Precision Radiotherapy Research Articles

PSMA-Targeted Therapy: Advancements in Detection and Treatment Modalities with Dr. Scott T. Tagawa.

Prostate cancer is one of the most challenging malignancies due to its high incidence and prevalence, as it is the most frequently diagnosed non-skin cancer in men. The timely identification of prostate cancer and its metastasis is paramount for ensuring favorable outcomes for patients. Prostate-specific membrane antigen (PSMA) emerges as a promising biomarker for its detection, due to its specificity. This makes it an ideal target for the early identification of a metastatic phenotype. Situated on the membrane of tumor cells, PSMA facilitates the attachment of PSMA-targeting particles, enabling their detection through positron emission tomography (PET) scans with relative ease. Utilizing these imaging agents in conjunction with PET scans enhances the accuracy of prostate cancer tumor detection compared to PET scans alone. The advancement in prostate cancer imaging has paved the way for innovative treatment modalities. Prostate-specific membrane antigen-targeted radionuclide therapies (PSMA-TRT) exploit PSMA imaging agents to target identified prostate cancer malignancies with precise radiation, thereby reducing or eliminating the tumor mass. PSMA-TRT exhibits significant promise in prostate cancer therapy, evident from the notable declines in prostate-specific antigen (PSA) levels post treatment. However, PSMA-TRT carries both beneficial and adverse effects. While it represents a substantial leap forward in tumor cell imaging, PSMA-based antigens, being larger particles than ligands, offer prolonged imaging capabilities. Yet, the long-term effects of PSMA-TRT remain unknown, with the short-term adverse ones including fatigue, nausea, pain flares, and potential radiation exposure to others.

Quantitative assessment of occupational radiation exposure in CT: a comparative study using two radiation survey meters for year-long dose monitoring of staff

Introduction: Computed Tomography (CT) is crucial in medical imaging but exposes healthcare workers to ionizing radiation. It is essential to quantify and mitigate occupational radiation exposure. This study provides a comprehensive quantitative analysis of CT settings, using two radiation survey meters, over a year-long monitoring period. Methodology: Healthcare workers operating CT scanners were included. Two radiation survey meters, Meter A (GMC-300E, uSv/h) and Meter B (RAR R311516, uSv/h), were used concurrently for continuous measurement and recording of radiation doses. Statistical analysis compared data from both meters and assessed compliance with regulatory limits and quality assurance standards. Results: The study demonstrated excellent consistency in dose measurements between Meter A and Meter B throughout the year, with no statistically significant discrepancies (p≤; 0.05). Cumulative radiation doses of staff remained within legal limits, indicating the efficacy of current safety measures. Conclusion: The study highlights the reliability of Meter A and Meter B for measuring occupational radiation exposure in CT settings. The convergence of results emphasizes their suitability for healthcare settings requiring precise radiation dose monitoring, enhancing radiation safety in CT scanning and protecting healthcare personnel from ionizing radiation exposure.

Computational Approach for Spatially Fractionated Radiation Therapy (SFRT) and Immunological Response in Precision Radiation Therapy.

The field of precision radiation therapy has seen remarkable advancements in both experimental and computational methods. Recent literature has introduced various approaches such as Spatially Fractionated Radiation Therapy (SFRT). This unconventional treatment, demanding high-precision radiotherapy, has shown promising clinical outcomes. A comprehensive computational scheme for SFRT, extrapolated from a case report, is proposed. This framework exhibits exceptional flexibility, accommodating diverse initial conditions (shape, inhomogeneity, etc.) and enabling specific choices for sub-volume selection with administrated higher radiation doses. The approach integrates the standard linear quadratic model and, significantly, considers the activation of the immune system due to radiotherapy. This activation enhances the immune response in comparison to the untreated case. We delve into the distinct roles of the native immune system, immune activation by radiation, and post-radiotherapy immunotherapy, discussing their implications for either complete recovery or disease regrowth.

