Radiobiological Parameters Research Articles

Dosimetric and radiobiological advantages from deep inspiration breath-hold and free breath technique for left-sided breast radiation using 3DCRT, IMRT and Rapid Arc methods-a complete assessment.

The verification and use of the best treatment approach using 3D conformal radiation therapy (3DCRT), intensity modulated radiation therapy (IMRT) and Rapid Arc methods for left breast radiation with dosimetric and radiobiological characteristics. The use of custom-built Python software for the estimation and comparison of volume, mean dose, maximum dose, monitor units and normal tissue integral dose along with radiobiological parameters such as NTCP, tumor control probability, equivalent uniform dose and LKB's effective volume from 3DCRT, IMRT and Rapid Arc planning with deep inspiration with breath holding (DIBH) and free breadth (FB) techniques. Volume growth of three-fourth in DIBH compared with FB causes a decrease in cardiac doses and complications because the left lung expands, pulling the heart away from the chest wall and the treatment area. A tiny area of the left lung was exposed during treatment, which reduced the mean dose. There was little difference in the treatment approaches because the spinal cord was immobile in both techniques. Rapid Arc is the unmatched modality for left-sided breast irradiation with significant patient breath-hold, as shown by the comparison of dosimetric and radiobiological parameters from treatment techniques with a deep inspiration breath-hold approach.

Assessment of Overall Treatment Time in Curative Radiotherapy

In radiotherapy, spread is a radiobiological parameter that corresponds to the total duration of treatment expressed in days. The objective of the study is to evaluate adherence to the theoretical spread among patients receiving curative irradiation.This was a prospective study conducted within the radiotherapy department at the National Oncology Institute of Rabat, including 285 patients receiving curative irradiation, regardless of tumor localization, from December 1, 2021, to February 28, 2022. Reasons for missed sessions were collected during end-of-treatment consultations.The median age of our patients was 47 years (range: 36-78 years), with 62% being female and 38% male. Among them, 47.3% were employed. Transportation methods varied; public transportation accounted for 59.2%, taxis for 9.1%, and only 8.7% used personal transportation. Travel time from home to the oncology institute was less than 20 minutes for 12.6% of patients, between 20 and 60 minutes for 75.7%, and over 60 minutes for 11.7%. The most common tumor sites were the breast in 32.2% of cases and the prostate in 23.5% of patients. The theoretical spread was adhered to in 29.8% of cases. In 56.4% of cases, the extension was between 1 and 5 days, and in 13.3% of cases, it was between 6 and 12 days.Causes of spread extension were diverse, with equipment breakdowns and maintenance accounting for 52.1% of cases, intercurrent illness for 10%, holidays for 16%, and treatment refusal for 0.6%. Evaluation of spread in radiotherapy is crucial as it represents a significant factor in local recurrence and indirectly affects distant progression, especially with prolonged treatment durations.

Tumor Control and Normal Tissue Complications in High-dose-rate Brachytherapy for Cervical Cancer Patients Using Ir-192 Radioactive Source.

The purpose of the study was to calculate, tumor control probability (TCP) and normal tissue complication probability (NTCP) in cervical cancer patients and to clinically correlate the outcomes with a follow-up period of 24 months. One hundred and fifty patients were included in the present study who received 46 Gy/23 fractions/4½ weeks of external beam radiotherapy with concurrent cisplatin chemotherapy, followed by intracavitary brachytherapy of 3 different fractionations regimens, i.e., 9.5 Gy per fraction of two fractions (50 patients in Arm1), 7.5 Gy per fraction of three fractions (50 patients in Arm2), and 6.0 Gy per fraction of four fractions (50 patients in Arm3). The median TCP value for Arm1, Arm2, and Arm3 was 99.6%, 94%, and 98.1%, respectively, (P < 0.01). The median NTCP value for bladder in Arm1, Arm2, and Arm3 was 0.17%, 0.04%, and 0.07%, respectively, (P = 0.05). The median NTCP value for rectum in Arm1, Arm2, and Arm3 was 4.73%, 4.35%, and 3.17%, respectively, (P = 0.052). The overall survival (OS) of 90%, 86%, and 84% was found for Arm1, Arm2, and Arm3, respectively, at 24 months of follow-up. TCP, NTCP, and OS rates were found higher in Arm1 as compared to the other two arms. The complications found in all arms were less, low grade, and manageable. Hence, Arm1, i.e., 9.5 Gy per fraction of two fractions can be concluded as the optimum fractionation regime in terms of radiobiological parameters as well as overall patient comfort.

