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Purpose: This study aimed to determine whether radiation therapy plans created using an automatic delineating system and a RapidPlan (RP) module could rapidly and accurately predict heart doses and benefit from deep inspiratory breath-hold (DIBH) in patients with left breast cancer., Methods and Materials: One hundred thirty-six clinically approved free breathing (FB) plans for patients with left breast cancer were included, defined as manual delineation-manual plan (MD-MP). A total of 104 of 136 plans were selected for RP model training. A total of 32 of 136 patients were automatically delineated by software, after which the RP generated plans, defined as automatic delineation-RapidPlan (AD-RP). In addition, 40 patients who used DIBH were included to analyze differences in heart benefits from DIBH., Results: Two RP models were established for post-breast-conserving surgery (BCS) and post-modified radical mastectomy. There were no significant differences in most of the dosimetric parameters between the MD-MP and AD-RP. The heart doses of the 2 plans were strongly correlated in patients after BCS (0.80 ≤ r ≤ 0.88, P < .05) and moderately correlated in patients after postmodified radical mastectomy (0.46 ≤ r ≤ 0.58, P <.05). The RP model predicted the mean heart dose (MHD) within ± 59.67 cGy and ± 63.32 cGy for patients who underwent the 2 surgeries described above. The heart benefits from DIBH were significantly greater in patients with FB-MHD ≥ 4 Gy than in those with FB-MHD < 4 Gy., Conclusions: The combined automatic delineation RP model allows for the rapid and accurate prediction of heart dose under FB in patients with left breast cancer. FB-MHD ≥ 4 Gy can be used as a dose threshold to select patients suitable for DIBH., (Published by Elsevier Inc.)

Purpose: Pencil-beam scanning proton therapy has been considered a potential modality for the 3D form of spatially fractionated radiation therapy called lattice therapy. However, few practical solutions have been introduced in the clinic. Existing limitations include degradation in plan quality and robustness when using single-field versus multifield lattice plans, respectively. We propose a practical and robust proton lattice (RPL) planning method using multifield and evaluate its dosimetric characteristics compared to clinically acceptable photon lattice plans., Methods and Materials: Seven cases previously treated with photon lattice therapy were used to evaluate a novel RPL planning technique using 2-orthogonal beams: a primary beam (PB) and a robust complementary beam (RCB) that deliver 67% and 33%, respectively, of the prescribed dose to vertices inside the gross target volume (GTV). Only RCB is robustly optimized for setup and range uncertainties. The number and volume of vertices, peak-to-valley dose ratios (PVDRs), and volume of low dose to GTV of proton and photon plans were compared. The RPL technique was then used in the treatment of 2 patients and their dosimetric parameters were reported., Results: The RPL strategy was able to achieve the clinical planning goals. Compared to previously treated photon plans, the average number of vertices increased by 30%, the average vertex volume by 49% (18.2 ± 25.9 cc vs 12.2 ± 14.5 cc, P = .21), and higher PVDR (10.5 ± 4.8 vs 2.5 ± 0.9, P < .005) was achieved. In addition, RPL plans show more conformal dose with less low dose to GTV (V30%, 60.9% ± 7.2% vs 81.6% ± 13.9% and V10%, 88.3% ± 4.5% vs 98.6% ± 3.6% [P < .01]). The RPL plan for 2 treated patients showed PVDRs of 4.61 and 14.85 with vertices-to-GTV ratios of 1.52% and 1.30%, respectively., Conclusions: A novel RPL planning strategy using a pair of orthogonal beams was developed and successfully translated to the clinic. The proposed method can generate better quality plans, a higher number of vertices, and higher PVDRs than currently used photon lattice plans., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Primary soft tissue sarcoma (STS) is rare, with many tumors occurring in extremities. Local management is limb-sparing surgery and preoperative/postoperative radiation therapy (RT) for patients at high risk of local recurrence. We prospectively investigated late normal tissue toxicity and limb function observed after intensity modulated RT (IMRT) in extremity STS., Methods and Materials: Patients with extremity STS, age ≥16 years. Two treatment cohorts: IMRT 50 Gy in 25 × 2 Gy fractions (preoperative) or 60/66 Gy in 30/33 × 2 Gy fractions (postoperative). The primary endpoint was the rate of grade ≥2 late soft tissue fibrosis (subcutaneous tissue) at 24 months after IMRT (Radiation Therapy Oncology Group late radiation morbidity scoring)., Results: One hundred sixty-eight patients were registered between March 2016 and July 2017. Of those, 159 (95%) received IMRT (106, 67% preoperative RT; and 53, 33% postoperative RT) with a median follow-up of 35.2 months (IQR, 32.9-36.6); 62% men, median age 58 years. Of 111 patients assessable for the primary endpoint at 24 months, 12 (10.8%; 95% CI, 5.7%-18.1%) had grade ≥2 subcutaneous fibrosis. The overall rate at 24 months of Radiation Therapy Oncology Group late skin, bone, and joint toxicity was 7 of 112 (6.3%), 3 of 112 (2.7%), and 10 of 113 (8.8%), respectively, and for Stern's scale edema was 6 of 113 (5.3%). More wound complications were observed with preoperative than postoperative RT (29.2% vs 3.8%). Overall survival at 24 months was 84.6%, and the local recurrence event rate at 24 months was 10%., Conclusions: The rate of grade ≥2 subcutaneous fibrosis at 24 months after IMRT was 10.8%, consistent with other recent trials of IMRT and lower than historically reported rates in patients treated with 3-dimensional conformal RT. This trial provides further evidence for the benefits of IMRT in this patient population., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Proton beam therapy (PBT) plays an important role in the management of primary spine tumors. The purpose of this consensus statement was to summarize safe and optimal delivery of PBT for spinal tumors., Methods and Materials: The Particle Therapy Cooperative Group Skull Base/Central nervous system/Sarcoma Subcommittee consisting of radiation oncologists and medical physicists with specific expertise in spinal irradiation developed expert recommendations discussing treatment planning considerations and current approaches in the treatment of primary spinal tumors., Results: Computed tomography simulation: factors that require significant consideration include (1) patient comfort, (2) setup reproducibility and stability, and (3) accessibility of appropriate beam angles., Spine Stabilization Hardware: If present, hardware should be placed with cross-links well above/below the level of the primary tumor to reduce the metal burden at the level of the tumor bed. New materials that can reduce uncertainties include polyether-ether-ketone and composite polyether-ether-ketone-carbon fiber implants., Field Arrangement: Appropriate beam selection is required to ensure robust target coverage and organ at risk sparing. Commonly, 2 to 4 treatment fields, typically from posterior and/or posterior-oblique directions, are used., Treatment Planning Methodology: Robust optimization is recommended for all pencil beam scanning plans (the preferred treatment modality) and should consider setup uncertainty (between 3 and 7 mm) and range uncertainty (3%-3.5%). In the presence of metal hardware, use of an increased range uncertainty up to 5% is recommended., Conclusions: The Particle Therapy Cooperative Group Skull Base/Central nervous system/Sarcoma Subcommittee has developed recommendations to enable centers to deliver PBT safely and effectively for the management of primary spinal tumors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Radiation-induced lymphopenia (RIL) is common among patients undergoing radiation therapy (RT)' Severe RIL has been linked to adverse outcomes. The severity and risk of RIL can be predicted from baseline clinical characteristics and dosimetric parameters. However, dosimetric parameters, e.g. dose-volume (DV) indices, are highly correlated with one another and are only weakly associated with RIL. Here we introduce the novel concept of "composite dosimetric score" (CDS) as the index that condenses the dose distribution in immune tissues of interest to study the dosimetric dependence of RIL. We derived an improved multivariate classification scheme for risk of grade 4 RIL (G4RIL), based on this novel RT dosimetric feature, for patients receiving chemo RT for esophageal cancer., Methods and Materials: DV indices were extracted for 734 patients who received chemo RT for biopsy-proven esophageal cancer. Nonnegative matrix factorization was used to project the DV indices of lung, heart, and spleen into a single CDS; XGBoost was employed to explore significant interactions among predictors; and logistic regression was applied to combine the resultant CDS with baseline clinical factors and interaction terms to facilitate individualized prediction of immunotoxicity. Five-fold cross-validation was applied to evaluate the model performance., Results: The CDS for selected immune organs at risk (ie, heart, lung, and spleen) (OR 1.791; 95 CI [1.350, 2.377]) was a statistically significant risk determinant for G4RIL. Pearson correlation coefficients for CDS versus G4RIL risk for individual immune organs at risk were greater than any single DV indicx. Personalized prediction of G4RIL based on CDS and 4 clinical risk factors yielded an area under the curve value of 0.78. Interaction between age and CDS revealed that G4RIL risk increased more sharply with increasing CDS for patients aged ≥65 years., Conclusions: Risk of immunotoxicity for patients undergoing chemo RT for esophageal cancer can be predicted by CDS. The CDS concept can be extended to immunotoxicity in other cancer types and in dose-response models currently based on DV indices. Personalized treatment planning should leverage composite dosimetric scoring methods rather than using individual or subsets of DV indices., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The objective of this study was to characterize the conditional risk of developing grade 2+ urinary or gastrointestinal (GI) toxicity for patients treated with external beam radiation therapy in Radiation Therapy Oncology Group 0126. A secondary objective was to analyze baseline patient and treatment characteristics and determine their relevance in predicting toxicity both at the time of trial enrollment and at later points of follow-up., Methods and Materials: One thousand five hundred thirty-two patients with localized prostate cancer were enrolled between March 2002 and August 2008, of whom 1499 were eligible and included in data analysis with a median follow-up of 8.4 years (range, 0.02-13 years). Patients were treated with either 3-dimensional conformal radiation therapy or intensity-modulated radiation therapy according to institutional practice without the addition of androgen deprivation and randomized to receive either standard-dose radiation therapy of 70.2 Gy or dose-escalated radiation therapy of 79.2 Gy of radiation therapy to the prostate only with standard fractionation. Univariate and multivariate analyses were performed to determine whether initial factors were predictive of late toxicity at the time of treatment and at later time points., Results: As patients proceed further from completion of radiation therapy without the development of toxicity, the subsequent risk of both grade 2+ genitourinary (GU) and GI toxicity decreases with time. At the time of enrollment, the risk of developing grade 2+ toxicity over the next 5 years was 9.57% and 17.89%, respectively. After 5 years of toxicity-free survival, the risk of developing grade 2+ GU or GI toxicity in the subsequent 5 years was 3.02% and 1.54%, respectively. Baseline treatment and patient-related factors predicted late toxicity both at trial enrollment and after 2 years of toxicity-free survivorship. Baseline urinary dysfunction and dose-escalated radiation therapy were associated with increased late GU toxicity. Acute GI toxicity and