The clinical roadmap in a dual-beam hadrontherapy centre: tumour-based and patient-tailored selection criteria, management of range uncertainties and oncological patient pathway

PurposeIn the present short report, we encompass the radiobiological and dosimetric advantages of particle beam radiotherapy and we illustrate the oncological pathway for patients eligible for hadrontherapy being used at the National Center for Oncological Hadrontherapy (CNAO).MethodsWith a narrative approach, we examined the clinical and practical aspects of hadrontherapy compared to traditional photon beam radiotherapy. We described the need to select patients considering the intrinsic characteristics both of the tumour and the patient. Moreover, we described the decisional oncological tree and the patient pathway by our facility.ResultsConsidering the dosimetric and radiobiological characteristics of particle beam radiotherapy, the selection of patients can not be done regardless of the intrinsic tumour and patient hallmarks. In particular, the tumour radioresistance, the patient radiosensitivity and the need to avoid post-actinic toxicities in long-term survivors should guide the clinical indication. The finite range of particles should be considered to avoid treatment uncertainties. Multidisciplinary national and international collaboration is crucial to better manage patients to treat with hadrontherapy and to create robust clinical evidence.ConclusionHadrontherapy, with its distinctive physical and biological advantages, heralds a promising era in the field of precision radiotherapy. Patients’ radiosensitivity, tumour radioresistance, and treatment uncertainties should be considered to enhance the efficacy and to ameliorate the selection of patients.

Targeted Intraoperative Radiotherapy (TARGIT-IORT) in Breast Cancer Surgery

According to the WHO, breast cancer (BC) has become the largest increase cancer in the world. The vast majority of cancers require radiotherapy and it is the mainstream treatment modality. Although there are numerous treatments, it still does not have a suitable one because of the side effects of radiotherapy. To reduce the harm to the body, people are attending to find a fewer side-effect one. Nowadays, the intraoperative radiation therapy（IORT）is starting to come into its own. TARGIT-IORT is a type of accelerated partial breast irradiation (APBI). The differences between TARGIT-IORT and traditional radiation are the localized radiating space and radiotherapy can be administered during surgery. Researchers have now found that it has a precise radiation range and can be performed simultaneously during surgery. Besides, it performs even better than traditional radiation therapy in various aspects. This is certainly a new trend in breast cancer treatment. TARGIT-IORT is expected to be the next trend in the treatment of BC.

Combined use of radiomics and artificial neural networks for the three‐dimensional automatic segmentation of glioblastoma multiforme

AbstractGlioblastoma multiforme (GBM) is the most prevalent and aggressive primary brain tumour that has the worst prognosis in adults. Currently, the automatic segmentation of this kind of tumour is being intensively studied. Here, the automatic three‐dimensional segmentation of the GBM is achieved with its related subzones (active tumour, inner necrosis, and peripheral oedema). Preliminary segmentations were first defined based on the four basic magnetic resonance imaging modalities and classic image processing methods (multithreshold Otsu, Chan–Vese active contours, and morphological erosion). After an automatic gap‐filling post processing step, these preliminary segmentations were combined and corrected by a supervised artificial neural network of multilayer perceptron type with a hidden layer of 80 neurons, fed by 30 selected radiomic features of gray intensity and texture. Network classification has an overall accuracy of 83.9%, while the complete combined algorithm achieves average Dice similarity coefficients of 89.3%, 80.7%, 79.7%, and 66.4% for the entire region of interest, active tumour, oedema, and necrosis segmentations, respectively. These values are in the range of the best reported in the present bibliography, but even with better Hausdorff distances and lower computational costs. Results presented here evidence that it is possible to achieve the automatic segmentation of this kind of tumour by traditional radiomics. This has relevant clinical potential at the time of diagnosis, precision radiotherapy planning, or post‐treatment response evaluation.

Reactive Oxygen Species Amplifier for Apoptosis-Ferroptosis Mediated High-Efficiency Radiosensitization of Tumors.

