Modulated Radiation Therapy Treatment Research Articles

Utility of learning health systems in radiation oncology.

413 Background: Current health information systems lack a robust framework for longitudinal integration of internal experiences and external evidence into existing workflows. The result is labor intensive, error-prone and fragmented systems plagued with process gaps. Learning health systems (LHS) can be a potential solution to address these gaps. We created and implemented a novel LHS framework in radiation oncology (RO). We hypothesize that this framework can be leveraged to identify and implement opportunities for improvement using a patient-oriented endpoint of time from radiation simulation to treatment start (RSTS). Methods: An RO-LHS was developed through a collaboration between an academic, multi-facility radiation oncology department and an industry partner (Medlever). The end-to-end clinical workflow was embedded into the Medlever platform following an interdisciplinary, iterative analysis with representatives from key teams (clerical, finance and clinical). A novel nomenclature was created to label standardized, customizable templates, which choreograph logic-driven tasks that cover all sub-steps of RSTS. The primary endpoint of RSTS was compared pre- and post-implementation, stratified by key variables, such as facility, staff member, and radiation treatment modality. Results: The iterative workflow analysis identified >700 variables and decision points necessary for >200 cancer and benign conditions routinely managed in RO. >450 treatment protocols were templated.180 logic-driven tasks were created and linked to key parameters, resulting in a choregraphed precision workflow for each patient. Using the first iteration of the build, a total of 512 patients were managed during a 50-day period (03/01/2024-04/20/2024) and were compared to 2875 patients treated prior to implementation. Post-implementation, RSTS was shortened by 36.4% (p<0.001). We identified significant differences in RSTS by radiation modalities (protons vs all others), across facilities, and by providers (p<0.01 for all). Analysis of fractional domain of RSTS, 56% of the time was driven by physician-directed tasks, while 44% was comprised of physics and dosimetry-driven work. Physician-directed tasks had the greatest heterogeneity in time to completion. The biggest variation was noted for the contouring completion task. Significant differences were identified by provider (p<0.001) in nearly each step of the process, including steps not directly tied to physician’s work. Conclusions: Through an inter-disciplinary implementation of the first iteration of a LHS in our RO department, we have significantly shortened RSTS. The implementation and analysis has also enabled us to better understand underlying heterogeneities and identify further opportunities for optimization of RSTS. An LHS framework provides a generalizable solution that could be adapted in other RO clinics.

Comprehensive assessment of pain characteristics, quality of life, and pain management in cancer patients: a multi-center cross-sectional study

IntroductionPain is the most common complaint among cancer patients, significantly impairing their health-related quality of life (HRQOL). There is limited evidence on the characteristics of pain among cancer patients in Nepal with low-resource settings.ObjectivesThe primary objective of this study was to evaluate the clinical characteristics of pain, factors influencing pain intensity, and the association of pain severity with quality of life (QoL) among cancer patients. Secondary objectives included investigating perceived barriers to pain management and medication adherence among these patients.MethodsThis multi-center, cross-sectional study enrolled adult patients (over 18 years old) with reported cancer diagnoses experiencing pain. Socio-demographic characteristics (e.g., age, gender, educational status), clinical characteristics (e.g. cancer diagnosis, staging), and pain characteristics (e.g., duration, type, location, medicines used for pain management, etc.) were recorded. Outcomes were assessed using the Numeric rating scale (NRS), Pain management Index, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire, Barriers Questionnaire II, Medication Adherence Rating Scale, and Hospital Anxiety and Depression Scale.ResultsFour hundred and eight patients participated in the study. The mean ± SD age was 54.87 ± 15.65, with 226 patients (55.4%) being female. The most common cancer diagnoses were cervical (17.6%), lung (11.8%), and colon/rectum (12.0%) cancers. The most common pain locations were the head and neck (27.0%); a majority (55.6%) reported pain duration of more than 3 months. Nociceptive pain was reported by 42.4% of patients; the mean ± SD of NRS was 4.31 ± 2.69, with 32.4% of patients experiencing moderate pain. Patients with mixed pain type (B = 1.458, p < 0.001) or pain in multiple sites (B = 1.175, p < 0.001), lower Karnofsky Performance Status (KPS) (B = -1.308, p < 0.001), and specific cancer diagnoses such as prostate (B = -2.045, p = 0.002), pancreatic (B = 1.852, p = 0.004), oesophageal (B = 1.674, p = 0.012), and ovarian cancer (B = 1.967, p = 0.047), experienced varying degrees of increased NRS score. The combined chemotherapy and radiotherapy treatment modality was associated with a lower NRS score (B = -0.583, p = 0.017). A significant inverse relationship was observed between pain severity and global health status/QoL (B = -37.36, p < 0.001. Key barriers to pain management included moderate perceptions of physiological effects, communication issues between doctors and patients, and concerns about the harmful effects of pain medicine. The prevalence of non-adherence to pain medications was 13.97%.ConclusionIn conclusion, this study highlights the multi-faceted nature of pain management and QoL for cancer patients in Nepal with low-resource settings. These findings underscore the multifactorial nature of pain perception in cancer patients, with mixed pain types, pain in multiple sites, lower KPS, and specific cancer diagnoses, all contributing significantly to pain severity. Additionally, pain severity was associated with declining QoL. These findings contribute valuable insights into the complex aspects of cancer pain and its broader implications for the well-being of patients, offering a foundation for targeted interventions and improved pain management strategies in the context of cancer care in low-resource settings.

