The influence of Gleason score ≤ 6 histology on the outcome of high-risk localized prostate cancer after modern radiotherapy.

We aimed to retrospectively review outcomes in patients with high-risk prostate cancer and a Gleason score ≤ 6 following modern radiotherapy. We analyzed the outcomes of 1374 patients who had undergone modern radiotherapy, comprising a high-risk low grade [HRLG] group (Gleason score ≤ 6; n = 94) and a high-risk high grade [HRHG] group (Gleason score ≥ 7, n = 1125). We included 955 patients who received brachytherapy with or without external beam radio-therapy (EBRT) and 264 who received modern EBRT (intensity-modulated radiotherapy [IMRT] or stereotactic body radiotherapy [SBRT]). At a median follow-up of 60 (2-177) months, actuarial 5-year biochemical failure-free survival rates were 97.8 and 91.8% (p = 0.017), respectively. The frequency of clinical failure in the HRLG group was less than that in the HRHG group (0% vs 5.4%, p = 0.012). The HRLG group had a better 5-year distant metastasis-free survival than the HRHG group (100% vs 96.0%, p = 0.035). As the HRLG group exhibited no clinical failure and better outcomes than the HRHG group, the HRLG group might potentially be classified as a lower-risk group.

A comparative study in left-sided breast cancer treated with moderate deep inspiratory breath hold versus free breathing.

BACKGROUND: The moderate deep inspiratory breath hold (mDIBH) is a modality famed for cardiac sparing. Prospective studies based on this are few from the eastern part of the world and India. We intend to compare the dosimetry between mDIBH and free-breathing (FB) plans. METHODS: Thirty-two locally advanced left breast cancer patients were taken up for the study. All patients received a dose of 50 Gy in 25 fractions to the chest wall/intact breast, followed by a 10-Gy boost to the lumpectomy cavity in the case of breast conservation surgery. All the patients were treated in mDIBH using active breath coordinator (ABC). The data from the two dose volume histograms were compared regarding plan quality and the doses received by the organs at risk. Paired t-test was used for data analysis. RESULTS: The dose received by the heart in terms of V5, V10, and V30 (4.55% vs 8.39%) and mean dose (4.73 Gy vs 6.74 Gy) were statistically significant in the ABC group than that in the FB group (all p-values < 0.001). Also, the dose received by the LADA in terms of V30 (19.32% vs 24.87%) and mean dose (32.99 Gy vs 46.65 Gy) were significantly less in the ABC group. The mean treatment time for the ABC group was 20 min, while that for the free-breathing group was 10 min. CONCLUSIONS: Incorporating ABC-mDIBH for left-sided breast cancer radiotherapy significantly reduces the doses received by the heart, LADA, and left and right lung, with no compromise in plan quality but with an increase in treatment time.

Multi-institutional evaluation of a Pareto navigation guided automated radiotherapy planning solution for prostate cancer.

BACKGROUND: Current automated planning solutions are calibrated using trial and error or machine learning on historical datasets. Neither method allows for the intuitive exploration of differing trade-off options during calibration, which may aid in ensuring automated solutions align with clinical preference. Pareto navigation provides this functionality and offers a potential calibration alternative. The purpose of this study was to validate an automated radiotherapy planning solution with a novel multi-dimensional Pareto navigation calibration interface across two external institutions for prostate cancer. METHODS: The implemented 'Pareto Guided Automated Planning' (PGAP) methodology was developed in RayStation using scripting and consisted of a Pareto navigation calibration interface built upon a 'Protocol Based Automatic Iterative Optimisation' planning framework. 30 previous patients were randomly selected by each institution (IA and IB), 10 for calibration and 20 for validation. Utilising the Pareto navigation interface automated protocols were calibrated to the institutions' clinical preferences. A single automated plan (VMATAuto) was generated for each validation patient with plan quality compared against the previously treated clinical plan (VMATClinical) both quantitatively, using a range of DVH metrics, and qualitatively through blind review at the external institution. RESULTS: PGAP led to marked improvements across the majority of rectal dose metrics, with Dmean reduced by 3.7 Gy and 1.8 Gy for IA and IB respectively (p < 0.001). For bladder, results were mixed with low and intermediate dose metrics reduced for IB but increased for IA. Differences, whilst statistically significant (p < 0.05) were small and not considered clinically relevant. The reduction in rectum dose was not at the expense of PTV coverage (D98% was generally improved with VMATAuto), but was somewhat detrimental to PTV conformality. The prioritisation of rectum over conformality was however aligned with preferences expressed during calibration and was a key driver in both institutions demonstrating a clear preference towards VMATAuto, with 31/40 considered superior to VMATClinical upon blind review. CONCLUSIONS: PGAP enabled intuitive adaptation of automated protocols to an institution's planning aims and yielded plans more congruent with the institution's clinical preference than the locally produced manual clinical plans.

