Radiobiological Models Research Articles

Abstract 3313: Single-cell level absorbed dose assessment and radiosensitivity modeling for alpha-emitter radiopharmaceutical therapy

Abstract The radiobiological response to alpha-emitter radiopharmaceutical therapy (αRPT) is often studied in cell monolayers. In these experiments, the goal is to establish the relationship between absorbed dose and cell survival probability. However, absorbed dose is not readily known and needs to be estimated. Current models to estimate this commonly idealize cells as biologically inert spheres (geometric model). This results in inaccurate and non-generalizable results, which could hamper the rigorous study of the underlying radiobiology. The purpose of this study was to estimate the variability in absorbed dose on a single-cell level by combining 3D measurements of cell geometries, as well as the dynamics of carrier molecule binding and trafficking in individual cells with full physics simulations of the alpha emissions. This comprehensive integration of the biological and physical aspects allows for a more accurate way to model cell survival in these αRPT experiments. Live cells were imaged on a confocal microscope. Experimental conditions of previous cell survival experiments with 212Pb on NT2.5 HER2+ breast cancer cells were replicated. A relevant antibody was tagged with AF488. 3D time lapses of membrane binding kinetics and internalization were recorded. All cells were segmented into nuclei, membrane and cytosol compartments using a purpose-build algorithm. Pharmacokinetic models were fit to the temporal antibody signals, which enabled validation with experimental binding assays. Monte Carlo simulations using the exact antibody locations in each time frame allowed for the precise estimation of dose rate over time. Single-cell absorbed dose estimates were used to model previously obtained cell survival curves. Over 300 cells were measured between 0 and 26 hours post incubation. A large range in absorbed doses was observed (coefficient of variation 0.74). The median contribution of membrane-bound activity to absorbed dose was in agreement with geometric models (error less than 6%). However the contribution of antibody internalization and perinuclear trafficking to absorbed dose varied widely between cells and over time. Cell clustering contributed 46% of the total dose, and was 6x higher than in the geometric model. Applying this to previous cell survival data yielded an estimated radiosensitivity kappa of 7.1 (geometric model: 2.8). Cell clustering has a larger, and cell geometry has a smaller impact than is assumed in current models. Perinuclear trafficking of internalized Ab positively impacts cell nucleus absorbed dose, which is typically ignored. Dose variability should be included in radiosensitivity modeling. More accurate absorbed dose estimations which result from a better understanding of the different contributing factors, will improve generalizability of the radiobiological models established in these cell monolayer experiments to more complex models. Citation Format: Remco Bastiaannet, Ioanna Liatsou, Robert Hobbs, George Sgouros. Single-cell level absorbed dose assessment and radiosensitivity modeling for alpha-emitter radiopharmaceutical therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3313.

Evaluation of the Radiobiological Models Predicting the Radiation-Induced Hypothyroidism in the Partially Irradiated Thyroid Gland of Patients with Breast Cancer

Background: Radiation-induced hypothyroidism (RHT) is one of the side effects that might have an impact on the quality of life of patients with breast cancer treated with radiotherapy. Objectives: The aim of the current study was to evaluate the performances of the Lyman-Kutcher-Burman (LKB) and Log-Logistic models in the prediction of hypothyroidism (HT) as well as the estimation of the model parameters for the incidence of RHT among patients with breast cancer. Methods: Fifty-two patients treated with radiation therapy (RT) for breast cancer were prospectively evaluated. Patients' serum samples [tri-iodothyronine, thyroxine, thyroid-stimulating hormone (TSH), free triiodothyronine, and free thyroxine] were measured before RT and also at a regular time interval until 1 year after the completion of RT. For each patient, dose-volume histograms (DVHs) of the thyroid gland were derived from their treatment planning dataset. Patients whose TSH levels were higher than normal with a decrease in FT4 levels were considered as cases with RHT. The LKB and Log-Logistic radiobiological models were evaluated by comparing them with the resultant follow-up data. The parameters for radiobiological models have been deduced by fitting the models to the follow-up data. The models were fitted in a Bayesian setting and compared according to the widely applicable information criterion (WAIC). Results: Twenty-one (40%) patients developed RHT at a follow-up of 1 year after the end of radiation treatment. The fitted values of D50 for the LKB and Log-Logistic models were 37.71 and 25.50 Gy, respectively for the partially irradiated thyroid of patients with breast cancer. The mean time to the incidence of RHT was obtained at 6.7 months in the studied group. Conclusions: A volumetric effect was found for the thyroid gland in the implemented normal tissue complication probability models. Compared to the follow-up data, the Log-Logistic model was ranked as the best model for predicting the rate of RHT in patients with breast cancer.