The expanding role of radiation oncology across the prostate cancer continuum.

Radiotherapy is used in the treatment of prostate cancer in a variety of disease states with significant reliance on imaging to guide clinical decision-making and radiation delivery. In the definitive setting, the choice of radiotherapy treatment modality, dose, and fractionation for localized prostate cancer is determined by the patient's initial risk stratification and other clinical considerations. Radiation is also an option as salvage therapy in patients with locoregionally recurrent disease after prior definitive radiation or surgery. In recent years, the role of radiation has expanded for patients with metastatic disease, including prostate-directed radiotherapy in de novo low volume metastatic disease, metastasis-directed therapy for oligorecurrent disease, and palliative management of symptomatic metastases in the advanced setting. Here we review the expanding role of radiation in the treatment of prostate cancer in the definitive, locoregionally recurrent, and metastatic settings, as well as highlight the role of imaging in clinical reasoning, radiation planning, and treatment delivery.

Abstract PO4-07-01: Deep learning guided radiation therapy machine selection via a multi-headed dose prediction model

Abstract Background: Accelerated Partial Breast Irradiation (APBI) is gaining popularity for the treatment of appropriately selected breast cancer patients in lieu of whole breast irradiation regimens due to its comparable clinical outcomes and improved patient convenience and quality-of-life. Currently, several machines for delivery of APBI are available such as CyberKnife, Elekta Unity, Varian Ethos and Varian TrueBeam. Each treatment machine yields a unique distribution of radiation dose, so a given modality may afford particular advantages or liabilities based on a patient’s anatomy. Existing methods for identification of an ideal modality that best suits a patient’s unique anatomical features are generally lacking, manual, and resource intensive. To overcome this limitation and personalize modality selection, we propose a deep learning (DL) based multi-modality dose prediction model. The model takes a patient’s computed tomography (CT) scan, segmented planning target volumes (PTVs) and segmented organs at risk (OARs) as input, and outputs predicted dose distributions for all trained modalities. Differences may then be evaluated between each radiation treatment modality’s corresponding dose distribution and dose volumetric histograms (DVH) to select the optimal modality for each patient. Methods: Our dataset contains 16 partial breast patients, each with 4 unique treatment plans generated for 4 distinct modalities – CyberKnife, Elekta Unity, Varian Ethos and Varian Truebeam. 10, 2, and 4 patients were dedicated to the train, validation and test datasets respectively. Our model’s architecture is a U-net with a shared encoder and 4 independent dose decoders, in which each decoder predicts dose for one modality. Each training patient’s CT scan, PTVs, OARs, and a PTV distance map are input to the model during training, and the shared encoder shares the input data’s latent representations with each of the 4 decoders. The 4 distinct dose distributions from each training patient are used as labels for the 4 corresponding decoders to supervise model training. The mean squared error, mean squared log error, and DVH losses are minimized during model training. The model trained until validation loss converged. The 4 dose distributions were predicted in ~ 1 minute per test patient, yielding 16 dose distributions in the test dataset. Model performance across the test dataset was evaluated by calculation of the mean absolute percent error (MAPE) of dose differences within the patient’s body between the model’s predicted doses and label doses, relative to patient prescription dose. Results: The performance of the multi-modal dose prediction model was evaluated in terms of dose differences throughout each patient’s body across the 16 test dose distributions as compared to the actual planned doses. The average MAPE of the multi-modal dose predictions was 1.27 ± 0.38% of a patient’s prescription dose as compared to the actual planned dose across the test dataset. For a prescription dose of 3000 cGy, that corresponds to an average MAPE of 38.1 ± 11.4 cGy. Conclusion: Our multi-modality dose prediction model’s novelty lies in its rapid provision and comparison of accurate and detailed dosimetric data for each treatment modality. This model can empower treating radiation oncologists to make informed decisions in radiation therapy machine selection on a patient-by-patient basis, potentially optimizing radiation treatment plans by reduction of delivered dose to organs at risk. Table. Citation Format: Austen Maniscalco, Ezek Mathew, David Parsons, Asal Rahimi, Mona Arbab, Prasanna Alluri, Xingzhe Li, Mu-Han Lin, Steve Jiang, Dan Nguyen. Deep learning guided radiation therapy machine selection via a multi-headed dose prediction model [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-07-01.

