Radiotherapy For Cancer Research Articles

Blood biomarkers for cardiac damage during and after radiotherapy for esophageal cancer: A prospective cohort study

PurposeThe aim of this study was to test the hypothesis that the levels of High Sensitive Troponin T (HS-TNT) and N-terminal Brain Natriuretic Peptide (NT-ProBNP) increase after radiation therapy in a dose dependent way and are predictive for clinical cardiac events. Materials and MethodsBlood samples during and after radiotherapy of 87 esophageal cancer patients were analysed regarding the course of HS-TNT and NT-ProBNP levels and their relationship with clinical toxicity endpoints and radiation dose volume parameters. ResultsHS-TNT values at the end of treatment correlated with the mean heart dose (p = 0.02), whereas the rise of NT-ProBNP correlated with the mean lung dose (p = 0.01). Furthermore, the course of both HS-TNT (p < 0.001) and NT-ProBNP (p < 0.01) levels were significantly different for patients who developed new cardiac events as opposed to those without new cardiac events. ConclusionSignificant correlations were found for both biomarkers with radiation dose and clinical toxicity endpoints after treatment. Therefore, these markers might be of additional value in NTCP models for cardiac events and might help us unravelling the mechanisms behind these toxicity endpoints.

P98. Stereotactic radiation therapy and spine surgery for metastatic breast cancer to the spine are associated with 1-, 2-, and 5-year mortality rates

P98. Stereotactic radiation therapy and spine surgery for metastatic breast cancer to the spine are associated with 1-, 2-, and 5-year mortality rates

Acute toxicity patterns and their management after moderate and ultra- hypofractionated radiotherapy for prostate cancer: A prospective cohort study

ObjectiveHypofractionation has become the new clinical standard for prostate cancer. We investigated the management of acute toxicity in patients treated with moderate hypofractionation (MHF) or Ultrahypofractionation (UHF). MethodsIn a prospective cohort setting, patients (N=316) received either MHF (20 fractions of 3/3.1 Gy, 5 fractions per week, N=156) or UHF (7 fractions of 6.1 Gy, 3 fractions per week, N=160) to the prostate +/- (base of the) seminal vesicles between 2019 and 2023. UHF was not indicated in case of significant lower urinary tract symptoms (LUTS) or T3b disease. Patient-reported outcomes (PRO) were online distributed at baseline, end of treatment (aiming at last fraction +/- 3 days), 3 months. Acute toxicity rates, management, and associations with baseline factors were analysed using Chi-square test and logistic regression. CTCAE scores (version 5) were calculated. ResultsTreatment for acute urinary complaints was prescribed in 46 % (MHF) and 29 % (UHF). Taking into consideration baseline LUTS, MHF and UHF showed similar rates of PROs and management. Medication for acute gastrointestinal (GI) symptoms was prescribed for 21.1 % (MHF) and 14.1 % (UHF) with more loperamide for diarrhea in MHF (9.0 %) vs UHF (1.9 %, p = 0.005). Grade ≥ 2 (MHF / UHF) was scored in 40 % / 28 % for GI (p = 0.03) and 50 % / 31 % for GU (p < 0.01). PROs for GI reported after last fraction of UHF were significantly worse compared to before last fraction. ConclusionUHF was safe with respect to acute toxicity risks in the selected population. MHF is associated with risks of significant diarrhea which needs further investigation. Furthermore, optimal registration of acute toxicity for UHF requires measurements up to 1–2 weeks after the last fraction.

The effect of increasing the prescribed dose in stereotactic body radiotherapy for primary lung cancer without lymph node metastasis.