The unified approach of radiation action on biological matter: The induction of oncogenic transformation by heavy charged particles in C3H10T1/2 cells

The induction of oncogenic transformation to C3H10T1/2 cells by different types of ionizing radiation has been widely studied in various radiological laboratories. Based on the information available in literature, a database is structured to include radiological parameters, that manifest oncogenic effects as well as cellular inactivation of C3H10T1/2 cells, resulted from exposure to different types of heavy charged ions including neutrons. We find that oncogenic transformation effective cross-section is best correlated with mean free path for linear primary ionization. A simple radiobiological model is proposed merely to quantize cross-sections against mean free path. The model reveals saturations of; cellular inactivation cross-section of about 75 mm2, and oncogenic transformation cross-section of about 3.98 x 10-2 mm2, both started at mean free path of 1.8 nm (inflection points) and lower values. Since the interspacing distance between the DNA strands is about 1.8 nm, the model explains the crucial roles of DNA lesions (caused by heavy charged particles) to play as the starting point leading to cell death or oncogenic transformation. The effective cross -sections in the sloping regions are primarily due to repairable DNA single strand breaks while saturation regions are essentially due to unrepaired or incorrectly repaired DNA double strand breaks.

First application of the BIANCA biophysical model to carbon-ion patient cases

Objective. The main objective of this work consists of applying, for the first time, the BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) biophysical model to the RBE calculation for C-ion cancer patients, and comparing the outcomes with those obtained by the LEM I model, which is applied in clinics. Indeed, the continuous development of heavy-ion cancer therapy requires modelling of biological effects of ion beams on tumours and normal tissues. The relative biological effectiveness (RBE) of heavy ions is higher than that of protons, with a significant variation along the beam path. Therefore, it requires a precise modelling, especially for the pencil-beam scanning technique. Currently, two radiobiological models, LEM I and MKM, are in use for heavy ions in scanned pencil-beam facilities. Approach. Utilizing an interface with the FLUKA Particle Therapy Tool, BIANCA was applied to re-calculate the RBE-weighted dose distribution for carbon-ion treatment of three patients (chordoma, head-and-neck and prostate) previously irradiated at CNAO, where radiobiological optimization was based on LEM I. The predictions obtained by BIANCA were based either on chordoma cell survival (RBE surv ), or on dicentric aberrations in peripheral blood lymphocytes (RBE ab ), which are indicators of late normal tissue damage, including secondary tumours. The simulation outcomes were then compared with those provided by LEM I. Main results. While in the target and in the entrance channel BIANCA predictions were lower than those obtained by LEM I, the two models provided very similar results in the considered OAR. The observed differences between RBE surv and RBE ab (which were also dependent on fractional dose and LET) suggest that in normal tissues the information on cell survival should be integrated by information more closely related to the induction of late damage, such as chromosome aberrations. Significance. This work showed that BIANCA is suitable for treatment plan optimization in ion-beam therapy, especially considering that it can predict both cell survival and chromosome aberrations and has previously shown good agreement with carbon-ion experimental data.

Radiotherapy treatment interruptions during the Covid-19 pandemic: The UK experience and implications for radiobiology training

Unintended treatment interruptions during a course of radiotherapy can lead to extended overall treatment times which allow increased tumour cell repopulation to occur. Extra dose may therefore be required to offset any loss of tumour control. However, the manner in which the extra dose is delivered requires careful consideration in order to avoid the risk of increased normal tissue toxicity. Radiobiological modelling techniques can allow quantitative examination of such problems and may be used to derive revised pattens of radiation delivery which can help restore a degree of tumour control whilst limiting the likelihood of excess normal tissue morbidity. Unintended treatment interruptions can occur in any radiotherapy department but the rapid spread of the Covid-19 pandemic caused a major increase in the frequency of such interruptions due to staff and patient illness and the consequent self-isolation requirements. This article summarises the radiobiological considerations and caveats involved in assessing treatment interruptions and outlines the UK experience of dealing with the new challenges posed by Covid-19. The world-wide need for more education programmes in cancer radiobiology is highlighted.

