Dosimetry Planning Research Articles

VMAT-Based Planning Allows Sparing of a Spatial Dose Pattern Associated with Radiation Pneumonitis in Patients Treated with Radiotherapy for a Locally Advanced Lung Cancer.

Simple SummaryA sub-region localized in the posterior right lung was significantly associated with the risk of grade ≥ 2 acute pulmonary toxicity in patients with locally advanced lung cancer treated with radiotherapy. Avoiding this sub-region with volumetric-arctherapy-based planification leads to a significant reduction of the predicted APT risk by reclassifying 43.2% (19/44) of the patients.Introduction: In patients treated with radiotherapy for locally advanced lung cancer, respect for dose constraints to organs at risk (OAR) insufficiently protects patients from acute pulmonary toxicity (APT), such toxicities being associated with a potential impact on the treatment’s completion and the patient’s quality of life. Dosimetric planning does not take into account regional lung functionality. An APT prediction model combining usual dosimetry features with the mean dose (DMeanPmap) received by a voxel-based volume (Pmap) localized in the posterior right lung has been previously developed. A DMeanPmap of ≥30.3 Gy or a predicted APT probability (ProbAPT) of ≥8% were associated with a higher risk of APT. In the present study, the authors aim to demonstrate the possibility of decreasing the DMeanPmap via a volumetric arctherapy (VMAT)-based adapted planning and evaluate the impact on the risk of APT. Methods: Among the 207 patients included in the initial study, only patients who presented with APT of ≥grade 2 and with a probability of APT ≥ 8% based on the prediction model were included. Dosimetry planning was optimized with a new constraint (DMeanPmap < 30.3 Gy) added to the usual constraints. The initial and optimized treatment plans were compared using the t-test for the independent variables and the non-parametric Mann–Whitney U test otherwise, regarding both doses to the OARs and PTV (Planning Target Volume) coverage. Conformity and heterogeneity indexes were also compared. The risk of APT was recalculated using the new dosimetric features and the APT prediction model. Results: Dosimetric optimization was considered successful for 27 out of the 44 included patients (61.4%), meaning the dosimetric constraint on the Pmap region was achieved without compromising the PTV coverage (p = 0.61). The optimization significantly decreased the median DMeanPmap from 28.8 Gy (CI95% 24.2–33.4) to 22.1 Gy (CI95% 18.3–26.0). When recomputing the risk of APT using the new dosimetric features, the optimization significantly reduced the risk of APT (p < 0.0001) by reclassifying 43.2% (19/44) of the patients. Conclusion: Our approach appears to be both easily implementable on a daily basis and efficient at reducing the risk of APT. Regional radiosensitivity should be considered in usual lung dose constraints, opening the possibility of new treatment strategies, such as dose escalation or innovative treatment associations.

Abstract 3447: Tumor treating fields (TTFields) treatment planning for a patient with astrocytoma in the spinal cord

Abstract Objectives: The use of TTFields following resection and chemoradiation has increased survival in patients with Glioblastoma (Stupp, et al. JAMA. 2015;314:2535-2543). Randomized data provide a strong rationale for the treatment of high grade gliomas using TTFields with individualized array placement that maximizes the dose at the tumor in a patient-specific manner: providing higher TTFields intensity (≥1.0 V/cm) and power density (≥1.1 mW/cm3) which are associated with improved overall survival (Ballo, et al. Int J Radiat Oncol Biol Phys. 2019;104:1106-11). Here for the first time, we present a case demonstrating the use of numerical simulations for patient-specific TTFields treatment planning for a spinal tumor. Methods: Treatment planning was performed for a 48 year old patient following T10-L1 laminectomy, gross total resection, and postoperative chemoradiation for an anaplastic astrocytoma of the spinal cord. An MRI at 3 weeks following chemoradiation showed tumor recurrence. Based on the post-chemoradiation MRI, a patient-specific model was created. The model was created by modifying a realistic computational phantom of a healthy female. To mimic the laminectomy, the lamina in T10-L1 was removed and the region was assigned an electric conductivity similar to that of muscle. A virtual mass was introduced into the spinal cord. Virtual transducer arrays were placed on the model at multiple positions, and delivery of TTFields simulated. The dose delivered by different transducer array layouts was calculated, and the layouts that yielded maximal dose to the tumor and spine identified. Results: Combinations of the best layouts targeting the tumor (all above 2.5 mW/cm3) and the best layouts targeting the spinal cord were investigated. Transducer array layouts where the arrays were placed on the back of the patient with one above the tumor and one below yielded the highest doses at the tumor site. Such layouts yielded TTFields doses of over 2.5mW/cm3, which is well above the threshold dose of 1.1 mW/cm3. Three such layouts were presented as possibilities for a recommended treatment plan. As patient usage, or time on treatment, is correlated with improved patient outcomes, an interactive process was followed to adjust the treatment so that it incorporates both increased therapeutic dose to the tumor and increased overall patient usage and comfort. Conclusions: These data represent the first ever study on utilizing numerical simulations to plan treatment for a spinal tumor in a patient-specific manner. This is an important milestone in the development of a framework for TTFields dosimetry and treatment planning. This framework will have the potential to increase dose delivery to the tumor bed while optimizing placement that may enhance comfort and encourage device usage. Citation Format: Jennifer De Los Santos, Smadar Arvatz, Oshrit Zeevi, Shay Levi, Noa Urman, Melissa Shackelford, Ariel Naveh, Tal Marciano. Tumor treating fields (TTFields) treatment planning for a patient with astrocytoma in the spinal cord [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3447.