Evaluation of Dosimetric and Radiobiological Parameters for Different TPS Dose Calculation Algorithms and Plans for Lung Cancer Radiotherapy

Lung cancer presents a major public health concern in our country and around the globe. Radiotherapy is one of the main treatment modalities for lung cancer management for several years. This study aims to evaluate differences in the dosimetric and radiobiological parameters and in the dose distributions of Planning Target Volume (PTV) and organs at risk (OAR) in patients with lung tumors using different Treatment Planning System (TPS) algorithms and Volumetric Modulated Arc Therapy (VMAT) technique. This study was accomplished in a group of 19 patients with lung tumors who were treated in our clinic. In the treatment planning of the patients; Elekta-Monaco with Monte Carlo (XVMC), Pencil Beam algorithm; Varian-Eclipse with Anisotropic Analytical Algorithm (AAA), Acuros XB (AXB)algorithms and Tomo-plan Treatment Planning System with Convolution Superposition algorithm of Tomotherapy device were used. In these treatment planning systems, plans were done by 6 MV photon energy using Volumetric Arc Therapy (VMAT) techniques. The prescribed dose to the PTV was 60 Gy in 30 fractions. Statistical analysis was performed using SPSS Statistics v.29.0.2.0 programme. Statistically, significant differences were found in Dmean, Dmax, D2 and D98 values for PTV between the algorithms, while small differences were found in Dmax values of the contralateral lung, total lung and esophagus in critical organs. It is concluded that the difference between algorithms for PTV increases especially as the volume of the target tumor decreases. TPS with C/S algorithm gave closer results with XVMC. Algorithms were found to have an impact on radiobiological parameters.

Comparative analysis of simultaneous integrated boost and sequential boost radiotherapy in node-positive cervical cancer: dosimetric and radiobiological considerations.

For locally advanced cervical cancer, the standard therapeutic approach involves concomitant chemoradiation therapy, supplemented by a brachytherapy boost. Moreover, an external beam radiotherapy (RT) boost should be considered for treating gross lymph node (LN) volumes. Two boost approaches exist with Volumetric Intensity Modulated Arc Therapy (VMAT): Sequential (SEQ) and Simultaneous Integrated Boost (SIB). This study undertakes a comprehensive dosimetric and radiobiological comparison between these two boost strategies. The study encompassed ten patients who underwent RT for cervical cancer with node-positive disease. Two sets of treatment plans were generated for each patient: SIB-VMAT and SEQ-VMAT. Dosimetric as well as radiobiological parameters including tumour control probability (TCP) and normal tissue complication probability (NTCP) were compared. Both techniques were analyzed for two different levels of LN involvement - only pelvic LNs and pelvic with para-aortic LNs. Statistical analysis was performed using SPSS software version 25.0. SIB-VMAT exhibited superior target coverage, yielding improved doses to the planning target volume (PTV) and gross tumour volume (GTV). Notably, SIB-VMAT plans displayed markedly superior dose conformity. While SEQ-VMAT displayed favorable organ sparing for femoral heads, SIB-VMAT appeared as the more efficient approach for mitigating bladder and bowel doses. TCP was significantly higher with SIB-VMAT, suggesting a higher likelihood of successful tumour control. Conversely, no statistically significant difference in NTCP was observed between the two techniques. This study's findings underscore the advantages of SIB-VMAT over SEQ-VMAT in terms of improved target coverage, dose conformity, and tumour control probability. In particular, SIB-VMAT demonstrated potential benefits for cases involving para-aortic nodes. It is concluded that SIB-VMAT should be the preferred approach in all cases of locally advanced cervical cancer.

Artificial neural network-assisted prediction of radiobiological indices in head and neck cancer.

We proposed an artificial neural network model to predict radiobiological parameters for the head and neck squamous cell carcinoma patients treated with radiation therapy. The model uses the tumor specification, demographics, and radiation dose distribution to predict the tumor control probability and the normal tissue complications probability. These indices are crucial for the assessment and clinical management of cancer patients during treatment planning. Two publicly available datasets of 31 and 215 head and neck squamous cell carcinoma patients treated with conformal radiation therapy were selected. The demographics, tumor specifications, and radiation therapy treatment parameters were extracted from the datasets used as inputs for the training of perceptron. Radiobiological indices are calculated by open-source software using dosevolume histograms from radiation therapy treatment plans. Those indices were used as output in the training of a single-layer neural network. The distribution of data used for training, validation, and testing purposes was 70, 15, and 15%, respectively. The best performance of the neural network was noted at epoch number 32 with the mean squared error of 0.0465. The accuracy of the prediction of radiobiological indices by the artificial neural network in training, validation, and test phases were determined to be 0.89, 0.87, and 0.82, respectively. We also found that the percentage volume of parotid inside the planning target volume is the significant parameter for the prediction of normal tissue complications probability. We believe that the model has significant potential to predict radiobiological indices and help clinicians in treatment plan evaluation and treatment management of head and neck squamous cell carcinoma patients.