Dosimetry and Biochemical Comparison of Early Radiation-Induced Lung Toxicity in Breast Cancer Patients Treated with 3D-CRT and IMRT: the Role of Serum Interleukin-6 and Pulmonary Surfactant Protein-D.

Radiation-induced lung disease is a potentially fatal, dose-limiting toxicity commonly seen after radiotherapy of thoracic malignancies, including breast cancer. To evaluate and compare the early lung toxicity induced by 3D-CRT and IMRT radiotherapy treatment modalities in breast cancer female patients using biochemical, dosimetry and clinical data. this study included 15 normal healthy controls, 15 breast cancer patients treated with IMRT, and 15 breast cancer patients treated with 3D-CRT. One blood sample was obtained from the control group and 3 blood samples were withdrawn from cases before RT, after RT and after 3 months of RT. IMRT delivered higher radiation dose to the breast tumor and lower doses to the lung as an organ at risk. There was a non-significant increase in the serum levels of IL-6 before IMRT and 3D-CRT compared with its levels in the control group. There were significant increases in serum levels of IL-6 after RT (IMRT and 3DCRT) compared with its levels before RT. There was a non-significant decrease in the serum levels of IL-6 after 3 months of RT (IMRT and 3D-CRT) compared with its serum levels immediately after RT. There was a non-significant increase in the serum levels of SP-D before RT (IMRT and 3D-CRT) compared with its levels in the control group. There were significant-increases in serum levels of SP-D after RT (IMRT and 3D-CRT) compared with its levels before RT. There was a non-significant decrease in the serum levels of SP-D after 3 months of radiotherapy (IMRT and 3D-CRT) compared with its serum levels immediately after RT. serum of levels IL-6 and SP-D can be used to diagnose the occurrence of early lung toxicity due to radiotherapy and the rate of recovery from radiation pneumonitis is apparent in case of IMRT than 3D-CRT.

Understanding and Managing Pineal Parenchymal Tumors of Intermediate Differentiation: An In-Depth Exploration from Pathology to Adjuvant Therapies.

Pineal parenchymal cell tumors constitute a rare group of primary central nervous system neoplasms (less than 1%). Their classification, especially the intermediate subtype (PPTIDs), remains challenging. A literature review was conducted, navigating through anatomo-pathological, radiotherapy, and neurosurgical dimensions, aiming for a holistic understanding of these tumors. PPTIDs, occupying an intermediate spectrum of malignancy, reveal diverse histological patterns, mitotic activity, and distinct methylation profiles. Surgical treatment is the gold standard, but when limited to partial removal, radiotherapy becomes crucial. While surgical approaches are standardized, due to the low prevalence of the pathology and absence of randomized prospective studies, there are no shared guidelines about radiation treatment modalities. Surgical removal remains pivotal, demanding a personalized approach based on the tumor extension. This review underscores the considerable variability in treatment approaches and reported survival rates within the existing literature, emphasizing the need for ongoing research to better define optimal therapeutic strategies and prognostic factors for PPTIDs, aiming for further and more detailed stratification among them.

A spatial measure-valued model for radiation-induced DNA damage kinetics and repair under protracted irradiation condition

In the present work, we develop a general spatial stochastic model to describe the formation and repair of radiation-induced DNA damage. The model is described mathematically as a measure-valued particle-based stochastic system and extends in several directions the model developed in Cordoni et al. (Phys Rev E 103:012412, 2021; Int J Radiat Biol 1–16, 2022a; Radiat Res 197:218–232, 2022b). In this new spatial formulation, radiation-induced DNA damage in the cell nucleus can undergo different pathways to either repair or lead to cell inactivation. The main novelty of the work is to rigorously define a spatial model that considers the pairwise interaction of lesions and continuous protracted irradiation. The former is relevant from a biological point of view as clustered lesions are less likely to be repaired, leading to cell inactivation. The latter instead describes the effects of a continuous radiation field on biological tissue. We prove the existence and uniqueness of a solution to the above stochastic systems, characterizing its probabilistic properties. We further couple the model describing the biological system to a set of reaction–diffusion equations with random discontinuity that model the chemical environment. At last, we study the large system limit of the process. The developed model can be applied to different contexts, with radiotherapy and space radioprotection being the most relevant. Further, the biochemical system derived can play a crucial role in understanding an extremely promising novel radiotherapy treatment modality, named in the community FLASH radiotherapy, whose mechanism is today largely unknown.