In vitro modified microdosimetric kinetic model–based predictions for B14-150 cells survival in 450 MeV/u carbon ion beam with aluminum ridge filter for biologically optimized spread-out Bragg peak

The relative biological efficiency of particle irradiation could be predicted with a wide variety of radiobiological models for various end-points. We validate the forecast of modified Microdosimetric Kinetic Model in vitro using combined data of reference Co-60 radiation and carbon ion plateau data for specific cell line to optimize the survival function in spread-out Bragg Peak obtained with an especially designed ridge filter. We used Geant4 Monte-Carlo software to simulate the fragment contribution along Bragg curve inside water phantom, open-source toolkit Survival to predict the expected linear-quadratic model parameters for each fragment, and in-house software to form the total survival curve in spread-out Bragg Peak. The irradiation was performed at U-70 synchrotron with an especially designed Aluminum ridge filter under the control of PTW and in-house ionization chambers. The cell clonogenic assay was conducted with the B14–150 cell line. The data analysis was accomplished using scipy and CERN ROOT. The clonogenic assay represents the survival in spread-out Bragg Peak at different points and qualitatively follows the modeled survival curve very well. The quantitative difference is within 3σ, and the deviation might be explained by the uncertainties of physical modeling using Monte-Carlo methods. Overall, the obtained results are promising for further usage in radiobiological studies or carbon ion radiotherapy. Shaping the survival curve in the region of interest (i.e., spread-out Bragg Peak) is a comprehensive task that requires high-performance computing approaches. Nevertheless, the method’s potential application is related to the development of next-generation treatment planning systems for ion beams. This can open a wide range of improvements in patient treatment outcome, provide new optimized fractionation regimes or optimized dose delivery schemes, and serve as an entrance point to the translational science approach.

Radiobiological modeling of radiation-induced acute proctitis: A single-institutional study of prostate carcinoma.

To estimate the fitting parameters of the sigmoidal dose response (SDR) curve of radiation-induced acute proctitis in prostate cancer patients treated with intensity modulated radiation therapy (IMRT) for the calculation of normal tissue complication probability (NTCP). Twenty-five prostate cancer patients were enrolled and evaluated weekly for acute radiation-induced (ARI) proctitis toxicity. Their scoring was performed as per common terminology criteria for adverse events version 5.0. The radiobiological parameters namely n, m, TD50, and γ50 were calculated from the fitted SDR curve obtained from the clinical data of prostate cancer patients. ARI toxicity for rectum in carcinoma of prostate patients was calculated for the endpoint of acute proctitis. The n, m, TD50, and γ50 parameters from the SDR curve of Grade 1 and Grade 2 acute proctitis are found to be 0.13, 0.10, 30.48 ± 1.52 (confidence interval [CI] 95%), 3.18 and 0.08, 0.10, 44.37 ± 2.21 (CI 95%), 4.76 respectively. This study presents the fitting parameters for NTCP calculation of Grade-1 and Grade-2 ARI rectum toxicity for the endpoint of acute proctitis. The provided nomograms of volume versus complication and dose versus complication for different grades of acute proctitis in the rectum help radiation oncologists to decide the limiting dose to reduce the acute toxicities.