This study aimed to identify the efficacy of increasing the dose of stereotactic body radiotherapy (SBRT) for lung cancer. Patients who received SBRT for primary lung cancer between 2002 and 2021 were evaluated retrospectively. The patients were categorized into the 48, 50, and 55 Gy groups according to the prescribed dose. Analyses were performed for all matched patients. A total of 323 patients underwent SBRT for lung lesions at doses of 48, 50, and 55 Gy in four fractions. The median follow-up period in the 55 Gy group (32.3 months; Interquartile range (IQR), 15.1-54.1 months, P = 0.01) was significantly shorter than in the 48 Gy (47.0 months; IQR, 16,2-107.7 months) and 50 Gy (78.9 months; IQR 47.2-104.2 months) groups. The 3-year local progression-free survival (LPFS) was 90% in the 55 Gy group (95% confidence interval (CI), 62.4%-94.0%), 75.7% in the 48 Gy group (62.1%-85.0%), and 79.1% in the 50 Gy group (62.2%-89.1%). LPFS in the 55 Gy group was significantly higher than that in the 48 Gy group (hazard ratio (HR), 0.40; 95% CI, 0.20-0.79; P = 0.025). There is no significant difference in the local control rate between the 55 Gy group and the 50 Gy group (HR 0.60, CI 0.27-1.39). After propensity score matching, the 3-year LPFS in the 55 Gy group was 88.3% (CI, 71.2-95.5%). LPFS in the 55 Gy group did not significantly differ from that of the 48 Gy group (HR, 0.47; CI, 0.17-1.35) and the 50 Gy group (HR, 0.83; CI, 0.28-2.51). We conducted the analysis using propensity score matching. It was not apparent whether there was a significant difference in the effect of increasing the dose, owing to a lack of power caused by the small number of cases after propensity score matching. A prospective study is in progress, and the results are awaited.

Targeting DNA damage repair mechanism by using RAD50-silencing siRNA nanoparticles to enhance radiotherapy in triple negative breast cancer

Radiotherapy (RT) is one of major therapeutic modalities in combating breast cancer. In RT, ionizing radiation is employed to induce DNA double-strand breaks (DSBs) as a primary mechanism that causes cancer cell death. However, the induced DNA damage can also trigger the activation of DNA repair mechanisms, reducing the efficacy of RT treatment. Given the pivotal role of RAD50 protein in the radiation-responsive DNA repair pathways involving DSBs, we developed a novel polymer-lipid based nanoparticle formulation containing RAD50-silencing RNA (RAD50-siRNA-NPs) and evaluated its effect on the RAD50 downregulation as well as cellular and tumoral responses to ionizing radiation using human triple-negative breast cancer as a model. The RAD50-siRNA-NPs successfully preserved the activity of the siRNA, facilitated its internalization by cancer cells via endocytosis, and enabled its lysosomal escape. The nanoparticles significantly reduced RAD50 expression, whereas RT alone strongly increased RAD50 levels at 24 h. Pretreatment with RAD50-siRNA-NPs sensitized the cancer cells to RT with ∼2-fold higher level of initial DNA DSBs as determined by a γH2AX biomarker and a 2.5-fold lower radiation dose to achieve 50 % colony reduction. Intratumoral administration of RAD50-siRNA-NPs led to a remarkable 53 % knockdown in RAD50. The pretreatment with RAD50-siRNA-NPs followed by RT resulted in approximately a 2-fold increase in DNA DSBs, a 4.5-fold increase in cancer cell apoptosis, and 2.5-fold increase in tumor growth inhibition compared to RT alone. The results of this work demonstrate that RAD50 silencing by RAD50-siRNA-NPs can disrupt RT-induced DNA damage repair mechanisms, thereby significantly enhancing the radiation sensitivity of TNBC MDA-MB-231 cells in vitro and in orthotopic tumors as measured by colony forming and tumor regrowth assays, respectively.

Radiosensitizing effects of CDK4/6 inhibitors in hormone receptor-positive and HER2-negative breast cancer mediated downregulation of DNA repair mechanism and NF-κB-signaling pathway

CDK4/6 inhibitors combined with endocrine therapy prolonged survival in hormone receptor (HR)-positive and HER2-negative advanced breast cancer. We investigated whether CDK4/6 inhibitors enhance radiosensitivity and their underlying mechanisms of this subtype of breast cancer. In vitro and in vivo experiments were conducted using two HR-positive and HER2-negative breast cancer cell lines (MCF-7 and T-47D), CDK4/6 inhibitors (ribociclib and palbociclib) and radiotherapy (RT) to assess the biological functions and mechanisms. The radiation-enhancing effect was assessed using clonogenic assays; γH2AX and 53BP1 levels were assessed by immunofluorescence to evaluate DNA damage. The levels of phospho (p)-ERK, c-Myc, and DNA-double strand break (DSB)-related molecules, p-DNA-PKcs, Rad51, and p-ATM, were assessed by western blotting. We used an NF-κB p65 transcription factor assay kit to evaluate NF-κB activity. We evaluated the antitumor effect of the combination of RT and ribociclib through the MCF-7 orthotopic xenograft model. The synergistic effects of combining RT with ribociclib and palbociclib pretreatment were demonstrated by clonogenic assay. CDK4/6 inhibitors synergistically increased the numbers of RT-induced γH2AX and 53BP1, downregulated the expression of p-DNA-PKcs, Rad51 and p-ATM activated by RT, and reduced RT-triggering p-ERK expression, NF-κB activation, and its down-streaming gene, c-Myc. Combined ribociclib and RT reduced the growth of MCF-7 cell xenograft tumors, and downregulated the immunohistochemical expression of p-ERK, p-NF-κB p65, and c-Myc compared to that in the control group. Combining CDK4/6 inhibitors enhanced radiosensitivity of HR-positive and HER2-negative breast cancer cells at least by reducing DNA-DSB repair and weakening the activation of ERK and NF-κB signaling by RT.