Effects of tissue heterogeneity and comparisons of collapsed cone and Monte Carlo fast neutron patient dosimetry using the University of Washington clinical neutron therapy system (CNTS)

Fast neutron therapy is a high linear energy transfer (LET) radiation treatment modality offering advantages over low LET radiations. Multileaf collimator technology reduces normal-tissue dose (toxicity) and makes neutron therapy more comparable to MV x-ray treatments. Published clinical-trial and other experiences with fast neutron therapy are reported. Early comparative studies failed to consider differences in target-dose spatial conformality between x-ray and neutron treatments, which is especially important for organs-at-risk close to tumor targets. Treatments planning systems (TPS) for high-energy neutrons lag behind TPS tools for MV x-rays, creating challenges for comparative studies of clinical outcomes. A previously published Monte Carlo model of the University of Washington (UW) Clinical Neutron Therapy System (CNTS) is refined and integrated with the RayStation TPS as an external dose planning/verification tool. The collapsed cone (CC) dose calculations in the TPS are based on measured dose profiles and output factors in water, with the absolute dose determined using a tissue-equivalent ionization chamber. For comparison, independent (external) Monte Carlo simulation computes dose on a voxel-by-voxel basis using an atlas that maps Hounsfield Unit (HU) numbers to elemental composition and density. Although the CC algorithm in the TPS accurately computes neutron dose to water compared to Monte Carlo calculations, calculated dose to water differs from bone or tissue depending largely on hydrogen content. Therefore, the elemental composition of tissue and bone, rather than the material or electron density, affects fast neutron dose. While the CC algorithm suffices for reproducible patient dosimetry in fast neutron therapy, adopting methods that consider tissue heterogeneity would enhance patient-specific neutron dose accuracy relative to national standards for other types of ionizing radiation. Corrections for tissue composition have a significant impact on absolute dose and the relative biological effectiveness (RBE) of neutron treatments compared to other radiation types (MV x-rays, protons, and carbon ions).

A Study on Workload of a Medical Linear Accelerator at a High Throughput Cancer Treatment Centre in Sri Lanka

Radiotherapy bunker design depends on several factors, and among them, workload is one of the important factors. Workload is calculated from the radiation dose delivered at the isocenter. Due to the introduction of new radiotherapy treatment modalities and an increasing number of new cancer patients, there is a higher possibility to increase the workload. Therefore, this study aims to assess the workload of Varian linear accelerator vault at Apeksha Hospital, Maharagama. Data were collected from 1st of August 2020 to 30th November 2020. Dose delivered at isocenter from the 3D-CRT procedures with 6 MV and 15 MV photon energy, the IMRT procedures with 6 MV photon energy and the quality assurance (QA) procedures were collected from ARIA patient management system and transferred into Excel spread sheet for data analysis. The calculated weekly workload was 2326 Gy/week with a 43% contribution from the IMRT procedures with 6 MV, 39% contribution from the 3D-CDT procedures with 6 MV, 16% contribution from the 3D-CDT procedures with 15 MV and 2% contribution from physics workload (QA procedures). The evaluated workload is higher than the NCRP recommended workload of 1000 Gy/week. This study recommends for at least a one-year survey for more accuracy on workload assessment, and also to evaluate the use factor since most of the advanced radiotherapy treatment techniques use high number of monitor units which will increase the leakage radiation.

Sensitivity and specificity of Monte Carlo based independent secondary dose computation for detecting modulation-related dose errors in intensity modulated radiotherapy

BackgroundThe recent availability of Monte Carlo based independent secondary dose calculation (ISDC) for patient-specific quality assurance (QA) of modulated radiotherapy requires the definition of appropriate, more sensitive action levels, since contemporary recommendations were defined for less accurate ISDC dose algorithms. PurposeThe objective is to establish an optimum action level and measure the efficacy of a Monte Carlo ISDC software for pre-treatment QA of intensity modulated radiotherapy treatments. MethodsThe treatment planning system and the ISDC were commissioned by their vendors from independent base data sets, replicating a typical real-world scenario. In order to apply Receiver-Operator-Characteristics (ROC), a set of treatment plans for various case classes was created that consisted of 190 clinical treatment plans and 190 manipulated treatment plans with dose errors in the range of 1.5–2.5%. All 380 treatment plans were evaluated with ISDC in the patient geometry. ROC analysis was performed for a number of Gamma (dose-difference/distance-to-agreement) criteria. QA methods were ranked according to Area under the ROC curve (AUC) and optimum action levels were derived via Youden’s J statistics. ResultsOverall, for original treatment plans, the mean Gamma pass rate (GPR) for Gamma(1%, 1 mm) was close to 90%, although with some variation across case classes. The best QA criterion was Gamma(2%, 1 mm) with GPR > 90% and an AUC of 0.928. Gamma criteria with small distance-to-agreement had consistently higher AUC. GPR of original treatment plans depended on their modulation degree. An action level in terms of Gamma(1%, 1 mm) GPR that decreases with modulation degree was the most efficient criterion with sensitivity = 0.91 and specificity = 0.95, compared with Gamma(3%, 3 mm) GPR > 99%, sensitivity = 0.73 and specificity = 0.91 as a commonly used action level. ConclusionsISDC with Monte Carlo proves highly efficient to catch errors in the treatment planning process. For a Monte Carlo based TPS, dose-difference criteria of 2% or less, and distance-to-agreement criteria of 1 mm, achieve the largest AUC in ROC analysis

Radiation Therapy for Ocular Melanoma – a Narrative Review with Insides from TRIUMF, Canada’s Only Proton Beam Therapy Center