[Research Photon Energy Spectrum of Medical Linear Accelerator by Monte Carlo Method].

Objective: The distribution of the photon energy spectrum in isocenter plane of the medical linear accelerator and the influence of secondary collimator on the photon energy spectrum are studied. Methods Use the BEAMnrc program to simulate the transmission of the 6 MeV electrons and photons in 5 cm×5 cm,10 cm×10 cm,15 cm×15 cm and 20 cm×20 cm fields in treatment head of the medical linear accelerator, where a phase space file was set up at the isocenter plane to record the particle information passing through this plane. The BEAMdp program is used to analyze the phase space file, in order to obtain the distribution of the photon energy spectrum in isocenter plane and the influence of secondary collimator on the photon energy spectrum. Results: By analyzing the photon energy spectrum of a medical linear accelerator with a nominal energy of 6 MV, it is found that the secondary collimator has little effect on the photon energy spectrum; different fields have different photon energy spectrum distributions; the photon energy spectrum in different central regions of the same field have the same normalized distribution. Conclusion: In the dose calculation of radiation therapy, the influence of photon energy spectrum should be carefully considered.

[Research on Position Verification of Multi-Leaf Collimator (MLC) and Dose Verification Based on Electronic Portal Imaging Device].

Objective: A quality control (QC) system based on the electronic portal imaging device (EPID) system was used to realize the Multi-Leaf Collimator (MLC) position verification and dose verification functions on Primus and VenusX accelerators. Methods: The MLC positions were calculated by the maximum gradient method of gray values to evaluate the deviation. The dose of images acquired by EPID were reconstructed using the algorithm combining dose calibration and dose calculation. The dose data obtained by EPID and two-dimensional matrix (MapCheck/PTW) were compared with the dose calculated by Pinnacle/TiGRT TPS for γ passing rate analysis. Results: The position error of VenusX MLC was less than 1 mm. The position error of Primus MLC was significantly reduced after being recalibrated under the instructions of EPID. For the dose reconstructed by EPID, the average γ passing rates of Primus were 98.86% and 91.39% under the criteria of 3%/3 mm, 10% threshold and 2%/2 mm, 10% threshold, respectively. The average γ passing rates of VenusX were 98.49% and 91.11%, respectively. Conclusion: The EPID-based accelerator quality control system can improve the efficiency of accelerator quality control and reduce the workload of physicists.

Brachytherapy on-a-chip: a clinically-relevant approach for radiotherapy testing in 3d biology.

We describe the first microfluidic device for in vitro testing of brachytherapy (BT), with applications in translational cancer research. Our PDMS-made BT-on-chip system allows highly precise manual insertion of clinical BT seeds, reliable dose calculation using standard clinically-used TG-43 formalism and easy culture of naturally hypoxic spheroids in less than 3 days, thereby increasing the translational potential of the device. As the BT-on-chip platform is designed to be versatile, we showcase three different gold-standard post-irradiation bioassays and recapitulate, for the first time on-chip, key clinical observations such as dose rate effect and hypoxia-induced radioresistance. Our results suggest that BT-on-chip can be used to safely and efficiently integrate BT and radiotherapy to translational research and drug development pipelines, without expensive equipment or complex workflows.