Histology-driven hypofractionated radiation therapy schemes for early-stage lung adenocarcinoma and squamous cell carcinoma

Background and PurposeHistology was found to be an important prognostic factor for local tumor control probability (TCP) after stereotactic body radiotherapy (SBRT) of early-stage non-small-cell lung cancer (NSCLC). A histology-driven SBRT approach has not been explored in routine clinical practice and histology-dependent fractionation schemes remain unknown. Here, we analyzed pooled histologic TCP data as a function of biologically effective dose (BED) to determine histology-driven fractionation schemes for SBRT and hypofractionated radiotherapy of two predominant early-stage NSCLC histologic subtypes adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Material and MethodsThe least-χ2 method was used to fit the collected histologic TCP data of 8510 early-stage NSCLC patients to determine parameters for a well-developed radiobiological model per the Hypofractionated Treatment Effects in the Clinic (HyTEC) initiative. ResultsA fit to the histologic TCP data yielded independent radiobiological parameter sets for radiotherapy of early-stage lung ADC and SCC. TCP increases steeply with BED and reaches an asymptotic maximal plateau, allowing us to determine model-independent optimal fractionation schemes of least doses in 1–30 fractions to achieve maximal tumor control for early-stage lung ADC and SCC, e.g., 30, 44, 48, and 51 Gy for ADC, and 32, 48, 54, and 58 Gy for SCC in 1, 3, 4, and 5 fractions, respectively. ConclusionWe presented the first determination of histology-dependent radiobiological parameters and model-independent histology-driven optimal SBRT and hypofractionated radiation therapy schemes for early-stage lung ADC and SCC. SCC requires substantially higher radiation doses to maximize tumor control than ADC, plausibly attributed to tumor genetic diversity and microenvironment. The determined optimal SBRT schemes agree well with clinical practice for early-stage lung ADC. These proposed optimal fractionation schemes provide first insights for histology-based personalized radiotherapy of two predominant early-stage NSCLC subtypes ADC and SCC, which require further validation with large-scale histologic TCP data.

Optimal hypofractionated radiation therapy schemes for early-stage hepatocellular carcinoma

PurposeStereotactic body radiation therapy (SBRT) has been emerging as an efficacious and safe treatment modality for early-stage hepatocellular carcinoma (HCC), but optimal fractionation regimens are unknown. This study aims to analyze published clinical tumor control probability (TCP) data as a function of biologically effective dose (BED) and to determine radiobiological parameters and optimal fractionation schemes for SBRT and hypofractionated radiation therapy of early-stage HCC. Material and MethodsClinical 1- to 5-year TCP data of 4313 patients from 41 published papers were collected for hypofractionated radiation therapy at 2.5–4.5 Gy/fraction and SBRT of early-stage HCC. BED was calculated at isocenter using three representative radiobiological models developed per the Hypofractionated Treatment Effects in the Clinic (HyTEC) initiative. Radiobiological parameters were determined from a fit to the TCP data using the least χ2 method with one set of model parameters regardless of tumor stages or Child-Pugh scores A and B. ResultsThe fits to the clinical TCP data for SBRT of early-stage HCC found consistent α/β ratios of about 14 Gy for all three radiobiological models. TCP increases sharply with BED and reaches an asymptotic maximal plateau, which results in optimal fractionation schemes of least doses to achieve asymptotic maximal tumor control for SBRT and hypofractionated radiation therapy of early-stage HCC that are found to be model-independent. ConclusionFrom the fits to the clinical TCP data, we presented the first determination of radiobiological parameters and model-independent optimal fractionation regimens in 1–20 fractions to achieve maximal tumor control whenever safe for SBRT and hypofractionated radiation therapy of early-stage HCC. The determined optimal fractionation schemes agree well with clinical practice for SBRT of early-stage HCC. However, most existing hypofractionated radiation therapy schemes of 3–5 Gy/fraction are not optimal, higher doses are required to maximize tumor control, further validation of these findings is essential with clinical TCP data.

Radiobiological analysis of VMAT treatment plan with flattened and flattening filter free photon beam: an EUD and TCP based comparative study.