"Ocular melanoma (OM) originates from melanocytes in the eye, predominantly in the uvea, particularly the choroid. The yearly incidence is around six cases per million. OM is not primarily driven by ultraviolet exposure like skin melanoma, but is usually caused by mutations in GNAQ or GNA11. Symptoms like blurry vision and visual field defects appear late. Diagnosis is often made via eye exams, specialized ultrasound, and rarely biopsy. This narrative review describes the radiation treatment modalities of OM and highlights the landscape of proton beam irradiation in Canada. Historically, enucleation was the standard of care for OM. However, current strategies consider tumor size, location, patient age, visual potential, and metastatic presence. Primary treatments include radiation therapy and surgery. Radiation therapy includes plaque brachytherapy (PB), proton beam irradiation (PBI), stereotactic radiosurgery (SRS), and stereotactic radiotherapy (SRT). Surgery includes endoresection, exoresection, and enucleation. Tebentafusp-tebn has been FDA-approved for metastatic cases. PB, the most common radiation therapy for OM, involves radioisotopes delivering radiation into the tumor. Comparable survival rates between PB and enucleation for medium choroidal melanoma have made PB the standard of care. PB has certain limitations, mainly surgical complications. PBI uses a particle accelerator for focused, high-energy proton radiation, yielding high tumor control and survival rates, though the availability of proton facilities is a significant limitation. Vancouver is the only center in Canada for PBI, administered not in a healthcare facility but at TRIUMF (Tri-University Meson Facility). TRIUMF, the world's largest cyclotron particle accelerator, in partnership with BC Cancer and UBC Department of Ophthalmology and Eye Care Center, has treated over 200 ocular melanoma patients between 1995 and 2017, achieving a 91% tumor control rate and 82% five-year survival rate. Emerging combination therapies like Ataxia Telangiectasia Mutated (ATM) protein kinase inhibition before PBI show potential, possibly reducing radiation dose and resistance."

Photon vs. Proton Radiotherapy in the Definitive Treatment of Nasopharyngeal Cancer: Single Institution Experience

Definitive therapy for nasopharyngeal cancer includes chemotherapy and radiation (RT). Common toxicities such as xerostomia, mucositis, and hearing loss are correlated with the RT dose delivered to associated organs at risk. We hypothesized that compared to our historical experience with IMRT, the implementation of proton therapy (PT) would reduce radiation dose to organs at risks without compromising oncologic outcomes. A retrospective review of all non-metastatic stage II-IV nasopharyngeal carcinoma (SCC, lymphoepithelioma, undifferentiated carcinomas) treated with definitive therapy at our institution from 2012-2022. Disease parameters and the mean dose to organs at risk were evaluated. Statistical comparison was made with the chi square test for categorical and Wilcoxon rank sum test for continuous variables. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS), using a log-rank test to compare IMRT and PT. PFS was defined as the time from the start of treatment to the first of either disease progression, relapse or death from any cause. PT was delivered with pencil-beam scanning in all patients. IMRT included multi-field treatment and volumetric-modulated arc therapy. A total of 80 patients were included in analyses: 48 treated with IMRT and 32 with PT. Comparing IMRT to PT cohorts, there was no difference in the median age of patients (51 vs 55 years, p = 0.73), nor the distribution by T stage (p = 0.57) or N stage (p = 0.34) or in the percentage of patients with ECOG 2/3 performance status at presentation (p = 0.11). All but one patient received concurrent systemic therapy and there was no difference in the use of concurrent cisplatin between cohorts (83% vs 78%, p = 0.57). The most common non-cisplatin concurrent regimen was weekly carboplatin and paclitaxel. Induction chemotherapy was more commonly used in patients treated with PT (10.4% vs 25%, p = 0.04) while there was no difference in the use of adjuvant chemotherapy (10.4% vs 9.4%, p = 0.88). Among 42 cases initiating treatment since the opening of our proton center, 32 (76%) have received PT. Comparing IMRT and PT dosimetry, patients treated with PT received significantly lower mean dose to the better spared parotid gland (32.8 vs 25.7 Gy, p = 0.001), lesser spared parotid gland (35.5 vs 31.1 Gy, p = 0.047), better spared cochlea (31.5 vs 25.5 Gy, p = 0.004), lesser spared cochlea (41.8 vs 33.2 Gy, p = 0.004), larynx (44.5 vs 21.7 Gy, p<0.001), and oral cavity (42.6 vs 17.0 Gy, p<0.001). After a median follow-up time of 30 months (45 mos IMRT, 23 mos PT) the estimated 2-year PFS was 63.9% with IMRT and 90.3% with PT (p = 0.047). The estimate of 2-year overall survival was 86.8% with IMRT and 96.8% with PT (p = 0.17). Comparing patients by radiation treatment modality, PT was associated with a statistically significant reduction in mean radiation dose to the parotid glands, cochlea, larynx, and oral cavity with excellent initial oncologic outcomes.