Insufficient reactive oxygen species (ROS) production and radioresistance have consistently contributed to the failure of radiotherapy (RT). The development of a biomaterial capable of activating ROS-induced apoptosis and ferroptosis is a potential strategy to enhance RT sensitivity. To achieve precision and high-efficiency RT, the theranostic nanoplatform Au/Cu nanodots (Au/CuNDs) were designed for dual-mode imaging, amplifying ROS generation, and inducing apoptosis-ferroptosis to sensitize RT. A large amount of ROS is derived from three aspects: (1) When exposed to ionizing radiation, Au/CuNDs effectively absorb photons and emit various electrons, which can interact with water to produce ROS. (2) Au/CuNDs act as a catalase-like to produce abundant ROS through Fenton reaction with hydrogen peroxide overexpressed of tumor cells. (3) Au/CuNDs deplete overexpressed glutathione, which causes the accumulation of ROS. Large amounts of ROS and ionizing radiation further lead to apoptosis by increasing DNA damage, and ferroptosis by enhancing lipid peroxidation, significantly improving the therapeutic efficiency of RT. Furthermore, Au/CuNDs serve as an excellent nanoprobe for high-resolution near-infrared fluorescence imaging and computed tomography of tumors. The promising dual-mode imaging performance shows their potential application in clinical cancer detection and imaging-guided precision RT, minimizing damage to adjacent normal tissues during RT. In summary, our developed theranostic nanoplatform integrates dual-mode imaging and sensitizes RT via ROS-activated apoptosis-ferroptosis, offering a promising prospect for clinical cancer diagnosis and treatment.

A prospective study on the effect of tumor shrinkage on exit fluence gamma pass rate in high precision radiotherapy and influence of phantom setup error in patient-specific quality assurance.

Objective parameters for decision on adaptive radiotherapy depend on patient, tumor and treatment related factors. Present study reports geometric uncertainties occurring during high precision radiotherapy, beam fluence analysis and serial exit dose measurement as a patient-specific tool for adaptive radiotherapy. Serial exit dose fluence of 24 patients (at baseline and mid-treatment) undergoing IMRT/VMAT treatment were measured. Baseline and midtreatment exit dose evaluation was done using gafchromic films in predefined region of interest. Difference of volume of GTV at baseline (from simulation CT scan) and midtreatment CBCT scan was calculated (ΔGTV). Population based systematic errors (mm) were 4.15, 2.26, 0.88 and random errors (mm) were 2.56, 3.69, and 2.03 in mediolateral (ML), craniocaudal (CC) and anteroposterior (AP) directions respectively. Gamma pass rate reduced with incremental shift. For a 5 mm shift, maximum deviation was found in anteroposterior axis (22.16 ± 7.50) and lowest in mediolateral axis (12.85 ± 4.95). On serial measurement of exit dose fluence, tumor shrinkage significantly influenced gamma pass rate. The mean gamma pass rate was significantly different between groups with 50% shrinkage of tumor volume (86.36 vs 96.24, P = 0.008, on multivariate analysis P = 0.026). Rapid fall of gamma pass rate was observed for set up error of ≥3 mm. Serial measurement of exit dose fluence by radiochromic film is a feasible method of exit dose comparison in IMRT/VMAT, where EPID dosimetry is not available with linear accelerator configuration. Our study suggests that there is a significant difference between gamma pass rates of baseline and mid treatment exit dose fluence with greater than 50% tumor shrinkage.

High Precision Radiation Induced Attenuation Measurements Enabled by Improved Phase Shifted Fiber Loop Ring-Down System

High Precision Radiation Induced Attenuation Measurements Enabled by Improved Phase Shifted Fiber Loop Ring-Down System

Analysis of the molecular alterations in cancer cells following nanotechnology-assisted targeted radiotherapy using Raman spectroscopy

