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Primary pericardial mesothelioma (PPM) has no accepted standard-of-care treatment options with management and outcomes often extrapolated from diffuse pleural mesothelioma. Disease-specific research is needed to better define PPM. We report our institutional experience with PPM highlighting the potential role for multimodality therapy.Patients with PPM diagnosed by a multidisciplinary team of medical oncologists, thoracic surgeons, thoracic pathologists, and radiologists between January 2011 and January 2022 were followed to February 2022. Clinicopathologic features and treatment outcomes were annotated. Overall survival (OS) was defined from the date of pathologic diagnosis.The median age at diagnosis of the 12 patients identified with having PPM was 51 (range: 21-71) years old. Most patients were of female sex (n = 8; 67%), 75% of the samples were epithelioid (n = 9), and 25% were nonepithelioid (two sarcomatoid and one biphasic). Most cases (92%, 11 of 12) had expression of at least two mesothelial markers on immunohistochemistry. The median OS of the cohort was 25.9 months. Five patients had an OS greater than 12 months; four of whom received pericardial radiation. Three of the patients who received radiation did so as part of a trimodality approach (surgical resection, adjuvant chemotherapy, and radiation); the OS for patients who received trimodality therapy was 70.3 months versus 8.2 months for those who did not.PPM represents a distinct disease with no universally accepted treatment options. Our findings suggest that trimodality therapy may improve outcomes in selected patients with PPM.

Introduction Paraspinal stereotactic body radiotherapy (SBRT) involves risks of severe complications. We evaluated the safety of the paraspinal SBRT program in a large academic hospital by applying failure modes and effects analysis. Methods The analysis was conducted by a multidisciplinary committee (two therapists, one dosimetrist, four physicists, and two radiation oncologists). The paraspinal SBRT workflow was segmented into four phases (simulation, treatment planning, delivery, and machine quality assurance (QA)). Each phase was further divided into a sequence of sub‐processes. Potential failure modes (PFM) were identified from each subprocess and scored in terms of the frequency of occurrence, severity and detectability, and a risk priority number (RPN). High‐risk PFMs were identified based on RPN and were studied for root causes using fault tree analysis. Results Our paraspinal SBRT process was characterized by eight simulations, 11 treatment planning, nine delivery, and two machine QA sub‐processes. There were 18, 29, 19, and eight PFMs identified from simulation, planning, treatment, and machine QA, respectively. The median RPN of the PFMs was 62.9 for simulation, 68.3 for planning, 52.9 for delivery, and 22.0 for machine QA. The three PFMs with the highest RPN were: previous radiotherapy outside the institution is not accurately evaluated (RPN: 293.3), incorrect registration between diagnostic magnetic resonance imaging and simulation computed tomography causing incorrect contours (273.0), and undetected patient movement before ExacTrac baseline (217.8). Remedies to the high RPN failures were implemented, including staff education, standardized magnetic resonance imaging acquisition parameters, and an image fusion process, and additional QA on beam steering. Conclusions A paraspinal SBRT workflow in a large clinic was evaluated using a multidisciplinary and systematic risk analysis, which led to feasible solutions to key root causes. Treatment planning was a major source of PFMs that systematically affect the safety and quality of treatments. Accurate evaluation of external treatment records remains a challenge.

ImportanceProton radiation therapy (PRT) has reduced radiation-induced toxic effects, such as mucositis and xerostomia, over conventional photon radiation therapy, leading to significantly improved quality of life in patients with head and neck cancers. However, the prevalence of osteoradionecrosis (ORN) of the jaw following PRT in these patients is less clear.ObjectiveTo report the prevalence and clinical characteristics of ORN in patients with oral and oropharyngeal cancer (OOPC) treated with PRT.Design, Setting, and ParticipantsThis case series reports a single-institution experience (Memorial Sloan Kettering Cancer Center, New York, New York) between November 2013 and September 2019 and included 122 radiation therapy–naive patients with OOPC treated with PRT. Data were analyzed from 2013 to 2019.Main Outcomes and MeasuresClinical parameters, including sex, age, comorbidities, tumor histology, concurrent chemotherapy, smoking, comorbidities, and preradiation dental evaluation, were obtained from the medical record. Patients with clinical or radiographic signs of ORN were identified and graded using the adopted modified Glanzmann and Grätz grading system. Characteristics of ORN, such as location, clinical presentation, initial stage at diagnosis, etiology, time to diagnosis, management, and clinical outcome at the last follow-up, were also collected.ResultsOf the 122 patients (mean [SD] age, 63 [13] years; 45 [36.9%] women and 77 [63.1%] men) included in this study, 13 (10.6%) developed ORN following PRT during a median (range) follow-up time of 40.6 (Conclusions and RelevanceIn this case series, the prevalence of ORN following PRT was found to be 10.6%, indicating that ORN remains a clinical challenge even in the era of highly conformal PRT. Clinicians treating patients with OOPC with PRT should be mindful of this complication.