dose-escalated radiation therapy were associated with increased risk of late GI toxicity. Treatment with intensity-modulated radiation therapy was associated with reduced risk of either toxicity., Conclusions: The conditional risk of grade 2+ toxicities decreases as patients proceed further from treatment, with most toxicities occurring in the first few years after treatment completion. Baseline patient and treatment characteristics remain relevant at both enrollment and later time points., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: This study aimed to investigate a dose rate optimization framework based on the spot-scanning patterns to improve ultrahigh-dose-rate coverage of critical organs at risk (OARs) for proton pencil beam scanning (PBS) FLASH radiation therapy (ultrahigh dose-rate (often referred to as >40 Gy per second) delivery) and present implementation of a genetic algorithm (GA) method for spot sequence optimization to achieve PBS FLASH dose rate optimization under relatively low nozzle beam currents., Methods and Materials: First, a multifield FLASH plan was developed to meet all the dosimetric goals and optimal FLASH dose rate coverage by considering the deliverable minimum monitor unit constraint. Then, a GA method was implemented into the in-house treatment platform to maximize the dose rate by exploring the best spot delivery sequence. A phantom study was performed to evaluate the effectiveness of the dose rate optimization. Then, 10 consecutive plans for patients with lung cancer previously treated using PBS intensity-modulated proton therapy were optimized using 45 GyRBE in 3 fractions for both transmission and Bragg peak FLASH radiation therapy for further validation. The spot delivery sequence of each treatment field was optimized using this GA. The ultrahigh-dose-rate-volume histogram and dose rate coverage V 40GyRBE/s were investigated to assess the efficacy of dose rate optimization quantitatively., Results: Using a relatively low monitor unit/spot of 150, corresponding to a nozzle beam current of 65 nA, the FLASH dose rate ratio V 40GyRBE/s of the OAR contour of the core was increased from 0% to ∼60% in the phantom study. In the patients with lung cancer, the ultrahigh-dose-rate coverage V 40GyRBE/s was improved from 15.2%, 15.5%, 17.6%, and 16.0% before the delivery sequence optimization to 31.8%, 43.5%, 47.6%, and 30.5% after delivery sequence optimization in the lungs-GTV (gross tumor volume), spinal cord, esophagus, and heart (for all, P < .001). When the beam current increased to 130 nA, V 40GyRBE/s was improved from 45.1%, 47.1%, 51.2%, and 51.4% to 65.3%, 83.5%, 88.1%, and 69.4% (P < .05). The averaged V 40GyRBE/s for the target and OARs increased from 12.9% to 41.6% and 46.3% to 77.5% for 65 and 130 nA, respectively, showing significant improvements based on a clinical proton system. After optimizing the dose rate for the Bragg peak FLASH technique with a beam current of 340 nA, the V 40GyRBE/s values for the lung GTV, spinal cord, esophagus, and heart were increased by 8.9%, 15.8%, 22%, and 20.8%, respectively., Conclusions: An optimal plan quality can be maintained as the spot delivery sequence optimization is a separate independent process after the plan optimization. Both the phantom and patient results demonstrated that novel spot delivery sequence optimization can effectively improve the ultrahigh-dose-rate coverage for critical OARs, which can potentially be applied in clinical practice for better OARs-sparing efficacy., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The goal of the study was to assess the impact of deep inspiration breath hold technique (DIBH), surface-guided radiotherapy (SGRT), and daily kilovoltage cone-beam computed tomography (kV-CBCT) on the dose to organs at risk (OAR) in left-sided breast cancer radiotherapy. Twenty-six consecutive left-sided breast cancer patients treated using Volumetric Intensity Modulated Arc Therapy (VMAT), DIBH, SGRT, and a hypofractionated regimen were retrospectively evaluated in this study. Dose parameters were extracted from dose-volume histograms (DVH). The Wilcoxon Matched Pairs test was used to test dose parameters obtained in free breathing (FB) and DIBH for statistical significance. Multivariable analysis of variance (ANOVA) and receiver operating characteristics (ROC) analysis were used to identify parameters and cut-off points associated with the reduction of the mean heart dose (MHD) by DIBH. Based on published models, the risk of cardiac and lung toxicity (pneumonitis) using SGRT or daily kV-CBCT was estimated and compared. DIBH substantially reduced the MHD (median, 43.6%; range, 4.2% to 75.1%; P < 0.00001). The risk of cardiac toxicity using SGRT increased by 1%, compared to 3.6% to 20.5% using daily kV-CBCT. No significant difference in the risk of radiation-induced pneumonitis using SGRT versus daily kV-CBCT was detected. The ANOVA revealed the relative increase of the left lung volume by DIBH as the only significant impact factor for the MHD. The ROC analysis of this parameter showed an area under the curve (AUC) of 0.89 (95%CI, 0.71 to 0.98; P < 0.0001). DIBH can substantially reduce the MHD in left-sided breast cancer patients treated with modern radiotherapy techniques and hypofractionation. Patient setup using SGRT compared to daily kV-CBCT may be the preferred option for many patients. In our patient cohort, the relative reduction of the left lung volume by DIBH can be used as a predictor to select patients who benefit from DIBH., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: The aim of this study was to evaluate the inter-fraction reproducibility and intra-fraction stability of breast radiotherapy using voluntary deep-inspiration breath hold (DIBH) and free breathing (FB) based on an optical surface imaging system (OSIS)., Methods: Seventeen patients (510 breath-hold sessions) treated using a field-in-field (FiF) technique and twenty patients (600 breath-free sessions) treated with a volume-modulated arc therapy (VMAT) technique were included in this retrospective study. All the patients were positioned with the guidance of CBCT and OSIS, and also monitored with OSIS throughout the whole treatment session. Eight setup variations in three directions were extracted from the treatment reports of OSIS for all sessions and were subsequently manually introduced to treatment plans, resulting in a total of 296 perturbed plans. All perturbed plans were recalculated, and the dose volume histograms (DVH) for the target and organs at risk (OAR) were analyzed., Results: The OSIS and CBCT for both DIBH and FB treatments showed a good agreement of less than 0.30 cm in each direction. The intra-fraction respiratory motion data during DIBH were -0.06 ± 0.07 cm, 0.12 ± 0.15 cm, and 0.12 ± 0.12 cm in the lateral, longitudinal, and vertical directions, respectively; for FB, the respiratory motion data were -0.02 ± 0.12 cm, 0.08 ± 0.18 cm, and 0.14 ± 0.20 cm, respectively. For the target, DIBH plans were more sensitive to setup errors; the mean deviations in D 95 for CTV were 39.78 Gy-40.17 Gy for DIBH and 38.46 Gy-40.52 Gy for FB, respectively. For the OARs, the mean deviations of V 10 , V 20 , and D mean to the heart; V 5 , V 20 , and D mean to the ipsilateral lung; and D mean to the breast were lower for the FB plan compared with the DIBH plan., Conclusion: Based on OSIS, our results indicate that both DIBH and FB can provide good reproducibility in the inter-fractions and stability in the intra-fractions. When the patient respiratory motion is large, the FB technology has greater possibility for the undercoverage of the target volume, while DIBH technology is more likely to result in increases in dose to OARs (the lung, heart, and contralateral breast)., Competing Interests: Declarations Ethics approval and consent to participate This retrospective study was approved by the Ethics Committee of our hospital (Approval Number No. SCCHEC-02-2021-026). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To evaluate the benefits of volumetric modulated arc therapy (VMAT) based on multicriteria optimization (MCO) for gastric cancer patients, particularly the protection of serial organs at risk (OARs) that overlap with the target volume., Methods: MCO and single-criterion optimization (SCO) VMAT plans were conducted among 30 gastric cancer patients, with a prescription dose of 50.4 Gy delivered in 28 fractions. All treatment plans underwent review, and a comparison was made between the active planning time and different dose-volume parameters., Results: Both the MCO and SCO VMAT plans achieved the target dose coverage, with no significant difference in the conformity index (CI) for the planning target volume (PTV), at median CI values of 0.887 and 0.891, respectively (P = 0.417). The MCO plans showed a slight but significant increase in the homogeneity index of the PTV, with a median increase of 0.029 (P < 0.001). Additionally, the MCO plans resulted in a lower D 2% to the small intestine and duodenum, with reductions of 3.43 Gy and 0.3 Gy, respectively (P < 0.05). Furthermore, the D max to the small intestine correlated moderately with the overlapping volume between the small intestine and the target volume (ρ = 0.42, P = 0.023). Except for the mean dose to the liver, the MCO plans performed better in terms of dose indicators for other OARs. Moreover, compared to the SCO plans, the median active planning time in the MCO plans was significantly reduced by 53.2 min (P < 0.0001)., Conclusions: MCO can effectively help the physicians to quickly select an optimal treatment plan for patients with gastric cancer. It has been shown that MCO VMAT plans can significantly reduce the dose to OARs and shorten the active planning time, with acceptable target coverage. In addition, these plans take less dosimetric time, thereby streamlining the treatment planning process., Competing Interests: Declarations Ethics approval and consent to participate This study, conducted in accordance with the Declaration of Helsinki, received approval from the ethics committee of West China Hospital, confirming that informed consent was obtained from all subjects and/or their legal guardians. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Stereotactic body radiation therapy (SBRT) has been widely used for pancreatic cancer. However, there is still a lack of studies comparing the latest SBRT techniques in terms of clinical efficacy and safety., Objectives: This study aims to evaluate three latest SBRT delivery platforms: CyberKnife (CK), Tomography Radixact (TOMO), and Halcyon volume rotation intensity modulation therapy (VMAT) for the treatment of pancreatic cancer., Methods: Sixteen patients with pancreatic cancer treated with CK were retrospectively analyzed. SBRT plans were designed using Precision and Eclipse software. CK plans were optimized in two forms: fixed collimator (CK-Fixed) and multi-leaf grating collimator (CK-MLC). TOMO plans were designed with 2.5 cm Fixed Jaw, pitch 0.123-0.43 and 4.0 modulation factors in precision system. In Eclipse 15.6 system, photon optimizer (OP) algorithm was used to design the coplanar two-arc Halcyon VMAT. The median radiation dose was 40 Gy (35-45 Gy) in 5 fractions. The effectiveness of clinical treatment was evaluated by comparing the homogeneity index (HI), conformity index (CI), coverage of the planning target volume (PTV) and dose distribution parameters of organs at risk (OAR)., Results: All plans met the limits of clinical target dose and OAR. CK-MLC plans had the lowest maximum dose of 2 cm normal tissue from PTV margin (D 2cm ), indicating a low risk of peripheral radiation damage. Additionally, the CK-MLC plans had the lowest dose parameters and provided the best protection for the kidney, spinal cord, small intestine, and duodenum, with a paired t-test p < 0.05, indicating a statistical difference., Conclusion: High conformity and adjustability of CK-MLC allowed for precise complex target localization and conformal dose distribution, benefiting tumor treatment while maximally reducing damage to OAR. This study provides valuable dosimetric evidence for SBRT technique selection for pancreatic cancer., (© 2024. The Author(s).)

