Safety of pelvic and abdominal radiation therapy for patients with inflammatory bowel disease: a dosimetric analysis of acute bowel toxicity.

OBJECTIVES: Inflammatory bowel disease (IBD) has been considered a relative contraindication to radiation therapy (RT) due to the potential greater risk of RT-induced toxicities. This study aims to assess acute toxicity outcomes in patients with IBD treated with abdominal/pelvic RT. METHODS: After institutional review board approval, patients with IBD who received RT to the abdomen/pelvis were identified from an institutional research repository and their electronic medical records were reviewed. The IBD cohort was matched 1:1 with controls according to all of the following: radiotherapy, gender, disease site, age, and year of RT. Acute toxicity was defined as toxicity occurring within 3 months of RT. Primary outcomes were assessed via univariable logistic regression models and predicted probability of acute toxicity and acute gastrointestinal (GI) toxicity were plotted for the most significant covariates. IBD and control control cohorts were compared on demographic and toxicity variables using chi-square/Fisher's exact tests and Kruskal-Wallis tests where appropriate. RESULTS: We identified 62 patients with median age of 64 years (interquartile range [IQR] 54-70) who received RT from 2006-2022. Patients were treated with intensity-modulated RT (38; 61.3%), 3-dimensional conformal RT (12; 19.4%), and stereotactic body RT/brachytherapy (12; 19.4%). After RT, 28 (45.2%) and 23 (37.1%) patients experienced grade ≥2 acute (any) and acute GI toxicity, respectively. Higher overall RT dose and RT dose to small bowel were found to be signicantly associated with increased risk of grade ≥2 acute toxicities (OR=1.041 per unit Gy, 95% CI 1.005-1.084, p=0.034 and OR=1.046, 95% CI 1.018-1.082, p=0.003, respectively). Between IBD and control cohorts, there were no significant differences in grade ≥2 acute (any) and acute GI toxicities (p=0.710 and p=0.704, respectively). CONCLUSION: In patients with IBD treated with abdominal/pelvic RT for malignancy, RT was effective and well-tolerated. RT treatment planning should carefully consider the location(s) of IBD inflammation and dose to bowel structures, in particular, dose to small bowel.

Cultural and social barriers to hope in gastrointestinal cancer patients.

Background: Hope is correlated with quality of life and overall survivorship among patients with cancer. We aimed to identify sociodemographic and clinical determinants of hope among patients with gastrointestinal (GI) cancer. Methods: Patients with GI cancer seen in radiation oncology between 10/2022 and 6/2023 were surveyed with the Adult Hope Scale (AHS) questionnaire, which assesses hope based on goal-setting and goal-striving beliefs. Linear regression and Pearson's/Spearman's correlation coefficients were used to evaluate associations between AHS scores and demographic or disease variables. Results: One-hundred and forty-five (71.1% response rate) patients were included in the analysis. Most (75%) patients were symptomatic from disease, and Asian American and Pacific Islander (AAPI) patients accounted for 30.3% of our cohort. Identifying as AAPI or needing an interpreter for clinic visits was significantly associated with lower AHS scores, and more AAPI patients required interpreter assistance compared to non-AAPI patients (P=0.04). Being divorced, unemployed, or female was also linked to less hope. No other differences in hope were found. Conclusions: Sociodemographic rather than prognostic clinical factors were predictive of hope among patients with GI cancer. Interventions to contextualize psychosocial risk factors have the potential to improve quality of life and oncologic outcomes.

Commissioning of a novel PET-Linac for biology-guided radiotherapy (BgRT).