PURPOSE: We sought to investigate the tumor control probability (TCP) of vestibular schwannomas (VS) following single-fraction stereotactic radiosurgery (SRS) or hypofractionated SRS over 2–5 fractions (fSRS). MATERIALS AND METHODS: Studies (PubMed Indexed from 1993 – 2017) were eligible for data extraction if they contained dosimetric details of SRS/fSRS correlated with local tumor control. The rate of tumor control at 5 years (or at 3 years if 5-year data were not available) were collated. Poisson modeling estimated the TCP per equivalent dose in 2 Gy per fraction (EQD2) and in 1, 3, and 5 fractions. RESULTS: Data were extracted from 35 publications containing a total of 5162 patients. TCP modeling was limited by the absence of analyzable data of

PurposeStereotactic body radiation therapy (SBRT) has become the standard of care for inoperable early-stage non-small cell lung cancer and is often used for recurrent lung cancer and pulmonary metastases. Radiation-induced lung toxicity (RILT), including radiation pneumonitis and pulmonary fibrosis, is a major concern for which it is important to understand dosimetric and clinical predictors.Methods and materialsThis study was undertaken through the American Association of Physicists in Medicine's Working Group on Biological Effects of Stereotactic Body Radiotherapy. Data from studies of lung SBRT published through the summer of 2016 that provided detailed information about RILT were analyzed.ResultsNinety-seven studies were ultimately considered. Definitions of the risk organ and complication endpoints as well as dose-volume information presented varied among studies. The risk of RILT, including radiation pneumonitis and pulmonary fibrosis, was reported to be associated with the size and location of the tumor. Patients with interstitial lung disease appear to be especially susceptible to severe RILT. A variety of dosimetric parameters were reported to be associated with RILT. There was no apparent threshold "tolerance dose-volume" level. However, most studies noted safe treatment with a rate of symptomatic RILT of

PURPOSE: Stereotactic body radiation therapy (SBRT) has emerged as a viable reirradiation strategy for locally recurrent previously-irradiated head and neck cancer. Doses in the literature have varied, which challenges clinical application of SBRT as well as clinical trial design. MATERIAL & METHODS: A working group was formed through the American Association of Physicists in Medicine to study tumor control probabilities for SBRT in head and neck cancer. We herein present a systematic review of the available literature addressing the dose/volume data for tumor control probability with SBRT in patients with locally recurrent previously-irradiated head and neck cancer. Dose-response models are generated that present tumor control probability as a function of dose. RESULTS: Data from more than 300 cases in 8 publications suggest that there is a dose-response relationship, with superior local control and possibly improved overall survival for doses of 35 to 45 Gy (in 5 fractions) compared with

Spinal cord tolerance data for stereotactic body radiation therapy (SBRT) were extracted from published reports, reviewed, and modelled. For de novo SBRT delivered in 1 to 5 fractions, the following spinal cord point maximum doses (Dmax) are estimated to be associated with a 1% to 5% risk of radiation myelopathy (RM): 12.4 to 14.0 Gy in 1 fraction, 17.0 Gy in 2 fractions, 20.3 Gy in 3 fractions, 23.0 Gy in 4 fractions, and 25.3 Gy in 5 fractions. For reirradiation SBRT delivered in 1 to 5 fractions, reported factors associated with a lower risk of RM include cumulative thecal sac equivalent dose in 2 Gy fractions with an alpha/beta of 2 (EQD22) Dmax ≤70 Gy; SBRT thecal sac EQD22 Dmax ≤25 Gy, thecal sac SBRT EQD22 Dmax to cumulative EQD22 Dmax ratio ≤0.5, and a minimum time interval to reirradiation of ≥5 months. Larger studies containing complete institutional cohorts with dosimetric data of patients treated with spine SBRT, with and without RM, are required to refine RM risk estimates.

Stereotactic body radiation therapy (SBRT) has emerged as an effective, noninvasive treatment option for primary liver cancer and metastatic disease occurring in the liver. Although SBRT can be highly effective for establishing local control in hepatic malignancies, a tradeoff exists between tumor control and normal tissue complications. The objective of the present study was to review the normal tissue dose-volume effects for SBRT-induced liver and gastrointestinal toxicities and derive normal tissue complication probability models.