Impact on Radiation Therapy Recommendation and Treatment Modality for Patients with Ductal Carcinoma In Situ Using the 7Gene Biosignature: Analysis of the PREDICT Study

Breast conserving surgery (BCS) followed by adjuvant radiotherapy (RT) has been a mainstay in the treatment of DCIS based on multiple randomized trials demonstrating a local recurrence benefit with RT. However, these studies have failed to identify subsets of patients who did or did not benefit from adjuvant RT after BCS, raising concerns regarding both over and undertreatment. Thus, better prognostic and predictive tools are needed to appropriately risk stratify patients and understand their benefit of RT. The 7-gene predictive DCIS biosignature provides a validated score (DS) for women undergoing BCS that assesses their 10-year risk of in-breast and invasive recurrence with and without adjuvant RT. This trail was designed to evaluate the decision impact of the 7-gene predictive biosignature score on DCIS treatment recommendations. The PREDICT study is a prospective, multi-institutional trial for patients who received DCISionRT testing as part of their routine care. The registry includes females 26 and older who are diagnosed with DCIS, are candidates for BCS, and eligible for RT. Treating physicians completed treatment recommendation forms before and after receiving test reports to capture surgical, radiation and hormonal treatment (HT) recommendations and patient preferences. Analysis was performed in 2,012 patients treated at 63 clinical sites. Median age was 62 years old with 32% grade 3 and 10% size 2.5 cm or greater. Post-test, RT recommendation changed for 38% of patients (p<0.001), with a net reduction of 20% in patients recommended to receive RT(p<0.001). The DCISionRT test results had the greatest impact (OR 26.2, 95% CI 19.1-36.4, when analyzed categorically using DS>3 cut-off; 2.3 per DS, 95% CI 2.1-2.6, when evaluated continuously) on post-test RT recommendation in multivariable analysis when compared to all other factors including patient preference, patient clinical and tumor pathological factors, patient race/ethnicity, treatment facility, physician specialty. The post-test RT recommendation rate increased with increasing DS (0-2, 2-4, 4-10) on a categorical basis, with odds ratios of 6.8 DS (2-4 vs 0-2), and 35.0 for DS (4-10 vs 0-2). After DCISionRT test result, patient preference was the second most important factor in post-testing RT recommendation. There was also a significant change in the modality of RT recommended to 34% of those patients recommended RT pre-test and post-test by radiation oncologists (n = 937), with intensified RT modality for higher DS (p<0.001) and de-escalation for lower DS (p<0.001). This analysis of over 2,000 patients demonstrates significant changes in recommendations to add or omit RT based on the 7-gene predictive. The integration of DCISionRT into clinical decision processes has substantial impact on recommendations aimed at optimal management to prevent over- or under-treatment.

Proton Based Stereotactic Radiotherapy for Skull Base Patients: Dosimetric Comparison to 4 Modern Radiation Treatment Modalities

Re-irradiation with ablative doses to a smaller target volume and strict critical structure constraint is a challenge for modern radiation planning and delivery systems. Several advanced radiation treatment techniques can be used for fractionated stereotactic ablative radiosurgery (FSRS) in select patients with unresectable recurrent head and neck tumors. In this study, in order to better understand the dosimetry advantage of each technique, we compare the stereotactic treatment plans of our new small spot size Hitachi proton treatment unit to those of CyberKnife stereotactic radiosurgery (CK), Gamma Knife radiosurgery (GK), volumetric modulated arc therapy (VMAT), and MR Linac radiotherapy (MRL). Ten FSRS skull base patients treated at our institution using VMAT (n = 5) or GK (n = 5) techniques. Intensity-modulated proton therapy (IMPT) plans were created in Raystation using Monte Carlo dose calculation algorithm. VMAT, CK, GK and MRL plans were generated in RayStation, Accuray Precision, Leksell Gamma Plan, and Monaco treatment planning systems, separately. Planning goals were to achieve the best target coverage of prescribed dose without compromising the critical organs at risk dose volume constraints of the clinical treatment plans. Plans were compared based on percent CTV coverage, Paddick conformity index (PCI), gradient index (GI, V50/V100), dose homogeneity index (HI, (D2-D98)/D50), low dose bath volume (LDBV, ratio of total volume irradiated between 20% and 50% prescription dose and the target volume), beam-on-time (BOT), and mean/maximum doses to brainstems. The median target volume was 15.5 cm3 (range 1.0 - 36.23 cm3). The prescription was 45 Gy in 5 fractions for VMAT patients, and 21 - 27 Gy in 3 fractions for GK patients. The comparison of the treatment plans of these 5 delivery modalities was shown in table. All techniques achieved comparable CTV coverage. GI was superior for GK plans and outstanding in CK and IMPT plans. IMPT plans were also outstanding in regard to BOT and PCI. Significantly improved HI, LDBV and brainstem mean doses were achieved in IMPT plans. For adjacent brainstem and other OARs, maximum doses were comparable among all techniques. In these five advanced radiation therapy modalities, proton therapy SBRT showed dosimetric advantage over other modalities to spare nearby OARs without sacrifice of target coverage. Further studies are needed to utilize this clinical benefit and investigate plan robustness.