Magnetic resonance imaging‐only‐based radiation treatment planning for simultaneous integrated boost of multiparametric magnetic resonance imaging‐defined dominant intraprostatic lesions

Objective To assess the feasibility of using synthetic computed tomography for treatment planning of the dominant intraprostatic lesion (DIL), a high-risk region of interest that offers potential for increased local tumor control. Methods A dosimetric study was performed on 15 prostate cancer patients with biopsy-proven prostate cancer who had undergone magnetic resonance imaging. DILs were contoured based on the turbo spin echo T2-weighted and diffusion weighted images. Air, bone, fat, and soft tissue were segmented and assigned bulk-density HU values of –1000, 285, –50, and 40, respectively, to create a synthetic computed tomography. Simultaneous integrated boost (SIB) and standard treatment plans were created for each patient. The total dose was 79.2 Gy to the non-boosted planning target volume for both plans with a boost of 100 Gy for the DIL in the SIB plan. A radiobiological model was created to determine individualized dose–response curves based on the patient's apparent diffusion coefficient maps. Results Mean doses to the non-boost planning target volume were 81.2 ± 0.3 Gy with the SIB and 81.0 ± 0.4 Gy without. For the DIL, the boosted mean dose was 102.6 ± 0.6 Gy. Total motor unit was 860 ± 100 with the SIB and 730 ±100 without. Femoral heads, rectum, bladder, and penile bulb were within established dose guidelines for either treatment technique. The average tumor control probability was 94% with the SIB compared with 78% without boosting the DIL. Conclusion This study showed the feasibility of magnetic resonance imaging-only treatment planning for patients with prostate cancer with a SIB to the DIL. DIL dose can be escalated to 100 Gy on synthetic computed tomography, while maintaining the original 79.2 Gy prescription dose and the organ of interest clinical dose limits.

Hypofractionated Whole-Breast Irradiation Focus on Coronary Arteries and Cardiac Toxicity-A Narrative Review.

Breast cancer is the most common cancer among women worldwide, which is often treated with radiotherapy. Whole breast irradiation (WBI) is one of the most common types of irradiation. Hypo-fractionated WBI (HF-WBI) reduces the treatment time from 5 to 3 weeks. Recent radiobiological and clinical evidence recommended the use of HF-WBI regardless of the age or stage of disease, and it is proven that hypo-fractionation is non-inferior to conventional fractionation regimen irradiation. However, some studies report an increased incidence of heart-related deaths in the case of breast irradiation by hypo-fractionation, especially in patients with pre-existing cardiac risk factors at the time of treatment. Due to the new technical possibilities of radiotherapy techniques, HF-WBI can reduce the risk of cardiac toxicity by controlling the doses received both by the heart and by the anatomical structures of the heart. The radiobiological “double trouble”, in particular “treble trouble”, for hypo-fractionated regimen scan be avoided by improving the methods of heart sparing based on image-guided irradiation (IGRT) and by using respiration control techniques so that late cardiac toxicity is expected to be limited. However, long-term follow-up of patients treated with HF-WBI with modern radiotherapy techniques is necessary considering the progress of systemic therapy, which is associated with long-term survival, and also the cardiac toxicity of new oncological treatments. The still unknown effects of small doses spread in large volumes on lung tissue may increase the risk of second malignancy, but they can also be indirectly involved in the later development of a heart disease. It is also necessary to develop multivariable radiobiological models that include histological, molecular, clinical, and therapeutic parameters to identify risk groups and dosimetric tolerance in order to limit the incidence of late cardiac events. MR-LINAC will be able to offer a new standard for reducing cardiac toxicity in the future, especially in neoadjuvant settings for small tumors.

The Use of Radiobiological Models for Later Radiation Damages Assessment for the Cervical Cancer Patients

Purpose: To assess the likelihood of late radiation damages after radiotherapy for cervical cancer patients using radiobiological models.Material and methods: The treatment plans of 94 patients at the age from 30 to 39 years (30 %) and from 40 to 49 years (33 %) were analyzed. The patients were diagnosed with squamous cell carcinoma of the cervix of 88 people, adenocarcinoma of the cervix — 1 person, mixed types of cancer tissue — 5. The combined radiation therapy course consisted of remote and intracavitary stages. In accordance with the recommendations of the GEC-ESTRO working group on gynecology, the total values of dose loads on organs at risk were found, namely: the bladder, rectum, sigmoid colon in volumes of 0.1; 1; 2, 5 and 10 cm3.Results: The dependences of the accumulated frequency of late radiation injuries, namely cystitis, rectitis and enterocolitis for two modes of irradiation Split and Fraction for the bladder, rectum and sigmoid colon, depending on the radiation dose and the volume of the corresponding organ, were obtained. The dose–effect relationships for the manifestation of cystitis, rectitis and enterocolitis were constructed for both regimes in volumes: 0.1; 1; 2; 5; 10 cm3. The threshold values for the occurrence of radiation damage were estimated for two modes of irradiation for the bladder, rectum and sigmoid colon.Conclusion: There is a decrease in the threshold of complications with an increase in the analyzed volume of irradiation. The threshold values of the probability of radiation injury for the two irradiation modes for the bladder and rectum coincided within ± 5 Gy. In the case of split-split treatment, radiation damage occurs earlier within 5 Gy. No reduction in the likelihood of late radiation injury was found when using this mode. The applied methods of treatment for these two groups of patients are equivalent in terms of the likelihood of late radiation damage and have the right for clinical use.