Based on an analysis of published literature, our department recently lowered the preferred mean esophagus dose (MED) constraint for conventionally fractionated (2 Gy/fraction in approximately 30 fractions) treatment of locally advanced non‐small cell lung cancer (LA‐NSCLC) with the goal of reducing the incidence of symptomatic acute esophagitis (AE). The goal of the change was to encourage treatment planners to achieve a MED close to 21 Gy while still permitting MED to go up to the previous guideline of 34 Gy in difficult cases. We compared all our suitable LA‐NSCLC patients treated with plans from one year before through one year after the constraint change. The primary endpoint for this study was achievability of the new constraint by the planners; the secondary endpoint was reduction in symptomatic AE. Planners were able to achieve the new constraint in statistically significantly more cases during the year following its explicit implementation than in the year before (P = 0.0025). Furthermore, 38% of patients treated after the new constraint developed symptomatic AE during their treatment as opposed to 48% of the patients treated before. This is a clinically desirable endpoint although the observed difference was not statistically significant. A subsequent power calculation suggests that this is due to the relatively small number of patients in the study.

This study compared the reproducibility of chestwall and heart position using surface-guided versus RPM (real-time position management)-guided deep inspiration breath hold (DIBH) radiotherapy for left sided breast cancer. Forty DIBH patients under either surface-guided radiotherapy (SGRT) or RPM guidance were studied. For patients treated with tangential fields, reproducibility was measured as the displacements in central lung distance (CLD) and heart shadow to field edge distance (HFD) between pretreatment MV (megavoltage) images and planning DRRs (digitally reconstructed radiographs). For patients treated with volumetric modulated arc therapy (VMAT), sternum to isocenter (ISO) distance (StID), spine to rib edge distance (SpRD), and heart shadow to central axis (CAX) distance (HCD) between pretreatment kV images and planning DRRs were measured. These displacements were compared between SGRT and RPM-guided DIBH. In tangential patients, the mean absolute displacements of SGRT versus RPM guidance were 0.19 versus 0.23 cm in CLD, and 0.33 versus 0.62 cm in HFD. With respect to planning DRR, heart appeared closer to the field edge by 0.04 cm with surface imaging versus 0.62 cm with RPM. In VMAT patients, the displacements of surface imaging versus RPM guidance were 0.21 versus 0.15 cm in StID, 0.24 versus 0.19 cm in SpRD, and 0.72 versus 0.41 cm in HCD. Heart appeared 0.41 cm further away from CAX with surface imaging, whereas 0.10 cm closer to field CAX with RPM. None of the differences between surface imaging and RPM guidance was statistically significant. In conclusion, the displacements of chestwall were small and were comparable with SGRT- or RPM-guided DIBH. The position deviations of heart were larger than those of chestwall with SGRT or RPM. Although none of the differences between SGRT and RPM guidance were statistically significant, there was a trend that the position deviations of heart were smaller and more favorable with SGRT than with RPM guidance in tangential patients.

Purpose Deep inspiration breath hold (DIBH) and respiratory gating (RG) are widely used to reduce movement of target and healthy organs caused by breathing during irradiation. We hypothesized that accuracy and efficiency comparable to DIBH can be achieved with RG for pancreas treatment. Methods and Materials Twenty consecutive patients with pancreatic cancer treated with DIBH (eight) or RG (twelve) volumetric modulated arc therapy during 2017–2019 were included in this study, with radiopaque markers implanted near or in the targets. Seventeen patients received 25 fractions, while the other three received 15 fractions. Only patients who could not tolerate DIBH received RG treatment. While both techniques relied on respiratory signals from external markers, internal target motions were monitored with kV X‐ray imaging during treatment. A 3‐mm external gating window was used for DIBH treatment; RG treatment was centered on end‐expiration with a duty cycle of 40%, corresponding to an external gating window of 2–3 mm. During dose delivery, kV images were automatically taken every 20◦ or 40◦ gantry rotation, from which internal markers were identified. The marker displacement from their initial positions and the residual motion amplitudes were calculated. For the analysis of treatment efficiency, the treatment time of every session was calculated from the motion management waveform files recorded at the treatment console. Results Within one fraction, the displacement was 0–5 mm for DIBH and 0–6 mm for RG. The average magnitude of displacement for each patient during the entire course of treatment ranged 0–3 mm for both techniques. No statistically significant difference in displacement or residual motion was observed between the two techniques. The average treatment time was 15 min for DIBH and 17 min for RG, with no statistical significance. Conclusions The accuracy and efficiency were comparable between RG and DIBH treatment for pancreas irradiation. RG is a feasible alternative strategy to DIBH.

