Organs At Risk Constraints Research Articles

Mixed- and multi-relative biological effectiveness model simultaneous optimization in carbon ion radiotherapy: A proof-of-concept

Background and purposeIn carbon ion radiotherapy (CIRT), different relative biological effectiveness (RBE) models have been used for calculating RBE-weighted dose (DRBE). Conversion between current RBE predictions and introduction of novel approaches remains a challenging task. Our aim is to introduce a framework considering multiple RBE models simultaneously during CIRT plan optimization, easing the translation between DRBE prescriptions. Materials and methodsAn in-house developed Monte Carlo treatment planning system was extended to incorporate the local effect model version I (LEM-I), the modified microdosimetric kinetic model (mMKM) and the MKM-derived Japanese biological model (NIRS-MKM). Four clinical cases (two head-and-neck and two prostate patients), initially optimized with LEM-I for both targets and organs at risk (OARs), underwent two further optimizations: to fulfill mMKM/NIRS-MKM-based target prescriptions (mixed-RBE approach) or to simultaneously consider two biological models within the target regions (multi-RBE approach). Both approaches retained LEM-I-derived dose constraints for OARs. ResultsThe developed optimization strategies have been successfully applied, fulfilling all the clinical criteria for the applied RBE models. One of the RBE models showed unfavorable dose distribution when not explicitly considered in the optimization, while multi-RBE model optimization allowed meeting dose objectives for the selected OARs for both models simultaneously. ConclusionsThe introduced optimization approaches allow for mixed- or multi-RBE optimization in CIRT through the selection of RBE models independently for each region of interest. This capability addresses challenges of adhering to multiple RBE frameworks and proposes an advanced solution for tailored patient treatment plans.

Effect of Different Dose Rates on Dosimetric Parameters and Accuracy of the Pretreatment Quality Assurance During Intensity-modulated Radiotherapy Planning Using Anthropomorphic Phantom

Background: This study investigates the impact of varying dose rates on dosimetric parameters and pretreatment quality assurance (QA) accuracy in intensity-modulated radiotherapy (IMRT) planning using anthropomorphic phantoms. The research explores the dosimetric effects of different dose rates ranging from 100 to 600 monitor units per minute (MU/min) on parameters such as Homogeneity Index (HI), Conformity Index (CI), and dose to organs at risk (OAR). Method: Anthropomorphic phantoms, mimicking human tissues, were employed for simulation. Treatment plans were generated using the Eclipse Treatment Planning System, and dosimetric evaluations were conducted using cumulative dose-volume histograms (DVH). Furthermore, pretreatment patient-specific QA was performed using EPID portal dosimetry and Delta4 dosimetry system. Result: Treatment plans adhere to institutional protocol, ensuring the target receives ≥95% of the prescription dose while meeting OAR constraints. All plans maintain target homogeneity and conformality, keeping maximum doses within the target below 107%. Low dose plans exhibit superior target coverage, conformality, and homogeneity compared to higher doses. However, increased dose rates elevate delivered Monitor Units and maximum doses to critical structures. Gamma passing rates vary with dose rates, with the lowest at 100 MU/min and the highest at 400 MU/min for 1% 1mm criteria. Dosimetric evaluations using Delta 4 and EPID QA methods confirm plan validity across different dose rates. Conclusion: Low dose rate dosimetry is superior to higher rates for target and organ-at-risk (OAR) delivery, albeit prolonging delivery time and affecting internal organ motion. Portal dosimetry offers a faster, more convenient tool for IMRT pretreatment quality assurance (QA). Optimal results are achieved at 400 MU/min, enhancing gamma agreement between calculated and measured portal doses for complex fields. This improvement in QA enhances IMRT treatment delivery quality. However, patient-specific QA using the DELTA4 dosimetry system and ICRU 83 recommendations are insufficient for discussing dosimetric differences relevant to patient treatment.

Dose-Painting Proton Radiotherapy Guided by Functional MRI in Non-enhancing High-Grade Gliomas

AimsThis study aimed to demonstrate the feasibility and evaluate the dosimetric effect and clinical impact of dose-painting proton radiotherapy (PRT) guided by functional MRI in non-enhancing high-grade gliomas (NE-HGGs). Materials and methodsThe 3D-ASL and T2 FLAIR MR images of ten patients with NE-HGGs before radiotherapy were studied retrospectively. The hyperintensity on T2 FLAIR was used to generate the planning target volume (PTV), and the high-perfusion volume on 3D-ASL (PTV-ASL) was used to generate the simultaneous integrated boost (SIB) volume. Each patient received pencil beam scanning PRT and photon intensity-modulated radiotherapy (IMRT). There were five plans in each modality: (1) Uniform plans (IMRT60 vs. PRT60): 60Gy in 30 fractions to the PTV. (2)–(5) SIB plans (IMRT72, 84, 96, 108 vs. PRT72, 84, 96, 108): Uniform plan plus additional dose boost to PTV-ASL in 30 fractions to 72, 84, 96, 108 Gy. The dosimetric differences between various plans were compared. The clinical effects of target volume and organs at risk (OARs) were assessed using biological models for both tumor control probability (TCP) and normal tissue complication probability (NTCP). ResultsCompared with the IMRT plan, the D2 and D50 of the PRT plans with the same prescription dose increased by 1.27–4.12% and 0.64–2.01%, respectively; the R30 decreased by > 32%; the dose of brainstem and chiasma decreased by > 27% and >32%; and the dose of normal brain tissue (Br-PTV), optic nerves, eyeballs, lens, cochlea, spinal cord, and hippocampus decreased by > 50% (P < 0.05). The maximum necessary dose was 96GyE to achieve >98% TCP for PRT, and it was 84Gy to achieve >91% TCP for IMRT. The average NTCP of Br-PTV was 1.30% and 1.90% for PRT and IMRT at the maximum dose escalation, respectively. The NTCP values of the remaining OARs approached zero in all PRT plans. ConclusionThe functional MRI-guided dose escalation using PRT is feasible while sparing the OARs constraints and demonstrates a potential clinical benefit by improving TCP with no or minimal increase in NCTP for tissues outside the PTV. This retrospective study suggested that the use of PRT-based SIB guided by functional MRI may represent a strategy to provide benefits for patients with NE-HGGs.