BACKGROUND: Biology-guided radiotherapy (BgRT) is a novel radiotherapy delivery technique that utilizes the tumor itself to guide dynamic delivery of treatment dose to the tumor. The RefleXion X1 system is the first radiotherapy system developed to deliver SCINTIX® BgRT. The X1 is characterized by its split arc design, employing two 90-degree positron emission tomography (PET) arcs to guide therapeutic radiation beams in real time, currently cleared by FDA to treat bone and lung tumors. PURPOSE: This study aims to comprehensively evaluate the capabilities of the SCINTIX radiotherapy delivery system by evaluating its sensitivity to changes in PET contrast, its adaptability in the context of patient motion, and its performance across a spectrum of prescription doses. METHODS: A series of experimental scenarios, both static and dynamic, were designed to assess the SCINTIX BgRT system's performance, including an end-to-end test. These experiments involved a range of factors, including changes in PET contrast, motion, and prescription doses. Measurements were performed using a custom-made ArcCHECK insert which included a 2.2 cm spherical target and a c-shape structure that can be filled with a PET tracer with varying concentrations. Sinusoidal and cosine4 motion patterns, simulating patient breathing, was used to test the SCINTIX system's ability to deliver BgRT during motion-induced challenges. Each experiment was evaluated against specific metrics, including Activity Concentration (AC), Normalized Target Signal (NTS), and Biology Tracking Zone (BTZ) bounded dose-volume histogram (bDVH) pass rates. The accuracy of the delivered BgRT doses on ArcCHECK and EBT-XD film were evaluated using gamma 3%/2 mm and 3%/3 mm analysis. RESULTS: In static scenarios, the X1 system consistently demonstrated precision and robustness in SCINTIX dose delivery. The end-to-end delivery to the spherical target yielded good results, with AC and NTS values surpassing the critical thresholds of 5 kBq/mL and 2, respectively. Furthermore, bDVH analysis consistently confirmed 100% pass rates. These results were reaffirmed in scenarios involving changes in PET contrast, emphasizing the system's ability to adapt to varying PET avidities. Gamma analysis with 3%/2 mm (10% dose threshold) criteria consistently achieved pass rates > 91.5% for the static tests. In dynamic SCINTIX delivery scenarios, the X1 system exhibited adaptability under conditions of motion. Sinusoidal and cosine4 motion patterns resulted in 3%/3 mm gamma pass rates > 87%. Moreover, the comparison with gated stereotactic body radiotherapy (SBRT) delivery on a conventional c-arm Linac resulted in 93.9% gamma pass rates and used as comparison to evaluate the interplay effect. The 1 cm step shift tests showed low overall gamma pass rates of 60.3% in ArcCHECK measurements, while the doses in the PTV agreed with the plan with 99.9% for 3%/3 mm measured with film. CONCLUSIONS: The comprehensive evaluation of the X1 radiotherapy delivery system for SCINTIX BgRT demonstrated good agreement for the static tests. The system consistently achieved critical metrics and delivered the BgRT doses per plan. The motion tests demonstrated its ability to co-localize the dose where the PET signal is and deliver acceptable BgRT dose distributions.

Chest wall pain after single-fraction thoracic stereotactic ablative Radiotherapy: Dosimetric analysis from the iSABR trial.

BACKGROUND AND PURPOSE: Concerns over chest wall toxicity has led to debates on treating tumors adjacent to the chest wall with single-fraction stereotactic ablative radiotherapy (SABR). We performed a secondary analysis of patients treated on the prospective iSABR trial to determine the incidence and grade of chest wall pain and modeled dose-response to guide radiation planning and estimate risk. MATERIALS AND METHODS: This analysis included 99 tumors in 92 patients that were treated with 25 Gy in one fraction on the iSABR trial which individualized dose by tumor size and location. Toxicity events were prospectively collected and graded based on the CTCAE version 4. Dose-response modeling was performed using a logistic model with maximum likelihood method utilized for parameter fitting. RESULTS: There were 22 grade 1 or higher chest wall pain events, including five grade 2 events and zero grade 3 or higher events. The volume receiving at least 11 Gy (V11Gy) and the minimum dose to the hottest 2 cc (D2cc) were most highly correlated with toxicity. When dichotomized by an estimated incidence of ≥ 20 % toxicity, the D2cc > 17 Gy (36.6 % vs. 3.7 %, p < 0.01) and V11Gy > 28 cc (40.0 % vs. 8.1 %, p < 0.01) constraints were predictive of chest wall pain, including among a subset of patients with tumors abutting or adjacent to the chest wall. CONCLUSION: For small, peripheral tumors, single-fraction SABR is associated with modest rates of low-grade chest wall pain. Proximity to the chest wall may not contraindicate single fractionation when using highly conformal, image-guided techniques with sharp dose gradients.