Introduction Durvalumab after concurrent chemoradiation (cCRT) is now standard of care for unresected stage III non–small cell lung cancer (NSCLC). However, there is limited data on radiation pneumonitis (RP) with this regimen. Therefore, we assessed RP and evaluated previously validated toxicity models in predicting for RP in patients treated with cCRT and durvalumab. Methods Patients treated with cCRT and ≥ 1 dose of durvalumab were evaluated to identify cases of ≥ grade 2 RP. The validity of previously published RP models was assessed in this cohort as well a reference cohort treated with cCRT alone. The timing and incidence of RP was compared between cohorts. Results In total, 11 (18%) of the 62 patients who received cCRT and durvalumab developed ≥ grade 2 RP a median of 3.4 months after cCRT. The onset of RP among patients treated with cCRT and durvalumab was significantly longer vs the reference cohort (3.4 vs 2.1 months; P = .01). Numerically more patients treated with cCRT and durvalumab developed RP than patients in the reference cohort (18% vs 9%, P = .09). Among patients treated with cCRT and durvalumab, 82% (n = 9) were responsive to treatment with high‐dose glucocorticoids. Previously published RP models widely underestimated the rate of RP in patients treated with cCRT and durvalumab [AUC ~ 0.50; p(Hosmer‐Lemeshow): 0.98‐1.00]. Conclusions Our data suggest a delayed onset of RP in patients treated with cCRT and durvalumab vs cCRT alone, and for RP to develop in a greater number of patients treated with cCRT and durvalumab. Previously published RP models significantly underestimate the rate of symptomatic RP among patients treated with cCRT and durvalumab., Radiation pneumonitis (RP) is a significant toxicity of thoracic radiation, yet little is known regarding RP in lung cancer patients treated with definitive chemoradiation (cCRT) and durvalumab. We found patients treated with cCRT and durvalumab to have a significantly later onset of RP and a greater frequency of RP compared to patients treated with cCRT alone, we also found previously published toxicity models to be unsuccessful in predicting for RP among patients treated with cCRT and durvalumab.

Background and purpose: Minimizing acute esophagitis (AE) in locally advanced non-small cell lung cancer (LA-NSCLC) is critical given the proximity between the esophagus and the tumor. In this pilot study, we developed a clinical platform for quantification of accumulated doses and volumetric changes of esophagus via weekly Magnetic Resonance Imaging (MRI) for adaptive radiotherapy (RT). Material and methods: Eleven patients treated via intensity-modulated RT to 60–70 Gy in 2–3 Gy-fractions with concurrent chemotherapy underwent weekly MRIs. Eight patients developed AE grade 2 (AE2), 3–6 weeks after RT started. First, weekly MRI esophagus contours were rigidly propagated to planning CT and the distances between the medial esophageal axes were calculated as positional uncertainties. Then, the weekly MRI were deformably registered to the planning CT and the total dose delivered to esophagus was accumulated. Weekly Maximum Esophagus Expansion (MEex) was calculated using the Jacobian map. Eventually, esophageal dose parameters (Mean Esophagus Dose (MED), V90% and D5cc) between the planned and accumulated dose were compared. Results: Positional esophagus uncertainties were 6.8 ± 1.8 mm across patients. For the entire cohort at the end of RT: the median accumulated MED was significantly higher than the planned dose (24 Gy vs. 21 Gy p = 0.006). The median V90% and D5cc were 12.5 cm3 vs. 11.5 cm3 (p = 0.05) and 61 Gy vs. 60 Gy (p = 0.01), for accumulated and planned dose, respectively. The median MEex was 24% and was significantly associated with AE2 (p = 0.008). Conclusions: MRI is well suited for tracking esophagus volumetric changes and accumulating doses. Longitudinal esophagus expansion could reflect radiation-induced inflammation that may link to AE. Keywords: MRI, Esophagus, Adaptive radiotherapy, Lung cancer, Dose accumulation

To evaluate the efficacy of using bronchoscopically implanted anchored electromagnetic transponders (EMTs) as surrogates for 1) tumor position and 2) repeatability of lung inflation during deep-inspiration breath-hold (DIBH) lung radiotherapy.Forty-one patients treated with either hypofractionated (HF) or conventional (CF) lung radiotherapy on an IRB-approved prospective protocol using coached DIBH were evaluated for this study. Three anchored EMTs were bronchoscopically implanted into small airways near or within the tumor. DIBH treatment was gated by tracking the EMT positions. Breath-hold cone-beam-CTs (CBCTs) were acquired prior to every HF treatment or weekly for CF patients. Retrospectively, rigid registrations between each CBCT and the breath-hold planning CT were performed to match to 1) spine, 2) EMTs and 3) tumor. Absolute differences in registration between EMTs and spine were analyzed to determine surrogacy of EMTs for lung inflation. Differences in registration between EMTs and the tumor were analyzed to determine surrogacy of EMTs for tumor position. The stability of the EMTs was evaluated by analyzing the difference between inter-EMT displacements recorded at treatment from that of the plan for the CF patients, as well as the geometric residual (GR) recorded at the time of treatment.A total of 219 CBCTs were analyzed. The average differences between EMT centroid and spine registration among all CBCTs were 0.45±0.42 cm, 0.29±0.28 cm, and 0.18±0.15 cm in superior-inferior (SI), anterior-posterior (AP) and lateral directions, respectively. Only 59% of CBCTs had differences in registration 0.5 cm for EMT centroid compared to spine, indicating that lung inflation is not reproducible from simulation to treatment. The average differences between EMT centroid and tumor registration among all CBCTs were 0.13±0.13 cm, 0.14±0.13 cm and 0.12±0.12 cm in SI, AP and lateral directions, respectively. Ninety-five percent of CBCTs resulted in a 0.5 cm change between EMT centroid and tumor registration, indicating that EMT positions correspond well with tumor position during treatments. Six out of the seven recorded CF patients had average differences in inter-EMT displacements ≤0.26 cm and average GR ≤0.22 cm, indicating that the EMTs are stable throughout treatment.Bronchoscopically implanted anchored EMTs are good surrogates for tumor position and are reliable for maintaining tumor position when tracked during DIBH treatment, as long as the tumor size and shape are stable. Large differences in registration between EMTs and spine for many treatments suggest that lung inflation achieved at simulation is often not reproduced.