Stereotactic body radiotherapy of central lung tumours using a 1.5 T MR-linac: First clinical experiences

BackgroundMRI-guidance may aid better discrimination between Organs at Risk (OARs) and target volumes in proximity of the mediastinum. We report the first clinical experiences with Stereotactic Body Radiotherapy (SBRT) of (ultra)central lung tumours on a 1.5 T MR-linac. Materials and MethodsPatients with an (ultra)central lung tumour were selected for MR-linac based SBRT treatment. A T2-weighted 3D sequence MRI acquired during free breathing was used for daily plan adaption. Prior to each fraction, contours of Internal Target Volume (ITV) and OARs were deformably propagated and amended by a radiation oncologist. Inter-fractional changes in volumes and coverage of target volumes as well as doses in OARs were evaluated in offline and online treatment plans. ResultsTen patients were treated and completed 60 Gy in 8 or 12 fractions. In total 104 fractions were delivered. The median time in the treatment room was 41 min with a median beam-on time of 8.9 min. No grade ≥3 acute toxicity was observed. In two patients, the ITV significantly decreased during treatment (58 % and 37 %, respectively) due to tumour shrinkage. In the other patients, 81 % of online ITVs were within ±15 % of the volume of fraction 1. Comparison with the pre-treatment plan showed that ITV coverage of the online plan was similar in 52 % and improved in 34 % of cases. Adaptation to meet OAR constraints, led to decreased ITV coverage in 14 %. ConclusionsWe describe the workflow for MR-guided Radiotherapy and the feasibility of using 1.5 T MR-linac for SBRT of (ultra) central lung tumours.

Enhancing dosimetric practices through knowledge-based predictive models: a case study on VMAT prostate irradiation.

Acquisition of dosimetric knowledge by radiation therapy planners is a protracted and complex process. This study delves into the impact of empirical predictive models based on the knowledge-based planning (KBP) methodology, aimed at detecting suboptimal results and homogenizing and improving existing practices for prostate cancer. Moreover, the dosimetric effect of implementing these models into routine clinical practice was also assessed. Based on the KBP method, we analyzed 25 prostate treatment plans performed using VMAT by expert operators, aiming to correlate dose indicators with patient geometry. The , and of the peritoneal cavity and the and of the rectum and bladder were linked to geometric characteristics such as the distance from the planning target volume (PTV) to the organs at risk (OAR), the volume of the OAR, or the overlap between the PTV and the OAR. In the second phase, the KBP was used in routine clinical practice in a prospective cohort of 25 patients and compared with the 41 patient plans calculated before implementing the tool. Using linear regression, we identified strong geometric predictive factors for the peritoneal cavity, rectum, and bladder (> 0.8), with an average prescribed dose of 97.8%, covering 95% of the target volume. The use of the model led to a significant dose reduction for all evaluated OARs. This trend was most notable for . Significant reductions were also obtained in average doses to the rectum and bladder, and respectively. Based on this model, we reduced the number of plans with OAR constraints above the clinical recommendations from 19% to 8%. The KBP methodology established a robust and personalized predictive model for dose estimation to organs at risk in prostate cancer. Implementing the model resulted in improved sparing of these organs. Notably, it yields a solid foundation for harmonizing dosimetric practices, alerting us to suboptimal results, and improving our knowledge.

Widening the therapeutic window for central and ultra-central thoracic oligometastatic disease with stereotactic MR-guided adaptive radiation therapy (SMART)

Background/PurposeCentral/ultra-central thoracic tumors are challenging to treat with stereotactic radiotherapy due potential high-grade toxicity. Stereotactic MR-guided adaptive radiation therapy (SMART) may improve the therapeutic window through motion control with breath-hold gating and real-time MR-imaging as well as the option for daily online adaptive replanning to account for changes in target and/or organ-at-risk (OAR) location. Materials/Methods26 central (19 ultra-central) thoracic oligoprogressive/oligometastatic tumors treated with isotoxic (OAR constraints-driven) 5-fraction SMART (median 50 Gy, range 35–60) between 10/2019–10/2022 were reviewed. Central tumor was defined as tumor within or touching 2 cm around proximal tracheobronchial tree (PBT) or adjacent to mediastinal/pericardial pleura. Ultra-central was defined as tumor abutting the PBT, esophagus, or great vessel. Hard OAR constraints observed were ≤ 0.03 cc for PBT V40, great vessel V52.5, and esophagus V35. Local failure was defined as tumor progression/recurrence within the planning target volume. ResultsTumor abutted the PBT in 31 %, esophagus in 31 %, great vessel in 65 %, and heart in 42 % of cases. 96 % of fractions were treated with reoptimized plan, necessary to meet OAR constraints (80 %) and/or target coverage (20 %). Median follow-up was 19 months (27 months among surviving patients). Local control (LC) was 96 % at 1-year and 90 % at 2-years (total 2/26 local failure). 23 % had G2 acute toxicities (esophagitis, dysphagia, anorexia, nausea) and one (4 %) had G3 acute radiation dermatitis. There were no G4-5 acute toxicities. There was no symptomatic pneumonitis and no G2 + late toxicities. ConclusionIsotoxic 5-fraction SMART resulted in high rates of LC and minimal toxicity. This approach may widen the therapeutic window for high-risk oligoprogressive/oligometastatic thoracic tumors.