Comparison of plan dosimetry on multi-targeted lung radiotherapy: A phantom-based computational study using IMRT and VMAT

This work analyzed the dosimetric difference between the intensity modulated radiotherapy (IMRT), partial/single/double-arc volumetric modulated arc therapy (PA/SA/DA-VMAT) techniques in treatment planning for treating more than one target of lung cancer at different isocenters. IMRT and VMAT plans at different isocenters were created systematically using a Harold heterogeneous lung phantom. The conformity index (CI), homogeneity index (HI), gradient index (GI), dose-volume histogram and mean and maximum dose of the PTV were calculated and analyzed. Furthermore, the dose-volume histogram and mean and maximum doses of the OARs such as right lung, contralateral lung and non GTV were determined from the plans. The IMRT plans showed the superior target dose coverage, higher mean and maximum values than other VMAT techniques. PA-VMAT technique shows more lung sparing and DA-VMAT increases the V5/10/20 values of contralateral lung than other VMAT and IMRT techniques. The IMRT technique achieves highly conformal dose distribution to the target than other VMAT techniques. Comparing to the IMRT plans, the higher V5/10/20 and mean lung dose were observed in the contralateral lung in the DA-VMAT.

Quantifying the Geometric and Dosimetric Impact of Inter-Observer Variability for Radiation Oncologists and Radiation Therapists When Contouring the Organs at Risk Within the Upper Abdomen

Purpose: Radiation therapy for liver cancer is the only viable treatment option for many patients with unresectable disease, and it requires a sophisticated, high precision approach to avoid serious detrimental impact on patient outcomes. Manual structure delineation is considered the major source of residual error in high precision radiotherapy process, but very little is known about this phenomenon for structures in the abdomen. Therefore, the purpose of this research was to quantify the geometric and dosimetric impact of inter-observer variability for Radiation Oncologists (ROs) and Radiation Therapists (RTs) when contouring the organs at risk within the upper abdomen on CT and MRI. Methods: This was a single centre, prospective study. 3 liver cancer test cases with standard CT and MR images were anonymized. Eligible volunteers participated in contouring 6 abdominal organs on CT and MR. The RTs received a simple online education session, then were asked to recontour the test case images. The clinical plan was then recalculated on the study contours to generate dose-volume histograms for the OARs. Volume, Dice Similarity Coefficient, Distance to Agreement and dose variation at critical OAR volumes were used to quantify the variation in the contours. Results: 5 ROs and 8 RTs participated in this research, generating 900 study contours and 75 dose-volume histograms. The magnitude of inter-observer variation in delineated volume varied substantially by organ, in some cases resulting in a 1.6 fold difference between the smallest and largest volumes. DTA of observer-related variation demonstrated differences between the largest and smallest surfaces of <7 mm for stomach and liver, but >20 mm for small bowel. Overall, dose differences between the observers were ∼420 cGy across all organs. Duodenum and small bowel were associated with the largest variation, whereas stomach and esophagus saw the smallest dosimetric variation. MR resulted in significantly larger stomach volumes compared to CT, whereas the small bowel was significantly larger on CT. There were no other significant differences in organ volume between CT and MR. After education, RT volumes were not significantly different from RO volumes for all OARs and both modalities. Conclusion: This study determined that the geometric magnitude of inter-observer delineation variability can be large, and vary by organ size and irregularity. Those delineation differences can have a substantial dosimetric impact that may be moderated by proximity to the target and the orientation of the plan dosimetry. MR did not uniformly reduce the delineation variability for the OARs, but this may have been due to limitations in the MR acquisition parameters. The simple education session was only minimally effective at reducing delineation variability for RTs with a high level of pre-existing expertise. Our study suggests that with appropriate experience and some training, RTs can delineate structures within the abdomen with an accuracy and precision comparable to ROs. As radiation therapy expands into the online adaptive realm, RTs can fully participate in these new processes, providing improved access to high quality precision treatment delivery, ensuring that every patient get the best possible care during their radiotherapy journey.

SMART ablation of lymphatic oligometastases in the pelvis and abdomen: Clinical and dosimetry outcomes