We share our experiences on uniformly implementing an effective and efficient SGRT procedure with a new clinical workflow for treating breast patients in deep-inspiration breath-hold (DIBH) among 9 clinical centers using 26 optical surface imaging (OSI) systems.Our procedures have five major components: (1) acquiring both free-breathing (FB) and DIBH computed tomography (CT) at simulation to quantify the rise of the anterior surface, (2) defining uniformly a large region of interest (ROI) to accommodate large variations in patient anatomy and treatment techniques, (3) performing two-step setup in FB by first aligning the arm and chin to minimize breast deformation and reproduce local lymphnode positions and then aligning the ROI, (4) aligning the vertical shift precisely from FB to DIBH, and (5) capturing a new on-site reference image at DIBH to separate residual setup errors from the DIBH motion monitoring uncertainties. Moreover, a new clinical workflow was developed for patient data preparation using 4 OSI offline workstations without interruption of SGRT treatment at 22 OSI online workstations. This procedure/workflow is suitable for all photon planning techniques, including 2-field, 3-field, 4-field, partial breast irradiation (PBI), and volumetric-modulated arc therapy (VMAT) with or without bolus.Since 2019, we have developed and applied the uniform breast SGRT DIBH procedure with optimized clinical workflow and ensured treatment accuracy among the nine clinics within our institution. About 150 breast DIBH patients are treated daily and two major upgrades are achieved smoothly throughout our institution, owing to the uniform and versatile procedure, adequate staff training, and efficient workflow with effective clinical supports and backup strategies.The uniform and versatile breast SGRT DIBH procedure and workflow have been developed to ensure smooth and optimal clinical operations, simplify clinical staff training and clinical troubleshooting, and allow high-quality SGRT delivery in a busy multi-center institution.

BACKGROUND AND PURPOSE: To develop a novel deep learning algorithm of sequential analysis, Seq2Seq, for predicting weekly anatomical changes of lung tumor and esophagus during definitive radiotherapy, incorporate the potential tumor shrinkage into a predictive treatment planning paradigm, and improve the therapeutic ratio. METHODS AND MATERIALS: Seq2Seq starts with the primary tumor and esophagus observed on the planning CT to predict their geometric evolution during radiotherapy on a weekly basis, and subsequently updates the predictions with new snapshots acquired via weekly CBCTs. Seq2Seq is equipped with convolutional long short term memory to analyze the spatial-temporal changes of longitudinal images, trained and validated using a dataset including sixty patients. Predictive plans were optimized according to each weekly prediction and made ready for weekly deployment to mitigate the clinical burden of online weekly replanning. RESULTS: Seq2Seq tracks structural changes well: DICE between predicted and actual weekly tumor and esophagus were (0.83±0.10, 0.79±0.14, 0.78±0.12, 0.77±0.12, 0.75±0.12, 0.71±0.17), and (0.72 ± 0.16, 0.73 ± 0.11, 0.75 ± 0.08,0.74 ± 0.09, 0.72 ± 0.14, 0.71 ± 0.14), respectively, while the average Hausdorff distances were within 2mm. Evaluating dose to the actual weekly tumor and esophagus, a 4.2Gy reduction in esophagus mean dose while maintaining 60Gy tumor coverage was achieved with the predictive weekly plans, compared to the plan optimized using the initial tumor and esophagus alone, primarily due to noticeable tumor shrinkage during radiotherapy. CONCLUSION: It is feasible to predict the longitudinal changes of tumor and esophagus with the Seq2Seq, which could lead to improving the efficiency and effectiveness of lung adaptive radiotherapy.