Dosimetric comparison of magnetic resonance-guided radiation therapy, intensity-modulated proton therapy and volumetric-modulated arc therapy for distal esophageal cancer

Advances in radiotherapy (RT) technologies permit significant decreases in the dose delivered to organs at risk (OARs) for patients with esophageal cancer (EC). Novel RT modalities such as proton beam therapy (PBT) and magnetic resonance-guided radiotherapy (MRgRT), as well as motion management techniques including breath hold (BH) are expected to further improve the therapeutic ratio. However, to our knowledge, the dosimetric benefits of PBT vs MRgRT vs volumetric-modulated arc therapy (VMAT) have not been directly compared for EC. We performed a retrospective in silico evaluation using the images and datasets of nine distal EC patients who were treated at our institution with a 0.35-Tesla MR linac to 50.4 Gy in 28 fractions in mid-inspiration BH (BH-MRgRT). Comparison free-breathing (FB) intensity-modulated PBT (FB-IMPT) and FB-VMAT plans were retrospectively created using the same prescription dose, target volume coverage goals, and OAR constraints. A 5 mm setup margin was used for all plans. BH-IMPT and BH-VMAT plans were not evaluated as they would not reflect our institutional practice. Planners were blinded to the results of the treatment plans created using different radiation modalities. The primary objective was to compare plan quality, target volume coverage, and OAR doses. All treatment plans met pre-defined target volume coverage and OAR constraints. The median conformity and homogeneity indices between FB-IMPT, BH-MRgRT and FB-VMAT were 1.13, 1.25, and 1.43 (PITV) and 1.04, 1.15, 1.04 (HI), respectively. For FB-IMPT, BH-MRgRT and FB-VMAT the median heart dose metrics were 52.8, 79.3, 146.8 (V30Gy, cc), 35.5, 43.8, 77.5 (V40Gy, cc), 16.9, 16.9, 32.5 (V50Gy, cc) and 6.5, 14.9, 17.3 (mean, Gy), respectively. Lung dose metrics were 8.6, 7.9, 18.5 (V20Gy, %), and 4.3, 6.3, 11.2 (mean, Gy), respectively. The mean liver dose (Gy) was 6.5, 19.6, 22.2 respectively. Both FB-IMPT and BH-MRgRT achieve substantial reductions in heart, lung, and liver dose compared to FB-VMAT. We plan to evaluate dosimetric outcomes across these RT modalities assuming consistent use of BH.

Dosimetric comparison of stereotactic MR-guided radiation therapy (SMART) and HDR brachytherapy boost in cervical cancer

The standard of care in locally advanced cervical cancer (LACC) is concomitant chemoradiotherapy followed by high-dose-rate brachytherapy (HDR-BT). Although previous studies compared HDR-BT with stereotactic body radiotherapy (SBRT), there is scarce data regarding the dosimetric outcomes of stereotactic MR-guided adaptive radiation therapy (SMART) boost in lieu of HDR-BT. In this single-institutional in-silico comparative study, LACC patients who were definitively treated with external beam radiotherapy followed by HDR-BT were selected. Target volumes and organs at risk (OARs) were delineated in MRI and HDR-planning CT. An HDR-BT and a SMART boost plan were generated with a prescribed dose of 28 Gy in four fractions for all patients. The HDR-BT and SMART boost plans were compared in regard to target coverage as well OARs doses. Mean EQD2 D90 to HR-CTV and IR-CTV for HDR-BT plans were 89.7 and 70.5 Gy, respectively. For SMART, the mean EQD2 D90 to HR-PTV, HR-CTV, and IR-CTV were 82.9, 95.4, and 70.2 Gy, respectively. The mean D2cc EQD2 of bladder, rectum, and sigmoid colon for HDR-BT plans were 86.4, 70.7, and 65.7 Gy, respectively. The mean D2cc EQD2 of bladder, rectum, and sigmoid colon for SMART plans were 81.4, 70.8, and 73.6 Gy, respectively. All dose constraints in terms of target coverage and OARs constraints were met for both HDR-BT and SMART plans. This dosimetric study demonstrates that SMART can be applied in cases where HDR-BT is not available or ineligible with acceptable target coverage and OAR sparing. However, prospective clinical studies are needed to validate these results.

Dosimetric Advantages of Online Adaptative Radiotherapy for Cervical Cancer on 1.5T MR-Linac

Online adaptative radiotherapy (ART) strategy can be applied to account for inter-fraction organ motion while limiting organ at risk (OAR) dose. This study aims to evaluate tumor target and OARs inter- and intrafraction motion using online MRI during the full course of MR-Linac radiotherapy fractions. Furthermore, quantify the dosimetric consequences of online adaptative compared with non-adaptative radiotherapy (non-ART) in cervical cancer. Six cervix cancer patients were treated with 150 fractions on the 1.5 T Unity MR-Linac. Each fraction, pre-treatment MRI scans were obtained at the start of every treatment session, and post-treatment MRI scans were obtained at the end of every treatment session. A total 300 MR images were included in this study and the CTV, bladder and rectum were delineated on each MRI by the same radiation oncologist. The inter-fraction and intrafraction changes of contours were evaluated by dice similarity coefficient (DSC), Hausdorff distance (HD), volume difference (ΔV). The reference treatment plans were generated using step-and-shoot IMRT and utilized 9 beam groups on original CT. Then, the online adaptative treatment plans were obtained by re-optimizing based on the contours on daily pre-treatment MRI by "adapt to shape" workflow using the same beam parameters and optimization objectives from the reference plans. Non-ART plans for each patient were generated by recalculating the dose from the reference plans on daily online MRI by "adapt to position" workflow. CTV coverage and OARs constraints were used to compare ART and non-ART plans. The results showed that large inter-fraction anatomical changes limited the efficacy of radiation therapy (CTV: DSC: 0.89±0.03, HD: 20.83±5.05mm, ΔV: 1.21%±5.44%; Bladder: DSC: 0.68±0.18, HD: 30.58±15.75mm, ΔV: -10.17%±61.19%; Rectum: DSC: 0.69±0.09, HD: 22.98±12.03mm, ΔV: 21.01%±20.59%).The intrafraction anatomical changes were smaller (CTV: DSC: 0.96±0.01, HD: 8.85±3.54mm, ΔV: -0.64%±1.90%; Bladder: DSC: 0.90±0.07, HD: 14.62±9.56mm, ΔV: 19.83%±21.71%; Rectum: DSC: 0.98±0.04, HD: 2.90±4.27mm, ΔV: 0.13%±5.04%) . Non-ART showed inadequate primary CTV coverage in 30% of the daily fractions. Online adaptative plans improved CTV coverage significantly (p<0.001) to 99%. Compared with non-ART, online ART decreased the fraction dose to bladder and rectum indicated by significant (p<0.001) improvements for daily D50%, D2% and Dmean. In cervical cancer radiotherapy, a non-adaptive strategy led to inadequate target coverage for individual patients. Online adaptative radiotherapy corrected for day-to-day anatomical variations and resulted in adequate target coverage in all fractions. The dose to rectum and bladder was decreased significantly when applying online adaptative radiotherapy.