Potentiating Salvage Radiotherapy in Radiorecurrent Prostate Cancer Through Anti-CTLA4 Therapy: Implications from a Syngeneic Model.

High-risk prostate cancer (PCa) is a leading cause in cancer death and can elicit significant morbidity and mortality. Currently, the salvage of local disease recurrence after radiation therapy (RT) is a major clinical problem. Immune checkpoint inhibitors (ICIs), which enhance immune activation, have demonstrated clinical therapeutic promise in combination with ionizing radiation (IR) in certain advanced cancers. We generated the TRAMP-C2 HF radiorecurrent syngeneic mouse model to evaluate the therapeutic efficacy of ICIs in combination with RT. The administration of anti-PDL1 and/or anti-CTLA4 did not achieve a significant tumor growth delay compared to the control. The combination of IR and anti-PDL1 did not yield additional a growth delay compared to IR and the isotype control. Strikingly, a significant tumor growth delay and complete cure in one-third of the mice were seen with the combination of IR and anti-CTLA4. Immune cells in tumor-draining lymph nodes and tumor-infiltrating lymphocytes from mice treated with IR and anti-CTLA4 demonstrated an upregulation of genes in T-cell functions and enrichment in both CD4+ and CD8+ T-cell populations compared to mice given IR and the isotype control. Taken together, these results indicate enhancement of T-cell response in radiorecurrent PCa by IR and anti-CTLA4.

Ligand Shell Thickness of PEGylated Gold Nanoparticles Controls Cellular Uptake and Radiation Enhancement.

The drive to improve the safety and efficacy of radiotherapies for cancers has prompted the development of nanomaterials that can locally amplify the radiation dose at a tumor without damaging the surrounding healthy tissue. Gold nanoparticles (Au NPs), in particular, exhibit promising radiosensitizing properties under kilovolt X-ray exposure, although the precise mechanism behind this enhancement is not fully understood. While most studies recognize the involvement of factors such as core composition, size, shape, and ligand chemistry in the effectiveness of Au NPs for radiation-induced cancer treatment, there is a scarcity of direct assessments that connect the photophysical properties of the nanomaterial with the observed cellular or biological outcomes. Despite previous evidence of low-energy electron (LEE) emission from Au NPs and their potential to initiate biological damage, to our knowledge, no studies directly correlate the secondary LEE emission with radiation-induced cell death. In this study we assessed Au NPs functionalized with polyethylene glycol (PEG) ligands of varying molecular weights and lengths (1, 5, and 20 kDa PEG) as potential radiosensitizers of A549 lung cancer cells using kilovolt X-ray source potentials (33-130 kVp). We assessed NP internalization using mass cytometry, radiation dose enhancement using clonogenic survival assays, and secondary LEE emission using a retarding field analyzer. Results reveal a statistically significant difference in cellular uptake and radiation dose enhancement for 5 kDa PEG-Au NPs compared to formulations using 1 and 20 kDa PEG, while analysis of secondary LEE emission spectra demonstrated that differences in the length of the PEG ligand did not cause statistically significant attenuation of secondary LEE flux. Consequently, we inferred increased cellular uptake of NPs to be the cause for the observed enhancement in radiosensitivity for 5 kDa PEGylated Au NPs. The approach used in this study establishes a more complete workflow for designing and characterizing the performance of nanomaterial radiosensitizers, allowing for quantification of secondary LEEs and cellular uptake, and ultimately correlation with localized dose enhancement that leads to cell death.

Local Control, Survival, and Toxicity Outcomes with High-Dose-Rate Peri-Operative Interventional Radiotherapy (Brachytherapy) in Head and Neck Cancers: A Systematic Review.

