberg, and McNamara. An α/β of 10 was assumed for the skin. ResultsIn the MinDepth cohort (n = 28), grade 1, 2, and 3 dermatitis accounted for 57%, 36%, and 7% of the cases, respectively. For SpotDelete (n = 27), the incidence rate of grade 1 and 2 acute radiation dermatitis was 67% and 37%, respectively. There were 0 instances of grade 3 dermatitis observed in the SpotDelete cohort. The onset of radiation dermatitis in the SpotDelete cohort was delayed compared to MinDepth, occurring 1 week later in the course of treatment. There was no significant difference in LET or in any of the variable RBE models when analyzing the 0.5 cm skin rind between the cohorts. ConclusionDespite the lack of correlation in LET or RBE, SpotDelete has been shown to reduce the severity and onset of radiation dermatitis. Possibly, more research into the α/β for skin and RBE models based on skin cell lines could provide insight into the efficacy of the SpotDelete technique.

Proton pencil beam scanning radiotherapy in the postoperative treatment of p16 positive squamous cell tonsillar cancer – evaluation of toxicity and effectivity

PurposePatients with p16 positive tonsillar cancer (p16 + TC) have an excellent prognosis and long-life expectancy. Deintensification of therapy is a prevalent topic of discussion. Proton radiotherapy is one way to reduce radiation exposure and thus reduce acute and late toxicity. The aim is to evaluate treatment outcomes and toxicity of postoperative treatment with intensity-modulated proton therapy (IMPT).MethodsBetween September 2013 and November 2021, 47 patients with p16 + TC were treated postoperatively with IMPT. Median age was 54.9 (38.2–74.9) years, 31 were males and 16 were females. All patients had squamous cell carcinoma and underwent surgery as a primary treatment. Median dose of radiotherapy was 66 GyE in 33 fractions. Bilateral neck irradiation was used in 39 patients and unilateral in 8. Concomitant chemotherapy was applied in 24 patients.ResultsMedian follow-up time was 4.2 (0.15–9.64) years. Five-year overall survival, relapse free survival and local control were 95.7%, 97.8% and 100%. The most common acute toxicities were dermatitis and mucositis, with grade 2 + in 61.7% and 70.2% of patients. No acute percutaneous gastrostomy insertion was necessary and intravenous rehydration was used in 12.8% of patients. The most common late toxicity was grade 1 xerostomia in 70.2% of patients and grade 2 in 10.6% of patients. Subcutaneous fibrosis of grades 2 and 3 occurred in 17.0% and 2.1% of patients, respectively. One patient developed late severe dysphagia and became PEG-dependent.ConclusionIMPT for the postoperative treatment of p16 + TC is feasible with excellent efficiency and acceptable acute and late toxicity.

PTCOG international survey of practice patterns and trends in utilization of proton therapy for breast cancer

Purpose/objectivesThe indications, techniques, and extent to which proton beam therapy (PBT) is employed for breast cancer are unknown. We seek to determine PBT utilization for breast cancer. Materials/methodsThe Particle Therapy Co-Operative Group (PTCOG) Breast Subcommittee developed an IRB-approved 29-question survey and sent it to breast cancer radiation oncologists at all active PBT centers worldwide in June 2023. Descriptive statistics were used to summarize responses, and comparisons by continent were performed using Fisher’s exact tests. ResultsOf 79 surveys distributed, 28 recipients submitted responses (35 % response rate) representing fifteen U.S., 8 European, and 5 Asian centers (continent response rate 50 %, 38 %, and 18 %, respectively). Overall, 93 % reported treating breast cancer patients with PBT; 13 (50 %) have treated ≥100 breast cancer patients at their center since opening. Most (89 %) have pencil beam scanning technology. Nearly half (46 %) use moderate hypofractionation (15–20 fractions) for regional nodal irradiation and 42 % conventional fractionation (25–30 fractions). More European centers prefer hypofractionation (88 %) vs. Asian (50 %) and U.S. (21 %) centers (p = 0.003). Common patient selection methods were practitioner determination/patient preference (n = 16) and comparative plan evaluation (n = 15). U.S. centers reported the most experience with breast PBT, with 71 % having treated ≥100 breast cancer patients vs. 38 % in Europe and none in Asia (p = 0.001). Of respondent centers, 39 % enrolled ≥75 % of breast PBT patients on a research study. ConclusionUtilization, patient selection methods, and dose-fractionation approaches for breast cancer PBT vary worldwide. These survey data serve as a benchmark from which successor surveys can provide insight on practice pattern evolution.

Response characterization of radiochromic OC-1 films in photon, electron, and proton beams.