Dosimetric and Clinical Risk Factors for the Development of Maxillary Osteoradionecrosis in Adenoid Cystic Carcinoma (ACC) Patients Treated With Carbon Ion Radiotherapy.

BackgroundThe present study aims to evaluate dosimetric and clinical risk factors for the development of maxillary osteoradionecrosis (ORN) in head and neck adenoid cystic carcinoma (ACC) patients treated with carbon ion radiotherapy (CIRT).MethodsClinical data and treatment plans of ACC patients, consecutively treated from January 2013 to September 2016 within the phase II clinical trial CNAO S9/2012/C, were retrospectively reviewed. ORN and other treatment-related toxicity were graded according to the Common Terminology Criteria for Adverse Events (CTACE), version 4.0. The maxillary bone was contoured on the planning CT, and only patients receiving more than 10% of the prescription dose at their maxilla were considered for the analysis (67 patients). The volumes of maxilla receiving doses from 10 Gy (RBE) to 60 Gy (RBE) (VD), with an increment of 10 Gy (RBE), and additional clinical factors were correlated to the incidence of ORN with univariate analysis (Chi-square test). The logistic regression model was subsequently applied for multivariate analysis. Treatment plans calculated with a local effect model (LEM)-based optimization were recalculated with the modified microdosimetric kinetic model (MKM), and compared with literature data from the Japanese experience.ResultsThe median time interval from the start of CIRT to ORN appearance was 24 months (range, 8–54 months). Maxillary ORN was observed in 11 patients (16.4%). Grade 1 ORN was observed in 2 patients (18.1%), G2 in 4 (36.3%), G3 in 4 (36.3%) and G4 in 1 (9.3%). From univariate analysis, the site of the tumor, the presence of teeth within the PTV and acute mucositis correlated with the development of maxillary ORN. VD were significantly higher for all the dose levels tested in patients with maxillary ORN than patients without necrosis, according to both radiobiological models. The multivariate analysis showed that V60 significantly correlated with ORN risk.ConclusionThe volume of maxilla irradiated with high dose values was relevant for ORN development in our cohort of ACC patients. These results are in line with previously published data obtained with a different radiobiological model. Our findings might be helpful to prevent the risk of ORN in patients receiving CIRT.

Carbon ion radiotherapy in the management of non‐small cell lung cancer

AbstractDespite advancements in local‐regional and systemic therapies, non‐small cell cancer (NSCLC) remains a leading cause of death worldwide. Among those treated with standard‐of‐care modalities, 30–60% experience disease recurrence. Carbon ion radiotherapy (CIRT) is a form of densely ionizing radiotherapy with unique physical and biological advantages over traditional photon and proton modalities. CIRT is expected to have a superior biological impact on tumors, and is believed to be less impacted by the presence of tumor hypoxia or cell cycle state. It also shows highly conformal physical dose deposition due to reduced lateral scattering of the particles, limiting the radiation dose delivered to adjacent organs at risk. To implement CIRT as a viable option in the treatment of NSCLC, technical aspects of treatment delivery – including appropriate beam arrangements, dose calculation algorithms, radiobiological models, and methods of motion management – must be thoroughly investigated. Furthermore, randomized clinical trials comparing CIRT versus traditional radiation modalities must be performed to show the benefits and risks associated with this novel treatment modality. This review discusses the rationale for utilizing CIRT in NSCLC, available clinical data to date, and the potential for future investigations that may pave the path for improving outcomes in those diagnosed with NSCLC.