This study aimed to evaluate the dosimetric and radiobiological differences between 6MV flattened filter (FF) and flattening filter free (FFF) using volumetric modulated arc (VMAT) technique for head and neck (H&N) cancer patients. Fifteen patients with H&N carcinoma were selected and treated with VMAT with FF (VMATFF) treatment plan. Retrospectively, additional VMAT treatment plans were developed using FFF beams (VMATFFF). Radiobiological parameters, such as equivalent uniform dose (EUD), tumor cure probability (TCP), and normal tissue complication probability (NTCP), were calculated using Niemierko's model for both VMATFF and VMATFFF. Correlation between dosimetric and radiobiological data were analyzed and compared. The conformity index (CI) was 0.975 ± 0.014 (VMATFF) and 0.964 ± 0. 019 (VMATFFF) with p ≥ 0.05. Statistically, there was an insignificant difference in the planning target volume (PTV) results for TCP (%) values, with values of 81.20 ± 0.88% (VMATFF) and 81.01 ± 0.92 (%) (VMATFF). Similarly, there was an insignificant difference in the EUD (Gy) values, which were 71.53 ± 0.33 Gy (VMATFF) and 71.46 ± 0.34 Gy (VMATFFF). The NTCP values for the spinal cord, left parotid, and right parotid were 6.54 × 10-07%, 8.04%, and 7.69%, respectively, in the case of VMATFF. For VMATFFF, the corresponding NTCP values for the spinal cord, parotids left, and parotid right were 3.09 × 10-07%, 6.57%, and 6.73%, respectively. The EUD and Mean Dose to PTV were strongly correlated for VMATFFF. An increased mean dose to the PTV and greater TCP were reported for the VMATFF, which can enhance the delivery of the therapeutic dose to the target.

A generalised method for calculating repopulation-corrected tumour EQD2 values in a wide range of clinical situations, including interrupted treatments

Any radiotherapy schedule can be characterised by its 2 Gy per fraction equivalent dose (EQD2). EQD2s are easily calculated for late-responding normal tissues but for tumours significant errors may arise if no allowance is made for any repopulation which occurs in the reference and/or the derived EQD2 schedule. This article presents a systematic approach to calculating tumour EQD2 values utilising the concept of biologically effective dose (BED) with inclusion of repopulation effects. A factor (f) is introduced which allows the inter-dependence between EQD2 and its delivery time (and, hence, the amount of repopulation involved) to be embedded within the formulation without any additional assumptions. There exists a transitional BED below which simple methods of calculating tumour EQD2 remain valid. In cases where simpler approaches are inadequate, the correct EQD2 may be determined from the reference schedule BED (BEDref) by the relationship: EQD2 = A × BEDref – B, where A and B are constants which involve the same radiobiological parameters as are conventionally used in deriving tumour BED values. Some Worked Examples illustrate application of the method to fractionated radiotherapy and indicate that there can be substantial differences with results obtained from using over-simplified approaches. Since reference BEDs are calculable for other types of radiotherapy (brachytherapy, permanent implants, high-LET applications, etc) the methodology allows estimation of tumour EQD2 values in a wide range of clinical circumstances, including cases which involve interrupted treatments.

Impact of Dose Calculation Algorithms and Radiobiological Parameters on Prediction of Cardiopulmonary Complications in Left Breast Radiation Therapy.

Breast cancer requires evaluating treatment plans using dosimetric and biological parameters. Considering radiation dose distribution and tissue response, healthcare professionals can optimize treatment plans for better outcomes. This study aimed to evaluate the effects of the different Dose Calculation Algorithms (DCAs) and Biologically Model-Related Parameters (BMRPs) on the prediction of cardiopulmonary complications due to left breast radiotherapy. In this practical study, the treatment plans of 21 female patients were simulated in the Monaco Treatment Planning System (TPS) with a prescribed dose of 50 Gy in 25 fractions. Dose distribution was extracted using the three DCAs [Pencil Beam (PB), Collapsed Cone (CC), and Monte Carlo (MC)]. Cardiopulmonary complications were predicted by Normal Tissue Complication Probability (NTCP) calculations using different dosimetric and biological parameters. The Lyman-Kutcher-Burman (LKB) and Relative-Seriality (RS) models were used to calculate NTCP. The endpoint for NTCP calculation was pneumonitis, pericarditis, and late cardiac mortality. The ANOVA test was used for statistical analysis. In calculating Tumor Control Probability (TCP), a statistically significant difference was observed between the results of DCAs in the Poisson model. The PB algorithm estimated NTCP as less than others for all Pneumonia BMRPs. The impact of DCAs and BMRPs differs in the estimation of TCP and NTCP. DCAs have a stronger influence on TCP calculation, providing more effective results. On the other hand, BMRPs are more effective in estimating NTCP. Consequently, parameters for radiobiological indices should be cautiously used s to ensure the appropriate consideration of both DCAs and BMRPs.