Background. Peri-operative interventional radiotherapy (POIRT) entails tumor resection, catheter implantation in the same surgery, and irradiation within the peri-operative period. It allows for maximal tumor burden reduction, better tumor bed identification, more flexible implant geometry, highly conformal irradiation, and treatment delay minimization. We reviewed the published local control, survival, toxicity, and quality of life (QOL) outcomes with POIRT for head and neck cancers (HNCs) in primary and re-irradiation settings. Materials and Methods. A systematic search of PubMed, Scopus, Science Direct, and other databases, supplemented by bibliography scanning and hand-searching, yielded 107 titles. Fifteen unique articles were eligible, five of which were merged with more updated studies. Of the ten remaining studies, four reported on primary POIRT, and seven reported on reirradiation POIRT. Given data heterogeneity, only qualitative synthesis was performed. Results. Primary POIRT in early tongue cancer results in 6-year recurrence-free (RFS) and overall survival (OS) of 92% for both; in advanced HNCs, the 9-year RFS and OS rates are 52% and 55%. Grade 1-2 toxicity is very common; grade 3-4 toxicity is rare, but grade 5 toxicity has been reported. POIRT re-irradiation for recurrent HNCs results in 5y RFS and OS rates of 37-55% and 17-50%; better outcomes are achieved with gross total resection (GTR). QOL data are lacking. Conclusions. Primary POIRT is safe and effective in early tongue cancers; its use in other HNC sites, especially in advanced disease, requires careful consideration. Re-irradiation POIRT is most effective and safe when combined with GTR; toxicity is significant and may be limited by careful case selection, implant planning and execution, use of smaller fraction sizes, and adherence to homogeneity constraints. Study Registration Number. PROSPERO Registry Number CRD42024548294.

Phytocompounds and Nanoformulations for Anticancer Therapy: A Review.

Cancer is a complex disease that affects millions of people and remains a major public health problem worldwide. Conventional cancer treatments, including surgery, chemotherapy, immunotherapy, and radiotherapy, have limited achievements and multiple drawbacks, among which are healthy tissue damage and multidrug-resistant phenotype onset. Increasing evidence shows that many plants' natural products, as well as their bioactive compounds, have promising anticancer activity and exhibit minimal toxicity compared to conventional anticancer drugs. However, their widespread use in cancer therapy is severely restricted by limitations in terms of their water solubility, absorption, lack of stability, bioavailability, and selective targeting. The use of nanoformulations for plants' natural product transportation and delivery could be helpful in overcoming these limitations, thus enhancing their therapeutic efficacy and providing the basis for improved anticancer treatment strategies. The present review is aimed at providing an update on some phytocompounds (curcumin, resveratrol, quercetin, and cannabinoids, among others) and their main nanoformulations showing antitumor activities, both in vitro and in vivo, against such different human cancer types as breast and colorectal cancer, lymphomas, malignant melanoma, glioblastoma multiforme, and osteosarcoma. The intracellular pathways underlying phytocompound anticancer activity and the main advantages of nanoformulation employment are also examined. Finally, this review critically analyzes the research gaps and limitations causing the limited success of phytocompounds' and nanoformulations' clinical translation.

Utilization of machine learning methods for prediction of acute and late rectal toxicity due to curative prostate radiotherapy.

Rectal toxicity is one of the primary dose-limiting side effects of prostate cancer radiotherapy, and consequential impairment on quality of life in these patients with long survival is an important problem. In this study, we aimed to evaluate the possibility of predicting rectal toxicity with artificial intelligence model which was including certain dosimetric parameters. One hundred and thirty-seven patients with a diagnosis of prostate cancer who received curative radiotherapy for prostate +/- pelvic lymphatics were included in the study. The association of the clinical data and dosimetric data between early and late rectal toxicity reported during follow-up was evaluated. The sample size was increased to 274 patients by synthetic data generation method. To determine suitable models, 15 models were studied with machine learning algorithms using Python 2.3, Pycaret library. Random forest classifier was used with to detect active variables. The area under the curve and accuracy were found to be 0.89-0.97 and 95%-99%, respectively, with machine learning algorithms. The sensitivity values for acute and toxicity were found to be 0.95 and 0.99, respectively. Early or late rectal toxicity can be predicted with a high probability via dosimetric and physical data and machine learning algorithms of patients who underwent prostate +/- pelvic radiotherapy. The fact that rectal toxicity can be predicted before treatment, which may result in limiting the dose and duration of treatment, makes us think that artificial intelligence can enter our daily practice in a short time in this sense.