PurposeTo demonstrate dosimetry benefits and report clinical outcomes of stereotactic magnetic resonance (MR)-guided online adaptive radiotherapy (SMART) of abdominopelvic lymphatic oligometastases. Patients & MethodsProspective registry data of 26 patients with 31 oligoprogressive lymphatic metastases (1–2 lesions) who received SMART between April 2020 and April 2021 was analyzed. Prostate cancer was the most common histology (69%). Most patients (63%) had received previous abdominopelvic radiotherapy (RT). SMART was delivered in 3–7 fractions based on planning target volume (PTV) location and previous dose exposures. For SMART, the baseline plan was recalculated on daily 3D MR-imaging (predicted plan), and plan adaptation was mandatory in case of planning objective violations. ResultsPlan adaptation was mostly performed due to violation of planning objectives in the predicted plan (134/140 fractions, 96%) and significantly improved plan dosimetry: (1) PTV coverage was increased (predicted: median 89%, adapted: median 95%, p < 0.001), (2) organs-at-risk (OAR) overdoses were reduced (predicted: 27/140 (19%), adapted: 1/140 (1%), p < 0.001) and (3) PTV overdoses were reduced (predicted: 21/140 (15%), adapted: 1/140 (1%), p < 0.001). After a median follow-up of 9.8 months, one patient had in-field tumor progression and twelve patients had out-field tumor progression (at 6 months: progression-free survival: 63% [46–88%], local control rate: 97% [90–100%]). Treatment was tolerated well and no grade ≥3 toxicity was reported. ConclusionSMART improves target volume coverage and yields superior OAR protection compared to non-adaptive radiotherapy, thus representing an innovative approach to challenging cases, such as repeated radiotherapy.

An image-based notion for therapeuticplanar organ activity dosimetry in a developing country: Masterdose software.

Planar dosimetry is often performed in developing countries due to its simplicity during basic quantitative dosimetry. The geometric mean method is often used during planar dosimetry and imaging counts can be corrected for background, attenuation and scatter. The aim of our study was to develop computerized software called Masterdose that may be used for therapeutic isotope planar organ personalized dosimetry. Masterdose software uses various methods to correct for background, scatter and attenuation.We also introduced a method to convert imaging counts to activity on the software,which is Java based and runs on Windows, Linux and Macintosh platforms. Three user interfaces named image processing, quantification and dosimetry were developed for the software. Masterdose could quantify kidney and liver doses of lutetium-177-DOTA-0-Tyr3-octreotate (177Lu-DOTATATE) patients. The software was validated throughcalculation of the kidney and liver doses of ten neuroendocrine tumour patients (NET) treated with 177Lu-DOTATATE. Masterdose presents an option for planar quantification that can be used as a quality control tool to verify imaging counts and perform dosimetry in particular organs.

Normal Tissue Complication Probability Modelling for Toxicity Prediction and Patient Selection in Proton Beam Therapy to the Central Nervous System: A Literature Review

Normal tissue complication probability (NTCP) models can guide clinical decision making in radiotherapy. In recent years, they have been used for patient selection for proton beam therapy (PBT) for some anatomical tumour sites. This review synthesizes the published evidence regarding the use of NTCP models to predict the toxicity of PBT, for different end points in patients with brain tumours. A search of Medline and Embase using the Patients, Intervention, Comparison, Outcome (PICO) criteria was undertaken. In total, 37 articles were deemed relevant and were reviewed in detail. Nineteen articles on NTCP modelling of toxicity end points were included. Of these, 11 were comparative NTCP studies of PBT versus conventional photon radiotherapy (XRT), which evaluated differences in plan dosimetry and then assumed that XRT-derived literature estimates of NTCP would be applicable to both. Seven papers derived NTCP models based on PBT outcome data, two of which provided model parameters. Among analysed end points, the reduced risk of secondary tumours with PBT as compared with XRT is estimated – through modelling studies – to be considerable and was highlighted by most authors. For other analysed end points, the clinical benefit of PBT mainly depends on tumour location in relation to organs at risk as well as prescription doses. NTCP models can be useful tools for treatment plan comparison. However, most published toxicity data were derived from XRT cohorts; this review has highlighted the need for further studies relating dose-volume parameters to observed toxicity in PBT-treated patients. Specifically, there is a need for PBT-specific NTCP models that can be implemented in the clinical practice. NTCP models built on robust clinical data for the most common radiotherapy toxicities in the brain would potentially redefine the current indications for PBT.

Оптимизация проведения сочетанного курса лучевой терапии у больных раком прямой кишки

Due to the new rapidly developed technological equipment for radiotherapy available in cancer clinics, the study of the optimal combination of topometric preparation of a patient with planning and the delivery of treatment in order to achieve the main goal of radiation therapy – maximum exposure of the foci with minimal damage to healthy tissue. The reduction of dose to critical or-gans and healthy tissues in general is an important and urgent task. The purpose of the paper is to explore the possibility of optimization of the combined radiation therapy in patients with rectal cancer, with account of advanced approaches to topometric preparation of a patient and dosime-try planning. Six patients 47-59 years of age, with the stage III of the lower ampullary rectal can-cer, received two-phase pre-operative combined radiotherapy at the Tomsk Cancer Research In-stitute NMRC. The Phase 1 – distant radiation therapy delivery in standard mode with a single fo-cal dose (ROD) of 2 Gy, 5 times a week, totally 20 fractions, to focal dose (SOD) of 40 Gy. The Phase 2 – intracavitary radiation therapy, ROD – 3 Gy, SOD – 15 Gy, locally in the tumor area, 2 times a week, total number – 5 fractions. The conventional radiation therapy planning was carried out with the use of the XiO 3-D dosimetry planning system for the "Theratron Equinox 80" (radia-tion of the isotope Co-60, Egamma=1.25 MeV), gamma-therapeutic apparatus, and for the SL75-5-MT (Electron braking radiation, E=6 MeV) linear accelerator. For conformal radial therapy the plan-ning system for linear accelerator «Elekta Synergy» (electron brake radiation, E=6 MeV) is used. For intracavitary radiotherapy the dosimetry planning system HDRPlus for the apparatus "Multi-Source" (radiation of isotope Co-60, Egamma=1.25 MeV) is used. Radiation doses to critical organs of pa-tients with lower ampullary rectal cancer exposed to combined course of radiotherapy was calculated. It has been shown that the use of advanced techniques for pretreatment topometric preparation of a patient and dosimetry planning makes possible optimization of combined radiotherapy with account of radiation doses to critical organs.