Purpose: In the adjuvant right breast radiation therapy, after breast-conserving surgery, we wanted to look for a parameter that would help in the choice between the 3D-CRT or VMAT techniques, considering the risk of pneumonia to the ipsilateral lung (IL) linked to high doses. We also investigated the risk of second tumors in the IL related to the VMAT low doses., Methods: We examined twenty-five 3D-CRT and thirty-five VMAT technique plans, between September 2022 and September 2023. We collected the MAximum Thickness of Ipsilateal Lung (MATIL) included between lateral and medial target borders for evaluating the risk of pneumonia due to the high dose (V 20Gy ), finally we calculated the Excess of Absolute Risk related to the second tumor risk due to the low dose., Results: VMAT technique showed a better dose conformity than 3D-CRT. We detected a linear relationship between the V 20Gy and MATIL of the IL only for the 3D-CRT technique; over a threshold value of MATIL the 3D-CRT is disadvantaged compared to the VMAT in terms of the risk of toxicity to the IL. We calculated that for every Gy more in average dose, a 12 % increase in the risk of induced cancer is expected., Conclusions: In the adjuvant right breast RT, the MATIL is a good surrogate parameter to predict the need to use a VMAT technique to limit high doses to IL. VMAT technique, according to the IL second tumor estimated risk, seems justified., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Purpose: This study aimed to determine the selection criteria for circular collimator (CC)- and multileaf collimator (MLC)-based stereotactic radiosurgery (SRS)/stereotactic radiotherapy (SRT) plans for brain metastases (BM) and benign intracranial disease (BID) in terms of geometric parameters using CyberKnife (CK)., Methods: Forty-eight and eighty-five patients with BM and BID, respectively, were included. Two plans using CC and MLC were created for each case. Six dosimetric parameters and mathematical scores (MS) were extracted from each plan to assess plan quality. Two geometric parameters in BM-equivalent radius (rGTV) and sphericity index (SI) of the gross tumor volume-and three in BID-rGTV, SI, and the distance between the GTV and organ at risk (dOAR)-were calculated. Their effect on the superiority of CC- or MLC-based plans in terms of dosimetric parameters and MS was evaluated using multiple regression analysis., Results: The rGTV was associated with improved dosimetric parameters of MLC-based plans, especially the GTV conformity in BM and BID cases (β: 0.70 and 0.51) and the OAR sparing in BM cases (β: 0.82), where β represents the regression coefficient. Based on the MS, where the weights for the GTV coverage and OAR sparing were equal, the thresholds at which the MLC-based plans become comparable or superior to the CC-based plans in BM and BID were rGTV > 7.6 and >17.5 mm, respectively. Meanwhile, SI and dOAR were weakly correlated (β ≤ 0.30)., Conclusions: In SRS/SRT plans for BM and BID cases using CyberKnife, geometric parameters, especially rGTV, must be considered when selecting CC or MLC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background/aim: Xerostomia following (chemo-) radiotherapy (CRT) is common in head and neck (HNC) patients. This prospective study focused on investigating the link between salivary gland function and the onset of malnutrition in HNC patients., Patients and Methods: Between 2018 and 2020, 61 HNC patients scheduled for curative CRT were prospectively recruited. Nutritional status was assessed by bioelectrical impedance analysis (BIA) and xerostomia was evaluated based on the Common Terminology Criteria for Adverse Events, (CTCAE). Patient-reported outcomes for xerostomia-related symptoms, such as "dry mouth" and "sticky saliva", were also collected. Data were assessed at the beginning of therapy, during treatment, at the end of treatment, and during follow-up. Organs at risk were contoured including the submandibular and parotid glands. Dose-volume parameters were extracted for the mean Dose (D mean ), V15 Gy, V30Gy and V45Gy., Results: No correlation was found between the dosimetric parameters [D mean , V15Gy (%), V30Gy (%) and V45Gy (%)] and the occurrence of malnutrition [defined by a fat-free mass index (FFMI) <15 kg/m 2 (♀) and <17 kg/m 2 (♂) kg/m 2 and/or body-mass index (BMI) <18.5 kg/m 2 ] at any of the three time points tested. However, the volume of the parotid glands prior to therapy appeared to be related to the development of malnutrition. This effect was not observed with the submandibular glands. A cumulative parotid gland volume of 55.3 cm 3 was identified as the threshold for malnutrition at the second follow-up examination., Conclusion: Although none of the dosimetric factors were associated with the development of malnutrition, the baseline parotid gland volume emerged as an independent predictor of malnutrition in head and neck cancer patients with xerostomia., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The current study aimed to evaluate a treatment planning method that is robust against tumor growth and to assess its effectiveness in particle therapy for head and neck cancer., Patients and Methods: The proposed method optimizes dose distribution by replacing the relative stopping power ratio (rSPR) of the clinical target volume (CTV) cavity region with a tumor-equivalent rSPR (Condition 1). The optimized initial treatment plan template was then recalculated using in-room CT images acquired in the same treatment position, and the doses to the tumor and organs at risk were compared with those in the initial treatment plan. We evaluated this method in 10 patients with head and neck cancer treated with carbon ion radiotherapy. To evaluate the effectiveness of the proposed method, we compared it to the initial treatment plan without the replacement (Condition 2)., Results: CTV V95% reduction relative to that of the initial treatment plan at the end of treatment was 1.3%±2.9% and 2.6%±3.7% for Condition 1 and Condition 2, respectively, with Condition 1 (Replacement condition) providing better CTV coverage. Subgroup analysis showed a higher change in target coverage in the mucosal melanoma than in the adenoid cystic carcinoma, suggesting that this was influenced by the rate of tumor growth., Conclusion: The proposed treatment planning method, which adjusts for tumor growth by modifying the rSPR in the cavity region, improved robustness in carbon ion radiotherapy for head and neck cancer. Condition 1 (with replacement) achieved better CTV coverage than Condition 2 (without replacement), particularly in fast-growing tumors like mucosal melanoma. This method ensures consistent dose delivery to tumors while maintaining safe doses to organs at risk, offering potential for improved treatment outcomes., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: In spot-scanning proton therapy, intra-fractional anatomical changes by organ movement can lead to deterioration in dose distribution due to beam range variation. To explore a more robust treatment planning method, this study evaluated the dosimetric characteristics and robustness of two proton therapy planning methods for liver cancer., Patients and Methods: Two- or three-field treatment plans were created for 11 patients with hepatocellular carcinoma or metastatic liver cancer using a single-field uniform dose (SFUD) technique. The plans were optimized using either beam-specific planning target volume (BSPTV) or worst-case optimization (WCO). The target coverage for the gross tumor volume (GTV), planning target volume (PTV), and organs at risk (OAR) parameters related to toxicity were calculated from the perturbed dose distributions, considering setup and range uncertainties. Statistical analyses of the BSPTV and WCO plans were performed using the Wilcoxon signed-rank sum test (p<0.05). The calculation times for a single optimization process were also recorded and compared., Results: The robustness of the WCO plans in the worst-case scenario was significantly higher than that of the BSPTV plan in terms of GTV target coverage, prevention of maximum dose increase to the gastrointestinal tract, and the dose received by normal liver regions. However, there were no significant differences in PTV, and the calculation time required to create the WCO plan was considerably longer., Conclusion: In SFUD proton therapy for liver cancer, the WCO plans required a longer optimization time but exhibited superior robustness in GTV coverage and sparing of OARs., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study aimed to compare the use of a rotating gantry in liver tumor carbon-ion radiotherapy using of a fixed-port for treatment planning., Materials and Methods: Thirty patients with liver tumors were analyzed. Three treatment plans were developed for each case: one with a rotating gantry with a 360° angle, one with fixed ports of 0° and 90° with a ±20° couch rolling setting, and one with fixed ports of 45° and 90° with a ±20° couch rolling setting. The dose-volume histogram parameters of the clinical target volume (CTV) and organs at risk (OARs) for each treatment plan were compared., Results: Significant differences in the volume of the liver-gross tumor volume (GTV) of normal liver irradiated with 5 Gy to 15 Gy were found between the gantry treatment plans and fixed-port treatment plans. There were no significant differences in the OARs, except for the CTV and liver GTV, between the gantry and fixed-port treatment plans., Conclusion: The study results support the potential of using a rotating gantry to reduce liver doses, especially in the low-to-medium dose range, while maintaining target and OAR doses except for the liver. A rotating gantry could be especially useful in cases in which the relationship between the tumor and OAR is complicated by location., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Brain metastases are the most common intracranial malignancy and remain a substantial source of morbidity and mortality in cancer patients. Linear accelerator based stereotactic radiosurgery (SRS) is widely used and is frequently delivered by hypo-fractionnated volumetric modulated arc therapy using non-coplanar beams, where geometric accuracy and planning margins are a major concern., Purpose: To give a practical analysis of intrafraction patient motion for multi-target, single isocentre, brain SRS treatments and to derive adapted GTV-to-PTV margins., Methods: Data of 154 lesions, spread over 85 fractions from 56 patients treated in our institution with the Varian HyperArc  SRS solution was processed. Intrafraction patient motion were recorded using an Optical Surface Monitoring System during irradiation. The present study focuses on small tumor volumes, roughly equal or inferior to 1.5  cm 3 ${\rm cm}^3$ , and frameless mask-based immobilization. For each treatment session, a tumor displacement vector matrix was calculated from the patient drifts as a function of time. Data were combined together into a representative treatment scenario and the dosimetric impact of GTV displacement was calculated., Results: Recommended margins due to patient motion range between 0.3 and 1 mm, depending on the distance tumor-isocentre, and the desired GTV edge dose coverage. Those values should be added quadratically with other sources of uncertainty, such as mechanical isocentre and kV-MV misalignment., Conclusion: Thorough analysis of intrafraction patient motion was performed, the dosimetric impact was calculated for different scenarios, and adequate GTV-to-PTV margins were derived. These values vary according to the distance isocentre-to-GTV, as well as the desired dose coverage, and should be chosen adequately., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: To explore the feasibility of a novel intensity-modulated proton arc technique that uses a single-energy beam from the cyclotron. The beam energy is externally modulated at each gantry angle by a tertiary energy modulator (EM). We hypothesize that irradiating in an arc without requiring an energy change from the cyclotron will achieve a faster delivery (main advantage of our technique) while keeping clinically desirable dosimetric results., Methods: In a retrospective cohort of four patients with female pelvis, prostate, lung, and brain cancers, we investigated our volumetric-modulated proton arc therapy (VPAT) technique. Arcs were simulated by sectors of 1°-spaced static beams. Keeping the energy requested from the cyclotron the same for each entire arc was supported by a predesigned EM placed in front of the nozzle. As a feasibility measure, EM thicknesses were calculated. Delivery times and doses to targets and organs at risk (OARs) were compared to those of the clinical plans., Results: VPAT plans were comparable to their clinical counterparts in achieving target dose conformity, being robust to uncertainties, and meeting clinical dose-volume constraints. Cyclotron energies for the four cases were within 159-220 MeV, and energy modulation range was 69-100 MeV, equivalent to 13-19 cm of water-equivalent thickness (WET). Plan delivery times were reduced from > 5 min in our clinical practice to < 3.5 min in VPAT., Conclusion: For the evaluated plans, the novel VPAT approach achieved shorter delivery times without sacrificing robustness, OAR sparing or target coverage. VPAT's EMs had WETs implementable in a clinical setup., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: The advancements in artificial intelligence and computational power have made deep learning an attractive tool for radiotherapy treatment planning. Deep learning has the potential to significantly simplify the trial-and-error process involved in inverse planning required by modern treatment techniques such as volumetric modulated arc therapy (VMAT). In this study, we explore the ability of deep learning to predict organ-at-risk (OAR) dose-volume histograms (DVHs) of left-sided breast cancer patients undergoing VMAT treatment based solely on their anatomical characteristics. The predicted DVHs could be used to derive patient-specific dose constraints and dose objectives, streamlining the treatment planning process, standardizing the quality of the plans, and personalizing the treatment planning., Purpose: This study aimed to develop a deep learning-based framework for the prediction of organ-specific dose-volume histograms (DVH) based on structures delineated for left-sided breast cancer treatment., Methods: We used a dataset of 249 left-sided breast cancer patients treated with tangential VMAT fields. We extracted delineated structures and dose distributions for each patient and derived slice-by-slice DVHs for planning target volume (PTV) and organs-at-risk. The patients were divided into training (70%, n = 174), validation (10%, n = 24), and test (20%, n = 51) sets. Collected data were used to train a deep learning model for the prediction of the DVHs based on the delineated structures. The developed deep learning model comprised a modified DenseNet architecture followed by a recurrent neural network., Results: In the independent test set (n = 51), the point-wise differences in the slice-by-slice DVHs between the clinical and predicted DVHs were small; the mean squared errors were 3.53, 1.58, 2.28, 3.37, and 1.44 [×10 -4 ] for PTV, heart, ipsilateral lung, contralateral lung, and contralateral breast, respectively. With the derived cumulative DVHs, the mean absolute difference ± standard deviation of mean doses between the clinical and the predicted DVH were 0.08 ± 0.04 Gy, 0.24 ± 0.22 Gy, 0.73 ± 0.46 Gy, 0.07 ± 0.06 Gy, and 0.14 ± 0.14 Gy for PTV, heart, ipsilateral lung, contralateral lung, and contralateral breast, respectively., Conclusions: The deep learning-based approach enabled automatic and reliable prediction of the DVH based on delineated structures. The predicted DVHs could potentially serve as patient-specific clinical goals used to aid treatment planning and avoid suboptimal plans or to derive optimization objectives and constraints for automated treatment planning., (© 2024 The Author(s). Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: Kilovoltage cone beam computed tomography (kVCBCT)-guided adaptive radiation therapy (ART) uses daily deformed CT (dCT), which is generated automatically through deformable registration methods. These registration methods may perform poorly in reproducing volumes of the target organ, rectum, and bladder during treatment. We analyzed the registration errors between the daily kVCBCTs and corresponding dCTs for these organs using the default optical flow algorithm and two registration procedures. We validated the effectiveness of these registration methods in replicating the geometry for dose calculation on kVCBCT for ART., Methods: We evaluated three deformable image registration (DIR) methods to assess their registration accuracy and dose calculation effeciency in mapping target and critical organs. The DIR methods include (1) default intensity-based deformable registration, (2) hybrid deformable registration, and (3) a two-step deformable registration process. Each technique was applied to a computerized imaging reference system (CIRS) phantom (Model 062 M) and to five patients who received volumetric modulated arc therapy to the prostate. Registration accuracy was assessed using the 95% Hausdorff distance (HD 95 ) and Dice similarity coefficient (DSC), and each method was compared with the intensity-based registration method. The improvement in the dCT image quality of the CIRS phantom and five patients was assessed by comparing dCT with kVCBCT. Image quality quantitative metrics for the phantom included the signal-to-noise ratio (SNR), uniformity, and contrast-to-noise ratio (CNR), whereas those for the patients included the mean absolute error (MAE), mean error, peak signal-to-noise ratio (PSNR), and structural similarity index measure (SSIM). To determine dose metric differences, we used a dose-volume histogram (DVH) and 3.0%/0.3 mm gamma analysis to compare planning computed tomography (pCT) and kVCBCT recalculations with restimulated CT images used as a reference., Results: The dCT images generated by the hybrid (dCT H ) and two-step (dCT C ) registration methods resulted in significant improvements compared to kVCBCT in the phantom model. Specifically, the SNR improved by 107% and 107.2%, the uniformity improved by 90% and 75%, and the CNR improved by 212.2% and 225.6 for dCT H and dCT C methods, respectively. For the patient images, the MAEs improved by 98% and 94%, the PSNRs improved by 16.3% and 22.9%, and the SSIMs improved by 1% and 1% in the dCT H and dCT C methods, respectively. For the geometric evaluation, only the two-step registration method improved registration accuracy. The dCT H method yielded an average HD 95 of 12 mm and average DSC of 0.73, whereas dCT C yielded an average HD 95 of 2.9 mm and average DSC of 0.902. The DVH showed that the dCT C -based dose calculations differed by <2% from the expected results for treatment targets and volumes of organs at risk. Additionally, gamma indices for dCT C -based treatment plans were >95% at all points, whereas they were <95% for kVCBCT-based treatment plans., Conclusion: The two-step registration method outperforms the intensity-based and hybrid registration methods. While the hybrid and two-step-based methods improved the image quality of kVCBCT in a linear accelerator, only the two-step method improved the registration accuracy of the corresponding structures among the pCT and kVCBCT datasets. A two-step registration process is recommended for applying kVCBCT to ART, which achieves better registration accuracy for local and global image structures. This method appears to be beneficial for radiotherapy dose calculation in patients with pelvic cancer., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: The aim of the current study is to compare the dosimetry of 3 radiation therapy (RT) techniques used in the EORTC 22922/10925 trial for irradiating the internal mammary (IM) and medial supraclavicular nodes (MS) using a treatment planning system available nowadays for dose calculation., Methods: We performed a retrospective dosimetry analysis of anonymised data; thus, ethics approval was not required. Ten cases of left-sided breast were randomly selected for RT planning to a total dose of 50 Gy in 25 fractions. The treatment planning was done according to the trial's protocol and under the supervision of the EORTC trial's coordinators. Doses to planning target volumes (PTV) and to organs at risk (OARs) are reported. Data is presented in descriptive statistics., Results: A total of 10 cases and 40 treatment plans (4 plans per case: standard-plan A, modified standard-plan B, individualised-plan C and breast-only-plan D). For all planning techniques, the mean dose to the PTV of the left breast (plan A-D) and the PTV-MS (plan A-C) exceeded 95% of the prescribed dose (>47.5 Gy). The individualised technique (plan C) had a lower coverage for PTV-IM, with a mean of 87% of the prescribed dose compared to ∼102% for plans A and B. The dose to OARs varied between techniques, with the mean heart dose being higher in the standard and modified standard techniques (18.3 and 16.6 Gy, respectively) compared to the individualised technique (9.5 Gy)., Conclusions: The 3 RT techniques used in the trial varied in target coverage and OARs dose. Our results may help to understand the observed larger absolute benefit of individualised IM-MS treatment planning in terms of breast cancer outcomes., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Purpose: Total body irradiation before bone marrow transplantation for hematological malignancies using Radixact, a high-precision radiotherapy machine, can potentially reduce side effects and the risk of secondary malignancies. However, stable control of couch speed is critical, and direct assessment methods outlined in quality assurance guidelines are lacking. This study aims to develop a real-time couch speed verification system for the Radixact., Methods: The developed system used a linear encoder to measure couch speed directly. Accuracy was verified via a linear stage, comparing measurements with a laser distance sensor. After placing a phantom simulating the human body on the Radixact couch, the couch speed was verified using predefined speed plans., Results: Operating the linear stage at 0.1, 0.5, and 1.0 mm/s revealed that the maximum position error of the developed verification system compared to the laser distance sensor was nearly equivalent to the distance resolution of the system (0.05 mm/pulse), with negligible average speed error. When the Radixact couch operated at 0.1, 0.5, and 1.0 mm/s, the values obtained by the verification system agreed with the theoretical values within the sampling period (0.01 s) and distance resolution (0.05 mm)., Conclusion: The verification system developed provides real-time monitoring of the speed of the Radixact table, ensuring treatment effectiveness and patient safety. It would guarantee the couch speed's soundness and contribute to the "visualization" of safety., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background and Purpose: Fast and automated generation of treatment plans is desirable for magnetic resonance imaging (MRI)-guided adaptive radiotherapy (MRIgART). This study proposed a novel patient-specific auto-planning method and validated its feasibility in improving the existing online planning workflow., Materials and Methods: Data from 40 patients with prostate cancer were collected retrospectively. A patient-specific auto-planning method was proposed to generate adaptive treatment plans. First, a population dose-prediction model (M 0 ) was trained using data from previous patients. Second, a patient-specific model (M ps ) was created for each new patient by fine-tuning M 0 with the patient's data. Finally, an auto plan was optimized using the parameters derived from the predicted dose distribution by M ps . The auto plans were compared with manual plans in terms of plan quality, efficiency, dosimetric verification, and clinical evaluation., Results: The auto plans improved target coverage, reduced irradiation to the rectum, and provided comparable protection to other organs-at-risk. Target coverage for the planning target volume (+0.61 %, P = 0.023) and clinical target volume 4000 (+1.60 %, P < 0.001) increased. V 2900cGy (-1.06 %, P = 0.004) and V 1810cGy (-2.49 %, P < 0.001) to the rectal wall and V 1810cGy (-2.82 %, P = 0.012) to the rectum were significantly reduced. The auto plans required less planning time (-3.92 min, P = 0.001), monitor units (-46.48, P = 0.003), and delivery time (-0.26 min, P = 0.004), and their gamma pass rates (3 %/2 mm) were higher (+0.47 %, P = 0.014)., Conclusion: The proposed patient-specific auto-planning method demonstrated a robust level of automation and was able to generate high-quality treatment plans in less time for MRIgART in prostate cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: This paper describes the implementation of an instantaneous low-dose-rate total body irradiation (TBI) technique using block-filtered 6 MV X-rays with a linear accelerator (LINAC) to reduce pulmonary toxicity., Methods: In the absence of dedicated TBI-specific meter-set dose rates in LINAC and sufficient treatment room size, a 2-cm-thick transmission block was used together with a 200-cm source-to-surface distance (SSD) to reduce the instantaneous dose rates of 6 MV x-rays down to 10 cGy/min, thus alteration to the beam properties. A TBI-specific dose calculation model was built with data acquired at the treatment planning system (TPS)-permitted maximum 140-cm SSD and was validated in phantoms at a 180-cm SSD. As for planning strategies, we adopted large anterior-to-posterior/posterior-to-anterior (AP/PA) open fields with multi-leaf collimator shielding for lungs to achieve target coverage, lung protection, and efficient dose delivery. A custom-designed sliding couch (Patent No. ZL202123085880.1) was manufactured to support patients during treatment. Measures to control the quality and safety of TBI treatment include machine interlocks, pretreatment checklists, and in-vivo dose monitoring., Results: The instantaneous dose rate of block-filtered 6MV X-ray was reduced to approximately 7.0 cGy/min at 12.5-7.5 cm depth with a 185-200 cm SSD. The dose calculated by TPS differs from the measurements by 0.15%-1.55% in the homogeneous phantom and 1.2%-4.85% in the CIRS thorax phantom. The open-field TBI technique achieved V 90% (PTV) ≈ 96.8% and MLD = 6.6 Gy with 1-h planning and 50-min beam delivery in a single fraction. From February 2021 to July 2023, 30 patients received TBI treatments in our center, and in-vivo monitoring results differed from TPS calculations by -1.49%-2.10%. After 6-12 months of follow-ups, all the patients treated in our center showed no pulmonary toxicities of grade 2 or higher., Conclusion: A low instantaneous dose rate TBI technique can be implemented in the clinic., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Introduction: HyperArc (HA) auto-planning offers simplicity for the end user and consistently high-quality SRS plans. The "Ask For It" (AFI) optimization strategy offers a manual planning technique that, when coupled with R50% Analytic , can be guided to deliver a plan with an intermediate dose spill "as low as reasonably achievable" and high target dose conformity. A direct comparison of SRS plan quality obtained using the manual planning AFI strategy and HA has been performed., Methods: Using a CT data set available from the Radiosurgery Society, 54 PTVs were created and used to generate 19 individual SRS/SRT cases. Case complexity ranged from single PTV plans to multiple PTV plans with a single isocenter. PTV locations ranged from relative isolation from critical structures to lesions within 1.5 mm of the optic apparatus and abutting the brainstem. All cases were planned using both the AFI and HA optimization strategies as implemented in the Varian Medical Systems Eclipse Treatment Planning System. A range of treatment plan quality metrics were obtained including Intermediate Dose Spill (R50%), Conformity Indices CI RTOG and CI Paddick , PTV Dose Coverage (Dn%), PTV Mean Dose, and Modulation Factor. The Wilcoxon Signed Rank Sum non-parametric statistical method was utilized to compare the obtained plan quality metrics., Results: Statistically significant improvements were found for the AFI strategy for metrics R50%, CI RTOG , CI Paddick , and PTV Mean Dose (p < 0.001). HA achieved superior coverage for Dn% (p = 0.018), while the Modulation Factors were not significantly different for AFI compared to HA optimization (p = 0.13)., Conclusion: This study provides evidence that the AFI manual planning strategy can produce high-quality planning metrics similar to the HA auto-planning method., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background: Patients may undergo anatomical changes during radiotherapy, leading to an underdosing of the target or overdosing of the organs at risk (OARs)., Purpose: This study developed a deep-learning method to predict the tumor response of patients with nasopharyngeal carcinoma (NPC) during treatment. This method can predict the anatomical changes of a patient., Methods: The participants included 230 patients with NPC. The data included planning computed tomography (pCT) and routine cone-beam CT (CBCT) images. The CBCT image quality was improved to the CT level using an advanced method. A long short-term memory network-generative adversarial network (LSTM-GAN) is proposed, which can harness the forecasting ability of LSTM and the generation ability of GAN. Four models were trained to predict the anatomical changes that occurred in weeks 3-6 and named LSTM-GAN-week 3 to LSTM-GAN-week 6. The pCT and CBCT were used as input, and the tumor target volumes (TVs) and OARs were delineated on the predicted and real images (ground truth). Finally, the models were evaluated using contours and dosimetry parameters., Results: The proposed method predicted the anatomical changes, with a dice similarity coefficient above 0.94 and 0.90 for the TVs and surrounding OARs, respectively. The dosimetry parameters were close between the prediction and ground truth. The deviations in the prescription, minimum, and maximum doses of the tumor targets were below 0.5 Gy. For serial organs (brain stem and spinal cord), the deviations in the maximum dose were below 0.6 Gy. For parallel organs (bilateral parotid glands), the deviations in the mean dose were below 0.8 Gy., Conclusion: The proposed method can predict the tumor response to radiotherapy in the future such that adaptation can be scheduled on time. This study provides a proactive mechanism for planning adaptation, which can enable personalized treatment and save clinical time by anticipating and preparing for treatment strategy adjustments., (© 2024 American Association of Physicists in Medicine.)