Displacement of the Tongue Base and Soft Palate Because of Breathing Patterns During Radiation Therapy for Head and Neck Cancer

Displacement of the Tongue Base and Soft Palate Because of Breathing Patterns During Radiation Therapy for Head and Neck Cancer

Association of Inflammation and Immune Cell Infiltration with Estrogen Receptor Alpha in an Estrogen and Ionizing Radiation-Induced Breast Cancer Model.

Breast cancer is the most diagnosed cancer in the world, and it is the primary cause of cancer death for women. The risk of breast cancer is increased by endogenous factors like hormones and exogenous factors like radiation exposure that causes damage to the mammary epithelial cells leading to an inflammatory response. Chronic inflammation creates a microenvironment composed of, among other factors, chemokines, and interleukins, which promote cancer. The gene expression of the interleukin 1 receptor type 1, the interleukin 1 receptor antagonist, the Interleukin 1 Receptor Accessory Protein, the interleukin 6 cytokine family signal transducer, the C-X-C motif chemokine ligand 3, the C-X-C motif chemokine ligand 5, and the C-X-C motif chemokine ligand 6 were analyzed in an estrogen and radiation experimental breast cancer model. Furthermore, the expression of these genes was correlated with immune cell infiltration, estrogen receptor expression, and their clinical relevance in breast cancer patients based on data provided by The Cancer Genome Atlas database online. Results given by the experimental breast cancer model showed that all genes related to inflammation respond to ionizing radiation alone or in combination with estrogen. On the other hand, the immune response depended on the breast cancer type and on the expression of the gene that encoded the estrogen receptor. Finally, the importance of the expression of these genes in breast cancer is such that high IL1R1 or IL1RAP is strongly related to patient survival. These findings may help to improve the understanding of the role of immune molecules in carcinogenesis and enhance therapeutic approaches.

BC Cancer Radiation Therapists' perspective on the impact of COVID-19 precautions in clinical practice

IntroductionThere were many policy and procedure (P&P) changes implemented in health care facilities to combat the spread of the coronavirus disease 2019 (COVID-19). Common changes included an increase in personal protective equipment usage, room occupancy limits, limitations in visitors/family members and the absence of volunteers. This study evaluated the current views and opinions of Radiation Therapists (RTs) in British Columbia relating to how COVID-19 P&P changes have impacted their clinical practice. The goal was to identify gaps in the areas of RT practice, allow for self-reflection among RTs and potentially guide future P&Ps with patient-centred care at the forefront. MethodsA 24-item cross-sectional questionnaire was created and sent via e-mail to all RTs working across the province. Key sections explored in the questionnaire were: 1) patient care delivery, 2) staff-work environment, and 3) work satisfaction. Descriptive analysis was performed on the questionnaire responses. ResultsOf the approximate 300 invited participants, 107 responses were received from all areas of Radiation Therapy (Treatment units, CT simulation, Dosimetry, etc.) and from all cancer centres in the province. RT staff indicated that COVID-19 P&P negatively impacted patient care, including the ability to verbally and non-verbally communicate with patients (82 %), assess for side effects (85 %), and build rapport (62 %). A majority (79 %) of RT staff felt that communication with co-workers had been negatively impacted as well. When queried regarding the impact on staff environment, 51 % of RT staff agreed that the absence of volunteers increased their workload and the responses were polarized (46 % disagree, 35 % agree) when asked if RT staff have enough time for cleaning their clinical areas with new COVID-19 P&Ps in place. 78 % of RTs were aware of where to go with COVID-19 safety concerns and thought they received adequate education concerning COVID P&Ps. When asked to rank the factors that most impacted RT practice, RTs identified increased PPE usage (83 %), absence of volunteers (74 %), and room occupancy limits (70 %) as the leading P&P changes that negatively impacted their practice; while plexiglass barriers (39 %), re-arranged workspaces (37 %) and working remotely (12 %) were the least negatively impactful. ConclusionThe majority of RTs across BC Cancer responding to the questionnaire indicated that their ability to provide patient care and their staff-work environment were negatively impacted by implemented COVID-19 P&Ps. Views regarding COVID-19 P&P training/education was positive, yet there was no consensus regarding whether the changes were implemented smoothly. This study can facilitate reflection among both clinical leadership and RTs on how P&Ps can be implemented in the future and can encourage further retrospective analyses in aiding the development of P&Ps regarding future public health outbreaks.