PURPOSE: To identify published normal tissue complication probability (NTCP) models suitable for patient-specific dose-prescription in locally advanced non-small cell lung cancer (LA-NSCLC) through in-house validation. MATERIAL AND METHODS: From eight previously published candidate NTCP models (≥grade 2 acute esophagitis and radiation pneumonitis; AE2, RP2), patient-specific dose-responses were calculated using model variables and fractionation-corrected doses for 241 LA-NSCLC patients treated with chemo-IMRT to 50-80Gy@1.8-2.0Gy between 2004 and 2014 (AE2/RP2 rate: 50%/12%). A model was judged final if it significantly predicted AE2 or RP2 (p≤0.05), was discriminative and well calibrated (AUC>0.60; Hosmer-Lemeshow test p(HL)>0.05), which were assessed as the median over 1000 bootstrap samples. RESULTS: Models for AE2 had superior discrimination to RP2 models (AUC=0.63–0.65 vs. 0.51–0.65). The final AE2 model included mean esophageal dose and concurrent chemotherapy (AUC=0.65; p

Introduction Detailed guidelines regarding the use of radiation therapy for malignant pleural mesothelioma (MPM) are currently lacking because of the rarity of the disease, the wide spectrum of clinical presentations, and the paucity of high-level data on individual treatment approaches. Methods In March 2017, a multidisciplinary meeting of mesothelioma experts was cosponsored by the U.S. National Cancer Institute, International Association for the Study of Lung Cancer Research, and Mesothelioma Applied Research Foundation. Among the outcomes of this conference was the foundation of detailed, multidisciplinary consensus guidelines. Results Here we present consensus recommendations on the use of radiation therapy for MPM in three discrete scenarios: (1) hemithoracic radiation therapy to be used before or after extrapleural pneumonectomy; (2) hemithoracic radiation to be used as an adjuvant to lung-sparing procedures (i.e., without pneumonectomy); and (3) palliative radiation therapy for focal symptoms caused by the disease. We discuss appropriate simulation techniques, treatment volumes, dose fractionation regimens, and normal tissue constraints. We also assess the role of particle beam therapy, specifically, proton beam therapy, for MPM. Conclusion The recommendations provided in this consensus statement should serve as important guidelines for developing future clinical trials of treatment approaches for MPM.

Purpose Beam gating with deep inspiration breath hold (DIBH) has been widely used for motion management in radiotherapy. Normally it relies on some external surrogate for estimating the internal target motion, while the exact internal motion is unknown. In this study, we used the intrafraction motion review (IMR) application to directly track an internal target and characterized the residual motion during DIBH treatment for pancreatic cancer patients through their full treatment courses. Methods and Materials Eight patients with pancreatic cancer treated with DIBH volumetric modulated arc therapy in 2017 and 2018 were selected for this study, each with some radiopaque markers (fiducial or surgical clips) implanted near or inside the target. The Varian Real‐time Position Management (RPM) system was used to monitor the breath hold, represented by the anterior‐posterior displacement of an external surrogate, namely reflective markers mounted on a plastic block placed on the patient's abdomen. Before each treatment, a cone beam computed tomography (CBCT) scan under DIBH was acquired for patient setup. For scan and treatment, the breath hold reported by RPM had to lie within a 3 mm window. IMR kV images were taken every 20° or 40° gantry rotation during dose delivery, resulting in over 5000 images for the cohort. The internal markers were manually identified in the IMR images. The residual motion amplitudes of the markers as well as the displacement from their initial positions located in the setup CBCT images were analyzed. Results Even though the external markers indicated that the respiratory motion was within 3 mm in DIBH treatment, significant residual internal target motion was observed for some patients. The range of average motion was from 3.4 to 7.9 mm, with standard deviation ranging from 1.2 to 3.5 mm. For all patients, the target residual motions seemed to be random with mean positions around their initial setup positions. Therefore, the absolute target displacement relative to the initial position was small during DIBH treatment, with the mean and the standard deviation 0.6 and 2.9 mm, respectively. Conclusions Internal target motion may differ from external surrogate motion in DIBH treatment. Radiographic verification of target position at the beginning and during each fraction is necessary for precise RT delivery. IMR can serve as a useful tool to directly monitor the internal target motion.