Performance of a knowledge-based planning model for optimizing intensity-modulated radiotherapy plans for partial breast irradiation.

PurposeTo evaluate a knowledge‐based (KB) planning model for RapidPlan, generated using a five‐field intensity‐modulated radiotherapy (IMRT) class solution beam strategy and rigorous dosimetric constraints for accelerated partial breast irradiation (APBI).Materials and methodsThe RapidPlan model was configured using 64 APBI treatment plans and validated for 120 APBI patients who were not included in the training dataset. KB plan dosimetry was compared to clinical plan dosimetry, the clinical planning constraints, and the constraints used in phase III APBI trials. Dosimetric differences between clinical and KB plans were evaluated using paired two‐tailed Wilcoxon signed‐rank tests.ResultsKB planning was able to produce IMRT‐based APBI plans in a single optimization without manual intervention that are comparable or better than the conventionally optimized, clinical plans. Comparing KB plans to clinical plans, differences in PTV, heart, contralateral breast, and ipsilateral lung dose–volume metrics were not clinically significant. The ipsilateral breast volume receiving at least 50% of the prescription dose was statistically and clinically significantly lower in the KB plans.ConclusionKB planning for IMRT‐based APBI provides equivalent or better dosimetry compared to conventional inverse planning. This model may be reliably applied in clinical practice and could be used to transfer planning expertise to ensure consistency in APBI plan quality.

Abstract IACC0601: Radiopharmaceuticals and their future in cancer care

Abstract Radiopharmaceutical agents have been an appealing treatment approach since the use of 131I to treat thyroid malignancies. Advances in cancer radiobiology and radiochemistry have brought radiopharmaceuticals forward to the cutting edge of oncology clinical research. The National Cancer Institute (NCI) and its partnering academic and clinical research networks monitor radiopharmaceutical discoveries that might be incorporated into cancer treatment strategies for patients with unmet therapeutic needs. Such endeavors happen through leveraged partnerships between NCI's Cancer Therapy Evaluation Program (CTEP), its Radiation Research Program (RRP), and academic institutions in the Experimental Therapeutics Clinical Trials Network (ETCTN). If innovative discoveries are made, NCI supports clinician scientists to plan new and original radiopharmaceutical phase I and II monotherapy or combination trials. The clinical trial infrastructure needs, such as radiopharmaceutical dosimetry and treatment planning, are now available in government workflow and regulatory oversight. This presentation introduces a modern approach to the clinical development of radiopharmaceutical agents in an era of molecular targets and personalized cancer therapeutics. Citation Format: Charles A. Kunos. Radiopharmaceuticals and their future in cancer care [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr IACC0601.

Relationship between Treatment Plan Dosimetry, Toxicity, and Survival following Intensity-Modulated Radiotherapy, with or without Chemotherapy, for Stage III Inoperable Non-Small Cell Lung Cancer.

Simple SummaryVarious radiotherapy treatment methods are available for patients with stage III non-small-cell lung cancer (NSCLC). A multidisciplinary tumor board review is recommended to determine the best treatment strategy. In fit patients with inoperable tumors, concurrent chemoradiotherapy (cCRT) is preferred over sequential CRT (sCRT), due to better survival. Nonetheless, the use of cCRT in stage III NSCLC varies significantly, with concerns about treatment toxicity being a contributory factor. Many reports describing the relationship between overall survival, toxicity, and dosimetry in patients with locally advanced NSCLC are based on clinical trials, with strict criteria for patient selection, including good performance status, pulmonary function, etc. These trials have not always mandated the use of IMRT/VMAT. We therefore performed an institutional analysis to study the relationship between dosimetric parameters and overall survival and toxicity in patients with stage III NSCLC treated with IMRT/VMAT-based techniques in routine clinical practice.Concurrent chemoradiotherapy (cCRT) is the preferred treatment for stage III NSCLC because surgery containing multimodality treatment is often not appropriate. Alternatives, often for less fit patients, include sequential CRT and RT alone. Many reports describing the relationship between overall survival (OS), toxicity, and dosimetry are based on clinical trials, with strict criteria for patient selection. We performed an institutional analysis to study the relationship between dosimetric parameters, toxicity, and OS in inoperable patients with stage III NSCLC treated with (hybrid) IMRT/VMAT-based techniques in routine clinical practice. Eligible patients had undergone treatment with radical intent using cCRT, sCRT, or RT alone, planned to a total dose ≥ 50 Gy delivered in ≥15 fractions. All analyses were performed for two patient groups, (1) cCRT (n = 64) and (2) sCRT/RT (n = 65). The toxicity rate differences between the two groups were not significant, and OS was 29 and 17 months, respectively. For sCRT/RT, no dosimetric factors were associated with OS, whereas for cCRT, PTV-volume, esophagus V50 Gy, and contralateral lung V5 Gy were associated. cCRT OS was significantly lower in patients with esophagitis ≥ G2. The overall rate of ≥G3 pneumonitis was low (3%), and the rate of high-grade esophagitis the OS in this real-world patient population was comparable to those reported in clinical trials. Based on this hypothesis-generating data, more aggressive esophageal sparing merits consideration. Institutional auditing and benchmarking of the planning strategy, dosimetry, and outcome have an important role to play in the continuous quality improvement process.