Lung Cancer Survival Trends in the Veterans Health Administration.

INTRODUCTION: Lung cancer survival is improving in the United States. We investigated whether there was a similar trend within the Veterans Health Administration (VHA), the largest integrated healthcare system in the United States. MATERIALS AND METHODS: Data from the Veterans Affairs Central Cancer Registry were analyzed for temporal survival trends using Kaplan-Meier estimates and linear regression. RESULTS: A total number of 54,922 Veterans were identified with lung cancer diagnosed from 2010 to 2017. Histologies were classified as non-small-cell lung cancer (NSCLC) (64.2%), small cell lung cancer (SCLC) (12.9%), and 'other' (22.9%). The proportion with stage I increased from 18.1% to 30.4%, while stage IV decreased from 38.9% to 34.6% (both P < .001). The 3-year overall survival (OS) improved for stage I (58.6% to 68.4%, P < .001), stage II (35.5% to 48.4%, P < .001), stage III (18.7% to 29.4%, P < .001), and stage IV (3.4% to 7.8%, P < .001). For NSCLC, the median OS increased from 12 to 21 months (P < .001), and the 3-year OS increased from 24.1% to 38.3% (P < .001). For SCLC, the median OS remained unchanged (8 to 9 months, P = .10), while the 3-year OS increased from 9.1% to 12.3% (P = .014). Compared to White Veterans, Black Veterans with NSCLC had similar OS (P = .81), and those with SCLC had higher OS (P = .003). CONCLUSION: Lung cancer survival is improving within the VHA. Compared to White Veterans, Black Veterans had similar or higher survival rates. The observed racial equity in outcomes within a geographically and socioeconomically diverse population warrants further investigation to better understand and replicate this achievement in other healthcare systems.

First-Year Experience of Stereotactic Body Radiation Therapy/Intensity Modulated Radiation Therapy Treatment Using a Novel Biology-Guided Radiation Therapy Machine.

Purpose: The aim of this study was to present the first-year experience of treating patients using intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) with a biology-guided radiation therapy machine, the RefleXion X1 system, installed in a clinical setting. Methods and Materials: A total of 78 patients were treated on the X1 system using IMRT and SBRT from May 2021 to May 2022. Clinical and technical data including treatment sites, number of pretreatment kilovoltage computed tomography (kVCT) scans, beam-on time, patient setup time, and imaging time were collected and analyzed. Machine quality assurance (QA) results, machine performance, and user satisfactory survey were also collected and reported. Results: The most commonly treated site was the head and neck (63%), followed by the pelvis (23%), abdomen (8%), and thorax (6%). Except for 5 patients (6%) who received SBRT treatments for bony metastases in the pelvis, all treatments were conventionally fractionated IMRT. The number of kVCT scans per fraction was 1.2 ± 0.5 (mean ± standard deviation). The beam-on time was 9.2 ± 3.5 minutes. The patient setup time and imaging time per kVCT was 4.8 ± 2.6 minutes and 4.6 ± 1.5 minutes, respectively. The daily machine output deviation was 0.4 ± 1.2% from the baseline. The patient QA had a passing rate of 97.4 ± 2.8% at 3%/2 mm gamma criteria. The machine uptime was 92% of the total treatment time. The daily QA and kVCT image quality received the highest level of satisfaction. The treatment workflow for therapists received the lowest level of satisfaction. Conclusions: One year after the installation, 78 patients were successfully treated with the X1 system using IMRT and/or SBRT. With the recent Food and Drug Administration clearance of biology-guided radiation therapy, our department is preparing to treat patients using positron emission tomography-guidance via a new product release, which will address deficiencies in the current image-guided radiation therapy workflow.