Incidence and risk factors associated with the development of hypothyroidism after postoperative chemoradiotherapy for head and neck cancer patients with high-risk features: Supplementary analysis of JCOG1008

Background and purposeHypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data. Materials and methodsIn 2012–2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism. ResultsThe analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3–9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632–36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001–0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V60Gy [OR=1.069 (CI: 0.999–1.143, p = 0.054)] was potentially associated with the development of hypothyroidism. ConclusionThe study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials.

Development of a biocompatible radiotherapy spacer using 3D printing and microcellular foaming process for enhanced prostate cancer treatment

In this study, a new active spacer was developed using three-dimensional (3D) printing technology and microcellular foaming process to overcome the limitations of current spacers used in prostate cancer treatment. In prostate cancer treatment, a spacer is inserted between the prostate and rectum to increase the distance between the two organs so as to reduce the radiation dose to the rectum. Radiotherapy spacer is widely used in particle therapy, such as proton and carbon beams, and X-ray radiation therapies, including intensity-modulated radiotherapy and stereotactic body radiation therapy. However, existing spacers have been reported to cause significant side effects. Therefore, this study introduces a 3D printing technique using polycaprolactone to develop a spacer that provides customized treatment and minimizes side effects. This technique utilizes the volume expansion that occurs when a 3D spacer printed to fit a patient&amp;rsquo;s organs undergoes foaming through a supercritical carbon dioxide (scCO2)-assisted microcellular foaming process. Additionally, the use of scCO2 allows simultaneous gas absorption and sterilization, thereby reducing the number of process steps. This study confirms the potential of the newly developed spacer to provide effective and safe radiotherapy for prostate cancer, reduce patient discomfort, and minimize rectal side effects during radiation treatment.

A framework for in-field and out-of-field patient specific secondary cancer risk estimates from treatment plans using the TOPAS Monte Carlo system

Objective. To allow the estimation of secondary cancer risks from radiation therapy treatment plans in a comprehensive and user-friendly Monte Carlo (MC) framework. Method. Patient planning computed tomography scans were extended superior-inferior using the International Commission on Radiological Protection’s Publication 145 computational mesh phantoms and skeletal matching. Dose distributions were calculated with the TOPAS MC system using novel mesh capabilities and the digital imaging and communications in medicine radiotherapy extension interface. Finally, in-field and out-of-field cancer risk was calculated using both sarcoma and carcinoma risk models with two alternative parameter sets. Result. The TOPAS MC framework was extended to facilitate epidemiological studies on radiation-induced cancer risk. The framework is efficient and allows automated analysis of large datasets. Out-of-field organ dose was small compared to in-field dose, but the risk estimates indicate a non-negligible contribution to the total radiation induced cancer risk. Significance. This work equips the TOPAS MC system with anatomical extension, mesh geometry, and cancer risk model capabilities that make state-of-the-art out-of-field dose calculation and risk estimation accessible to a large pool of users. Furthermore, these capabilities will facilitate further refinement of risk models and sensitivity analysis of patient specific treatment options.

Integrating Deep Learning-Based Dose Distribution Prediction with Bayesian Networks for Decision Support in Radiotherapy for Upper Gastrointestinal cancer.

Selecting the better techniques to harbor optimal motion management, either a stereotactic linear accelerator delivery using TrueBeam (TBX) or Magnetic Resonance (MR)-guided gated delivery using MRIdian (MRG), is time-consuming and costly. To address this challenge, we aimed to develop a decision-supporting algorithm based on a combination of deep learning-generated dose distributions and clinical data. We retrospectively analyzed 65 patients with liver or pancreatic cancer who underwent both TBX and MRG simulations and planning process. We trained three-dimensional U-Net deep learning models to predict dose distributions and generated dose volume histograms (DVHs) for each system. We integrated predicted DVH metrics into a Bayesian network (BN) model incorporating clinical data. The MRG prediction model outperformed the TBX model, demonstrating statistically significant superiorities in predicting normalized dose to the PTV and liver. We developed a final BN prediction model integrating the predictive DVH metrics with patient factors like age, PTV size, and tumor location. This BN model an area under the receiver operating characteristic curve index of 83.56%. The decision tree derived from the BN model showed that the tumor location (abutting vs. apart of PTV to hollow viscus organs) was the most important factor to determine TBX or MRG. We demonstrated a decision-supporting algorithm for selecting optimal RT plans in upper gastrointestinal cancers, incorporating both deep learning-based dose prediction and BN-based treatment selection. This approach might streamline the decision-making process, saving resources and improving treatment outcomes for patients undergoing RT.