Clinical and Dosimetric Outcomes of MR Guided Prostate SBRT With Daily Online Plan Adaptation

Stereotactic body radiotherapy (SBRT) is increasingly being utilized in the management of localized prostate cancer. MR guided adaptive radiotherapy may be a valuable tool for delivery of prostate SBRT as it allows for MR based soft tissue contouring, real time MR motion management and daily plan adaptation to account for interfraction anatomic variability. The goal of the present study is to identify dosimetric gains that can be achieved with an MR guided adaptive prostate SBRT platform and describe acute clinical outcomes.We reviewed our institutional experience treating patients with prostate cancer with MR guided adaptive SBRT to a dose of 36.25 Gy in 5 fractions. The adaptive workflow involves development of an "original" plan which is re-optimized daily based on anatomical variation for each fraction. "Predicted" plan dosimetry is generated for each fraction by re-calculating the original plan on the re-contoured daily anatomy, estimating what would have been delivered without adaptive capabilities. A "re-optimized" plan is developed based on the anatomy of the day to improve target coverage and organ-at-risk (OAR) metrics. Wilcoxon rank sum testing was used to compare predicted dosimetry to re-optimized dosimetry. Acute urinary and GI toxicity rates were assessed according to CTCAE v5.A cohort of 16 patients treated was analyzed with median follow up time of 3 months. Acute G2+ GU toxicity was observed in 19% and acute G2+ GI toxicity in 6%. No G3+ events were noted. Comparison of dosimetry metrics for PTV coverage, urethra, rectum and bladder are shown in table 1; 100% of fractions required plan adaptation due to either exceeding OAR metrics (68%) or sub-optimal PTV coverage (33%). Adaptive planning increased the proportion of fractions meeting prescription metrics for PTV coverage (V34.44 from 71% to 100%), urethra (V38.78 from 58% to 100%) and rectum (V38.06 from 80% to 100%). Urethral metrics were most frequently violated in predicted plans (42% of fractions) and re-optimized to acceptable dosimetry in 100% of fractions. Re-optimization significantly improved PTV coverage, rectal metrics and urethral metrics.Online adaptive re-optimization significantly improved plan dosimetry and achieved minimal acute toxicity. The clinical benefits of MR guided adaptive prostate SBRT for optimizing target coverage with urethral protection warrant further investigation.

Impact of Stereotactic MR-Guided Adaptive Radiation Therapy on Early Clinical and Dosimetric Outcomes in Patients With Pancreatic Cancer

Dose escalated stereotactic body radiotherapy (SBRT) may improve both local control and overall survival for patients with pancreatic cancer. However, escalated dose cannot be routinely offered because of the risk of injury to adjacent normal organs. Stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) represents an innovation that may achieve safer delivery of ablative doses and improve outcomes. The goal of the present study is to identify specific dosimetric gains that can be achieved with MR-guided adaptive pancreatic SBRT and describe acute clinical outcomes.We performed a single institution IRB approved retrospective analysis of 37 consecutive pancreatic cancer patients treated with 40 Gy in 5 fractions with SMART on a MR-linear accelerator using a light inspiration breath hold. The adaptive workflow starts with an "original" plan which is then adapted daily based on anatomical variation for each fraction. "Predicted" plan dosimetry is generated for each fraction by re-calculating the original plan on the re-contoured pre-treatment anatomy, estimating what would have been delivered without adaptive capabilities. A "re-optimized" plan is developed based on the anatomy of the day to improve target coverage and meet critical organ-at-risk (OAR) metrics, including stomach, duodenum, large bowel and small bowel V33 < 1cc. Acute GI toxicity rates were assessed according to CTCAE v5.The median age of our cohort was 71 (range 35-87) with 23/37 (62%) patients having locally advanced disease and 14/37 (38%) having borderline resectable disease. Adaptive planning was used in all cases with a prescription goal of 40 Gy in 5 fractions prescribed to 90% of the target volume. The median CTV was 80.5 cc (range, 10-180cc) and the PTV was a 3mm expansion. Adaptive planning was required in 156/185 fractions to meet either the stomach (63.8%), duodenum (33.5%), large bowel (12.4%) or small bowel (11.4%) V33 < 1cc metric. Of the plans adapted for OAR sparing, 90 plans required adaptation for one gastrointestinal organ, 50 plans for two, 10 plans for three and 1 plan for four. For predicted plans exceeding the V33 < 1cc metric, the median V33 for duodenum was 2.475cc (range: 1.01-10.68cc), stomach was 2.67cc (range: 1.01-8.21cc), small bowel was 2.71cc (range: 1.14-9.54cc) and large bowel was 1.93cc (range: 1.05-8.36cc). All re-optimized plans met the V33 < 1cc metric. No local failure or acute grade 3 toxicities were observed with a median follow-up of 6 months (range 3-15).Online adaptive re-optimization was necessary for the majority of fractions and improved plan dosimetry was achieved specifically for duodenum, stomach, large and small bowel, achieving low rates of acute toxicity. The clinical benefits of MR-guided adaptive pancreatic SBRT for dose escalation warrant further investigation.