Patient Selection and Outcomes for Hypofractionated Accelerated Radiation and Concurrent Chemotherapy for Non-Small-Cell Lung Cancer.

PURPOSE/OBJECTIVES: Adoption of hypofractionated accelerated radiation therapy (HART) with concurrent chemotherapy has been limited by toxicity concerns. We aimed to describe outcomes of patients treated with HART and concurrent chemotherapy and to evaluate dosimetry to organs at risk to guide patient selection. MATERIALS/METHODS: We evaluated a retrospective cohort of NSCLC patients treated with concurrent chemotherapy with HART (>2.2 Gy per fraction) or standard fractionated radiation therapy (SFRT; 2-2.2 Gy fractions). Dosimetric parameters to key organs at risk were compared, and toxicity, patterns of recurrence and survival were calculated for the cohorts. RESULTS: Fifty-three patients treated with HART were compared with 100 patients treated with SFRT. Median dose per fraction for the HART cohort was 2.75 Gy (range 2.4-3 Gy). HART patients had significantly lower doses to the lung, heart, and esophagus due to patient selection. The HART group and had rates of grade 2+ pneumonitis (9.4 vs. 19%, P = .16) and grade 2+ esophagitis (20.8 vs. 45%, P < .01) that compared favorably to SFRT. Cumulative incidence of in-field recurrence trended lower in the HART cohort (7.6% vs. 23.1%, P = .058). Among the HART group, 88.7% (47/53) met the newly proposed lung constraints based on the degree of hypofractionation CONCLUSION: In select patients with favorable dosimetry to organs at risk, definitive HART with concurrent chemotherapy achieved excellent local control with low toxicity. These results are being used to inform a prospective study on the safety and efficacy of HART with concurrent chemotherapy for select NSCLC patients.

Personalized Accelerated ChEmoRadiation (PACER) for Lung Cancer: Protocol for a Bayesian Optimal Phase I/II Trial.

INTRODUCTION: Prior attempts to escalate radiation dose for non-small cell lung cancer (NSCLC) have not improved survival. Given the high risk for cardiopulmonary toxicity with treatment and heterogenous presentation of locally advanced NSCLC, it is unlikely that a single dose regimen is optimal for all patients. This phase I/II trial aims to evaluate a novel treatment approach where the level of accelerated hypofractionation is determined by the predicted toxicity from dose to organs at risk (OARs). METHODS: Patients ≥ 18 years old with lung cancer planned for fractionated radiotherapy to the lung with concurrent chemotherapy will be eligible. Radiation therapy (RT) will be delivered to a total dose of 60 to 66 Gy in 30, 25, or 20 fractions depending on the ability to meet constraints to key organs at risk including the lungs, heart, and esophagus. The primary endpoint is high grade pulmonary, esophageal, or cardiac toxicity. A Bayesian optimized design is used to determine stopping boundaries and evaluate the primary endpoint. CONCLUSION: PACER will evaluate the safety and feasibility of personalized accelerated chemoradiotherapy for lung cancer.

Volumetric MRI with sparse sampling for MR-guided 3D motion tracking via sparse prior-augmented implicit neural representation learning.