Temporospatial Feathering of Hot Spots for Computed Tomography-Guided Stereotactic Adaptive Radiotherapy (CT-STAR) for the Ultra-Central Thorax

SBRT to the ultra-central thorax is limited by potential toxicity. It has been demonstrated that exposing proximal bronchial tree or pulmonary arteries to high dose per fraction (fx) treatment may induce bronchopulmonary hemorrhage, amongst other serious complications. Online adaptive radiotherapy is a technique that adjusts a treatment plan to the anatomy-of-the-day and benefits have been demonstrated in ultra-central thoracic disease. In addition, feathering is a treatment planning technique that generates several plans to avoid consistent organ-at-risk (OAR) doses throughout treatment. With daily adaptation, it may be possible to adjust the position of a hot spot (>120% prescription (Rx)) within the tumor each fx (temporospatial feathering) while respecting hard OAR constraints. We investigated the feasibility and plan quality of using CBCT-guided stereotactic adaptive radiotherapy (CT-STAR) for ultra-central lung tumors with hotspot temporospatial feathering. Seven patients with ultra-central thoracic disease (6 patients with parenchymal tumors in contact with the trachea, proximal bronchial tree, great vessels, esophagus, or heart; 1 patient with a subcarinal lymph node) receiving standard of care radiotherapy were enrolled on an imaging study. An in-silico planning study first generated an SBRT plan (in silico Rx: 55 Gy in 5fx) that used a GTV_OPT (GTV minus OAR plus a safety margin) to optimize the location of the plan hotspot. Five spherical boost structures were manually created inside of the GTV_OPT structure. The same planning template was used except the boost structures were iteratively used in plan optimization instead of the GTV_OPT structure, to simulate the five CT-STAR fx hotspot temporospatially feathering. The five-plan composite was compared to the initial plan. All plans generated met strict OAR constraints. Table 1 shows the mean difference in PTV, GTV, and OARs percent coverage by various isodose levels. Feathering the hotspot had negligible impact on target coverage by 50 Gy and 55 Gy isodose lines as well as OAR doses compared to the base SBRT plan. The feathered plan sum resulted in 14.7% increase in V66 Gy of the GTV. One patient saw a decrease in V66 Gy coverage to all target structures, though V50 Gy and V55 Gy were not affected. We demonstrated the feasibility and utility of temporospatially adapting the hotspot for central lung SBRT, which safely increases the amount of tumor receiving more than 120% Rx.

Development and Assessment of a Multi-Purpose Knowledge-Based Planning Model (RapidPlan) for Prostate Radiation

RapidPlan (RP) is a knowledge-based planning (KBP) tool to improve plan quality, planning speed, and reduce inter-patient plan variability. For small to medium institutions, it is difficult to find sufficient patient numbers to configure a reliable KBP-RP model. This study aimed to build a multi-purpose KBP-RP model for prostate cancers. A total of 124 prostate plans from 2018-2022 at our institution were selected to configure the initial RP model. After model training, outliers were removed. 77 patients were used for the final RP model. Three fine-tuned RP sub-models with different optimized constraints corresponding to prostate bed, prostate + seminal vesicles (SV), and prostate boost plans were generated. RP models were validated by comparing plan quality with the original manually optimized plans (MP). 54 independent plans were selected to validate the RP models. Validation included: dose to 99% and 2% of PTV (D99%, D2%), PTV conformity index (CI); for organs at risk (OARs), volume receiving >70Gy and >60Gy (V70Gy, V60Gy) to bladder and rectum, maximum dose (Dmax) to femur heads (FHs) and small bowel. Statistical t-test analysis was performed with a significance of p<0.05. A total of 48/54 model-based plans were clinically approved after single RP optimization. 6/54 failed plans were prostate bed plans and were deemed acceptable after additional minor constraint adjustments. For PTV, D99%, D2%, and CI were comparable (p>0.05) to MP. Bladder and rectum V70Gy were comparable (p>0.05), and V60Gy were significantly lower to MP (p<0.05), with an average Dmean of 23.21±14.58Gy and 16.41±10.63Gy vs 26.36±16.89Gy and 18.24±12.81Gy for RP and MP. RP significantly reduced Dmax to FHs and small bowel (p<0.05), with average Dmax of 34.95±6.06Gy and 35.62±18.99Gy vs 36.81±7.05Gy and 38.14±17.81Gy, respectively. Multi-purpose prostate RP model was configured and approved plans were generated after single optimization. Prostate RP plans had equivalent PTV coverage with better or comparable OAR constraints.

Quality Assurance of Protocol Compliance in a Multicenter Randomized Trial Investigating the Role of Hypofractionated Comprehensive Reginal Nodal Irradiation in Node-Positive Breast Cancer (HARVEST)