Dosimetric Predictors of Toxicity and Quality of Life Following Single Fraction High Dose-Rate Prostate Brachytherapy

<h3>Purpose/Objective(s)</h3> Little is known about optimal dose constraints when high dose rate (HDR) brachytherapy is used as monotherapy for prostate cancer. Most dose constraints for HDR monotherapy were extrapolated from predictors of toxicity when HDR brachytherapy was combined with external beam radiotherapy as a boost. We sought to determine clinical and dosimetric predictors of toxicity and health related quality of life (HRQOL) in men treated with HDR brachytherapy as monotherapy. <h3>Materials/Methods</h3> Eligible patients were treated with single fraction HDR brachytherapy as monotherapy on two prospective clinical trials at a single institution. Patients in the first trial (HDR-mono) received a single fraction of 19 Gy without a dominant intraprostatic lesion (DIL) boost, and patients from the second trial (MARS) received 19 Gy in a single fraction with an MRI-guided DIL boost to ≥ 23 Gy. ADT was not used. Univariable and multivariable logistic regression was used to evaluate clinical (age, IPSS score, prostate volume, alpha blocker use at baseline, and receipt of a DIL boost) and dosimetric (prostate V100, V150, V200, D90, Urethral Dmax and D10, and Rectal Dmax and V80) predictors of CTCAE v4 acute/late toxicity and HRQOL changes measured with expanded prostate index composite (EPIC). Three classifications of late minimally clinically important changes (MCICs) were evaluated: small (> 0.5 standard deviation [SD]), moderate (> 1.0 SD) and severe (> 2.0 SD) declines compared to baseline. <h3>Results</h3> 147 patients were included (87 from HDR-mono, 60 from MARS). Median follow-up was 62.8 months. Only increasing prostate size predicted acute GU toxicity ≥ grade 2 (OR 1.05, 95% CI 1.01–1.09, <i>P</i> = 0.021). On multivariable regression, predictors of late GU toxicity ≥ grade 2 were not receiving a DIL boost (OR 3.78, 95% CI 1.88–7.83, <i>P</i> < 0.001) and higher baseline IPSS score (OR 1.89, 95% CI 1.89–3.18, <i>P</i> = 0.015). Rectal and urethral dose constraints were not associated with late GU/GI toxicity ≥ grade 2. Contrary to our hypothesis, small (OR 0.91, 95% CI 0.81–0.98, <i>P</i> = 0.032) and moderate (OR 0.91, 95% CI 0.80–0.98, <i>P</i> = 0.037) urinary MCICs were less frequent in those with higher urethral Dmax. No impact of urethra D10 on urinary MCICs was seen. Rectal Dmax and V80 did not predict bowel MCIC changes at any threshold. <h3>Conclusion</h3> We were unable to identify dose constraints that were predictive of late toxicity or relevant HRQOL changes in single fraction HDR brachytherapy. This suggests dose parameters used in these trials were safe, and that minor variability in plan dosimetry likely has little clinical significance. While increasing urethral Dmax paradoxically predicted for less frequent urinary MCICs, we do not believe this finding is clinically relevant. Further research exploring optimal dose constraints to be used in HDR brachytherapy as monotherapy for prostate cancer is warranted.

Reduction of Intra-Dosimetrist Variation, and Improvement of Overall Plan Quality as Assessed by Dose-Volume Histograms, Through Training and Implementation of Advanced Optimization Tools