A Novel Radiotherapeutic Approach to Treat Bulky Metastases Even From Cutaneous Squamous Cell Carcinoma: Its Rationale and a Look at the Reliability of the Linear-Quadratic Model to Explain Its Radiobiological Effects.

IntroductionMetastatic cutaneous squamous cell carcinoma (cSCC) is a very rare condition. The lack of definition of an oligometastatic subgroup means that there is no consensus for its treatment, unlike the mucosal head and neck counterpart. Like the latter, the cutaneous form is able to develop bulky tumor masses. When this happens, the classic care approach is just for palliative intent due to a likely unfavorable benefit–risk balance typical of aggressive treatments. Here we proposed a novel radiotherapy (RT) technique to treat bulky metastases from cSCC in the context of an overall limited tumor burden and tried to explain its clinical outcome by the currently available mathematical radiobiological and ad hoc developed models.MethodsWe treated a case of facial cSCC with three metastases: two of them by classic stereotactic RT and the other by lattice RT supported by metabolic imaging (18F-FDG PET) due to its excessively large dimensions. For the latter lesion, we compared four treatment plans with different RT techniques in order to define the best approach in terms of normal tissue complication probability (NTCP) and tumor control probability (TCP). Moreover, we developed an ad hoc mathematical radiobiological model that could fit better with the characteristics of heterogeneity of this bulky metastasis for which, indeed, a segmentation of normoxic, hypoxic, and necrotic subvolumes might have been assumed.ResultsWe observed a clinical complete response in all three disease sites; the bulky metastasis actually regressed more rapidly than the other two treated by stereotactic RT. For the large lesion, NTCP predictions were good for all four different plans but even significantly better for the lattice RT plan. Neither the classic TCP nor the ad hoc developed radiobiological models could be totally adequate to explain the reported outcome. This finding might support a key role of the host immune system.ConclusionsPET-guided lattice RT might be safe and effective for the treatment of bulky lesions from cSCC. There might be some need for complex mathematical radiobiological models that are able to take into account any immune system’s role in order to explain the possible mechanisms of the tumor response to radiation and the relevant key points to enhance it.

Alpha-Emitter Radiopharmaceuticals and External Beam Radiotherapy: A Radiobiological Model for the Combined Treatment.

Simple SummaryThe linear–quadratic (LQ) model was adapted to 223Ra therapy using brachytherapy formalism for a mixture of radionuclides, considering the contribution of all daughter isotopes in the decay chain. The LQ model allowed us to predict the two-year overall survival and neutropenia rates with a combination of external beam radiotherapy and 223Ra treatment. The fitted model could be used to guide future optimization and personalization of combined treatments.Previously published studies combined external beam radiotherapy (EBRT) treatments with different activities of 223Ra. The data of two-year overall survival (2y-OS) and neutropenia (TOX) incidence when combining EBRT and 223Ra are not homogeneous in literature. We adapted the linear–quadratic model (LQ) to 223Ra therapy using brachytherapy formalism for a mixture of radionuclides, considering the contribution of all daughter isotopes in the decay chain. A virtual cohort of patients undergoing 223Ra therapy was derived using data from the literature. The doses delivered using 223Ra and EBRT were converted into biologically equivalent doses. Fixed-effect logistic regression models were derived for both the 2y-OS and TOX and compared with available literature. Based on the literature search, four studies were identified to have reported the 223Ra injection activity levels varying from the placebo (0) to 80 kBq/kg, associated or not with EBRT. Logistic regression models revealed a dose-dependent increase in both the 2y-OS (intercept = −1.364; slope = 0.006; p-value ≤ 0.05) and TOX (−5.035; 0.018; ≤0.05) using the EBRT schedule of 8 Gy in 1 fr. Similar results were obtained for other schedules. Discrepancies between our TOX model and those derived for EBRT combined with chemotherapy are discussed. Radiobiological models allow us to estimate dose-dependent relationships, to predict the OS and TOX following combined 223Ra + EBRT treatment, which will guide future treatment optimization.