BACKGROUND: Volumetric reconstruction of magnetic resonance imaging (MRI) from sparse samples is desirable for 3D motion tracking and promises to improve magnetic resonance (MR)-guided radiation treatment precision. Data-driven sparse MRI reconstruction, however, requires large-scale training datasets for prior learning, which is time-consuming and challenging to acquire in clinical settings. PURPOSE: To investigate volumetric reconstruction of MRI from sparse samples of two orthogonal slices aided by sparse priors of two static 3D MRI through implicit neural representation (NeRP) learning, in support of 3D motion tracking during MR-guided radiotherapy. METHODS: A multi-layer perceptron network was trained to parameterize the NeRP model of a patient-specific MRI dataset, where the network takes 4D data coordinates of voxel locations and motion states as inputs and outputs corresponding voxel intensities. By first training the network to learn the NeRP of two static 3D MRI with different breathing motion states, prior information of patient breathing motion was embedded into network weights through optimization. The prior information was then augmented from two motion states to 31 motion states by querying the optimized network at interpolated and extrapolated motion state coordinates. Starting from the prior-augmented NeRP model as an initialization point, we further trained the network to fit sparse samples of two orthogonal MRI slices and the final volumetric reconstruction was obtained by querying the trained network at 3D spatial locations. We evaluated the proposed method using 5-min volumetric MRI time series with 340 ms temporal resolution for seven abdominal patients with hepatocellular carcinoma, acquired using golden-angle radial MRI sequence and reconstructed through retrospective sorting. Two volumetric MRI with inhale and exhale states respectively were selected from the first 30 s of the time series for prior embedding and augmentation. The remaining 4.5-min time series was used for volumetric reconstruction evaluation, where we retrospectively subsampled each MRI to two orthogonal slices and compared model-reconstructed images to ground truth images in terms of image quality and the capability of supporting 3D target motion tracking. RESULTS: Across the seven patients evaluated, the peak signal-to-noise-ratio between model-reconstructed and ground truth MR images was 38.02 ± 2.60 dB and the structure similarity index measure was 0.98 ± 0.01. Throughout the 4.5-min time period, gross tumor volume (GTV) motion estimated by deforming a reference state MRI to model-reconstructed and ground truth MRI showed good consistency. The 95-percentile Hausdorff distance between GTV contours was 2.41 ± 0.77 mm, which is less than the voxel dimension. The mean GTV centroid position difference between ground truth and model estimation was less than 1 mm in all three orthogonal directions. CONCLUSION: A prior-augmented NeRP model has been developed to reconstruct volumetric MRI from sparse samples of orthogonal cine slices. Only one exhale and one inhale 3D MRI were needed to train the model to learn prior information of patient breathing motion for sparse image reconstruction. The proposed model has the potential of supporting 3D motion tracking during MR-guided radiotherapy for improved treatment precision and promises a major simplification of the workflow by eliminating the need for large-scale training datasets.

BIOGUIDE-X: A First-in-Human Study of the Performance of Positron Emission Tomography-Guided Radiation Therapy.

PURPOSE: Positron emission tomography (PET)-guided radiation therapy is a novel tracked dose delivery modality that uses real-time PET to guide radiation therapy beamlets. The BIOGUIDE-X study was performed with sequential cohorts of participants to (1) identify the fluorodeoxyglucose (FDG) dose for PET-guided therapy and (2) confirm that the emulated dose distribution was consistent with a physician-approved radiation therapy plan. METHODS AND MATERIALS: This prospective study included participants with at least 1 FDG-avid targetable primary or metastatic tumor (2-5 cm) in the lung or bone. For cohort I, a modified 3 + 3 design was used to determine the FDG dose that would result in adequate signal for PET-guided therapy. For cohort II, PET imaging data were collected on the X1 system before the first and last fractions among patients undergoing conventional stereotactic body radiation therapy. PET-guided therapy dose distributions were modeled on the patient's computed tomography anatomy using the collected PET data at each fraction as input to an "emulated delivery" and compared with the physician-approved plan. RESULTS: Cohort I demonstrated adequate FDG activity in 6 of 6 evaluable participants (100.0%) with the first injected dose level of 15 mCi FDG. In cohort II, 4 patients with lung tumors and 5 with bone tumors were enrolled, and evaluable emulated delivery data points were collected for 17 treatment fractions. Sixteen of the 17 emulated deliveries resulted in dose distributions that were accurate with respect to the approved PET-guided therapy plan. The 17th data point was just below the 95% threshold for accuracy (dose-volume histogram score = 94.6%). All emulated fluences were physically deliverable. No toxicities were attributed to multiple FDG administrations. CONCLUSIONS: PET-guided therapy is a novel radiation therapy modality in which a radiolabeled tumor can act as its own fiducial for radiation therapy targeting. Emulated therapy dose distributions calculated from continuously acquired real-time PET data were accurate and machine-deliverable in tumors that were 2 to 5 cm in size with adequate FDG signal characteristics.