Dosimetric feasibility study ("proof of concept") of refractory ventricular tachycardia radioablation using proton minibeams.

PURPOSE: Preclinical data demonstrated that the use of proton minibeam radiotherapy reduces the risk of toxicity in healthy tissue. Ventricular tachycardia radioablation is an area under clinical investigation in proton beam therapy. We sought to simulate a ventricular tachycardia radioablation with proton minibeams and to demonstrate that it was possible to obtain a homogeneous coverage of an arrhythmogenic cardiac zone with this technique. MATERIAL AND METHODS: An arrhythmogenic target volume was defined on the simulation CT scan of a patient, localized in the lateral wall of the left ventricle. A dose of 25Gy was planned to be delivered by proton minibeam radiotherapy, simulated using a Monte Carlo code (TOPAS v.3.7) with a collimator of 19 0.4 mm-wide slits spaced 3mm apart. The main objective of the study was to obtain a plan ensuring at least 93% of the prescription dose in 93% of the planning target volume without exceeding 110% of the prescribed dose in the planning target volume. RESULTS: The average dose in the planning treatment volume in proton minibeam radiotherapy was 25.12Gy. The percentage of the planning target volume receiving 93% (V93%), 110% (V110%), and 95% (V95%) of the prescribed dose was 94.25%, 0%, and 92.6% respectively. The lateral penumbra was 6.6mm. The mean value of the peak-to-valley-dose ratio in the planning target volume was 1.06. The mean heart dose was 2.54Gy versus 5.95Gy with stereotactic photon beam irradiation. CONCLUSION: This proof-of-concept study shows that proton minibeam radiotherapy can achieve a homogeneous coverage of an arrhythmogenic cardiac zone, reducing the dose at the normal tissues. This technique, ensuring could theoretically reduce the risk of late pulmonary and breast fibrosis, as well as cardiac toxicity as seen in previous biological studies in proton minibeam radiotherapy.

Assessment of radio-activation using spectroscopy in medical linear accelerators.

In radiotherapy, when photon energy exceeding 8 MV is utilized, photoneutrons can activate the components within the gantry of the linear accelerator (linac). At the end of the linac's lifecycle, radiation workers are tasked with its dismantling and disposal, potentially exposing them to unintentional radiation. This study aims to identify and measure the radioisotopes generated by this activation through spectroscopy, and to evaluate the effective dose rate. We selected nine medical linacs, considering various factors such as manufacturer (Siemens, Varian, and Elekta), model, energy, period of operation, and workload. We identified the radionuclides in the linac head by employing an in situ high-purity germanium (HPGe) detector. Spectroscopy and dose-rate measurements were conducted post-shutdown. We also measured the dose rates at the beam-exit window following irradiation with 10 MV and 15 MV photon beams. As a result of the spectroscopy, we identified approximately 20 nuclides including those with half-lives of 100 days or longer, such as 54Mn, 60Co, 65Zn, 122Sb, and 198Au. The dose rate measurements after 10 MV irradiation decreased to the background level in 10 min. By contrast, on 15 MV irradiation, the dose rate was 628 nSv/h after 10 min and decreased to 268 nSv/h after 1.5 hours. It was confirmed that the difference in the level of radiation and the type of nuclide depends on the period of use, energy, and workload. However, the type of nuclide does not differ significantly between the linacs. It is necessary to propose appropriate guidelines for the safety of workers, and disposal/move-install should be planned while taking into consideration the equipment's energy usage rate.

An artificial neural network based approach for predicting the proton beam spot dosimetric characteristics of a pencil beam scanning technique.