Neutron autoradiography with nuclear tracks detectors: an imaging technique for Boron Neutron Capture Therapy

Boron Neutron Capture Therapy (BNCT) is a radiation treatment modality for cancer based on the 10B(n,α)7Li (BNC) reaction. Knowledge of the spatial location of boron atoms is essential when considering a BNCT treatment, since the BNC reaction products cause lethal damage in a range comparable to cell diameter. Neutron autoradiography is a technique able to provide this information with high resolution at relatively low cost. First a boron-loaded biological matrix is laid on a nuclear track detector (NTD). By irradiating this assembly with thermal neutrons, the emitted particles of the BNC reaction produce damaged zones in the NTD along each incident ion trajectory, and by mapping these nuclear tracks boron spatial distribution in the sample can be assessed. In our laboratory, we have established different approaches: high fluence autoradiography (HFA), to observe boron microdistribution through differences in shades of gray; quantitative autoradiography (QTA), which allows the correlation between track density measurements and boron concentration; and UV-C sensitization of polymers (UVC-a), which produces an imprint of the biological material in the NTD, thus improving the spatial resolution. Moreover, we aim to develop a technique using commercial CMOS sensors in order to simultaneously detect the BNC events and the image of the biological sample during irradiation. The objective of this work is to describe the mentioned approaches and to discuss future perspectives.

Hydrogenated amorphous silicon high flux x-ray detectors for synchrotron microbeam radiation therapy

Objective. Microbeam radiation therapy (MRT) is an alternative emerging radiotherapy treatment modality which has demonstrated effective radioresistant tumour control while sparing surrounding healthy tissue in preclinical trials. This apparent selectivity is achieved through MRT combining ultra-high dose rates with micron-scale spatial fractionation of the delivered x-ray treatment field. Quality assurance dosimetry for MRT must therefore overcome a significant challenge, as detectors require both a high dynamic range and a high spatial resolution to perform accurately. Approach. In this work, a series of radiation hard a-Si:H diodes, with different thicknesses and carrier selective contact configurations, have been characterised for x-ray dosimetry and real-time beam monitoring applications in extremely high flux beamlines utilised for MRT at the Australian Synchrotron. Results. These devices displayed superior radiation hardness under constant high dose-rate irradiations on the order of 6000 Gy s−1, with a variation in response of 10% over a delivered dose range of approximately 600 kGy. Dose linearity of each detector to x-rays with a peak energy of 117 keV is reported, with sensitivities ranging from (2.74 ± 0.02) nC/Gy to (4.96 ± 0.02) nC/Gy. For detectors with 0.8 μm thick active a-Si:H layer, their operation in an edge-on orientation allows for the reconstruction of micron-size beam profiles (microbeams). The microbeams, with a nominal full-width-half-max of 50 μm and a peak-to-peak separation of 400 μm, were reconstructed with extreme accuracy. The full-width-half-max was observed as 55 ± 1 μm. Evaluation of the peak-to-valley dose ratio and dose-rate dependence of the devices, as well as an x-ray induced charge (XBIC) map of a single pixel is also reported. Significance. These devices based on novel a-Si:H technology possess a unique combination of accurate dosimetric performance and radiation resistance, making them an ideal candidate for x-ray dosimetry in high dose-rate environments such as FLASH and MRT.

First-Year Experience of Stereotactic Body Radiation Therapy/Intensity Modulated Radiation Therapy Treatment Using a Novel Biology-Guided Radiation Therapy Machine

The aim of this study was to present the first-year experience of treating patients using intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) with a biology-guided radiation therapy machine, the RefleXion X1 system, installed in a clinical setting. A total of 78 patients were treated on the X1 system using IMRT and SBRT from May 2021 to May 2022. Clinical and technical data including treatment sites, number of pretreatment kilovoltage computed tomography (kVCT) scans, beam-on time, patient setup time, and imaging time were collected and analyzed. Machine quality assurance (QA) results, machine performance, and user satisfactory survey were also collected and reported. The most commonly treated site was the head and neck (63%), followed by the pelvis (23%), abdomen (8%), and thorax (6%). Except for 5 patients (6%) who received SBRT treatments for bony metastases in the pelvis, all treatments were conventionally fractionated IMRT. The number of kVCT scans per fraction was 1.2 ± 0.5 (mean ± standard deviation). The beam-on time was 9.2 ± 3.5 minutes. The patient setup time and imaging time per kVCT was 4.8 ± 2.6 minutes and 4.6 ± 1.5 minutes, respectively. The daily machine output deviation was 0.4 ± 1.2% from the baseline. The patient QA had a passing rate of 97.4 ± 2.8% at 3%/2 mm gamma criteria. The machine uptime was 92% of the total treatment time. The daily QA and kVCT image quality received the highest level of satisfaction. The treatment workflow for therapists received the lowest level of satisfaction. One year after the installation, 78 patients were successfully treated with the X1 system using IMRT and/or SBRT. With the recent Food and Drug Administration clearance of biology-guided radiation therapy, our department is preparing to treat patients using positron emission tomography-guidance via a new product release, which will address deficiencies in the current image-guided radiation therapy workflow.