Purpose: Dose-escalation in lung cancer comes with a high risk of severe toxicity. This study aimed to calculate the delivered dose in a Scandinavian phase-III dose-escalation trial., Methods: The delivered dose was evaluated for 21 locally-advanced non-small cell lung cancer (LA-NSCLC) patients treated as part of the NARLAL2 dose-escalation trial. The patients were randomized between standard and escalated heterogeneous dose-delivery. Both treatment plans were created and approved before randomization. Daily cone-beam CT (CBCT) for patient positioning, and adaptive radiotherapy were mandatory. Standard and escalated plans, including adaptive re-plans, were recalculated on each daily CBCT and accumulated on the planning CT for each patient. Dose to the clinical target volume (CTV), organs at risk (OAR), and the effects of plan adaptions were evaluated for the accumulated dose and on each treated fraction scaled to full treatment., Results: For the standard treatment, plan adaptations reduced the number of patients with CTV-T underdosage from six to one, and the total number of fractions with CTV-T underdosage from 161 to 56; while for the escalated treatment, the number of patients was reduced from five to zero and number of fractions from 81 to 11. For dose-escalation, three patients had fractions exceeding trial constraints for heart, bronchi, or esophagus, and one had an accumulated heart dose above the constraints., Conclusion: Dose-escalation for LA-NSCLC patients, using daily image guidance and adaptive radiotherapy, is dosimetrically safe for the majority of patients. Dose calculation on daily CBCTs is an efficient tool to monitor target coverage and OAR doses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To evaluate the feasibility of an open-source, semi-automated, and reproducible vertex placement tool to improve the efficiency of lattice radiotherapy (LRT) planning. We used polymer gel dosimetry with a Cone Beam CT (CBCT) readout to commission this LRT technique., Material and Methods: We generated a volumetric modulated arc therapy (VMAT)-based LRT plan on a 2 L NIPAM polymer gel dosimeter using our Eclipse Acuros version 15.6 AcurosXB beam model, and also recalculated the plan with a pre-clinical Acuros v18.0 dose calculation algorithm with the enhanced leaf modelling (ELM). With the assistance of the MAAS-SFRThelper software, a lattice vertex diameter of 1.5 cm and center-to-center spacing of 3 cm were used to place the spheres in a hexagonal, closed packed structure. The verification plan included four gantry arcs with 15°, 345°, 75°, 105° collimator angles. The spheres were prescribed 20 Gy to 50% of their combined volume. The 6 MV Flattening Filter Free beam energy was used to deliver the verification plan. The dosimetric accuracy of the LRT delivery was evaluated with 1D dose profiles, 2D isodose maps, and a 3D global gamma analysis., Results: Qualitative comparisons between the 1D dose profiles of the Eclipse plan and measured gel showed good consistency at the prescription dose mark. The average diameter measured 13.3 ± 0.2 mm (gel for v15.6), 12.6 mm (v15.6 plan), 13.1 ± 0.2 mm (gel for v18.0), and 12.3 mm (v18.0 plan). 3D gamma analysis showed that all gamma pass percent were > 95% except at 1% and 2% at the 1 mm distance to agreement criteria., Conclusion: This study presents a novel application of gel dosimetry in verifying the dosimetric accuracy of LRT, achieving excellent 3D gamma results. The treatment planning was facilitated by publicly available software that automatically placed the vertices for consistency and efficiency., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: Functional lung avoidance (FLA) radiation therapy is an evolving field. The aim of FLA planning is to reduce dose to areas of functioning lung, with comparable target coverage and dose to organs at risk. Multicriteria optimization (MCO) is a planning tool that may assist with FLA planning. This study assessed the feasibility of using MCO to adapt radiation therapy plans to avoid functional regions of lung that were identified using a 68 Ga-4D-V/Q positron emission tomography/computed tomography., Methods and Materials: A prospective clinical trial U1111-1138-4421 was performed in which patients had a 68 Ga-4D-V/Q positron emission tomography/computed tomography before radiation treatment. Of the 72 patients enrolled in this trial, 38 patients had stage III non-small cell lung cancer and were eligible for selection into this planning study. Functional lung target volumes HF lung (highly functioning lung) and F lung (functional lung) were defined using the ventilated and perfused lung. Using knowledge-based planning, a baseline anatomic plan was created, and then a functional adapted plan was generated using multicriteria optimization. The primary aim was to spare dose to HF lung. Using the MCO tools, a clinician selected the final FLA plan. Dose to functional lung, target volumes, organs at risk and measures of plan quality were compared using standard statistical methods., Results: The HF lung volume was successfully spared in all patients. The F lung volume was successfully spared in 36 of the 38 patients. There were no clinically significant differences in dose to anatomically defined organs at risk. There were differences in the planning target volume near maximum and minimum doses. Across the entire population, there was a statistically significant reduction in the functional mean lung dose but not in the functional volume receiving 20 Gy. All trade-off decisions were made by the clinician., Conclusions: Using MCO for FLA was achievable but did result in changes to planning target volume coverage. A distinct advantage in using MCO was that all decisions regarding the cost and benefits of FLA could be made in real time., Competing Interests: Disclosures Michael S. Hofman acknowledges grant support from AAA/Novartis, ANSTO, Bayer, and Isotopia; consulting fees for lectures or advisory boards from Astellas, AstraZeneca, Janssen, Merck/MSD, Mundipharma, and Point Biopharma. Nicholas Hardcastle, Shankar Siva, and Tomas Kron receives research grants from Varian Medical Systems and Reflexion Medical for unrelated work. Shankar Siva receives research grants from Merck-Sharp-Dohme and Bayer Pharmaceuticals. Shankar Siva acknowledges consulting fees for lectures or advisory boards from Astra Zeneca and Reflexion. Nicholas Bucknell acknowledges consulting fees for lectures or advisory boards from Astra Zeneca. The remaining authors declare there are no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background and Purpose: Chemoradiotherapy (CRT) for locally-advanced non-small cell lung cancer (LA-NSCLC) has undergone advances, including increased overall survival (OS) when combined with immune checkpoint blockade (ICB), and using cardiac-sparing techniques to reduce the radiotoxicity. This research investigated 1) how radiotherapy schedules can be optimised with CRT-ICB schemes, and 2) how cardiac-sparing might change the OS for concurrent CRT (cCRT)., Methods and Materials: Survival data and dosimetric indices were sourced from published studies, with 2-year OS standardised and the hazard ratio of mean heart dose (MHD) against radiotoxicity tabulated in purpose. A published CRT dose-response model was selected, then modified with ICB and cardiac-sparing hypotheses. Models were maximum likelihood fitted, then visualised the prediction outcomes after bootstrapping., Results: The modelled 2-year OS rate of cCRT-ICB reached 71 % (95 % confidence intervals, CI 62 %, 84 %) and 66 % (95 % CI: 53 %, 81 %) for stage IIIA and IIIB/C, respectively, given 60 Gy in 2 Gy-per-fraction. 60 Gy in 30 fractions remained the best schedule for cCRT-ICB, whereas modest dose de-escalation to 55 Gy only reduced the OS in 2 %. Sequential CRT (sCRT)-ICB provided 6 % OS increases versus the best OS rate achieved by sCRT alone. Photon MHD-sparing achieved a 5-10 % increase in modelled 2-year OS, with protons providing a further roughly 5-10 % increase., Conclusion: Neither dose-escalation nor de-escalation relative to 60 Gy in 30 fractions influenced the survival with cCRT-ICB, while 5 Gy dose de-escalation might benefit patients with heavily irradiated organs at risk. Cardiac-sparing improved OS, and protons provided advantages for tumours anatomically overlapped or lay below the heart., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Purpose: A retrospective evaluation of dosimetric predictors and leveraged dose-volume data for gastrointestinal (GI) toxicities for locally-advanced pancreatic cancer (LAPC) treated with daily stereotactic MRI-guided online-adaptive radiotherapy (SMART)., Materials and Methods: 147 patients with LAPC were treated with SMART at our institution between 2018 and 2021. Patients were evaluated using CTCAE V5.0 for RT-related acute (≤3 months) and late (>3 months) toxicities. Each organ at risk (OAR) was matched to a ≥ grade 2 (Gr2+) toxicity endpoint composite group. A least absolute shrinkage selector operator regression model was constructed by dose-volumes per OAR to account for OAR multicollinearity. A receiver operator curve (ROC) analysis was performed for the combined averages of significant toxicity groups to identify critical volumes per dose levels., Results: 18 of 147 patients experienced Gr2+ GI toxicity. 17 Gr2+ duodenal toxicities were seen; the most significant predictor was a V33Gy odds ratio (OR) of 1.69 per cc (95 % CI 1.14-2.88). 