Obtaining organ-specific radiobiological parameters from clinical data for radiation therapy planning of head and neck cancers

Objective. Different radiation therapy (RT) strategies, e.g. conventional fractionation RT (CFRT), hypofractionation RT (HFRT), stereotactic body RT (SBRT), adaptive RT, and re-irradiation are often used to treat head and neck (HN) cancers. Combining and/or comparing these strategies requires calculating biological effective dose (BED). The purpose of this study is to develop a practical process to estimate organ-specific radiobiologic model parameters that may be used for BED calculations in individualized RT planning for HN cancers. Approach. Clinical dose constraint data for CFRT, HFRT and SBRT for 5 organs at risk (OARs) namely spinal cord, brainstem, brachial plexus, optic pathway, and esophagus obtained from literature were analyzed. These clinical data correspond to a particular endpoint. The linear-quadratic (LQ) and linear-quadratic-linear (LQ-L) models were used to fit these clinical data and extract relevant model parameters (alpha/beta ratio, gamma/alpha, d T and BED) from the iso-effective curve. The dose constraints in terms of equivalent physical dose in 2 Gy-fraction (EQD2) were calculated using the obtained parameters. Main results. The LQ-L and LQ models fitted clinical data well from the CFRT to SBRT with the LQ-L representing a better fit for most of the OARs. The alpha/beta values for LQ-L (LQ) were found to be 2.72 (2.11) Gy, 0.55 (0.30) Gy, 2.82 (2.90) Gy, 6.57 (3.86) Gy, 5.38 (4.71) Gy, and the dose constraint EQD2 were 55.91 (54.90) Gy, 57.35 (56.79) Gy, 57.54 (56.35) Gy, 60.13 (59.72) Gy and 65.66 (64.50) Gy for spinal cord, optic pathway, brainstem, brachial plexus, and esophagus, respectively. Additional two LQ-L parameters d T were 5.24 Gy, 5.09 Gy, 7.00 Gy, 5.23 Gy, and 6.16 Gy, and gamma/alpha were 7.91, 34.02, 8.67, 5.62 and 4.95.Significance. A practical process was developed to extract organ-specific radiobiological model parameters from clinical data. The obtained parameters can be used for biologically based radiation planning such as calculating dose constraints of different fractionation regimens.

Estimation of the relative biological effectiveness (RBE) of the 177Lu − DOTA − iPSMA radiopharmaceutical

Relative biological effectiveness is a radiobiological parameter relevant in radiotherapy planning and useful in evaluating the physiological impact of radiation in different tissues. Targeted radionuclide therapy allows the selective and specific deposition of higher radiation doses in a noninvasive way and without collateral effects through the administration of radiopharmaceuticals. Lu−DOTA−177(hydrazinylnicotinoyl−Lys−(Nal)−NH−CO−NH−Glu) also called Lu−iPSMA177 is a third generation radiopharmaceutical composed by a peptide that recognizes the prostate-specific membrane antigen (PSMA), a membrane protein overexpressed in several types of cancer and that mediates the radiopharmaceutical's recognition of cancer cells. The present study reports radiobiological parameters of Lu−iPSMA177 and demonstrates the superiority of targeted radiopharmaceuticals over external radiotherapy treatment options in terms of their relative biological effectiveness. The relative biological effectiveness value of 1.020±0.003 for the LINAC, estimated by fitting the linear-quadratic model equation to the resulting survival curves, was like those of 1.25±0.04,1.060±0.005and1.00±0.04 obtained by an alternative method in relation to the mean lethal doses at 90, 80 or 60 survival percent respectively. While the relative biological effectiveness values of 5.65±0.13,4.72±0.27and2.87±0.19 estimated for Lu−iPSMA177 were significantly higher than those for the LINAC. The results confirm that the biological effect produced by the deposition of a radiation absorbed dose delivered by the LINAC can be induced with a quarter of that dose using Lu−iPSMA177 due to the energy distribution, dose-rate and energy fluence.