Utilising Machine Learning (ML) models to predict dosimetric parameters in pencil beam scanning proton therapy presents a promising and practical approach. The study developed Artificial Neural Network (ANN) models to predict proton beam spot size and relative positional errors using 9000 proton spot data. The irradiation log files as input variables and corresponding scintillation detector measurements as the label values. The ANN models were developed to predict six variables: spot size in thex-axis,y-axis, major axis, minor axis, and relative positional errors in thex-axis andy-axis. All ANN models used a Multi-layer perception (MLP) network using one input layer, three hidden layers, and one output layer. Model performance was validated using various statistical tools. The log file recorded spot size and relative positional errors, which were compared with scintillator-measured data. The Root Mean Squared Error (RMSE) values for the x-spot and y-spot sizes were 0.356 mm and 0.362 mm, respectively. Additionally, the maximum variation for the x-spot relative positional error was 0.910 mm, while for the y-spot, it was 1.610 mm. The ANN models exhibit lower prediction errors. Specifically, the RMSE values for spot size prediction in the x, y, major, and minor axes are 0.053 mm, 0.049 mm, 0.053 mm, and 0.052 mm, respectively. Additionally, the relative spot positional error prediction model for the x and y axes yielded maximum errors of 0.160 mm and 0.170 mm, respectively. The normality of models was validated using the residual histogram and Q-Q plot. The data over fit, and bias were tested using K (k = 5) fold cross-validation, and the maximum RMSE value of the K fold cross-validation among all the six ML models was less than 0.150 mm (R-Square 0.960). All the models showed excellent prediction accuracy. Accurately predicting beam spot size and positional errors enhances efficiency in routine dosimetric checks.

Tuning spatially fractionated radiotherapy dose profiles using the moiré effect.

Spatially Fractionated Radiotherapy (SFRT) has demonstrated promising potential in cancer treatment, combining the advantages of reduced post-radiation effects and enhanced local control rates. Within this paradigm, proton minibeam radiotherapy (pMBRT) was suggested as a new treatment modality, possibly producing superior normal tissue sparing to conventional proton therapy, leading to improvements in patient outcomes. However, an effective and convenient beam generation method for pMBRT, capable of implementing various optimum dose profiles, is essential for its real-world application. Our study investigates the potential of utilizing the moiré effect in a dual collimator system (DCS) to generate pMBRT dose profiles with the flexibility to modify the center-to-center distance (CTC) of the dose distribution in a technically simple way.We employ the Geant4 Monte Carlo simulations tool to demonstrate that the angle between the two collimators of a DCS can significantly impact the dose profile. Varying the DCS angle from 10 ∘ to 50 ∘ we could cover CTC ranging from 11.8 mm to 2.4 mm, respectively. Further investigations reveal the substantial influence of the multi-slit collimator's (MSC) physical parameters on the spatially fractionated dose profile, such as period (CTC), throughput, and spacing between MSCs. These findings highlight opportunities for precision dose profile adjustments tailored to specific clinical scenarios.The DCS capacity for rapid angle adjustments during the energy transition stages of a spot scanning system can facilitate dynamic alterations in the irradiation profile, enhancing dose contrast in normal tissues. Furthermore, its unique attribute of spatially fractionated doses in both lateral directions could potentially improve normal tissue sparing by minimizing irradiated volume. Beyond the realm of pMBRT, the dual MSC system exhibits remarkable versatility, showing compatibility with different types of beams (X-rays and electrons) and applicability across various SFRT modalities.Our study illuminates the dual MSC system's potential as an efficient and adaptable tool in the refinement of pMBRT techniques. By enabling meticulous control over irradiation profiles, this system may expedite advancements in clinical and experimental applications, thereby contributing to the evolution of SFRT strategies.

Pelvic target volume inter-fractional motion during radiotherapy for cervical cancer with daily iterative cone beam computed tomography.