17 Gr2+ small bowel (SB) toxicities were seen; the most significant predictor was a V33Gy OR of 1.60 per cc (95 % CI 1.01-2.53). The AUC was 0.72 for duodenum and SB. The optimal duodenal cut-point was 1.00 cc (true positive (TP): 17.8 %; true negative (TN); 94.9 %). The SB cut-point was 1.75 cc (TP: 16.7 %; TN: 94.3 %). No stomach or large bowel dose toxicity predictors were identified., Conclusions: For LAPC treated with SMART, the dose-volume threshold of V33Gy for duodenum and SB was associated with Gr2+ toxicities. These metrics can be utilized to guide future dose-volume constraints for patients undergoing upper abdominal SBRT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Cardiac substructure dose metrics are more strongly linked to late cardiac morbidities than to whole-heart metrics. Magnetic resonance (MR)-guided radiation therapy (MRgRT) enables substructure visualization during daily localization, allowing potential for enhanced cardiac sparing. We extend a publicly available state-of-the-art deep learning framework, "No New" U-Net, to incorporate self-distillation (nnU-Net.wSD) for substructure segmentation for MRgRT., Methods and Materials: Eighteen (institute A) patients who underwent thoracic or abdominal radiation therapy on a 0.35 T MR-guided linear accelerator were retrospectively evaluated. On each image, 1 of 2 radiation oncologists delineated reference contours of 12 cardiac substructures (chambers, great vessels, and coronary arteries) used to train (n = 10), validate (n = 3), and test (n = 5) nnU-Net.wSD by leveraging a teacher-student network and comparing it to standard 3-dimensional U-Net. The impact of using simulation data or including 3 to 4 daily images for augmentation during training was evaluated for nnU-Net.wSD. Geometric metrics (Dice similarity coefficient, mean distance to agreement, and 95% Hausdorff distance), visual inspection, and clinical dose-volume histograms were evaluated. To determine generalizability, institute A's model was tested on an unlabeled data set from institute B (n = 22) and evaluated via consensus scoring and volume comparisons., Results: nnU-Net.wSD yielded a Dice similarity coefficient (reported mean ± SD) of 0.65 ± 0.25 across the 12 substructures (chambers, 0.85 ± 0.05; great vessels, 0.67 ± 0.19; and coronary arteries, 0.33 ± 0.16; mean distance to agreement, <3 mm; mean 95% Hausdorff distance, <9 mm) while outperforming the 3-dimensional U-Net (0.583 ± 0.28; P <.01). Leveraging fractionated data for augmentation improved over a single MR simulation time point (0.579 ± 0.29; P <.01). Predicted contours yielded dose-volume histograms that closely matched those of the clinical treatment plans where mean and maximum (ie, dose to 0.03 cc) doses deviated by 0.32 ± 0.5 Gy and 1.42 ± 2.6 Gy, respectively. There were no statistically significant differences between institute A and B volumes (P >.05) for 11 of 12 substructures, with larger volumes requiring minor changes and coronary arteries exhibiting more variability., Conclusions: This work is a critical step toward rapid and reliable cardiac substructure segmentation to improve cardiac sparing in low-field MRgRT., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The occurrence of genitourinary (GU) toxicity is a common adverse event observed after external beam radiation therapy (EBRT) for prostate cancer (PCa). Recent findings suggest that the dose delivered to specific urinary organs at risk (OARs) such as the ureters, bladder trigone, and urethra is involved in the development of GU toxicity., Methods and Materials: A multidisciplinary task force including 3 radiation oncologists, a uroradiologist, and a urologist was created in 2022. First, OARs potentially involved in GU toxicity were identified and discussed. A literature review was performed, addressing several questions relative to urinary OARs: anatomic and radiological definition, radiation-induced injury, and dose-volume parameters. Second, results were presented and discussed with a panel of radiation oncologists and members of the "Francophone Group of Urological Radiation Therapy." Thereafter, the "Francophone Group of Urological Radiation Therapy" experts were asked to answer a dedicated questionnaire, including 35 questions on the controversial issues related to the delineation of urinary OARs., Results: The following structures were identified as critical for PCa EBRT: ureters, bladder, bladder neck, bladder trigone, urethra (intraprostatic, membranous, and spongious), striated sphincter, and postenucleation or posttransurethral resection of the prostate cavity. A consensus was obtained for 32 out of 35 items., Conclusions: This consensus highlights contemporary urinary structures in both the upper and lower urinary tract to be considered for EBRT treatment planning of PCa. The current recommendations also propose a standardized definition of urinary OARs for both daily practice and future clinical trials., Competing Interests: Disclosures None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Radiotherapy aims to deliver a prescribed dose to the tumor while sparing neighboring organs at risk (OARs). Increasingly complex treatment techniques such as volumetric modulated arc therapy (VMAT), stereotactic radiosurgery (SRS), stereotactic body radiotherapy (SBRT), and proton therapy have been developed to deliver doses more precisely to the target. While such technologies have improved dose delivery, the implementation of intra-fraction motion management to verify tumor position at the time of treatment has become increasingly relevant. Artificial intelligence (AI) has recently demonstrated great potential for real-time tracking of tumors during treatment. However, AI-based motion management faces several challenges, including bias in training data, poor transparency, difficult data collection, complex workflows and quality assurance, and limited sample sizes. This review presents the AI algorithms used for chest, abdomen, and pelvic tumor motion management/tracking for radiotherapy and provides a literature summary on the topic. We will also discuss the limitations of these AI-based studies and propose potential improvements., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: Osteoradionecrosis (ORN) of the mandible remains a significant complication in the intensity modulated radiation therapy (IMRT) era. Dental dose cannot be predicted from heterogeneous IMRT dose distributions; mandibular dose metrics cannot guide dentist avulsion decisions in high-risk ORN situations. Using a mapping tool to report dental root dose, avulsions, and ORN sites, we re-examined ORN risk factors in a case-control study., Methods and Materials: From 2008 to 2019, 897 consecutive patients with oral cavity/oropharynx or unknown primary cancer undergoing IMRT were analyzed to identify ORN cases. These were matched (1 ORN/2 controls) retrospectively for tumor location, surgery, and tobacco consumption in a monocentric case-control study. Univariate and multivariate analyses integrated ORN factors and accurate dental dose data (grouped into 4 mandibular sectors). Generalizability was investigated in a simulated population database., Results: A total of 171 patients were included. The median follow-up was 5.2 and 4.5 years in the ORN and control groups, respectively. The median time to ORN was 12 months. In univariate analysis, post-IMRT avulsions at the ORN site (hazard ratio [HR] = 3.6; 95% confidence interval [CI] = 1.5-8.9; P = .005), tumor laterality (HR, 4.4; 95% CI, = 1.4-14, P = .01), mean mandibular dose (HR, 1.1; 95% CI, = 1.01-1.1; P = .018) and mean dose to the ORN site (HR, 1.1; 95% CI, = 1.1-1.2; P < .001) correlated with higher ORN risk. In multivariate analysis, mean dose to the ORN site (HR, 1.1; 95% CI, = 1.1-1.2; P < .001) and post-IMRT avulsions at the ORN site (HR, 4.6; 95% CI, = 1.5-14.7; P = .009) were associated with ORN. For each increase in gray in dental dose, the ORN risk increased by 12%. Simulations confirmed study observations., Conclusions: Dental dose and avulsions are associated with ORN, with a 12% increase in risk with each additional gray. Accurate dose information can help dentists in their decisions after IMRT., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Respiratory movement, as one of the main challenges in proton therapy for pancreatic cancer patients, could not only lead to harm to normal tissues but also lead to failure of the tumor control, resulting in irreversible consequences. Including respiratory movements into the plan optimization, i.e. 4D robust optimization, may mitigate the interplay effect. However, 4D robust optimization considering images of all breathing phases is time-consuming and less efficient. This work aims to investigate the effect of the breathing phase number on the 4D robust optimization for pancreatic cancer intensity modulated proton therapy (IMPT) by examining plan quality and computational efficiency., Methods: A total of 15 pancreatic cancer patients were retrospectively analyzed. In this study, both anterior-fields and posterior-fields plans were created for each patient. For each plan, six four-dimensional (4D) robust treatment planning strategies with different numbers of respiratory phases and one three-dimensional (3D) treatment plan were created. Optimization of the plans were performed on all ten phases (10phase plan), two extreme phases (2phase plan), two extreme phases plus an intermediate state (3phase plan), two extreme phases plus the 3D CT (3Aphase plan), six phases during the exhalation stage (6Exphase plan), six phases during the inhalation stage (6Inphase plan) and 3D Computed Tomography (CT) scan image (3D plan), respectively. 4D dynamic dose (4DDD) was then calculated to access the interplay effect by considering respiratory motion and dynamic beam delivery. Plan quality and dosimetric parameters for the target and organs at risk (OARs) were then analyzed., Results: Compared to the 4D plans, 3D plan performed terribly in terms of target coverage and organs at risk. Target dose in anterior-fields plan varied slightly among all six 4D treatment planning strategies. Both the 6Exphase and 6Inphase plans demonstrated performance that was comparable to the 10phase plan in target coverage, outperforming the other five plans for anterior-fields plan. It's basically the same for the posterior-fields plan. The six strategies showed similar OARs sparing effect for both anterior-fields and posterior-fields plan. Compared with the 10phase plan, the average decline rates of the optimization time of the six plans of 2phase, 3phase, 3Aphase, 6Exphase, 6Inphase, and 3D were 73.26 ± 6.54% vs. 74.48 ± 6.63%, 65.80 ± 7.89% vs. 65.81 ± 9.58%, 54.67 ± 11.52% vs. 65.75 ± 9.58%, 42.14 ± 13.57% vs. 39.63 ± 16.93%, 37.72 ± 11.70% vs. 40.79 ± 13.62% and 75.52 ± 8.21% vs. 80.67 ± 5.62%, respectively (anterior vs. posterior). With the decrease of the number of phases selected for optimization, the decline rates increased, while the other dosimetry parameters generally showed a deterioration trend., Conclusion: In this study, a comprehensive evaluation of six 4D robust treatment planning strategies and one 3D treatment planning strategy for pancreatic cancer patients receiving IMPT was performed. The results showed that six 4D robust optimization strategies were comparable in common posterior field therapy. 2phase and 3phase (including 3Aphase) treatment planning strategies could replace the 10phase treatment planning strategy. It should be noted that patients with large motion amplitudes should receive special attention. The dosimetric performance of the 6Exphase and 6Inphase plans closely aligned with that of the 10phase plan in anterior fields. These plans offered a feasible alternative to 10phase treatment planning strategy by reducing optimization time while maintaining dose coverage of the target and protection of OARs. This research provides guidelines to reduce optimization time and improve clinical efficiency for pancreatic cancer IMPT., (© 2024. The Author(s).)