Spatiotemporal Optimization of Pelvic Radiation Therapy

Conformal and adaptive Radiation Therapy (RT) remains critical in the treatment of locally advanced pelvic cancers despite acute and late bowel complications. This work introduces spatiotemporal optimization of pelvic RT including mathematical modelling of intestinal radiobiology to evaluate a novel treatment planning approach for fractionated pelvic RT. A single-plan fractionated RT delivery has n-fractions at dose/fraction = d and has biologically effective dose BED = nd ( 1 + d / [α/β] ) - ln(2) ([T - Tk] / [αTp]), where Tk and Tp are the kickoff time and doubling time of repopulation, and T is the time to deliver all fractions (including off-days). We present a parameterization of the repopulation BED-term to estimate a range of daily recovered BED including uncertainties in α and Tp. Recovery of BED as currently formulated is independent of the delivered dose; however, the assumption of spatiotemporal optimization is that a regional reduction of dose during RT by mixing treatment plans is critical to allow for normal tissue healing. We evaluate an achievable spatiotemporal optimization treatment planning strategy for an advanced stage prostate and a cervical cancer patient using 25-fraction delivery over 5-weeks and 4-weekends (T = 33 days) and propose 3 treatment plans: (1) a conformal "clinical standard" plan, (2) a right-bowel sparing plan, and (3) a left-bowel sparing plan. The plans are optimized to ensure no increased dose in opposing bowel or normal organs at risk (OARs). For radiobiological parameters ranging from α = 0.2-0.35/Gy, α/β = 2-3 Gy, Tk = 5-10 days, and Tp = 3-7 days, parameterization shows daily BED recovery of 0.44±0.08 Gy (range = 0.28-0.69 Gy), or an average of 4Gy BED recovery for 5-days treatment surrounded by 2 weekends. Conservatively evaluating the 3.6Gy BED distribution in treatment planning may identify regions for complete recovery (after Tk days). In a prostate 3-plan set, the right- and left- bowel sparing plans deliver equivalent mean dose to targets and OARs to within 5cGy/fx. The clinical plan includes 298cc of bowel under 14Gy, but this same bowel will be spared throughout treatment. Delivery of the clinical plan in week 1 to achieve Tk days, followed by alternating the left and right plan each week has the potential to reduce BED to zero for an additional 116cc of bowel using the left-sparing plan in weeks 2 and 4, and 91cc using the right-bowel sparing plan in weeks 3 and 5. The cervical cancer plan-set was more challenging due to right-sided nodal volumes and higher clinical bowel dose; OAR mean dose variations were >8cGy/fx in a few organs, but the left- and right- sided sparing plans results in 394 cc and 139cc, respectively of unique spared bowel at the 3.6Gy/week threshold to potentially reach zero BED during treatment. A novel spatiotemporal optimization of pelvic RT has the potential to preserve bowel, allow for increased intra-treatment intestinal tissue regeneration, and reduce radiation-induced complications.

A systematic review of the normal tissue complication probability models and parameters: Head and neck cancers treated with conformal radiotherapy.

This systematic review study aims to provide comprehensive data on different radiobiological models, parameters, and endpoints used for calculating the normal tissue complication probability (NTCP) based on clinical data from head and neck cancer patients treated with conformal radiotherapy. A systematic literature search was carried out according to the PRISMA guideline for the identification of relevant publications in six electronic databases of Embase, PubMed, Scopus, and Google Scholar to July 2022 using specific keywords in the paper's title and abstract. The initial search resulted in 1368 articles for all organs for the review article about the NTCP parameters. One hundred and seventy-eight articles were accepted for all organs with complete parameters for the mentioned models and finally, 20 head and neck cancer articles were accepted for review. Analysis of the studies shows that the Lyman-Kutcher-Burman (LKB) model properly links the NTCP curve parameters to the postradiotherapy endpoints. In the LKB model for esophagus, the minimum, and maximum corresponding parameters were reported as TD50 = 2.61 Gy with grade ≥3 radiation-induced esophagitis endpoints as the minimum TD50 and TD50 = 68 Gy as the maximum ones. nmin = 0.06, nmax = 1.04, mmin = 0.1, and mmax = 0.65, respectively. Unfortunately, there was not a wide range of published articles on other organs at risk like ear or cauda equina except Burman et al. (Fitting of normal tissue tolerance data to an analytic function. Int J Radiat Oncol Biol Phys Ther. 1991;21:123-135). Findings suggest that the validation of different radiobiological models and their corresponding parameters need to be investigated in vivo and in vitro for developing a more accurate NTCP model to be used for radiotherapy treatment planning optimization.