Radiochromic film (RCF) dosimeters with their high spatial resolution and tissue equivalent properties are conveniently used for two-dimensional and small-field dosimetry. OC-1 is a new model of RCF dosimeter that was commercially introduced recently. Due to its novelty there is a need to characterize its response in various radiation beam types. To study the response of OC-1 RCFs to megavoltage clinical x-ray, electron, and proton beams, as well as kilovoltage x-ray beams used in a small animal research irradiator. OC-1 RCFs were cut into ∼4×4 cm2 pieces. RCF samples were irradiated at various dose levels in the range 0.5-120Gy using different modalities; a small animal radiation research platform (SARRP) (220 kVp), a medical linear accelerator (6 MV, 10 MV, 15 MV, 6 MV FFF, 10 MV FFF photon beams, as well as 6 and 20 MeV electron beams), and a gantry-mounted proton therapy synchrocyclotron. In order to study any dependency on the fractionation scheme, same dose was delivered at several fractions to a set of films. Different dose rates in the range 200-600 MU/min were delivered to a set of films to investigate any dose rate dependency. The films were scanned pre-irradiation and at 48h post-irradiation using a flatbed scanner. The net optical density (OD) was measured for red, green, and blue color channel for each film. The orientation dependency was studied by scanning the films at eight different orientations. In order to study the temporal evolution of the response of the films, film samples were irradiated at 10 and 50Gy using 6 MV photon beams and were scanned upon irradiation at certain time intervals up to 3 months. The spectral response of the films were studied over the visible range using a spectrometer. For megavoltage photon, electron, and plateau region of the proton beams, we did not observe a significant dependency on the beam quality, dose rate, and fractionation scheme. At the kV beam, an unusual over-response was observed in the films' net OD. An orientation dependency in the response of the films with a sinusoidal trend was observed. The response of the films increased with time following a double or triple exponential trend. The spectral absorption peaks were blue-shifted with dose. OC-1 RCFs were found to be reliable dosimeters with no significant energy dependency in MV range for photon and electron beams including the FFF beams. They over-respond when irradiated bykV x-ray beams compared to MV x-ray beams. Caution must be exercised to maintain the orientation of the films when scanning. Due to the temporal growth in the net OD of the films, same post-irradiation time interval must be used for scanning the calibration and test films.

Investigation of linear energy transfer (LET)-dependence behavior and dosimetric response of a flat-panel detector in pencil beam scanning proton therapy

PurposeThis study aims to elucidate the dependence of the flat-panel detector’s response on the linear energy transfer (LET) and evaluate the practical viability of employing flat-panel detectors in proton dosimetry applications through LET-dependent correction factors. MethodsThe study assessed the flat-panel detector’s response across varying depths using solid water and distinct 100, 150, and 200 MeV proton beams by comparing the flat-panel readings against reference doses measured with an ionization chamber. A Monte Carlo code was used to derive LET values, and an LET-dependent response correction factor was determined based on the ratio of the uncorrected flat-panel dose to the ionization chamber dose. The implications of this under-response correction were validated by applying it to a measurement involving a spread-out Bragg peak (SOBP), followed by a comparative analysis against doses calculated using the Monte Carlo code and MatriXX ONE measurement. ResultsThe association between LET and the flat-panel detector’s under-response displayed a positive correlation that intensified with increasing LET values. Notably, with a 10 keV/µm LET value, the detector’s under-response reached 50 %, while the measurement points in the SOBP demonstrated under-response greater than 20 %. However, post-correction, the adjusted flat-panel profile closely aligned with the Monte Carlo profile, yielding a 2-dimensional 3 %/3mm gamma passing rate of 100 % at various verification depths. ConclusionThis study successfully defined the link between LET and the responsiveness of flat-panel detectors for proton dosimetric measurements and established a foundational framework for integrating flat-panel detectors in clinical proton dosimetry applications.

Secondary Cancer in Prostate Cancer Patients Treated With Advanced External Beam Radiation Therapy

PurposePrevious studies have shown that external beam radiation therapy is associated with an increased risk of second primary cancer (SPC) among prostate cancer (PCa) patients, but the relative risks associated with newer and advanced radiation modalities such as proton beam therapy (PBT) and stereotactic body radiation therapy (SBRT) are unclear. This study aimed to assess the relative probability of SPC among patients treated with these newer modalities compared to intensity-modulated radiation therapy (IMRT). Patients and MethodsUsing the National Cancer Database (NCDB), N0M0 PCa cases diagnosed between 2004 and 2018 were identified. Second primary cancer probabilities were compared among those treated with curative-intent PBT, SBRT, and IMRT. Multivariable logistic regression and inverse probability of treatment weighting were used to generate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). ResultsIn total, 133 898 patients were included, with a median age of 69 years and median follow-up of 6.4 years. As their first course of treatment, 3420 (2.6%) received PBT, 121 211 (90.5%) received IMRT, and 9267 (6.9%) received SBRT. Compared with IMRT, PBT and SBRT were associated with lower SPC risk (aORs and 95% CIs, PBT: 0.49 [0.40-0.60], SBRT: 0.57 (0.51-0.63), P < .001). Inverse probability of treatment weighting analyses corroborated these results. ConclusionIn this large national cohort, PBT and SBRT performed similarly and were associated with reduced SPC risk compared to IMRT when used as the first course of treatment.

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.