Our Cancer Center network comprises a research Cancer Center as well as 10 independent community practices, with 18 total Dosimetrists. Many steps have been taken to increase treatment planning standardization, while dosimetry techniques and practices across the system have remained independent, with limited use of advanced optimization tools, knowledge-based planning (KBP) and multi-criteria optimization (MCO). With the objective to improve standardization of techniques, identify best practices, and improve overall quality, we implemented an in-house dosimetry plan challenge and solicited participation from 18 dosimetrists within the network.We anonymized an existing intermediate risk prostate adenocarcinoma clinical T1c N0 M0 patient dataset with physician drawn target contours (prostate plus proximal 1cm seminal vesicles) and normal structures, to create an identical test case for each dosimetrist. Clinically relevant planning objectives were provided in addition to instructions to produce a plan of clinical quality, committing typical clinical time/effort, using only standard optimization tools. Following submission of all plans, the results were discussed with the dosimetry team, including evaluations of dose-volume histograms (DVH). Instruction was provided on the advanced optimization tools KBP and MCO. Dosimetrists were instructed to repeat the challenge with the explicit instruction to use KBP and MCO. KBP/MCO plan results were compared to the plan results without KBP/MCO use to show the overall impact of advanced tools on achieved plan quality and intra-dosimetrist variation. All plans were explicitly normalized to the PTV D100% = 95% to allow direct comparison of DVHs.All initial plans submitted by 16 dosimetrists met the prescribed objectives outlined for clinical practice. However, plans demonstrated a wide range of acceptable dose-volume histograms. In addition to visual evaluation of the DVHs, multiple dose points for the Target (PTV), Rectum and Bladder, were exported for comparison between groups of plans. The group average achieved bladder doses were reduced from 52.8%Rx to 41.9%Rx, 23.9%Rx to 15.5%Rx, and 6.3%Rx to 5.5%Rx at D15%, D30%, and D60% respectively. The group average achieved rectal doses were reduced from 62.3%Rx to 45.8%Rx, 49.3%Rx to 32.7%Rx, and 33.9%Rx to 19.9%Rx at D10%, D20%, and D40% respectively. Similarly, the standard deviations also showed marked decrease with those for the bladder reduced from 0.084 to 0.044, 0.067 to 0.02, and 0.014 to 0.010 for D15%, D30%, and D60% respectively, and those for rectum reduced from 0.106 to 0.0690, 0.109 to 0.066, 0.086 to 0.038 at D10%, D20%, and D40% respectively.Standardization of clinical treatment planning objectives and consistent use of advanced optimization tools can improve overall planning quality and reduce intra-dosimetrist variation of treatment planning results based on clinical DVH metrics.

Skin Dose Distributions from Total Skin Electron Irradiation Therapy (TSET)

Skin Dose Distributions from Total Skin Electron Irradiation Therapy (TSET)

Multivariate Model for Predicting Overall Survival in Malignant Pleural Mesothelioma After Adjuvant Radiotherapy

<h3>Purpose/Objective(s)</h3> Malignant pleural mesothelioma (MPM) is a rare but aggressive cancer arising from the cells of the thoracic pleura. Its anatomic complexity, large surface area, and unique location pose challenges for target coverage while sparing adjacent organs at risk (OARs) during treatment planning for adjuvant radiotherapy after pleurectomy and decortication. We aimed to investigate the associations between patient/target characteristics and achievable dosimetric plan quality with overall survival. <h3>Materials/Methods</h3> Sixty patients with MPM patients who were treated on a tomotherapy unit between 2013-2018 at a single institution were included. All patients received helical IMRT with 45 Gy/25 fractions. Dosimetric quantities for the lungs, heart, and liver were systematically examined for 37 right-sided (RSM) and 23 left-sided mesothelioma (LSM) patients. Patient characteristics and/or planning dosimetric metrics were input into machine learning algorithms, e.g., LASSO regression, support vector machine (SVM), and multiple layer perceptron (MLP), in order to construct predictive models for overall survival. The performance of predictive models was evaluated with area under the curve (AUC) using 3-fold cross validation. Normal tissue complication probabilities (NTCP) for selected OARs were estimated using the Lyman-Kutcher-Burman model based on individual dose volume histograms. <h3>Results</h3> The achieved dosimetric endpoints were significantly different (<b>P</b> < 0.05) between LSM vs. RSM patients, respectively: ipsilateral lung V20_Gy of 91.2 ± 6.7 vs. 85.3 ± 6.5%, ipsilateral mean lung doses of 39.1 ± 3.8 vs. 36.9 ± 2.5 Gy, heart mean doses of 25.2 ± 3.6 vs. 18.8 ± 3.7 Gy, and liver mean doses of 10.6 ± 2.7 vs. 23.4 ± 4.2 Gy. There was no significant difference in total lung – planning target volume (PTV) mean dose, 13.4 ± 2.0 vs. 14.4 ± 1.5 Gy, nor expected lung pneumonitis for the LSM vs. RSM. No differences were observed between PTV coverage of 94.2 ± 1.2 vs. 93.4 ± 2.4%, and average survival intervals were 16.8 ± 14.4 months and 18.0 ± 18.0 months after RT between LSM vs. RSM. The MLP model achieved AUCs of 0.65, 0.67 and 0.71 using patient characteristics, dosimetric features, and combined features. The identified predictors most associated with overall survival were age, PTV volume, ipsilateral lung volume/V20_Gy, and ipsilateral lung – PTV V20_Gy <h3>Conclusion</h3> We demonstrated correlations between patient specific characteristics and achieved planning dosimetric parameters for left- and right-sided MPM treatment planning endpoints. Combining patient characteristics and dosimetric endpoints, the multivariate predictive model achieved decent performance in predicting overall survival. The predictive model may guide treatment planning to achieve optimal planning dosimetry, and to improve clinical outcome via personalized treatment for MPM.