Treatment planning parameters in radiotherapy are key elements that dictate the success of treatment outcome. While some parameters are commonly evaluated irrespective of cancer type, others are site-dependent and strongly patient specific. Given the critical influence of planning parameters on personalized therapy, the aim of this study was to evaluate the correlations between the dosimetric indices (conformity, homogeneity and mismatch indices) related to tumor coverage and the patient-specific parameters which encompass parameters pertaining to organs at risk (widths and lengths of heart and ipsilateral lung included in treatment fields, mean/maximum doses to heart, ipsilateral lung, left anterior descending aorta and contralateral breast) and tumor volume. Forty breast cancer patients were divided into two groups according to tumor location: twenty with left-sided (group A) and twenty with right-sided breast cancer (group B). Conformal (3DCRT), intensity modulated (IMRT) and volumetric arc modulated (VMAT) radiotherapy techniques were used for plan creation. Moderate to strong correlations were found for ipsilateral lung parameters for both groups of patients regardless of the treatment technique. Moderate to strong correlations were found for heart parameters in group A patients, while no correlations were observed in group B. The mismatch index presented moderate to strong correlations with tumor volume for all treatment techniques (r = -0.861 3DCRT, r = -0.556 IMRT, r = -0.533 VMAT) particularly in group A. The evaluated correlations indicate the role of dosimetric indices in personalized treatment planning., (© 2024. The Author(s).)

Background and Purpose: Intensity Modulated Proton Therapy (IMPT) faces challenges in lung cancer treatment, like maintaining plan robustness for moving tumors against setup, range errors, and interplay effects. Proton Arc Therapy (PAT) is an alternative to maintain target coverage, potentially improving organ at risk (OAR) sparing, reducing beam delivery time (BDT), and enhancing patient experience. We aim to perform a systematic plan comparison study between IMPT and energy layer (EL) and spot assignment algorithm - Proton Arc Therapy (ELSA-PAT) to assess its potential for lung cancer treatment., Material and Methods: A total of 14 Lung ELSA-PAT plans were compared retrospectively with IMPT plans. 4D worst-case minimax robust optimization was performed, including 84 scenarios (3%, 3 mm). Dosimetry assessment included target (clinical tumor volume [CTV]) and important OARs, on nominal and worst-case scenarios. Most relevant normal tissue complication probabilities (NTCP), target coverage robustness against interplay effect, and BDT were evaluated., Results: CTV D95% and D98% showed no significant difference in comparison. PAT demonstrated better conformality by 66% (p = 0.00012) but delivered a higher heart mean dose (HMD, 23%). There was a 2% increase in NTCP 2-year mortality risk with PAT. Total BDT was comparable among techniques. IMPT was more robust than PAT against interplay effect, considering both D1% (1.0 ± 0.8 Gy vs 1.1 ± 1.4 Gy) and D98% bandwidths (0.9 ± 0.9 Gy vs 1.1 ± 1.3 Gy)., Interpretation: Both techniques provide a similar level of dose coverage to the target volume. Although PAT improved dose conformality, higher HMD translated into increased heart toxicity, presumably due to chosen planning methodology and OAR proximity to target. Increased ELs and spots raised PAT BDT, although it could improve daily treatment workflow.

Objective. This study proposes a robust optimization (RO) strategy utilizing virtual CTs (vCTs) predicted by an anatomical model in intensity-modulated proton therapy (IMPT) for nasopharyngeal cancer (NPC). Methods and Materials. For ten NPC patients, vCTs capturing anatomical changes at different treatment weeks were generated using a population average anatomy model. Two RO strategies of a 6 beams IMPT with 3 mm setup uncertainty (SU) and 3% range uncertainty (RU) were compared: conventional robust optimization (cRO) based on a single planning CT (pCT), and anatomical RO incorporating 2 and 3 predicted anatomies (aRO2 and aRO3). The robustness of these plans was assessed by recalculating them on weekly CTs (week 2-7) and extracting the voxel wise-minimum and maximum doses with 1 mm SU and 3% RU (voxmin\voxmax 1mm3% ). Results. The aRO plans demonstrated improved robustness in high-risk CTV1 and low-risk CTV 2 coverage compared to cRO plans. The weekly evaluation showed a lower plan adaptation rate for aRO3 (40%) vs. cRO (70%). The weekly nominal and voxmax 1mm3% doses to OARs, especially spinal cord, are better controlled relative to their baseline doses at week 1 with aRO plans. The accumulated dose analysis showed that CTV1&2 had adequate coverage and serial organs (spinal cord and brainstem) were within their dose tolerances in the voxmin\voxmax 1mm3% , respectively. Conclusion. Incorporating predicted weekly CTs from a population based average anatomy model in RO improves week-to-week target dose coverage and reduces false plan adaptations without increasing normal tissue doses. This approach enhances IMPT plan robustness, potentially facilitating reduced SU and further lowering OAR doses., (Creative Commons Attribution license.)

Objective. LATTICE, a spatially fractionated radiation therapy (SFRT) modality, is a 3D generalization of GRID and delivers highly modulated peak-valley spatial dose distribution to tumor targets, characterized by peak-to-valley dose ratio (PVDR). Proton LATTICE is highly desirable, because of the potential synergy of the benefit from protons compared to photons, and the benefit from LATTICE compared to GRID. Proton LATTICE using standard proton RT via intensity modulated proton therapy (IMPT) (with a few beam angles) can be problematic with poor target dose coverage and high dose spill to organs-at-risk (OAR). This work will develop novel proton LATTICE method via proton ARC (with many beam angles) to overcome these challenges in target coverage and OAR sparing, with optimized delivery efficiency via energy layer optimization and optimized biological dose distribution via linear energy transfer (LET) optimization, to enable the clinical use of proton LATTICE. Approach. ARC based proton LATTICE is formulated and solved with energy layer optimization, during which plan quality and delivery efficiency are jointly optimized. In particular, the number of energy jumps (NEJ) is explicitly modelled and minimized during plan optimization for improving delivery efficiency, while target dose conformality and OAR dose objectives are optimized. The plan deliverability is ensured by considering the minimum-monitor-unit (MMU) constraint, and the plan robustness is accounted for using robust optimization. The biological dose is optimized via LET optimization. The optimization solution algorithm utilizes iterative convex relaxation method to handle the dose-volume constraint and the MMU constraint, with spot-weight optimization subproblems solved by proximal descent method. Main results. ARC based proton LATTCE substantially improved plan quality from IMPT based proton LATTICE, such as (1) improved conformity index (CI) from 0.47 to 0.81 for the valley target dose and from 0.62 to 0.97 for the peak target dose, (2) reduced esophagus dose from 0.68 Gy to 0.44 Gy (a 12% reduction with respect to 2 Gy valley prescription dose) and (3) improved PVDR from 4.15 to 4.28 in the lung case. Moreover, energy layer optimization improved plan delivery efficiency for ARC based proton LATTICE, such as (1) reduced NEJ from 71 to 56 and (2) reduction of energy layer switching time by 65% and plan delivery time by 52% in the lung case. The biological target and OAR dose distributions were further enhanced via LET optimization. On the other hand, proton ARC LATTCE also substantially improved plan quality from VMAT LATTICE, such as (1) improved CI from 0.45 to 0.81 for the valley target dose and from 0.63 to 0.97 for the peak target dose, (2) reduced esophagus dose from 0.59 Gy to 0.38 Gy (a 10.5% reduction with respect to 2 Gy valley prescription dose) and (3) improved PVDR from 3.88 to 4.28 in the lung case. Significance. The feasibility of high-plan-quality proton LATTICE is demonstrated via proton ARC with substantially improved target dose coverage and OAR sparing compared to IMPT, while the plan delivery efficiency for ARC based proton LATTICE can be optimized using energy layer optimization., (Creative Commons Attribution license.)

Objective . MRI is the standard imaging modality for high-dose-rate brachytherapy of cervical cancer. Precise contouring of organs at risk (OARs) and high-risk clinical target volume (HR-CTV) from MRI is a crucial step for radiotherapy planning and treatment. However, conventional manual contouring has limitations in terms of accuracy as well as procedural time. To overcome these, we propose a deep learning approach to automatically segment OARs (bladder, rectum, and sigmoid colon) and HR-CTV from female pelvic MRI. Approach . In the proposed pipeline, a coarse multi-organ segmentation model first segments all structures, from which a region of interest is computed for each structure. Then, each organ is segmented using an organ-specific fine segmentation model separately trained for each organ. To account for variable sizes of HR-CTV, a size-adaptive multi-model approach was employed. For coarse and fine segmentations, we designed a dual convolution-transformer UNet (DCT-UNet) which uses dual-path encoder consisting of convolution and transformer blocks. To evaluate our model, OAR segmentations were compared to the clinical contours drawn by the attending radiation oncologist. For HR-CTV, four sets of contours (clinical + three additional sets) were obtained to produce a consensus ground truth as well as for inter/intra-observer variability analysis. Main results . DCT-UNet achieved dice similarity coefficient (mean ± SD) of 0.932 ± 0.032 (bladder), 0.786 ± 0.090 (rectum), 0.663 ± 0.180 (sigmoid colon), and 0.741 ± 0.076 (HR-CTV), outperforming other state-of-the-art models. Notably, the size-adaptive multi-model significantly improved HR-CTV segmentation compared to a single-model. Furthermore, significant inter/intra-observer variability was observed, and our model showed comparable performance to all observers. Computation time for the entire pipeline per subject was 12.59 ± 0.79 s, which is significantly shorter than the typical manual contouring time of >15 min. Significance . These experimental results demonstrate that our model has great utility in cervical cancer brachytherapy by enabling fast and accurate automatic segmentation, and has potential in improving consistency in contouring. DCT-UNet source code is available athttps://github.com/JHU-MICA/DCT-UNet., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background: Using dose-painted intensity-modulated radiation therapy, specific dose volume constraints or implantation of tissue expanders prior to radiotherapy are validated options for reducing radiation dose on the bowel and therefore minimizing acute gastrointestinal toxicity during chemoradiation for anorectal malignancies. We describe the rare case of a female patient with a locally advanced anal carcinoma where a large myomatous uterus served as a natural spacer to protect the bowel during radiation therapy., Case Presentation: Initially the patient presented with anal pain, proctoscopy followed by an excisional biopsy confirmed the diagnosis of a squamous cell carcinoma of the anus. Imaging examination showed a locally advanced tumor and in addition a large uterus with typical leiomyomas up to 11.5 cm in diameter. The patient underwent chemoradiation; because of the large leiomyomas there was almost no dose burden for the small intestine and therefore practically no gastrointestinal toxicity., Conclusion: As we know, this report describes the situation that a large myomatous uterus served as a natural spacer during radiation therapy in a way that is unique to date., (© 2024. The Author(s).)