Patterns of Recurrence After Poor Response to Neoadjuvant Chemotherapy in Gastric Cancer and the Role for Adjuvant Radiation.

BACKGROUND: Improved treatment strategies are needed for patients with locally advanced gastric cancer with poor response to neoadjuvant chemotherapy. We aimed to describe patterns of failure for patients with no or partial response (NR, PR) to preoperative chemotherapy. PATIENTS AND METHODS: We analyzed patients with locally advanced gastric cancer treated from 2008 to 2022 with preoperative chemotherapy followed by surgery with D2 resection. We excluded patients who received radiation. Cumulative incidence of locoregional failure (LRF) and distant metastases (DM) were calculated. For patients with recurrent abdominal disease, hypothetical radiation clinical treatment volumes (CTV) were contoured on postoperative scans and compared with patterns of recurrence. RESULTS: A total of 60 patients were identified. The most used preoperative chemotherapy was FLOT (38.6%), followed by FOLFOX (30%) and ECF/ECX/EOX (23.3%). Four (6.7%), 40 (66.7%), and 9 patients (15%) had a complete pathologic response (CR), PR, and NR to neoadjuvant therapy, respectively. Among patients without a CR, 3-year overall and progression-free survival rates were 62.3% (95% CI 48-76.6%) and 51.3% (95% CI 36.9-65.7%), respectively. Three-year cumulative incidence of LRF and DM were 8.4% (95% CI 0.4-16.4%) and 41.0% (95% CI 26.3-55.4%), respectively. Absolute rates of patients having the first site of recurrence encompassed by a postoperative radiation CTV was 2.0% for patients without a CR and 0% for patients with NR. CONCLUSIONS: Patients with locally advanced gastric cancer with less than a CR to chemotherapy have poor outcomes due to high rates of DM. Adjuvant locoregional therapy such as radiation is unlikely to affect survival.

Individualized Stereotactic Ablative Radiotherapy for Lung Tumors: The iSABR Phase 2 Nonrandomized Controlled Trial.

Importance: Stereotactic ablative radiotherapy (SABR) is used for treating lung tumors but can cause toxic effects, including life-threatening damage to central structures. Retrospective data suggested that small tumors up to 10 cm3 in volume can be well controlled with a biologically effective dose less than 100 Gy. Objective: To assess whether individualizing lung SABR dose and fractionation by tumor size, location, and histological characteristics may be associated with local tumor control. Design, Setting, and Participants: This nonrandomized controlled trial (the iSABR trial, so named for individualized SABR) was a phase 2 multicenter trial enrolling participants from November 15, 2011, to December 5, 2018, at academic medical centers in the US and Japan. Data were analyzed from December 9, 2020, to May 10, 2023. Patients were enrolled in 3 groups according to cancer type: initial diagnosis of non-small cell lung cancer (NSCLC) with an American Joint Committee on Cancer 7th edition T1-3N0M0 tumor (group 1), a T1-3N0M0 new primary NSCLC with a history of prior NSCLC or multiple NSCLCs (group 2), or lung metastases from NSCLC or another solid tumor (group 3). Intervention: Up to 4 tumors were treated with once-daily SABR. The dose ranged from 25 Gy in 1 fraction for peripheral tumors with a volume of 0 to 10 cm3 to 60 Gy in 8 fractions for central tumors with a volume greater than 30 cm3. Main outcome: Per-group freedom from local recurrence (same-lobe recurrence) at 1 year, with censoring at time of distant recurrence, death, or loss to follow-up. Results: In total, 217 unique patients (median [IQR] age, 72 [64-80] years; 129 [59%] male; 150 [69%] current or former smokers) were enrolled (some multiple times). There were 240 treatment courses: 79 in group 1, 82 in group 2, and 79 in group 3. A total of 285 tumors (211 [74%] peripheral and 74 [26%] central) were treated. The most common dose was 25 Gy in 1 fraction (158 tumors). The median (range) follow-up period was 33 (2-109) months, and the median overall survival was 59 (95% CI, 49-82) months. Freedom from local recurrence at 1 year was 97% (90% CI, 91%-99%) for group 1, 94% (90% CI, 87%-97%) for group 2, and 96% (90% CI, 89%-98%) for group 3. Freedom from local recurrence at 5 years ranged from 83% to 93% in the 3 groups. The proportion of patients with grade 3 to 5 toxic effects was low, at 5% (including a single patient [1%] with grade 5 toxic effects). Conclusions and Relevance: The results of this nonrandomized controlled trial suggest that individualized SABR (iSABR) used to treat lung tumors may allow minimization of treatment dose and is associated with excellent local control. Individualized dosing should be considered for use in future trials. Trial Registration: ClinicalTrials.gov Identifier: NCT01463423.