Abstract DEB2-2: Con - One Week of Whole Breast RT is the New Standard of Care

Abstract The dual role of breast irradiation post lumpectomy for conservative treatment is to yield local cancer control comparable to that achieved with mastectomy while maintaining a sensate and cosmetically acceptable breast. Through application of a linear quadratic equation that characterizes the radiobiological relationship of total dose and dose per fraction to predict efficacy as well as tissue specific toxicity, breast radiation that is equally effective can be delivered with fewer treatments. This has allowed standard post lumpectomy breast radiation to be reduced to 15 -16 treatments from 25-28 with similar efficacy and toxicity confirmed in multiple clinical trials. The recent Fast Forward trial (Lancet 2020; 395: 1613-26) has now further advanced the application of this radiobiological model evaluating breast irradiation delivered in 5 treatments. This resulted in non-inferior recurrence events compared to 15-treatment breast irradiation. When using fewer treatments of larger radiation dose, small changes can result in significant toxicity effects. For example, with 1 Gy difference between 26 Gy and 27 Gy total dose treatment arms on the Fast Forward trial, significantly higher rates of breast adverse outcomes were seen. Additional experience with the 5-fraction breast irradiation is needed prior to its replacing the current 15-16 treatment standard. Citation Format: J White. Con - One Week of Whole Breast RT is the New Standard of Care [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr DEB2-2.

A Multi-Compartment Model of Glioma Response to Fractionated Radiation Therapy Parameterized via Time-Resolved Microscopy Data.

PurposeConventional radiobiology models, including the linear-quadratic model, do not explicitly account for the temporal effects of radiation, thereby making it difficult to make time-resolved predictions of tumor response to fractionated radiation. To overcome this limitation, we propose and validate an experimental-computational approach that predicts the changes in cell number over time in response to fractionated radiation.MethodsWe irradiated 9L and C6 glioma cells with six different fractionation schemes yielding a total dose of either 16 Gy or 20 Gy, and then observed their response via time-resolved microscopy. Phase-contrast images and Cytotox Red images (to label dead cells) were collected every 4 to 6 hours up to 330 hours post-radiation. Using 75% of the total data (i.e., 262 9L curves and 211 C6 curves), we calibrated a two-species model describing proliferative and senescent cells. We then applied the calibrated parameters to a validation dataset (the remaining 25% of the data, i.e., 91 9L curves and 74 C6 curves) to predict radiation response. Model predictions were compared to the microscopy measurements using the Pearson correlation coefficient (PCC) and the concordance correlation coefficient (CCC).ResultsFor the 9L cells, we observed PCCs and CCCs between the model predictions and validation data of (mean ± standard error) 0.96 ± 0.007 and 0.88 ± 0.013, respectively, across all fractionation schemes. For the C6 cells, we observed PCCs and CCCs between model predictions and the validation data were 0.89 ± 0.008 and 0.75 ± 0.017, respectively, across all fractionation schemes.ConclusionBy proposing a time-resolved mathematical model of fractionated radiation response that can be experimentally verified in vitro, this study is the first to establish a framework for quantitative characterization and prediction of the dynamic radiobiological response of 9L and C6 gliomas to fractionated radiotherapy.

Three discipline collaborative radiation therapy (3DCRT) special debate: FLASH radiotherapy needs ongoing basic and animal research before implementing it to a large clinical scale.

Three discipline collaborative radiation therapy (3DCRT) special debate: FLASH radiotherapy needs ongoing basic and animal research before implementing it to a large clinical scale.

Determining the optimum tumor control probability model in radiotherapy of glioblastoma multiforme using magnetic resonance imaging data pre- and post- radiation therapy