Prostate Cancer Volumetric Arc Therapy (VMAT) Analysis

Aim: The purpose of this study was to derive radiobiological parameters from the dose volume histogram of patients that undergone prostate cancer radiotherapy via the VMAT technique. Material and Methods: A total of twenty-two cases of prostate cancer of 70.2 and 81 Gy were selected for this study. Radiobiological parameters were evaluated by the Poisson equation for the tumor and LKB model for organs at risk. Results: For prostate tumor, the average TCP was 96.28, 86.45, 68.57 for α/β of 1.2, 3.0, and 10, respectively. The average EUD was 37.98 Gy, 59.23 Gy, 21.19 Gy, 20.65 Gy, 16.32 Gy, and 21.87 Gy for bladder, rectum, right femoral head, left femoral head, small bowel, and large bowel respectively. The average NTCP was 7.6 % for the rectum and negligible for other organs at risk. Conclusion: NTCP for critical organs and TCP for prostate cancer can be determined via dose volume histogram.

Relationship between the Patients’ Setup Errors with Dosimetric and Radiobiologic Parameters in Whole Breast Radiotherapy

Purpose: This study aimed to investigate the effect of the patients’ setup errors on dosimetric and radiobiologic parameters for left-sided Whole-Breast Irradiation (WBI) in three different radiotherapy techniques, including Intensity-Modulated Radiation Therapy (IMRT), Field-In-Field (FIF), and Conventional Wedge (CW).&#x0D; Materials and Methods: Computed Tomography (CT) images of 10 female patients with early-stage left-sided breast cancer were used to simulate different radiotherapy techniques (IMRT, FIF, and CW). The dosimetric parameters; Conformity Index (CI), Homogeneity Index (HI), the dose received by at least 95% (D95%) of Planning Tumor Volume (PTV), the volume of lung and heart that respectively received at least 20% (V20%) and 40% (V40%) of the prescribed dose, as well as, the radiobiologic parameters, including Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) were assessed for setup errors in patients. The setup errors were assessed by shifting the isocenters and gantry angles of the treatment plans.&#x0D; Results: The D95% of the PTV for an isocenter misplacement plan in the posterior direction decreased by 66.99 (IMRT), 71.86 (CW), and 68.25% (FIF). The TCP of the PTV was reduced by 26.66, 39.16, and 36.97% for IMRT, CW, and FIF techniques, respectively. Increasing gantry angle by a ±10 degree caused a 43%, 41%, and 41% decrease in the D95% of IMRT, FIF, and CW techniques, respectively. The TCP values decreased about 18% in all three techniques with a ±10 degree gantry angle shift; however, the NTCP values of the heart and lungs increased for all three methods. The CI and HI values had significantly more changes with increasing setup errors in the IMRT than in the two techniques.&#x0D; Conclusion: The radiobiologic parameters in IMRT were less sensitive to setup errors compared to FIF and CW techniques. The radiobiological parameters can help estimate the setup errors along with physical parameters during breast radiotherapy.

Hypothesis about Celluar Structure of Tumor Tissues and Probability of Her Curing Depending on Plan of RT

Purpose: In 1988 Withers H.R., Taylor J.M., Maciejewski B., proposed a hypothesis about the cellular structure of normal body tissues, according to which their radioresistance is determined by the presence of functional cellular units (FСU) in them. But, unfortunately, in their work there was no substantiation of this hypothesis.&#x0D; In our work, we substantiate the hypothesis that tumor tissue contains structured tissue-like formations (TLF) from malignant cells that determine its radioresistance. The success of radiation therapy is determined both by the destruction of TLF and the death of their fragments and free clonogenic cells formed as a result of the breakdown of TLF.&#x0D; Material and methods: To substantiate the hypothesis, mathematical models were created that made it possible to describe the results of radiation exposure to squamous cell carcinoma of the larynx (CL) and breast cancer (BC) after surgical removal of the BC tumor and total irradiation of breast to destroy cells that could migrate from tumor. For segregation of the parameters values that characterize the radiosensitivity of the tumor and for plotting a dose-response curve, a special method was developed for Reconstruction the Radiobiological Tumor Parameters (RRTP), based on the Poisson mathematical model and other mathematical models used in radiation therapy planning.&#x0D; Results: Dependencies of radiobiological parameters on the dose were plotted using the RRTP method:&#x0D; 1. Dependence of the number of tumor units N on the dose, which include TLF, TLF fragments and independent tumor cells formed as a result of TLF decay after irradiation.&#x0D; 2. Dependence of the radiobiological parameter t (D,d) Gy–1 on the total dose and dose per fraction.&#x0D; 3. Dependence of the radiobiological parameter g (D,d) Gy on total dose and dose per fraction.&#x0D; In this paper, it is shown that for CL the number of tumor units N and the parameter t (D,d) are increasing functions of the dose D. This confirms the hypothesis that CL consists of TLF, which, after irradiation, decompose into TLF fragments and independent tumor cells. For breast cancer, it was found, as expected, that the number of tumor units N is a decreasing function of the dose D, i.e., that there are no TLF formations in breast cancer.&#x0D; Conclusion: The hypothesis that the CL tumor contains TPO formations from malignant cells, which increase its radioresistance was confirmed. At a dose close to the therapeutic dose, the number of tumor units becomes close to the number of all tumor cells.