The study unveiled an innovative strategy for precise radiation targeting in cancer treatment, along with the monitoring of molecular changes induced by this therapeutic approach. In this research, we explored the impact of administering anti-HER2-AgNPs nanoconjugates either individually or in conjunction with gamma irradiation on the viability of SKBR3 breast cancer cells. The utilization of nanoconjugates resulted in an enhancement of cellular sensitivity toward radiation. The viability of the cells exhibited a decline as the dose of irradiation increased, and this decrease was further exacerbated by the passage of time following irradiation. The analysis of RS revealed distinct cellular responses in varying conditions. The observed increase in SERS intensity, resulting from the increment in dose from 0 to 2 Gy, can be attributed to the probable upregulation of HER2 expression induced by irradiation. The observed decrease in SERS intensity at doses of 4 and 6 Gy can be attributed to the likely reduction in HER2 expression. It was illustrated that the analysis of Raman spectroscopy data can aid in the identification of radiation-induced biochemical alterations in cancer cells during the application of nanoconjugates-based radiotherapy. The findings revealed that nanoconjugates have the potential to enhance cellular sensitivity to radiation along with facilitating the detection of radiation-induced biochemical alterations within cancer cells.

Comparative Efficacy of Whole-Brain Radiotherapy Combined with Supplemental Precision Radiotherapy and Whole-Brain Radiotherapy Alone for Brain Metastases

Objective: To investigate the efficacy of whole-brain radiotherapy combined with supplemental precision radiotherapy compared to whole-brain radiotherapy alone for brain metastasis. Methods: Twenty-six cases of patients with brain metastasis were observed from January 2020 to June 2023. Thirteen cases each were randomly assigned to the observation group and the control group. The patients in the observation group received whole-brain radiotherapy combined with supplemental precision radiotherapy, while those in the control group received only whole-brain radiotherapy. Results: Comparing the quality of life scores between the two groups, the data from the observation group was significantly superior (P < 0.05). The survival rate of the observation group was higher than that of the control group, and their survival time was longer (P < 0.05). Additionally, compared with the control group, the observation group exhibited lower levels of various serum tumor factors after treatment (P < 0.05). Conclusion: Whole-brain radiotherapy combined with supplemental precision radiotherapy demonstrates improved clinical efficacy, prolonged survival time, and enhanced quality of life for patients with brain metastasis. These findings warrant further study and promotion.

A model that predicts a real-time tumour surface using intra-treatment skin surface and end-of-expiration and end-of-inhalation planning CT images.

To develop a mapping model between skin surface motion and internal tumour motion and deformation using end-of-exhalation (EOE) and end-of-inhalation (EOI) 3D CT images for tracking lung tumours during respiration. Before treatment, skin and tumour surfaces were segmented and reconstructed from the EOE and the EOI 3D CT images. A non-rigid registration algorithm was used to register the EOE skin and tumour surfaces to the EOI, resulting in a displacement vector field that was then used to construct a mapping model. During treatment, the EOE skin surface was registered to the real-time, yielding a real-time skin surface displacement vector field. Using the mapping model generated, the input of a real-time skin surface can be used to calculate the real-time tumour surface. The proposed method was validated with and without simulated noise on 4D CT images from 15 patients at Léon Bérard Cancer Center and the 4D-lung dataset. The average centre position error, dice similarity coefficient (DSC), 95%-Hausdorff distance and mean distance to agreement of the tumour surfaces were 1.29 mm, 0.924, 2.76 mm, and 1.13 mm without simulated noise, respectively. With simulated noise, these values were 1.33 mm, 0.920, 2.79 mm, and 1.15 mm, respectively. A patient-specific model was proposed and validated that was constructed using only EOE and EOI 3D CT images and real-time skin surface images to predict internal tumour motion and deformation during respiratory motion. The proposed method achieves comparable accuracy to state-of-the-art methods with fewer pre-treatment planning CT images, which holds potential for application in precise image-guided radiation therapy.