Background:Glioblastoma multiforme (GBM) is the most common and malignant brain tumor. The current standard of care is surgery followed by radiation therapy (RT). Radiotherapy treatment plan evaluation relies on radiobiological models for accurate estimation of tumor control probability (TCP). This study aimed to assess the impact of obtained magnetic resonance imaging (MRI) data before and 12 weeks after RT to achieve the optimum TCP model to improve dose prescriptions in radiation therapy of GBM.Materials and Methods::In this quasi-experimental study, MR images and its relevant data from 30 patients consisting of 9 females and 21 males (mean age of 46.3 ± 15.8 years) diagnosed with GBM, whose referred for radiotherapy were selected. The data of age, gender, tumor size, volume, and signal intensity using analysis of MRI data pre- and postradiotherapy were used for calculating TCP. TCP was calculated from three common radiobiological models including Poisson, linear quadratic, and equivalent uniform dose. The impact of some radiobiological parameters on final TCP in all patients planned with three-dimensional conformal radiation therapy was obtained.Results:A statistically significant difference was found among TCP in Poisson model compared to the other two models (P < 0.001). Changes in tumor volume and size after treatment were statistically significant (P < 0.05). Different combinations of radiobiological parameters (α/β and SF2 in all models) observed were meaningful (P < 0.05).Conclusion:The results showed that among TCP radiobiological models, the optimum is the Poisson. The results also identified the importance of TCP radiobiological models in order to improve radiotherapy dose prescriptions.

Radiobiological approach to treatment gaps in locally advanced head and neck cancers radical radiotherapy arising from the COVID-19 pandemic.

Gaps of radiotherapy treatment are one of the factors recognized as unfavorable in terms of tumor control and disease prognosis. All strategies for compensating the negative effect of radiotherapy treatment gaps are based on radiobiological models. Using the modified square linear formalism (Dale`s equation) it is possible to calculate the additional dose in order to compensate the accelerated tumor repopulation effect. SARS-CoV-2 infection is an important factor that can lead to an interruption of irradiation for medium and long- term intervals. We aim to present the radiobiological data underlying the recalculation of radiotherapy treatment and exemplification for different clinical scenarios in the case of head and neck cancers (Ref. 17). Keywords: adiobiology, treatment gaps, locally advanced head and neck cancers, radical radiotherapy, COVID-19 pandemic.

Commissioning and Dosimetric Results of an Indigenously Developed Intra-Vaginal Template for Interstitial Plus Intracavitary High dose Rate Image-Guided Brachytherapy of Advanced Cervix Cancer.

The goal of this study is to discuss the commissioning and dosimetric parameters achieved during the clinical implementation of an indigenously developed intracavitary (IC) plus interstitial (IS) template for high dose rate (HDR) image-guided brachytherapy (IGBT) in cancer (Ca) cervix. We want to discuss our achieved values of cumulative equi-effective doses (EQD2) for high-risk clinical target volume (HRCTV) and organ at risk (OAR) and compare it with available published results. Medanta anterior oblique/lateral oblique template has a total of 19 needles including the central tandem. For commissioning the template with needles, the indigenously made acrylic phantom was used. Oblique and straight needles were placed inside the acrylic phantom and a computed tomography (CT) scan was performed. Sixteen patients were treated in HDR IGBT using this template after external-beam radiotherapy. The IGBT plans were evaluated based on EQD2 of target coverage i.e., dose received by 98% (D98%_HRCTV), 90% (D90%_HRCTV), and 50% (D50%_HRCTV) volume of HRCTV, and dose received by 2 cc (D2cc) and 0.1 cc (D0.1cc) of OAR using linear quadratic (LQ) radiobiological model. The autoradiographic in radiochromic film shows that the distance between the needle tip and the middle of the source position is 6 mm. The mean D98%_HRCTV and D90%_HRCTV was 76.8 Gy (range: 70-87.7 Gy, P < 0.01) and 84.49 Gy (range: 76.6-96.7 Gy, P < 0.01), respectively. Mean EQD2 of D2cc of the bladder, rectum, and sigmoid was 85.6 Gy (range: 77.5-99.6 Gy, P < 0.03), 74.3 Gy (range: 70.9-76.7 Gy, P < 0.05), and 58.3 Gy (range: 50.6-67.9 Gy, P = 0.01), respectively. The mean total reference air kerma at a 1 m distance is 0.489cGy (range: 0.391-0.681cGy). The indigenously developed template could attain satisfactory standards in terms of set parameters for commissioning and acceptable dose volume relations in our clinical use for treating the advanced Ca cervix patients who need IC + IS type of HDR IGBT. The comparative analysis with contemporary applicators was acceptable.