BACKGROUND: Tumor regression and organ movements indicate that a large margin is used to ensure target volume coverage during radiotherapy. This study aimed to quantify inter-fractional movements of the uterus and cervix in patients with cervical cancer undergoing radiotherapy and to evaluate the clinical target volume (CTV) coverage. METHODS: This study analyzed 303 iterative cone beam computed tomography (iCBCT) scans from 15 cervical cancer patients undergoing external beam radiotherapy. CTVs of the uterus (CTV-U) and cervix (CTV-C) contours were delineated based on each iCBCT image. CTV-U encompassed the uterus, while CTV-C included the cervix, vagina, and adjacent parametrial regions. Compared with the planning CTV, the movement of CTV-U and CTV-C in the anterior-posterior, superior-inferior, and lateral directions between iCBCT scans was measured. Uniform expansions were applied to the planning CTV to assess target coverage. RESULTS: The motion (mean ± standard deviation) in the CTV-U position was 8.3 ± 4.1 mm in the left, 9.8 ± 4.4 mm in the right, 12.6 ± 4.0 mm in the anterior, 8.8 ± 5.1 mm in the posterior, 5.7 ± 5.4 mm in the superior, and 3.0 ± 3.2 mm in the inferior direction. The mean CTV-C displacement was 7.3 ± 3.2 mm in the left, 8.6 ± 3.8 mm in the right, 9.0 ± 6.1 mm in the anterior, 8.4 ± 3.6 mm in the posterior, 5.0 ± 5.0 mm in the superior, and 3.0 ± 2.5 mm in the inferior direction. Compared with the other tumor (T) stages, CTV-U and CTV-C motion in stage T1 was larger. A uniform CTV planning treatment volume margin of 15 mm failed to encompass the CTV-U and CTV-C in 11.1% and 2.2% of all fractions, respectively. The mean volume change of CTV-U and CTV-C were 150% and 51%, respectively, compared with the planning CTV. CONCLUSIONS: Movements of the uterine corpus are larger than those of the cervix. The likelihood of missing the CTV is significantly increased due to inter-fractional motion when utilizing traditional planning margins. Early T stage may require larger margins. Personal radiotherapy margining is needed to improve treatment accuracy.

Current practices of craniospinal irradiation techniques in Turkey: a comprehensive dosimetric analysis.

OBJECTIVE: This study evaluates various craniospinal irradiation (CSI) techniques used in Turkish centers to understand their advantages, disadvantages and overall effectiveness, with a focus on enhancing dose distribution. METHODS: Anonymized CT scans of adult and pediatric patients, alongside target volumes and organ-at-risk (OAR) structures, were shared with 25 local radiotherapy centers. They were tasked to develop optimal treatment plans delivering 36 Gy in 20 fractions with 95% PTV coverage, while minimizing OAR exposure. The same CT data was sent to a US proton therapy center for comparison. Various planning systems and treatment techniques (3D conformal RT, IMRT, VMAT, tomotherapy) were utilized. Elekta Proknow software was used to analyze parameters, assess dose distributions, mean doses, conformity index (CI), and homogeneity index (HI) for both target volumes and OARs. Comparisons were made against proton therapy. RESULTS: All techniques consistently achieved excellent PTV coverage (V95 > 98%) for both adult and pediatric patients. Tomotherapy closely approached ideal Dmean doses for all PTVs, while 3D-CRT had higher Dmean for PTV_brain. Tomotherapy excelled in CI and HI for PTVs. IMRT resulted in lower pediatric heart, kidney, parotid, and eye doses, while 3D-CRT achieved the lowest adult lung doses. Tomotherapy approached proton therapy doses for adult kidneys and thyroid, while IMRT excelled for adult heart, kidney, parotid, esophagus, and eyes. CONCLUSION: Modern radiotherapy techniques offer improved target coverage and OAR protection. However, 3D techniques are continued to be used for CSI. Notably, proton therapy stands out as the most efficient approach, closely followed by Tomotherapy in terms of achieving superior target coverage and OAR protection.

A Comparative Study of Deep Learning Dose Prediction Models for Cervical Cancer Volumetric Modulated Arc Therapy.