The HARVEST trial (NCT03829553) is a phase III, multicenter, randomized clinical trial to explore efficacy and safety of hypofractionated irradiation (HFI) involving regional nodal irradiation (RNI, including internal mammary nodes, IMN) in N+ breast cancer patients treated with mastectomy or breast conserving surgery (BCS). Current study aims to analyze the dosimetric quality assurance so as to evaluate the compliance to the trial protocol. Eligible patients were randomly assigned (1:1) to receive conventional fractionated irradiation (CFI: 50 Gy/25Fx) or HFI (40.05 Gy/15Fx), which is delivered to ipsilateral chest wall or whole breast (CW/WB) with tumor bed boost (HFI: 10.68 Gy/4Fx; CFI: 10 Gy/5Fx) and comprehensive RNI (supra/infraclavicular nodes and IMN in each patient, lower axilla if indicated) by using IMRT technique. The plan quality was evaluated based on dose distribution, dose volume histogram (DVH) and field parameters. The target coverage, including planning target volume of CW/WB (PTV1) and tumor bed (PTV2) and doses of the organs at risk (OARs) were evaluated. The LQ model was used to convert doses of OARs in HFI group using α/β = 3 Gy (EQD23) for comparison. Between Feb 21, 2019 and Feb 14, 2022, 801 patients were enrolled at 8 centers with 401 and 400 in CFI and HFI group, respectively. There were 182 patients received BCS and 387 patients were with more than three positive lymph nodes. In the CFI group, the D90 and V45 of PTV1 reached the prescribed dose in 70.6% and 96.0% of the patients, respectively. In the HFI group, the D90 and V36 of PTV1 reached the prescribed dose in 87.8% and 95.5% of the patients, respectively. When the tumor bed was irradiated, the D90 of PTV2 reached the prescribed dose in 95.6% in the CFI group and 100% in the HFI group, respectively. The mean D90 of PTV1 and PTV2 were 50.09±0.65 Gy and 60.63±0.91 Gy in CFI group while 40.11±0.56 Gy and 50.79±2.03 Gy in HFI group. For OARs constraints, protocol compliance was all above 95% (heart: 95.3%; ipsilateral lung: 95.5%; contralateral lung: 97.1%; humeral head: 98.2% and spinal cord: 100%) with no significant difference between CFI and HFI groups. For patients with left-sided breast cancer, the Dmean of the heart was 5.10±1.75 Gy vs. 4.59±1.86 Gy (EQD23) in CFI and HFI groups (p = 0.51), respectively. No significant differences in Dmean of the heart (1.45±0.71 Gy vs. 1.33±0.77 Gy (EQD23), p = 0.40) was found either between two groups in right-sided patients. The differences were significant in the Dmean of the ipsilateral lung (13.37±1.99 Gy vs. 11.17±3.50 Gy (EQD23), p<0.01), contralateral lung (0.88±0.73 Gy vs. 0.74±0.61 Gy (EQD23), p<0.01) and the ipsilateral humeral head (15.27±7.62 Gy vs. 13.05±6.19 Gy (EQD23), p<0.01) and the Dmax of spinal cord (21.40±8.82 Gy vs. 19.47±7.99 Gy (EQD23), p = 0.05) between CFI and HFI groups. A high degree of compliance with protocol dose constraints was found for treatment plans in the HARVEST trial and doses to the most of OARs decreased in HFI group.

Feasibility of Using a Single Planning MRI for Two-Insertion Intracavitary Brachytherapy for Cervical Cancer

MRI is an essential tool in treatment planning for cervical cancer patients undergoing definitive chemoradiation involving brachytherapy. However, due access to MRI for many patients may be limited. We sought to examine the feasibility and quality of treatment planning for organs at risk (OAR) and target volumes of a single treatment planning MRI for a planned two-insertion HDR intracavitary cervical brachytherapy. Eighteen patients with cervical cancer who underwent MRI-based treatment planning for intracavitary brachytherapy were selected for analysis. Patients underwent two intracavitary applicator insertions using a tandem and ring applicator (TnR_1 and TnR_2) with both CT (for digitization only) and MRI following each insertion and two fractions delivered with each insertion (total 7 Gy x 4fx). MRI-based TnR_2 plans were retrospectively replanned with the following procedure: 1) register MRI from TnR_1 to TnR_2 CT, 2) transfer cervix contour (Cx_simul) and plan from TnR_1 to TnR_2 CT, simulating blinding from TnR_2 MRI, 3) crop Cx_simul from TnR_2 OARs, 4) adjust plan only to meet OAR constraints or clinical doses if clinical plan (TnR_2 original MRI plan summed with TnR_1 and EBRT doses) violates constraints. Coverage changes (∆_D90%) in actual MRI defined TnR_2 cervix (Cx_real) was compared to clinical plans and evaluated against our clinical target goal: >85 Gy EQD2 (EBRT+BT). Differences between Cx_simul and Cx_real contours were evaluated with Dice Similarity Coefficient (DSC). Changes in bladder, rectum, rectosigmoid, and bowel D2cc was evaluated. Procedure time was recorded to determine time added by MRI (time between CT and final MRI timestamps; n = 29). Plan modification to meet OAR constraints was required for 5/18 plans. Cx_real target coverage from clinical to simulated plans decreased in 7/18 plans (∆_D90% = 1.7±6%). Composite EQD2 was <85 Gy in 2/18 cases, with ∆_D90% of -1.3% (clinical EQD2<85 Gy for this case also) and -7.3%, which was due to inconsistent cervix shape between insertions 1 and 2. Cervix DSC values between Cx_simul and Cx_real ranged from 0.68-0.88 (mean = 0.78 ± 0.06). Bladder, rectum, rectosigmoid, and bowel D2cc increased on average 4 ± 12%, 3 ± 9%, 5 ± 10%, and 5 ± 17%, respectively. Including planning MRI increased procedure time by 41.8 ± 10.4 min. The proposed method of utilizing TnR_1 MRI contours for TnR_2 CT planning reduces procedure time and provides reasonable target coverage for most cases. OAR assessment varies between imaging modality which likely represents variability in OAR position rather than treatment planning modality. Next steps are to increase patients studied, and implement this technique prospectively while waiting for TnR_2 MRI completion and compare the clinical TnR_2 MRI plan with the TnR_2 CT plan created with Cx_simul. This will provide further confidence in validity of the approach and ensure plan quality is maintained prior to full implementation.