PurposeDosimetric and clinical predictors of radiation-induced optic nerve/chiasm neuropathy (RION) after single-fraction stereotactic radiosurgery (SRS) or hypofractionated (2-5 fractions) radiosurgery (fSRS) were analyzed from pooled data that were extracted from published reports (PubMed indexed from 1990 to June 2015). This study was undertaken as part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, investigating normal tissue complication probability (NTCP) after hypofractionated radiation.Methods and materialsEligible studies described dose delivered to optic nerve/chiasm and provided crude or actuarial toxicity risks, with visual endpoints (ie, loss of visual acuity, alterations in visual fields, and/or blindness/complete vision loss). Studies of patients with optic nerve sheath tumors, optic nerve gliomas, or ocular/uveal melanoma were excluded to obviate direct tumor effects on visual outcomes, as were studies not specifying causes of vision loss (ie, tumor progression vs RION).ResultsThirty-four studies (1578 patients) were analyzed. Histologies included pituitary adenoma, cavernous sinus meningioma, craniopharyngioma, and malignant skull base tumors. Prior resection (76% of patients) did not correlate with RION risk (P=.66). Prior irradiation (6% of patients) was associated with a crude 10-fold increased RION risk versus no prior radiation therapy. In patients with no prior radiation therapy receiving SRS/fSRS in 1-5 fractions, optic apparatus maximum point doses resulting in

Deep inspiration breath hold (DIBH) has dosimetric advantages for lung cancer patients treated with external beam therapy, but is difficult for many patients to perform. Proton therapy permits sparing of the downstream organs at risk (OAR). We compared conventionally fractionated proton (p) and photon(x) plans on both free breathing (FB) and DIBH planning CTs to determine the effect of DIBH with proton therapy. We evaluated 24 plans from 6 lung cancer patients treated with photon DIBH on a prospective protocol. All patients were re-planned using pencil beam scanning (PBS) proton therapy. New plans were generated for FB datasets with both modalities. All plans were renormalized to 60 Gy. We evaluated dosimetric parameters for heart, lung and esophagus. We also compared FB(p) to DIBH(x) parameters to quantify how FB(p) plans compare to DIBH(x) plans. Significant differences were found for lung metrics V20 and mean lung dose between FB and DIBH plans regardless of treatment modality. Furthermore, lung metrics for FB(p) were comparable or superior to DIBH(x), suggesting that FB protons may be a viable alternative for those patients that cannot perform DIBH with IMRT. The heart dose metrics were significantly different for the 5 out of 6 patients where the PTV overlapped the heart as DIBH moved heart out of the high dose volume. Heart dose metrics were further reduced by proton therapy. DIBH offers similar relative advantages for lung sparing for PBS as it does for IMRT but the magnitude of the DIBH related gains in OAR sparing were smaller for PBS than IMRT. FB(p) plans offer similar or better lung and heart sparing compared to DIBH(x) plans. For IMRT patients who have difficulty performing DIBH, FB protons may offer an alternative.

PURPOSE Accurate deformable registration between computed tomography (CT) and cone-beam CT (CBCT) images of pancreatic cancer patients treated with high biologically effective radiation doses is essential to assess changes in organ-at-risk (OAR) locations and shapes and to compute delivered dose. This study describes the development and evaluation of a deep-learning (DL) registration model to predict OAR segmentations on the CBCT derived from segmentations on the planning CT. METHODS The DL model is trained with CT-CBCT image pairs of the same patient, on which OAR segmentations of the small bowel, stomach, and duodenum have been manually drawn. A transformation map is obtained, which serves to warp the CT image and segmentations. In addition to a regularity loss and an image similarity loss, an OAR segmentation similarity loss is also used during training, which penalizes the mismatch between warped CT segmentations and manually drawn CBCT segmentations. At test time, CBCT segmentations are not required as they are instead obtained from the warped CT segmentations. In an IRB-approved retrospective study, a dataset consisting of 40 patients, each with one planning CT and two CBCT scans, was used in a fivefold cross-validation to train and evaluate the model, using physician-drawn segmentations as reference. Images were preprocessed to remove gas pockets. Network performance was compared to two intensity-based deformable registration algorithms (large deformation diffeomorphic metric mapping [LDDMM] and multimodality free-form [MMFF]) as baseline. Evaluated metrics were Dice similarity coefficient (DSC), change in OAR volume within a volume of interest (enclosing the low-dose PTV plus 1 cm margin) from planning CT to CBCT, and maximum dose to 5 cm3 of the OAR [D(5cc)]. RESULTS Processing time for one CT-CBCT registration with the DL model at test time was less than 5 seconds on a GPU-based system, compared to an average of 30 minutes for LDDMM optimization. For both small bowel and stomach/duodenum, the DL model yielded larger median DSC and smaller interquartile variation than either MMFF (paired t-test P