Interfractional Geometric Variations and Dosimetric Benefits of Online Adaptive Stereotactic Body Radiotherapy of Prostate Bed After Radical Prostatectomy

To evaluate volumetric and shape variations of target and organs-at-risk (OAR) of prostate patients receiving stereotactic body radiotherapy (SBRT) after radical prostatectomy and to investigate potential dosimetric benefits of MRI guided online adaptive planning (MRgART) to compensate for these variations.CTV and OAR were contoured by a single physician on the setup MRI images of 11 patients treated with an MR-Linac and enrolled on a phase II trial of post-prostatectomy SBRT. All patients followed institutional bladder and rectum filling protocols and received 5 fractions of 6-6.8 Gy to the prostate bed. Changes in interfractional volume were calculated and shape deformation was quantified by the Dice similar index (DSC). Dosimetric changes in CTV V95%, bladder maximum dose, V32.5 Gy, and rectal maximum dose, V32.5Gy and V27.5Gy were predicated by recalculating the initial treatment plan on the daily MRI. MRgART was retrospectively simulated if the predicted dose exceeds pre-set dosimetric criteria and the potential dosimetric improvement of MRgART was evaluated.Interfractional CTV volume and shape remained stable with median volumetric change of 3.0% (IQR -3.0% to 11.5%) and median DSC of 0.83 (IQR 0.79 to 0.88). Relatively large volumetric changes in bladder (median -24.5%, IQR -34.8% to 14.5%) and rectum (median 5.5%, IQR -9.7% to 20.7%) were observed while shape changes were moderate (median DSC of 0.79 and 0.67, respectively). Median CTV V95% was 98.4% (IQR 94.9% to 99.6%) for the predicted doses. However, MRgART would have been deemed necessary for 78% of the 55 fractions based on CTV undercoverage (16%), exceeding OAR constraints (50%), or both (11%). Simulated online ART improved the plan dosimetry and met dosimetric criteria in all adaptive fractions. Moderate correlations between CTV V95% and target DSC (R-squared = 0.73) and bladder mean dose versus bladder volumetric changes (R-squared = 0.61) were observed.Interfractional dosimetric variations resulting from target and OAR deformation are commonly encountered with post-prostatectomy RT and can be mitigated with MRgART.

Development and prospective validation of a spatial dose pattern based model predicting acute pulmonary toxicity in patients treated with volumetric arc-therapy for locally advanced lung cancer

Introduction(Chemo)-radiotherapy is the standard treatment for patients with locally advanced lung cancer (LALC) not accessible to surgery. Despite strict application of dose constraints, acute toxicities such as acute pulmonary toxicity (APT) remain frequent, and may impact treatment’s compliance and patients’ quality of life. Previously, on a population treated with intensity-modulated photon therapy or passive scattering proton therapy, spatial dose patterns associated with APT were identified in the lower lungs, especially in the posterior right lung. In the present study, we aim to define these spatial dose patterns on a retrospective cohort treated by volumetric-arctherapy (VMAT) and to validate our findings prospectively. MethodsFor the training cohort, we retrospectively included all patients treated in our institution by VMAT for a LALC between 2015 and 2018. APT was scored according to the CTCAE v4.0 scale. All dose maps were registered to a thorax phantom using a segmentation-based elastic registration. Voxel-based analysis of local dose differences was performed with a non-parametric permutation test accounting for n = 10.000 permutations, producing a 3-dimensional significance maps on which clusters of voxels that exhibited significant dose differences (p < 0.05) between the two toxicity groups (APT ≥ grade 2 vs APT < grade 2) were identified. A prediction model (Pmap-Model) was then built using a neural network approach and then applied to an observational prospective cohort for validation. The model was evaluated using the Area under the curve (AUC) and the balanced accuracy (Bacc: mean of the sensitivity and specificity). Results165 and 42 patients were included in the training and validation cohorts, with respective APT rates of 22.4% and 19.1%. In the training cohort, a cluster of voxels (Pmap-region) was identified in the posterior right lung. In the training cohort, the Pmap-Model combining 11 features among which the mean dose to the Pmap-region resulted in an AUC of 0.99 and a Bacc of 99.2 using an 8% probability threshold. Using the same voxel cluster on the validation cohort, the Pmap-model resulted in an AUC of 0.81 and a Bacc of 82.0. ConclusionOur APT-prediction model was successfully validated in a prospective cohort treated by VMAT. Regional radiosensitivity should be considered in usual lung dose constraints, opening the possibility of easily implementable adaptive dosimetry planning.

Proton Therapy and Gliomas: A Systematic Review

Background: Gliomas are primary cerebral tumors. Radiation therapy plays a key role in their treatment but with a risk of toxicity associated with the dose to and volume of normal tissue that is irradiated. With its precision properties allowing for the increased sparing of healthy tissue, proton therapy could be an interesting option for this pathology. Methods: Two reviewers performed a systematic review of original papers published between 2010 and July 2021 following PRISMA guidelines. We analyzed disease outcomes, toxicity outcomes, or dosimetry data in four separate groups: children/adults and individuals with low-/high-grade gliomas. Results: Among 15 studies, 11 concerned clinical and toxicity outcomes, and 4 reported dosimetry data. Proton therapy showed similar disease outcomes with greater tolerance than conventional radiation therapy, partly due to the better dosimetry plans. Conclusions: This review suggests that proton therapy is a promising technique for glioma treatment. However, studies with a high level of evidence are still needed to validate this finding.