Intensity-Modulated Proton Therapy (IMPT) Offered Advantageous Dosimetry Compared to Volumetric Arc Therapy (VMAT) or Helical Tomotherapy (HT) in Patients with Synchronous Bilateral Breast Cancer

Radiotherapy of synchronous bilateral breast cancer poses some technical challenges with regards to dose coverage and sparing of organs at risk (OAR). In this study, we aimed to evaluate dosimetric characteristics of 3 different techniques, IMPT vs photon (VMAT and HT). We hypothesized that IMPT would result in lower doses to organs at risk, as compared to the other 2 techniques. A total of 10 patients with synchronous bilateral breast cancer who were treated with VMAT at our institution were retrospectively analyzed. Clinical target volume (CTV) included chest wall and regional nodes (supraclavicular fossa and internal mammary chain) and prescription dose was 40.05 Gy in 15 daily fractions. HT and IMPT plans were generated for each patient. Dose-volume statistics, including planning target volume (PTV) coverage and dose to OAR: lungs, heart, thyroid, spinal cord, brachial plexus and esophagus, were compared between modalities using a paired T-test. Mean age of patients was 61 years (43-84). Majority of the patients (80%) were ER+ PR+ and HER2-. 40% of patients underwent breast reconstruction following surgery. All 3 techniques provided adequate target volume distribution and OAR sparing. Compared to VMAT and HT plans, IMPT had better heart and lung sparing effects, resulting in lower mean and V25 Gy heart dose; mean, V20 Gy and V5 Gy lung dose (p<0.0001). There was no significant difference in VMAT and HT plans for mean heart and lung dose. VMAT plans showed significantly lower V25 Gy heart dose on average (p = 0.04). V5 Gy lung dose was slightly lower in HT compared to VMAT plans, approaching statistical significance (p = 0.08). PTV coverage was adequate for all 3 techniques. All techniques fulfilled cord, esophagus, thyroid and brachial plexus constraints. IMPT plans showed significantly better OAR sparing compared to photon techniques. All 3 techniques met OAR constraints, and resulted in adequate target volume coverage. As IMPT is significantly more costly than VMAT or HT techniques, appropriate patient selection is important to deliver treatment in the most resource-effective manner for patients who would derive the most benefit, for example those with young age or existing heart or lung comorbidities.

Dosimetric Plan Evaluation of Biology Guided Radiotherapy Using [18F]-DCFPyL PSMA Radiotracer in Patients with Prostate Cancer

The X1 system represents a cutting-edge solution in radiotherapy delivery, with its capability to perform Biology Guided Radiotherapy (BgRT). The system utilizes real-time positron emission tomography (PET) signal as biological fiducials to provide tracked dose delivery and is initially available for use with [18F]-Fluorodeoxyglucose (FDG). The aim of this research study is to assess the quality of BgRT treatment plans for prostate cancer using patients' PSMA PET images obtained on the X1 system. Sixteen patients with at least one PET-avid tumor identified on their whole-body diagnostic PSMA PET scan were selected. These patients were scanned on X1 following their diagnostic scan without additional radiotracer administration. Based on the X1 PET images, a BgRT plan was created for each patient, with the prescription dose determined by the location of treatment sites. The planning objectives of organs-at-risk (OARs) were established in accordance with the 2018 Timmerman guidelines. Target coverage objective was the dose covering 95% (D95%) of the planning target volume (PTV) to be higher than 100%. The following parameters were analyzed: PTV D95%, the minimal dose (Dmin) of gross tumor volume (GTV), plan maximum dose (Dmax), conformity index (CI), gradient index (GI), and maximum point dose (D0.03cc) to the nearest OARs. The X1 BgRT planning system also generated dose volume histogram (DVH) bounds, which model variations in BgRT delivery. The low boundary of GTV Dmin, representing the minimum GTV dose in the worst-case scenario, was recorded. BgRT plans were created for all patients, except for one where the target signal was indistinguishable from the bladder. The prescription dose was 2700 cGy or 3000 cGy in 3 fractions for lymph node lesions, 2400 cGy to 3000 cGy in 3 fractions for bone metastasis, and 4500 cGy in 5 fractions for lesions in prostate. All plans met the dose constraints for OARs as per the Timmerman guidelines. The Dmax of all plans was 129.9% ± 6.9% (mean ± standard deviation). The PTV D95% and GTV Dmin were 101.7% ± 1.0% and 111.0% ± 7.6%, respectively. The low boundary of GTV Dmin was 95.9% ± 5.8%. The CI and GI were 1.22 ± 0.11 and 9.40 ± 2.12, respectively. The D0.03cc to nearest OARs was 84.6% ± 25.4%. The estimated treatment time was 699 ± 228 seconds. This study is a pioneering effort to evaluate the quality of BgRT plans for prostate cancer patients using the [18F]-DCFPyL PSMA radiotracer. Our results showed that all BgRT plans met the planning objectives defined in the Timmerman protocol. BgRT with [18F]-DCFPyL represents a promising treatment modality for patients with prostate cancer. Further research is needed to validate this approach, including a comprehensive assessment of the dosimetric and tracking accuracy through physical measurements.

Intratumoral Dose Escalation Using Lattice Radiotherapy for Hepatocellular Carcinoma with Unfavorable Size and Location