Purpose/Objective(s) This prospective multi-institutional study aimed to determine the safety and maximally tolerated dose of 3-fraction stereotactic body radiotherapy (SBRT) for locally advanced pancreatic cancer (LAPC). Materials/Methods Patients with localized, histologically confirmed pancreatic adenocarcinoma deemed unresectable on radiographic multidisciplinary review without distant progression following induction chemotherapy for at least 2 months were eligible. Patients received 3-fraction LINAC-based SBRT at 3 dose levels, 27Gy, 30Gy and 33Gy following a modified 3+3 design, allowing for enrollment of additional patients at the last dose level during the 90-day observation period, provided no dose-limiting toxicities (DLTs) were observed. DLTs were defined as ≥ Grade 3 treatment-related GI toxicity within 90 days of RT as scored by CTCAE v.4. The secondary endpoints were overall survival (OS), local progression-free and distant metastasis-free survival (LPFS and DMFS, respectively), treatment-related toxicity and quality of life. Results Between 3/2016 and 4/2019, 23 consecutive evaluable LAPC patients were enrolled at two academic hospitals (14 and 9 patients, respectively), including 8 patients at 27Gy, 8 patients at 30Gy and 7 patients at 33Gy. The median age was 67 years (range 52 - 79 years), 9 patients (39%) were male, all were stage III, 12 (52%) had a head/uncinate tumor location, with a median tumor size of 3.5cm (range, 1.0 - 6.4cm) and a median CA19-9 of 60U/mL (range, Conclusion For select LAPC patients, dose escalation to the target dose of 33Gy in 3 fractions resulted in no DLTs and disease outcomes comparable to conventional RT. These results warrant further exploration of hypofractionated SBRT schemes to maximize tumor control while enabling efficient integration of RT with systemic therapy for more expedient treatment options for these high-risk LAPC patients.

Purpose/Objective(s) Pleurectomy/Decortication (P/D) has become a common lung-sparing surgical approach for MPM. Chemotherapy may be delivered in the neoadjuvant or adjuvant setting. Adjuvant hemithoracic IMPRINT was developed at Memorial Sloan Kettering Cancer Center and found safe in a multi-institutional phase II study, with promising survival outcomes. CTEP approved a phase III randomized cooperative group trial (NRG LU-006) to evaluate the efficacy of this lung-sparing trimodality treatment approach for resectable MPM. Materials/Methods Patients with newly diagnosed MPM amenable to P/D are enrolled and undergo upfront P/D followed by adjuvant platinum/pemetrexed chemotherapy (preferred approach) or neoadjuvant chemotherapy followed by P/D. Patients are stratified by epithelioid vs. biphasic histologic subtype, achievement of a macroscopic complete resection (R0/1 vs. R2), and center patient volume (≤10 vs. > 10 P/Ds per year). Within 8 weeks after completion of the second modality, patients are randomized 1:1 to undergo hemithoracic IMPRINT vs. no further therapy. All IMPRINT contours and treatment plans are centrally reviewed. A contouring atlas and treatment planning constraints for target structures and organs at risk, including acceptable and unacceptable variations and deviations, were developed. Photon and proton therapy are permitted. The primary endpoint of the study is overall survival. Secondary endpoints include local failure-free, distant-metastases free and progression-free survival, treatment-related toxicities (CTCAE v5.0) and change in quality-of-life (EORTC QLQ-C30 mean score changes at 9 months post randomization). Exploratory objectives include correlation of clinical/radiographic staging with pathologic stage, immunologic and pathologic biomarkers as predictors of response, the rate of R0/R1 vs. R2 resections, and EORTC QLQ-C30 and LC13 symptom scores changes over time. This study was activated on January 29, 2020. As of 02/2021,16 sites are approved and 46 sites are pending approval to open the study. Treatment planning guidelines and helpful hints for photon and proton therapy will be presented. Two patients have been accrued, and the target accrual is 150 patients. Results TBD Conclusion NRG LU-006 is now open to accrual. This is the first NRG Oncology randomized phase III trial on malignant pleural mesothelioma and evaluates the use of IMPRINT following lung-sparing P/D and chemotherapy. Treatment planning aspects and current status will be presented.

Background and purpose Recently published HyTEC report summarized lung toxicity data and proposed guidelines of mean lung dose (MLD)

PURPOSE: Radiation pneumonitis (RP) is a common and potentially life-threatening toxicity from lung cancer radiotherapy. Data sets reporting RP rates after post-operative radiation therapy (PORT) have historically been small and with predominantly outdated field designs and radiation techniques. We examined a large cohort of patients in this context to assess the incidence and causes of RP in the modern era. MATERIALS AND METHODS: We reviewed 285 patients with non-small cell lung cancer (NSCLC) treated with PORT at our institution from 5/2004 to 1/2017. Complete dosimetric data and clinical records were reviewed and analyzed with grade 2 or higher RP as the endpoint (RP2+) (CTCAE v4.0). Patients were a median of 67 yo (range 28-87), and most had pathologic stage III NSCLC (91%) and received trimodality therapy (90%). Systematic dosimetric analyses using Dx increments of 5% and Vx increments of 2Gy were performed to robustly evaluate dosimetric variables. Lung V(5) was also evaluated. RESULTS: The incidence of RP2+ after PORT was 12.6%. Dosimetric factors most associated with RP2+ were total lungV(4) (HR 1.04, p