DICOM Standard and Its Application in Radioinformatics

The DICOM standard is the emerging standard in the field of medical informatics. It defines the standard network interface and data model makes the medical image equipment manufacturers on the standard network equipment interconnection, simplify the development of various types of medical image, promote open unrelated to the factory of medical digital image transmission and exchange, prompting the image archiving and communication system of PACS (Picture Archiving and Communication Systems) and the combination of various hospital information system HIS (Hospital Information Systems). Radiation therapy departments in many hospitals have purchased more than one manufacturer of radiotherapy planning systems, and treatment information has to be communicated using DICOM standards. The use of DICOM in radiotherapy is called DICOM RT. At home, doctors are not fully aware of its importance and researchers do not. This paper mainly discusses the implementation and application of DICOM and protocol in precision radiotherapy system. The main contents include: (1) DICOM RT defines a total of seven information objects, which play a pivotal role in the information exchange of radiotherapy system. Discuss the content of DICOM RT; discuss the development of radiotherapy technology at home and abroad. (2) At present, DICOM standard has been widely used in the field of medical informatics, but no authority can provide DICOM compatibility verification of imaging equipment or DICOM application system, which still has many difficulties in system interconnection, that is, the research and implementation of DICOM test method. (3) The application of DICOM in PACS system. (4) Impaired compression study without visual loss in medical images based on DICOM standard.

Abstract 224: Combining functional precision medicine and radiotherapy with bio-printed organoids in head and neck squamous cell carcinoma

Abstract The study aims to establish a high throughput ex vivo organoid-based drug screening platform for head and neck squamous cell carcinoma (HNSCC) to investigate interactions between radiotherapy and different chemotherapies or targeted therapy agents and ultimately provide functional precision medicine therapeutic suggestions. HNSCC is the sixth most common cancer worldwide. Both HPV+ and HPV- cancers can be treated with surgery, radiotherapy, chemotherapy, or a combination of these. Cetuximab is currently the only FDA-approved targeted agent for HNSCC. Few clinical trials to date have shown an improved clinical outcome when combining targeted agents with radiotherapy, thus there is a need to identify new therapeutic combinations to improve outcomes. In order to characterize HNSCC tumor behavior and sensitivity to therapy, we have leveraged our high throughput 3D tumor organoid screening platform. Our approach entails seeding tumor cells in extracellular matrix around the perimeter of tissue culture wells in ring-like structures, which we have successfully deployed in other cancer types (Phan et al, 2019; Al Shihabi et al, 2022; Nguyen et al, 2022; Al Shihabi et al 2023). To optimize a chemoradiation platform, we used the HN30, HN31, and SCC154 cell lines representing HPV- primary, HPV- metastatic, and HPV+ head and neck tumors. The cell-line-derived 3D models are exposed to both radiotherapy and various chemotherapy or targeted therapy drugs. We measured cell responses by ATP-release assays and by applying our machine learning-based brightfield image analysis pipeline (Al Shihabi et al, 2022). Our results showed that the HPV+ SCC154 was the most sensitive line to radiotherapy while HPV- metastatic HN31 was the most resistant. HN31 was resistant to most drug treatments except for gemcitabine, docetaxel, and mitomycin c, while HN30 and SCC154 were sensitive to a broader set of agents. We have investigated combinatorial efficacy of radiation and chemotherapy as well as targeted agents and extended this platform to HNSCC patient-derived tumor organoids. Our proof-of-concept study highlights how our organoid-based drug screening platform can be used to test chemoradiation approaches that are more effective and personalized. Citation Format: Luda Lin, Krishna K. Bommakanti, Andreanne V. Sannajust, Yazeed Alhiyari, Brandon Mo, Lauran Evans, Peyton Tebon, Maie St. John, Alice Soragni. Combining functional precision medicine and radiotherapy with bio-printed organoids in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 224.

Cancer‐on‐Chip and Integrative Tumor Microenvironment Sensor Technologies for Progressing Precision Radiotherapy

AbstractPrecision radiotherapy, such as targeted radioligand therapy, accentuates the precise delivery of radiation to tumor cells while limiting radiation damage to surrounding normal cells. Although recent clinical trial data has shown targeted radioligand therapy to have significant patient survival benefit, it is still unavoidable that the cancer cells will eventually adapt and develop radioresistance. Thus, the study of radiotherapy‐induced changes in the tumor microenvironment (TME) is crucial for developing strategies to best overcome radioresistance. To this end, organ‐on‐chip (OOC) systems with integrative sensors represent cutting‐edge pre‐clinical models for miniaturized 3D modelling and profiling of the TME. This Review features OOC systems which have demonstrated feasibility for radiation‐associated studies, as well as showcased the progress of different OOC systems for profiling core components of the TME. Furthermore, this Review discusses the knowledge gap in cancer‐on‐chip systems with integrative TME sensors for precision radiotherapy applications. It is anticipated that this Review can kickstart the propagation of new concepts and approaches to drive a new era of miniaturized sensors on OOC systems for precision radiotherapy.