Stereotactic body radiation therapy (SBRT) is a standard of care for unresectable hepatocellular carcinoma (HCC). However, its safe delivery is limited by tumor size and adjacent organs-at-risk (OARs). RTOG 1112 showed a survival benefit with local control in advanced HCC, but median dose was limited to 35 Gy in 5 fractions due to OARs. Here, we demonstrate the dosimetric feasibility of lattice radiation therapy (LRT) for dose escalation in advanced HCC. Five-fraction volumetric arc-based (VMAT) LRT plans were generated using a customized Python v3.6 script. For each combination of peak/valley doses and sphere size and spacing, a bounding box was generated around the gross tumor volume (GTV) and divided into equal segments in the x, y, and z planes. Individual spheres were constructed for a given parameter set and those fully encompassed within the target contracted by 2 cm were used to create peak dose targets with values of 30, 40, or 50 Gy. Valley dose target volumes over a range of 2 to 45 Gy were generated by subtracting an 8 mm expansion of the peak dose spheres from the overall target volume. Multi-criteria optimization (MCO) was applied to generate a final plan. The planning target volume (PTV) was a 5-mm uniform expansion from the GTV. All plans were generated at maximum inspiration on 4D-CT. OAR parameters were compared against a standard 5-fraction SBRT plan using Wilcoxon signed-rank testing. GTV and PTV measured 593 (23%) and 804 (32%) cm3, respectively, of a total liver volume of 2525 cm3. The minimum distance of GTV from stomach and duodenum was 6 mm and 2 mm, respectively. Plans were evaluated as per RTOG 1112 with stepwise reduction from a maximum PTV dose of 50 Gy based upon ability to meet mean liver dose (MLD, defined as liver-GTV) constraints; the 30 Gy threshold was the highest achievable. Of 7 eligible LRT plans, 5 with ablative 50 Gy peak doses were analyzed. Associated valley doses were 15 or 20 Gy. Median values of mean GTV and PTV doses for these plans were 36.2 (IQR, 34.6 - 37.8) and 32.9 (IQR, 31.3 - 33.4) Gy, respectively. A median of 12.4% (IQR, 7.4 - 28.4) of the GTV received a dose of 50 Gy. Median doses to 0.5 cc of stomach and duodenum were 16.7 Gy (range, 15.6 - 19.6) and 14.4 Gy (range, 12.3 - 23.9), respectively. The median value for MLD was 13.9 Gy (range, 13.6 to 14.8) and the median volume of normal liver spared 15 Gy was 1114 cm3 (range, 969 to 1154). These hepatic parameters were significantly decreased compared to a standard 30 Gy SBRT plan (18.1 Gy and 611.3 cc spared, p = 0.043 for both) which did not meet constraints. Dose escalation of advanced HCC using LRT is dosimetrically feasible. Though mean target doses remained limited by MLD, LRT allowed delivery of ablative dose to 12.4% of the GTV while meeting critical OAR constraints. Intratumoral dose-escalation may improve local control in advanced HCC patients.

CyberKnife Ultra-Hypofractionated SBRT for Localized Prostate Cancer with Dose Escalation to the Dominant Intraprostatic Lesion: In Silico Planning Study

The aim is to evaluate the feasibility of ultra-hypofractionated (UH) SBRT with CyberKnife® (CK) radiosurgery (Accuray Inc., Sunnyvale, California, USA) for localized prostate cancer (PCa) with a concomitant focal boost to the dominant intraprostatic lesion (DIL). Patients with intermediate/high-risk PCa, with at least one visible DIL on multi-parametric MRI, were included. For each, two CK-SBRT in silico plans were calculated using 95% and 85% isodose lines (CK-95%, CK-85%) and compared with the UH-DWA plan delivered with VERO®. All plans simulated a SIB prescription of 40 Gy to PTV-DIL and 36.25 Gy to the whole prostate (PTV-prostate) in five fractions every other day. Fifteen patients were considered. All plans reached the primary planning goal (D95% &gt; 95%) and compliance with organs at risk (OARs) constraints. DVH metrics median values increased (p &lt; 0.05) from UH-DWA to CK-85%. The conformity index of PTV-DIL was 1.00 for all techniques, while for PTV-prostate was 0.978, 0.984, and 0.991 for UH-DWA, CK-95%, and CK-85%, respectively. The CK-85% plans were able to reach a maximum dose of 47 Gy to the DIL while respecting OARs constraints. CK-SBRT plus a focal boost to the DIL for localized PCa appears to be feasible. These encouraging dosimetric results are to be confirmed in upcoming clinical trials such as the phase-II “PRO-SPEED” IEO trial.

Radiation Treatment Plan Evaluation: An Educational Tool for Radiation Oncology Trainees

Background Resident education in radiation treatment plan evaluation is variable, but it is a critical component of resident education as treatment plans are patient-tailored and customized. Prior studies have reported that over 90% of residents are interested in additional resources, but most report insufficient training. We developed a case-based educational curriculum to increase confidence and competence in plan evaluation by incorporating physics and dosimetry faculty input. We used this pilot study to evaluate feasibility of implementing dedicated treatment plan evaluation teaching sessions at an academic institution. Methods A single institution pilot study with 14 volunteer residents involving pre- and post-plan evaluation teaching session. Three de-identified central nervous system (CNS) cases, including high-grade and low-grade gliomas, were selected that corresponded to the topics of the residents' clinical lectures during the time they were administered. Physics faculty and dosimetrists developed treatment plans that incorporated common problems identified during plan evaluation including inaccurate contours, excessive doses to organs at risk (OARs), suboptimal beam arrangements, and inadequate target volume coverage. An interactive, dosimetry-led teaching session reviewed the cases and tips for requesting plan changes. Residents completed anonymous follow-up surveys regarding the cases and didactic session. Results Seven of 14 (50%) eligible residents completed the three initial case surveys which took on average 11 minutes and 55 seconds to complete (range 8 minutes 39 seconds -13 minutes 50 seconds). Of the participants, most correctly identified the major issues with each case: correctly indicating which plans they would approve and the differences between plans. However, a minority of residents were able to accurately discuss more nuanced details, with only 57% and 42% correctly rejecting inaccurate contours and OAR constraints, respectively; 29% accurately listed the pros and cons of specific beam arrangements; and 14% identified techniques dosimetry could use to improve target coverage. On the follow-up survey, 100% of residents reported that both the cases and the review session improved their confidence and understanding of treatment planning and plan evaluation and stated that they would like to see similar educational material incorporated in residency training in the future. Discussion We describe an effective, multidisciplinary tool to supplement resident education in plan evaluation. This curriculum simulates frequent problems that providers face and provides tools to collaborate with dosimetry and physics to improve treatment plans. Additional follow-up on evaluating and improving confidence and preparedness with plan evaluation in independent practice is warranted. Resident education in radiation treatment plan evaluation is variable, but it is a critical component of resident education as treatment plans are patient-tailored and customized. Prior studies have reported that over 90% of residents are interested in additional resources, but most report insufficient training. We developed a case-based educational curriculum to increase confidence and competence in plan evaluation by incorporating physics and dosimetry faculty input. We used this pilot study to evaluate feasibility of implementing dedicated treatment plan evaluation teaching sessions at an academic institution. A single institution pilot study with 14 volunteer residents involving pre- and post-plan evaluation teaching session. Three de-identified central nervous system (CNS) cases, including high-grade and low-grade gliomas, were selected that corresponded to the topics of the residents' clinical lectures during the time they were administered. Physics faculty and dosimetrists developed treatment plans that incorporated common problems identified during plan evaluation including inaccurate contours, excessive doses to organs at risk (OARs), suboptimal beam arrangements, and inadequate target volume coverage. An interactive, dosimetry-led teaching session reviewed the cases and tips for requesting plan changes. Residents completed anonymous follow-up surveys regarding the cases and didactic session. Seven of 14 (50%) eligible residents completed the three initial case surveys which took on average 11 minutes and 55 seconds to complete (range 8 minutes 39 seconds -13 minutes 50 seconds). Of the participants, most correctly identified the major issues with each case: correctly indicating which plans they would approve and the differences between plans. However, a minority of residents were able to accurately discuss more nuanced details, with only 57% and 42% correctly rejecting inaccurate contours and OAR constraints, respectively; 29% accurately listed the pros and cons of specific beam arrangements; and 14% identified techniques dosimetry could use to improve target coverage. On the follow-up survey, 100% of residents reported that both the cases and the review session improved their confidence and understanding of treatment planning and plan evaluation and stated that they would like to see similar educational material incorporated in residency training in the future. We describe an effective, multidisciplinary tool to supplement resident education in plan evaluation. This curriculum simulates frequent problems that providers face and provides tools to collaborate with dosimetry and physics to improve treatment plans. Additional follow-up on evaluating and improving confidence and preparedness with plan evaluation in independent practice is warranted.