Purpose: Deep learning (DL) is widely used in dose prediction for radiation oncology, multiple DL techniques comparison is often lacking in the literature. To compare the performance of 4 state-of-the-art DL models in predicting the voxel-level dose distribution for cervical cancer volumetric modulated arc therapy (VMAT). Methods and Materials: A total of 261 patients' plans for cervical cancer were retrieved in this retrospective study. A three-channel feature map, consisting of a planning target volume (PTV) mask, organs at risk (OARs) mask, and CT image was fed into the three-dimensional (3D) U-Net and its 3 variants models. The data set was randomly divided into 80% as training-validation and 20% as testing set, respectively. The model performance was evaluated on the 52 testing patients by comparing the generated dose distributions against the clinical approved ground truth (GT) using mean absolute error (MAE), dose map difference (GT-predicted), clinical dosimetric indices, and dice similarity coefficients (DSC). Results: The 3D U-Net and its 3 variants DL models exhibited promising performance with a maximum MAE within the PTV 0.83% ± 0.67% in the UNETR model. The maximum MAE among the OARs is the left femoral head, which reached 6.95% ± 6.55%. For the body, the maximum MAE was observed in UNETR, which is 1.19 ± 0.86%, and the minimum MAE was 0.94 ± 0.85% for 3D U-Net. The average error of the Dmean difference for different OARs is within 2.5 Gy. The average error of V40 difference for the bladder and rectum is about 5%. The mean DSC under different isodose volumes was above 90%. Conclusions: DL models can predict the voxel-level dose distribution accurately for cervical cancer VMAT treatment plans. All models demonstrated almost analogous performance for voxel-wise dose prediction maps. Considering all voxels within the body, 3D U-Net showed the best performance. The state-of-the-art DL models are of great significance for further clinical applications of cervical cancer VMAT.

Effects of bone marrow sparing radiotherapy on acute hematologic toxicity for patients with locoregionally advanced cervical cancer: a prospective phase II randomized controlled study.

OBJECTIVE: To evaluate effects of bone marrow sparing (BMS) radiotherapy on decreasing the incidence of acute hematologic toxicity (HT) for locoregionally advanced cervical cancer (LACC) patients treated by pelvic irradiation. MATERIALS AND METHODS: LACC patients were recruited prospectively from May 2021 to May 2022 at a single center and were evenly randomized into the BMS group and the control group. All patients received pelvic irradiation with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy and BM V40 < 25% in the BMS group was additionally prescribed. Acute HT was assessed weekly. Binary logistic regression model and receiver operating characteristic (ROC) curve were used for predictive value analysis. The trial was registered with Chinese clinical trial registry (ChiCTR2200066485). RESULTS: A total of 242 patients were included in the analysis. Baseline demographic, disease and treatment characteristics were balanced between the two groups. In the intention-to-treat population, BMS was associated with a lower incidence of grade ≥ 2 and grade ≥ 3 acute HT, leukopenia and neutropenia s(72.70% v 90.90%, P < 0.001*; 16.50% vs. 65.30%, P < 0.001*; 66.10% vs. 85.10%, P = 0.001*; 13.20% vs. 54.50%, P < 0.001*; 37.20% vs. 66.10%, P < 0.001*; 10.70% vs. 43.80%, P < 0.001*). BMS also resulted in decreased dose delivered to the organs at risk (OARs) including rectum, bladder and left and right femoral head. Univariate and multivariate analyses showed that BM V40 was an independent risk factor for grade ≥ 3 acute HT (odds ratio [OR] = 2.734, 95% confidence interval [CI] = 1.959-3.815, P < 0.001*). Cutoff value was 25.036% and area under the curve (AUC) was 0.786. The nomogram was constructed, which was rigorously evaluated and internally cross-validated, showing good predictive performance. CONCLUSIONS: Receiving BMS pelvic irradiation could reduce the incidence of acute HT in LACC patients, and BM V40 < 25% may be a significant factor in reducing the risks of acute HT.