Study protocol for a single-site feasibility study evaluating the adoption and fidelity of Prep-4-RT: prehabilitation for head and neck cancer patients undergoing radiotherapy

IntroductionPrep-4-RT is a co-designed stepped-care multimodal prehabilitation program for people scheduled to receive radiotherapy for head and neck cancer (HNC). Prehabilitation, which occurs between diagnosis and treatment commencement, aims to improve a patient’s health to reduce the incidence and severity of current and future impairments. HNC treatment can be distressing and has detrimental impacts on function and quality of life. HNC patients have increased social vulnerabilities including higher rates of socio-economic disadvantage and engagement in lifestyle habits which increase cancer risk. High levels of physical and psychological impacts of HNC treatment and increased social vulnerabilities of this population warrant investigation of optimal pathways of care, such as prehabilitation. This paper describes a research protocol to evaluate the feasibility of Prep-4-RT, which was designed to prepare HNC patients for the physical and psychological impacts of radiotherapy.Methods and analysisAt least sixty adult HNC patients, scheduled to receive radiotherapy (with or without chemotherapy), will be recruited over a five-month period. All participants will receive access to Prep-4-RT self-management resources. Participants identified through screening as high-risk will also be offered individualised interventions with relevant allied health professionals prior to the commencement of radiotherapy (psychologists, dietitians, speech pathologists and physiotherapists). Participants will complete evaluation surveys assessing their experiences with Prep-4-RT resources and interventions. Clinicians will also complete program evaluation surveys. Primary feasibility outcomes include adoption (uptake and intention to try) and fidelity (adherence to the specialist prehabilitation pathway). Secondary feasibility outcomes include acceptability (patient and clinician) of and satisfaction (patient) with Prep-4-RT as well as operational costs. Feasibility outcome data will be analysed using exact binomial and one-sample t tests, as appropriate.Ethics and disseminationEthics approval has been obtained at the Peter MacCallum Cancer Centre in Melbourne, Australia. Results will be presented at national conferences and published in peer-reviewed journal(s) so that it can be accessed by clinicians involved in the care of HNC patients receiving radiotherapy. If the model of care is found to be feasible and acceptable, the transferability and scalability to other cancer centres, or for other cancer types, may be investigated.Registration detailsANZCTA (Australian New Zealand Clinical Trials Registry) ACTRN12623000770662.

Association of Definitive Radiotherapy for Esophageal Cancer and the Incidence of Secondary Head and Neck Cancers: A SEER Population-Based Study.

Impact of radiotherapy (RT) for esophageal cancer (EC) patients on the development of secondary head and neck cancer (SHNC) remains equivocal. The objective of this study was to investigate the link between definitive RT used for EC treatment and subsequent SHNC. This study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of primary EC patients. Fine-Gray competing risk regression and standardized incidence ratio (SIR) and propensity score matching (PSM) method were used to match SHNC patients with only primary head and neck cancer (HNC) patients. Overall survival (OS) rates were applied by Kaplan-Meier analysis. In total, 14,158 EC patients from the SEER database were included, of which 9,239 patients (65.3%) received RT and 4,919 patients (34.7%) received no radiation therapy (NRT). After a 12-month latency period, 110 patients (1.2%) in the RT group and 36 patients (0.7%) in the NRT group experienced the development of SHNC. In individuals with primary EC, there was an increased incidence of SHNC compared to the general US population (SIR = 5.95, 95% confidence interval (CI): 5.15 - 6.84). Specifically, the SIR for SHNC was 8.04 (95% CI: 6.78 - 9.47) in the RT group and 3.51 (95% CI: 2.64 - 4.58) in the NRT group. Patients who developed SHNC after RT exhibited significantly lower OS compared to those after NRT. Following PSM, the OS of patients who developed SHNC after RT remained significantly lower than that of matched patients with only primary HNC. An association was discovered between RT for EC and increased long-term risk of SHNC. This work enables radiation oncologists to implement mitigation strategies to reduce the long-term risk of SHNC in patients who have received RT following primary EC.