Dares: A phase II trial of durvalumab and ablative radiation in extensive stage small cell lung cancer.

TPS8615 Background: Most patients diagnosed with small cell lung cancer have extensive stage disease (ES-SCLC) at presentation, portending a poor prognosis with median survival rate of 9 - 11 months and a 2-year overall survival (OS) of less than 5%. Checkpoint inhibitors have recently transformed the landscape for first-line treatment for ES-SCLC patients with the CASPIAN and IMpower133 trials demonstrating an OS benefit with the addition of Durvalumab and Atezolizumab to chemotherapy, respectively. Hypofractionated ablative radiation therapy (RT) provides effective local metastasis control. Increasing evidence suggests that apart from its direct effects, ablative RT can trigger the innate and adaptive immune system. Beyond synergistic mechanisms of modulating the immune response, direct tumor debulking by radiation may also be particularly well suited as an adjunct to immunotherapy. Such upfront cytoreduction can relieve tumor-related immunosuppression and prevent early treatment failure at sites of initial involvement. Prior studies have demonstrated OS and PFS benefits to the addition of local therapy in metastatic non-small cell lung cancer. Multi-site ablative RT has also been shown to be safe in the setting of immunotherapy in multiple published prospective trials. We hypothesize that the addition of RT to chemotherapy and Durvalumab for newly diagnosed ES-SCLC patients will improve PFS. Methods: 49 patients will be enrolled across four institutions in this phase II clinical trial. Treatment naive ES-SCLC patients with PS 0-2 who have at least one RECIST measurable lesion meeting criteria for ablative radiation will be eligible for enrollment. Patients with symptomatic brain metastasis will undergo cranial radiotherapy prior to starting on trial. Patients will be treated with four cycles of platinum/etoposide and Durvalumab. During cycle 2, patients will undergo ablative radiation therapy to 1 – 4 sites of extracranial disease. Radiation dose and organ at risk (OAR) constraints are consistent with NRG BR001. During planning, OAR constraints will be prioritized over tumor coverage. Following four cycles of chemotherapy and Durvalumab, patients will continue with maintenance Durvalumab 1500 mg q28 days until progression, toxicity, or study withdrawal. The primary endpoint is PFS. Using a historic control of 5 month median PFS with chemo/immunotherapy from CASPIAN and IMpower133, we hypothesized that the addition of ablative RT would improve the PFS from 5 months to 8 months. sample size of 49 patients was calculated for 80% power with alpha of 0.1. Secondary endpoints include overall survival, time to second line therapy, response rate, and rate of grade 3+ adverse events. Peripheral blood, stool, nasal, and buccal samples will be obtained at baseline, after RT, and at the time of progression and/or immune-related toxicity and will be used for exploratory analysis. NCT05068232. Clinical trial information: NCT05068232 .

ICON-P - A double-blind evaluation of quality improvements with individualized CONstraints from low-cost knowledge-based radiation therapy planning in prostate cancer.

/Objective(S)A low-cost, prior knowledge-based individualized dose-constraint generator for organs-at-risk has been developed for prostate cancer radiation therapy (RT) planning. In this study, we aimed to evaluate the feasibility and improvements in organs-at-risk (OAR) doses in prostate cancer RT planning using this tool served on a web application. A set of previously treated prostate cancer cases planned and treated with generic constraints were replanned using individualized dose constraints derived from a library of cases with similar volumes of target, OAR, and overlap regions and served on the web-based application. The goal was to assess the reduction in mean dose, specified dose volumes (V59Gy, V56Gy, V53Gy, V47Gy, and V40Gy), and generalized equivalent uniform dose (gEUD) to the rectum and bladder. Planners and assessors were blinded to the initial achieved doses and penalties. Sample size estimation was based on improvement in V53Gy for the rectum and bladder with a paired evaluation. Twenty-four patients were replanned. All the plans had a PTV D95 of at least 97% of the prescribed dose. The individualized OAR constraints could be met for 87.5% of patients for all dose levels. The mean dose, V59Gy, V53Gy, and V47Gy for the bladder was reduced by 7.5Gy, 1.12%, 5.51%, and 10.53% respectively. Similarly for the rectum, the mean dose, V59Gy, V53Gy, V47Gy and was reduced by 5.5Gy, 4.34%, 6.97%, and 11.61% respectively. All dose reductions were statistically significant. The gEUD of the bladder was reduced by 2.47Gy (p<0.001) and the rectum by 3.21Gy (p<0.001). Treatment planning based on individualized dose constraints served on a web application is feasible and leads to improvement at clinically important dose volumes in prostate cancer RT planning. This application can be served publicly for improvements in RT plan quality.