Background: To investigate the impact of using contrast-enhanced computed tomography (CHCT) in the dosimetry of stereotactic body radiation therapy (SBRT) for liver metastases treated with MR-Linac., Methods: A retrospective study was conducted on 21 liver cancer patients treated with SBRT (50 Gy in 5 fractions) using a 1.5 Tesla Unity MR-Linac. The clinical treatment plans optimised on plain computed tomography (pCT) were used as reference. The electronic density (ED) of regions of interest (ROIs) including the liver, duodenum, esophagus, spinal cord, heart, ribs, and lungs, from pCT and CHCT, was analysed. The average ED of each ROI from CHCT was used to generate synthetic CT (sCT) images by assigning the average ED value from the CHCT to the pCT. Clinical plans were recalculated on sCT images. Dosimetric comparisons between the original treatment plan (TP pCT ) and the sCT plan (TP sCT ) were performed using dose-volume histogram (DVH) parameters, and gamma analysis., Results: Significant ED differences (p < 0.05) were observed in the liver, great vessels, heart, lungs, and spinal cord between CHCT and pCT, with the lungs showing the largest differences (average deviation of 11.73% and 12.15% for the left and right lung, respectively). The target volume covered by the prescribed dose (V Dpre ), and the dose received by 2% and 98% of the volume (D 2% , and D 98% , respectively) showed statistical differences (p < 0.05), while the gradient index (GI) and the conformity index (CI) did not. Average deviations in target volume dosimetric parameters were below 1.02%, with a maximum deviation of 5.57% for. For the organs at risk (OARs), significant differences (p < 0.05) were observed for D 0.35cc and D 1.2cc of the spinal cord, D 10cc for the stomach, D 0.5cc for the heart, and D 30% for the liver-GTV, with mean deviations lower than 1.83% for all the above OARs. Gamma analysis using 2%-2 mm criteria yielded a median value of 95.64% (range 82.22-99.65%) for the target volume and 99.40% (range 58-100%) for the OARs., Conclusion: The findings suggest that the use of CHCT in the SBRT workflow for liver metastases may result in minor target volume overdosage, indicating its potential for adoption in clinical settings. However, its use should be further explored in a broader context and tied to personalized treatment approaches., (© 2024. The Author(s).)

This study aimed to investigate the influence of gantry angle increment (Inc) parameters on the Monaco treatment planning system for volumetric modulated arc therapy (VMAT) in right breast cancer, and to determine the optimal Inc parameters. Twenty-three patients with right breast cancer at the Sir Run Run Shaw Hospital from August 2022 to August 2023 were retrospectively selected. Four VMAT plans were generated for each patient incorporating Inc of 10°, 20° (control group), 30°, and 40°, while the other optimization parameters and constraint functions remained constant. The D98 and conformity index were lower in the Inc30 and Inc40 groups than in the Inc20 group. As Inc increased from 10° to 30°, the irradiated dose to the ipsilateral lung, including the V20, V5, and Dmax, mean dose, gradually increased. There were no statistically significant differences in the irradiated dose to the contralateral breast, contralateral lung, heart, esophagus, and brachial plexus. The number of monitor units and control points decreased with increasing Inc. Smaller Inc values can achieve higher target coverage and lower irradiated dose to the ipsilateral lung, but will reduce delivery efficiency. Considering the plan quality and delivery efficiency, an Inc of 10° or 20° is recommended for right breast cancer VMAT plans., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Volumetric modulated arc therapy (VMAT) planning optimization involves iterative adjustment of numerous parameters, and hence requires repeatedly dose recalculation. In this study, we used the deep learning method to develop a fast and accurate dose calculation method for VMAT., Methods: The classical 3D UNet was adopted and trained to learn the physics principle of dose calculation. The inputs included the projected fluence map (FM), computed tomography (CT) images, the radiological depth and the source-to-voxel distance (SVD). The projected FM was generated by projecting the accumulated FM between two consecutive control points (CPs) onto the patient's anatomy. The accumulated FM was calculated by simulating the movement of the multi-leaf collimator (MLC) from one CP to the next. The dose, calculated by the treatment planning system (TPS), was used as ground truth. 51 head and neck VMAT plans were used, with 43, 1 and 7 cases as training, validation, and testing datasets, respectively. Correspondingly, 7182, 180 and 1260 CP samples were included in the training, validation, and testing datasets., Results: This presented method was evaluated by comparing the derived dose distribution to the TPS calculated dose distribution. The dose profiles coincided for both the single CP and the entire plan (summation of all CPs). But the network derived dose was smoother than the TPS calculated dose. Gamma analysis was performed between the network derived dose and the TPS calculated dose. The average gamma pass rate was 96.56%, 98.75%, 98.03% and 99.30% under the criteria of 2% (tolerance) -2 mm (distance to agreement, DTA). 2%-3 mm, 3%-2 mm and 3%-3 mm. No significant difference was observed on the critical indices including the max, mean dose, and the relative volume covered by the 2000 cGy, 4000 cGy and the prescription dose. For one CP, the average computational time of the network and TPS was 0.09s and 0.53s. And for one patient, the average time was 16.51s and 95.60s., Conclusion: The dose distribution derived by the network showed good agreement with the TPS calculated dose distribution. The computational time was reduced to approximate one-sixth of its original duration. Therefore the presented deep learning-based dose calculation method has the potential to be used for planning optimization., (© 2024. The Author(s).)

Objectives: The study aims to emphasize the clinical importance of the Deep Inspiration Breath Hold (DIBH) technique by quantifying its dosimetric advantages over Free Breathing (FB) in reducing radiation exposure to the heart, liver, and lungs for right-sided breast cancer patients. This evidence supports its potential for routine clinical use to mitigate radiation-induced toxicity., Methods: A systematic retrieval of controlled trials comparing DIBH and FB techniques in postoperative radiotherapy for right-sided breast cancer was conducted utilizing the PubMed, Embase, Cochrane Library, and Web of Science databases. The primary outcomes assessed included the doses of adjacent normal tissues (heart, liver, and lungs). Summary standardized mean differences (SMD) along with 95% confidence intervals (CI) were computed, respectively. StataMP 17 software was selected to perform data analysis., Results: The study encompassed an analysis of 313 patients derived from seven online studies, comprising 168 individuals in the DIBH group and 269 individuals in the FB group. The findings indicated that the DIBH group received significantly lower irradiation doses to the heart, liver, and lungs in comparison to the FB group, with statistical significance (heart dose: SMD = -0.63, 95% CI -0.85 to -0.41, P < 0.05; liver dose: SMD = -1.15, 95% CI -1.91 to -0.38, P < 0.05; lung dose: SMD = -0.79, 95% CI -1.23 to -0.35, P < 0.05)., Conclusion: This meta-analysis indicated that the application of DIBH during postoperative radiotherapy for right-sided breast cancer markedly decreases radiation exposure to the heart, liver, and lungs, while maintaining consistent tumor dose coverage., Clinical Trial Number: Not applicable., (© 2024. The Author(s).)

Purpose: The aim was to study the potential for an online fully automated daily adaptive radiotherapy (RT) workflow for bladder cancer, employing a focal boost and fiducial markers. The study focused on comparing the geometric and dosimetric aspects between the simulated automated online adaptive RT (oART) workflow and the clinically performed workflow., Methods: Seventeen patients with muscle-invasive bladder cancer were treated with daily Cone Beam CT (CBCT)-guided oART. The bladder and pelvic lymph nodes (CTV elective ) received a total dose of 40 Gy in 20 fractions and the tumor bed received an additional simultaneously integrated boost (SIB) of 15 Gy (CTV boost ). During the online sessions a CBCT was acquired and used as input for the AI-network to automatically delineate the bladder and rectum, i.e. influencers. These influencers were employed to guide the algorithm utilized in the delineation process of the target. Manual adjustments to the generated contours are common during this clinical workflow prior to plan reoptimization and RT delivery. To study the potential for an online fully automated workflow, the oART workflow was repeated in a simulation environment without manual adjustments. A comparison was made between the clinical and automatic contours and between the treatment plans optimized on these clinical (D clin ) and automatic contours (D auto )., Results: The bladder and rectum delineated by the AI-network differed from the clinical contours with a median Dice Similarity Coefficient of 0.99 and 0.92, a Mean Distance to Agreement of 1.9 mm and 1.3 mm and a relative volume of 100% and 95%, respectively. For the CTV boost these differences were larger, namely 0.71, 7 mm and 78%. For the CTV boost the median target coverage was 0.42% lower for D auto compared to D clin . For CTV elective this difference was 0.03%. The target coverage of D auto met the clinical requirement of the CTV-coverage in 65% of the sessions for CTV boost and 95% of the sessions for the CTV elective ., Conclusions: While an online fully automated daily adaptive RT workflow shows promise for bladder treatment, its complexity becomes apparent when incorporating a focal boost, necessitating manual checks to prevent potential underdosage of the target., (© 2024. The Author(s).)

Thoracic bulky esophageal cancer shrinks during radiotherapy, changing the location and shape of the surrounding heart and lungs. The current study aimed to explore how replanning by volumetric-modulated arc radiotherapy (VMAT) and three-dimensional conformal radiotherapy (3DCRT) influences the target coverage and dose to organs at risk in locally advanced unresectable middle to lower thoracic esophageal cancer. We retrospectively collected CT simulation images of initial and boost radiotherapy plans for locally advanced unresectable thoracic esophageal cancer in 17 consecutive patients. First, we created boost plans of 20 Gy using 3DCRT and VMAT on the initially acquired CT images. Second, we replicated the process on CT images acquired after 20-40 Gy of radiotherapy. We then compared non-replanned boost radiotherapy plans with replanned boost plans. Replanned radiotherapy delivered more conformal doses to the target and reduced heart and lung doses. VMAT reduced more irradiated mean doses to the heart than 3DCRT in the case of replanning (1.7 and 1.1 Gy, p < 0.001). Replanning to accommodate tumor shrinkage during radiotherapy effectively lowers the irradiated doses to the heart and lungs in patients with locally advanced unresectable middle to lower thoracic esophageal cancer, especially those treated with VMAT., (© 2024. The Author(s).)

This study evaluates dosimetric differences in Stereotactic Body Radiation Therapy (SBRT) for lung tumors using plans of Gamma Knife, and Volumetric Modulated Arc Therapy (VMAT), Intensity-Modulated Radiation Therapy (IMRT) plans based on Linear Accelerator, aiming to inform the reader of appropriate treatment strategy selection. Ten patients with 23 lung tumor lesions treated with SBRT at Zhongshan Hospital of Dalian University were analyzed. Plans of Gamma Knife, and VMAT, IMRT plans based on Linear Accelerator were created for each lesion, totaling 18 plans per type. Lesions were treated with 30-50 Gy in 5-10 fractions. Dosimetric parameters, including gradient index (GI), heterogeneity index (HI), conformity index (CI), and doses to the plan target volumes (PTVs), the gross tumor volumes (GTVs) and organs at risk (OARs) were compared. Plans of Gamma Knife showed superior HI and GI, higher PTV and GTV doses, and reduced doses to the ipsilateral and contralateral lungs, esophagus, spinal cord, and heart compared to VMAT and IMRT plans (p < 0.05). However, Plans of Gamma Knife required longer delivery times. When comparing VMAT and IMRT plans, VMAT plans had shorter delivery times than IMRT plans, but required more monitor units (MUs). Additionally, IMRT plans delivered a lower mean dose to the ipsilateral lung compared to VMAT plans. Gamma Knife SBRT plans achieves steeper dose falloff and minimizes radiation to normal lung tissue compared to VMAT and IMRT plans, but with longer delivery times. VMAT and IMRT plans displayed similar dose distributions for lung SBRT., (© 2024. The Author(s).)