Construction and validation of classification models for predicting the response to concurrent chemo-radiotherapy of patients with esophageal squamous cell carcinoma based on multi-omics data

BackgroundConcurrent chemo-radiotherapy (CCRT) is the preferred non-surgical treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Unfortunately, some patients respond poorly, which leads to inappropriate or excessive treatment and affects patient survival. To accurately predict the response of ESCC patients to CCRT, we developed classification models based on the clinical, serum proteomic and radiomic data. MethodsA total of 138 ESCC patients receiving CCRT were enrolled in this study and randomly split into a training cohort (n = 92) and a test cohort (n = 46). All patients were classified into either complete response (CR) or incomplete response (non-CR) groups according to RECIST1.1. Radiomic features were extracted by 3Dslicer. Serum proteomic data was obtained by Olink proximity extension assay. The logistic regression model with elastic-net penalty and the R-package “rms” v6.2–0 were applied to construct classification and nomogram models, respectively. The area under the receiver operating characteristic curves (AUC) was used to evaluate the predictive performance of the models. ResultsSeven classification models based on multi-omics data were constructed, of which Model-COR, which integrates five clinical, five serum proteomic, and seven radiomic features, achieved the best predictive performance on the test cohort (AUC = 0.8357, 95 % CI: 0.7158–0.9556). Meanwhile, patients predicted to be CR by Model-COR showed significantly longer overall survival than those predicted to be non-CR in both cohorts (Log-rank P = 0.0014 and 0.027, respectively). Furthermore, two nomogram models based on multi-omics data also performed well in predicting response to CCRT (AUC = 0.8398 and 0.8483, respectively). ConclusionWe developed and validated a multi-omics based classification model and two nomogram models for predicting the response of ESCC patients to CCRT, which achieved the best prediction performance by integrating clinical, serum Olink proteomic, and radiomic data. These models could be useful for personalized treatment decisions and more precise clinical radiotherapy and chemotherapy for ESCC patients.

Millimeter wave-based patient setup verification and motion tracking during radiotherapy.

Position verification and motion monitoring are critical for safe and precise radiotherapy (RT). Existing approaches to these tasks based on visible light or x-ray are suboptimal either because they cannot penetrate obstructions to the patient's skin or introduce additional radiation exposure. The low-cost mmWave radar is an ideal solution for these tasks as it can monitor patient position and motion continuously throughout the treatment delivery. To develop and validate frequency-modulated continuous wave (FMCW) mmWave radars for position verification and motion tracking during RT delivery. A 77GHz FMCW mmWave module was used in this study. Chirp Z Transform-based (CZT) algorithm was developed to process the intermediate frequency (IF) signals. Absolute distances to flat Solid Water slabs and human shape phantoms were measured. The accuracy of absolute distance and relative displacement were evaluated. Without obstruction, mmWave based on the CZT algorithm was able to detect absolute distance within 1mm for a Solid Water slab that simulated the reflectivity of the human body. Through obstructive materials, the mmWave device was able to detect absolute distance within 5mm in the worst case and within 3.5mm in most cases. The CZT algorithm significantly improved the accuracy of absolute distance measurement compared with Fast Fourier Transform (FFT) algorithm and was able to achieve submillimeter displacement accuracy with and without obstructions. The surface-to-skin distance (SSD) measurement accuracy was within 8mm in the anterior of the phantom. With the CZT signal processing algorithm, the mmWave radar is able to measure the absolute distance to a flat surface within 1mm. But the absolute distance measurement to a human shape phantom is as large as 8mm at some angles. Further improvement is necessary to improve the accuracy of SSD measurement to uneven surfaces by the mmWave radar.