Predictors of Acute and Late Toxicity in Patients Receiving Chemoradiation for Unresectable Pancreatic Cancer

Patients with pancreatic cancer undergoing chemoradiation therapy may experience acute and chronic side effects. We conducted an exploratory analysis of patients with locally advanced pancreatic cancer (LAPC) undergoing definitive chemoradiation to identify factors influencing the occurrence of gastrointestinal (GI) bleeding, short-term radiation side effects, patterns of failure, and survival. Under an institutional review board-approved protocol, we retrospectively studied patients with LAPC treated with chemoradiation. Statistical models were used to test associations between clinical characteristics and outcomes, including upper GI bleeding, radiation treatment breaks, and weight loss during therapy. Between 1999 and 2012, 211 patients were treated with radiation for pancreatic cancer. All patients received concurrent chemotherapy with either gemcitabine (174) or 5-fluorouracil (27), and 67 received intensity modulated radiation therapy (IMRT). Overall, 18 patients experienced an upper GI bleed related to treatment, with 70% of bleeds occurring in the stomach or duodenum, and among those patients, 11 (61%) patients had a pancreatic head tumor and 17 (94%) patients had a metallic biliary stent. IMRT was associated with decreased risk of postradiation nausea (odds ratio, 0.27 [0.11, 0.67], P=.006) compared with 3-dimensional conformal radiation. Regarding long-term toxicities, patients with a metallic biliary stent at the time of radiation therapy were at a significantly higher risk of developing upper GI bleeding (unadjusted hazard ratio [HR], 15.41 [2.02, 117.42], P=.008), even after controlling for radiation treatment modality and prescribed radiation dose (adjusted HR, 17.38 [2.26, 133.58], P=.006). Furthermore, biliary stent placement was associated with a higher risk of death (HR, 1.99 [1.41, 2.83], P < .001) after adjusting for demographic, treatment-related, and patient-related variables. Metallic biliary stents may be associated with an increased risk of upper GI bleeding and mortality. Furthermore, IMRT was associated with less nausea and short-term toxicity compared with 3-dimensional conformal therapy.

HSSB1 (NABP2/OBFC2B) modulates the DNA damage and androgen-induced transcriptional response in prostate cancer.

Activation and regulation of androgen receptor (AR) signaling and the DNA damage response impact the prostate cancer (PCa) treatment modalities of androgen deprivation therapy (ADT) and radiotherapy. Here, we have evaluated a role for human single-strand binding protein 1 (hSSB1/NABP2) in modulation of the cellular response to androgens and ionizing radiation (IR). hSSB1 has defined roles in transcription and maintenance of genome stability, yet little is known about this protein in PCa. We correlated hSSB1 with measures of genomic instability across available PCa cases from The Cancer Genome Atlas (TCGA). Microarray and subsequent pathway and transcription factor enrichment analysis were performed on LNCaP and DU145 prostate cancer cells. Our data demonstrate that hSSB1 expression in PCa correlates with measures of genomic instability including multigene signatures and genomic scars that are reflective of defects in the repair of DNA double-strand breaks via homologous recombination. In response to IR-induced DNA damage, we demonstrate that hSSB1 regulates cellular pathways that control cell cycle progression and the associated checkpoints. In keeping with a role for hSSB1 in transcription, our analysis revealed that hSSB1 negatively modulates p53 and RNA polymerase II transcription in PCa. Of relevance to PCa pathology, our findings highlight a transcriptional role for hSSB1 in regulating the androgen response. We identified that AR function is predicted to be impacted by hSSB1 depletion, whereby this protein is required to modulate AR gene activity in PCa. Our findings point to a key role for hSSB1 in mediating the cellular response to androgen and DNA damage via modulation of transcription. Exploiting hSSB1 in PCa might yield benefits as a strategy to ensure a durable response to ADT and/or radiotherapy and improved patient outcomes.

Axial Axis Metastasis.

Axial axis metastasis remains a challenge for surgical as well as other treatment modalities, like chemotherapy, immunotherapy, and radiotherapy. It is unequivocal that surgery provides pain improvements and preservation of neurological status, but this condition remains when associated with radiotherapy and other treatment modalities. In this review, we emphasize the current forms of surgical treatment in the different regions of the spine and pelvis. The evident possibility of percutaneous treatments is related to early or late cases, and in cases in which there are greater risks and instability to conventional surgeries associated with radiotherapy and have been shown to be the appropriate option for local control of metastatic disease.