Comparative radiosensitization efficiency assessment of graphene oxide and Ti3C2 MXene as 2D carbon-based nanoparticles against breast cancer cells: characterization, toxicity and mechanisms

The efficacy of two carbon-based nanomaterials, graphene oxide (GO) and Ti3C2 MXene (MX), on the radiosensitivity of the breast cancer cells (BCCs) was investigated using clinical x-ray irradiation. The prepared GO and MX nanoparticles (NPs) were firstly characterized utilizing Fourier transform infrared, ultraviolet–visible, atomic force microscopy and transmission electron microscopy techniques and subsequently assessed in terms of their radiobiological properties. The results of the cell toxicity assay indicated that neither NPs exhibited significant cytotoxicity after 48 h incubation with BCC up to 50 µg ml−1 concentration without irradiation. The cell internalization results showed an approximately equivalent cellular uptake for both NPs after 6 h incubation with BCC. Our comparative studies with radiotherapy demonstrated that both NPs substantially increased cell proliferation inhibition and cell apoptosis of BCC under x-ray irradiation when compared to BCC treated with irradiation alone. Additionally, the 2ʹ,7ʹ-dichlorofluorescin diacetate flow cytometry results and fluorescent microscopy images revealed that both NPs remarkably increased the level of intracellular reactive oxygen species (ROS) generation in BCC under x-ray irradiation. The MX nanosheets exhibited superior radiosensitization efficiency than GO under x-ray irradiation due to its higher level of intracellular ROS generation (MX = 75.2% and GO = 65.2%). Clonogenic cell survival assay and extracted radiobiological parameters revealed that both NPs in combination with x-ray irradiation induced more lethal damage and less sublethal damage to BCC. Generally, the obtained results demonstrate that the MX NPs, as a stronger radiosensitizer than GO, could be a promising candidate for enhancing the effectiveness of radiotherapy in breast cancer treatment.

Large-scale in vitro microdosimetry via live cell microscopy imaging: implications for radiosensitivity and RBE evaluations in alpha-emitter radiopharmaceutical therapy

BackgroundAlpha-emitter radiopharmaceutical therapy (αRPT) has shown promising outcomes in metastatic disease. However, the short range of the alpha particles necessitates dosimetry on a near-cellular spatial scale. Current knowledge on cellular dosimetry is primarily based on in vitro experiments using cell monolayers. The goal of such experiments is to establish cell sensitivity to absorbed dose (AD). However, AD cannot be measured directly and needs to be modeled. Current models, often idealize cells as spheroids in a regular grid (geometric model), simplify binding kinetics and ignore the stochastic nature of radioactive decay. It is unclear what the impact of such simplifications is, but oversimplification results in inaccurate and non-generalizable results, which hampers the rigorous study of the underlying radiobiology.MethodsWe systematically mapped out 3D cell geometries, clustering behavior, agent binding, internalization, and subcellular trafficking kinetics for a large cohort of live cells under representative experimental conditions using confocal microscopy. This allowed for realistic Monte Carlo-based (micro)dosimetry. Experimentally established surviving fractions of the HER2 + breast cancer cell line treated with a 212Pb-labelled anti-HER2 conjugate or external beam radiotherapy, anchored a rigorous statistical approach to cell sensitivity and relative biological effectiveness (RBE) estimation. All outcomes were compared to a reference geometric model, which allowed us to determine which aspects are crucial model components for the proper study of the underlying radiobiology.ResultsIn total, 567 cells were measured up to 26 h post-incubation. Realistic cell clustering had a large (2x), and cell geometry a small (16.4% difference) impact on AD, compared to the geometric model. Microdosimetry revealed that more than half of the cells do not receive any dose for most of the tested conditions, greatly impacting cell sensitivity estimates. Including these stochastic effects in the model, resulted in significantly more accurate predictions of surviving fraction and RBE (permutation test; p < .01).ConclusionsThis comprehensive integration of the biological and physical aspects resulted in a more accurate method of cell survival modelling in αRPT experiments. Specifically, including realistic stochastic radiation effects and cell clustering behavior is crucial to obtaining generalizable radiobiological parameters.