Adaptive Region-Specific Loss for Improved Medical Image Segmentation.

Defining the loss function is an important part of neural network design and critically determines the success of deep learning modeling. A significant shortcoming of the conventional loss functions is that they weight all regions in the input image volume equally, despite the fact that the system is known to be heterogeneous (i.e., some regions can achieve high prediction performance more easily than others). Here, we introduce a region-specific loss to lift the implicit assumption of homogeneous weighting for better learning. We divide the entire volume into multiple sub-regions, each with an individualized loss constructed for optimal local performance. Effectively, this scheme imposes higher weightings on the sub-regions that are more difficult to segment, and vice versa. Furthermore, the regional false positive and false negative errors are computed for each input image during a training step and the regional penalty is adjusted accordingly to enhance the overall accuracy of the prediction. Using different public and in-house medical image datasets, we demonstrate that the proposed regionally adaptive loss paradigm outperforms conventional methods in the multi-organ segmentations, without any modification to the neural network architecture or additional data preparation.

Unilateral Diaphragmatic Paralysis After Stereotactic Ablative Radiation Therapy to a Lung Tumor Abutting the Course of the Phrenic Nerve.

We present the case of a woman with metastatic adenoid cystic carcinoma who received stereotactic ablative radiation therapy with a total dose of 50 Gy in 4 fractions to 2 lung metastases and developed symptomatic left phrenic nerve injury 2 years after radiation. The maximum dose to the approximate location of the phrenic nerve was 57.7 Gy, which corresponds to a biologically effective dose for late effects (using α/ß ratio = 3) of 335.14 Gy. Here, we discuss the case, planning considerations by radiation oncologists and medical physicists, and the multidisciplinary medical management of this patient.

Pulmonary Hemorrhage in Patients Treated With Thoracic Stereotactic Ablative Radiotherapy and Antiangiogenic Agents.

INTRODUCTION: Severe pulmonary hemorrhage can occur in patients treated with thoracic stereotactic ablative radiotherapy (SABR) and vascular endothelial growth factor inhibitors (VEGFis). There is limited understanding of which patients are at risk for toxicity with the combination of thoracic SABR and VEGFis or how the risk differs over either therapy alone. METHODS: We evaluated a prospectively maintained cohort of 690 patients with 818 pulmonary tumors treated with highly conformal SABR. Rates of any-grade and grade 3 plus (G3+) pulmonary hemorrhage were compared between patients treated with or without VEGFi therapy across tumor locations. Outcomes were compared between patients treated with SABR plus VEGFi and a propensity-matched cohort of those treated with VEGFi therapy alone. RESULTS: Treatment with VEGFi plus SABR was associated with higher rates of G3+ pulmonary hemorrhage compared with those treated with SABR alone for the overall cohort (3-y incidence: 7.9% versus 0.6%, p < 0.01) and those with central tumors (19.1% versus 3.3%, p = 0.04). When further subdivided, there were significantly higher toxicity rates with VEGFi for the ultracentral (9.0% versus 45.0%, p = 0.044), but not central nonabutting tumors (0.0% versus 1.3%, p = 0.69). There was an increased incidence of G3+ hemorrhage in patients treated with VEGFi plus SABR compared with VEGFi alone (9.6% versus 1.3%, p = 0.04). CONCLUSIONS: The combination of VEGFi and SABR was associated with an increased risk of high-grade pulmonary hemorrhage over either therapy alone. Low rates of toxicity were observed when excluding patients with SABR to ultracentral tumors and applying highly conformal SABR techniques.