Carbon-Iodine Polydiacetylene Nanofibers for Image-Guided Radiotherapy and Tumor-Microenvironment-Enhanced Radiosensitization.

Radiotherapy is a mainstay treatment used in clinics for locoregional therapy, although it still represents a great challenge to improve the sensitivity and accuracy of radiotherapy for tumors. Here, we report the conjugated polymer, polydiiododiacetylene (PIDA), with an iodine content of 84 wt %, as a highly effective computed tomography (CT) contrast agent and tumor microenvironment-responsive radiosensitizer. PIDA exhibited several key properties that contribute to the improvement of precision radiotherapy. The integrated PIDA nanofibers confined within the tumor envelope demonstrated amplified CT intensity and prolonged retention, providing an accurate calculation of dose distribution and precise radiation delivery for CT image-guided radiotherapy. Therefore, our strategy pioneers PIDA nanofibers as a bridge to cleverly connect a fiducial marker to guide accurate radiotherapy and a radiosensitizer to improve tumor sensitivity, thereby minimizing potential damage to surrounding tissues and facilitating on-demand therapeutic intervention in tumors.

Targeted irradiation in an autochthonous mouse model of pancreatic cancer.

The value of radiotherapy in the treatment of pancreatic cancer has been the subject of much debate but limited preclinical research. We hypothesise that the poor translation of radiation research into clinical trials of radiotherapy in pancreatic cancer is due, in part, to inadequate preclinical study models. Here, we developed and refined methods for targeted irradiation in autochthonous mouse models of pancreatic cancer, using a small animal radiotherapy research platform. We tested and optimised strategies for administration of contrast agents, iohexol and the liver imaging agent Fenestra LC, to enable the use of computed tomography imaging in tumour localisation. We demonstrate accurate tumour targeting, negligible off-target effects and therapeutic efficacy, depending on dose, number of fractions and tumour size, and provide a proof of concept that precise radiation can be delivered effectively to mouse pancreatic tumours with a clinically relevant microenvironment. This advance will allow investigation of the radiation response in murine pancreatic cancer, discovery of mechanisms and biomarkers of radiosensitivity or resistance, and development of radiosensitising strategies to inform clinical trials for precision radiotherapy in this disease.

An Analysis of Positron Emission Tomography Maximum Standard Uptake Value Among Patients With Head and Neck Cancer Receiving Photon and Proton Radiation

IntroOne main advantage of proton therapy versus photon therapy is its precise radiation delivery to targets without exit dose, resulting in lower dose to surrounding healthy tissues. This is critical given the proximity of head and neck tumors to normal structures. However, proton planning requires careful consideration of factors including air-tissue interface, anatomical uncertainties, surgical artifacts, weight fluctuations, rapid tumor response, and daily variations in setup and anatomy, as these heterogeneities can lead to inaccuracies in targeting and creating unwarranted hotspots to a greater extent than photon radiation. Additionally, the elevated relative biological effectiveness (RBE) at the Bragg peak's distal end can also increase hot spots within and outside the target area. Purpose/MethodsThe purpose of this study was to evaluate for a difference in PET SUV uptake following definitive treatment, between IMPT or IMRT. Additionally, we compared the biologic dose between PET areas of high and low uptake within the CTV-primary of patients treated with IMPT. This work is assuming that the higher SUV uptake may potentially result in higher toxicities. For the purposes of this short communication, we are strictly focusing on the SUV uptake, and do not have correlation with toxicity outcomes. To accomplish this, we compared the 3- and 6-month post-treatment FDG PET scans for 100 matched oropharyngeal cancer patients treated definitively without surgery using either IMPT (n=50) or IMRT (n=50). ResultsOur study found a significant difference in biologic dose between the high and low-uptake regions on 3-month post-treatment scans of IMPT. However, this difference did not translate to a significant difference in PET uptake in the CTV-primary at 3 and 6-months follow-up between IMPT and IMRT patients. ConclusionStudies propose proton's higher RBE at the Bragg peak could lead to tissue inflammation. Our study did not corroborate these findings. This study's conclusion underscores the need for further investigations with ultimate correlation with clinical toxicity outcomes.