Clinical consensus guideline on the management of phaeochromocytoma and paraganglioma in patients harbouring germline SDHD pathogenic variants.

Patients with germline SDHD pathogenic variants (encoding succinate dehydrogenase subunit D; ie, paraganglioma 1 syndrome) are predominantly affected by head and neck paragangliomas, which, in almost 20% of patients, might coexist with paragangliomas arising from other locations (eg, adrenal medulla, para-aortic, cardiac or thoracic, and pelvic). Given the higher risk of tumour multifocality and bilaterality for phaeochromocytomas and paragangliomas (PPGLs) because of SDHD pathogenic variants than for their sporadic and other genotypic counterparts, the management of patients with SDHD PPGLs is clinically complex in terms of imaging, treatment, and management options. Furthermore, locally aggressive disease can be discovered at a young age or late in the disease course, which presents challenges in balancing surgical intervention with various medical and radiotherapeutic approaches. The axiom-first, do no harm-should always be considered and an initial period of observation (ie, watchful waiting) is often appropriate to characterise tumour behaviour in patients with these pathogenic variants. These patients should be referred to specialised high-volume medical centres. This consensus guideline aims to help physicians with the clinical decision-making process when caring for patients with SDHD PPGLs.

Mitigation of Intensity Modulated Radiation Therapy and Stereotactic Body Radiation Therapy Treatment Planning Errors on the Novel RefleXion X1 System Using Failure Mode and Effect Analysis Within Six Sigma Framework.

Purpose: The aim of this study was to apply the Six Sigma methodology and failure mode and effect analysis (FMEA) to mitigate errors in intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) treatment planning with the first clinical installation of RefleXion X1. Methods and Materials: The Six Sigma approach consisted of 5 phases: define, measure, analyze, improve, and control. The define, measure, and analyze phases consisted of process mapping and an FMEA of IMRT and SBRT treatment planning on the X1. The multidisciplinary team outlined the workflow process and identified and ranked the failure modes associated with the plan check items using the American Association of Physicists in Medicine Task Group 100 recommendations. Items with the highest average risk priority numbers (RPNs) and severity ≥7 were prioritized for automation using the Eclipse Scripting Application Programming Interface (ESAPI). The "improve" phase consisted of developing ESAPI scripts before the clinical launch of X1 to improve efficiency and safety. In the "control" phase, the FMEA ranking was re-evaluated 1 year after clinical launch. Results: Overall, 100 plan check items were identified in which the RPN values ranged from 10.2 to 429.0. Fifty of these items (50%) were suitable for automation within ESAPI. Of the 10 highest-risk items, 8 were suitable for automation. Based on the results of the FMEA, 2 scripts were developed: Planning Assistant, used by the planner during preparation for planning, and Automated Plan Check, used by the planner and the plan checker during plan preparation for treatment. After 12 months of clinical use of the X1 and developed scripts, only 3 errors were reported. The average prescript RPN was 138.0, compared with the average postscript RPN of 47.8 (P < .05), signifying a safer process. Conclusions: Implementing new technology in the clinic can be an error-prone process in which the likelihood of errors increases with increasing pressure to implement the technology quickly. To limit errors in clinical implementation of the novel RefleXion X1 system, the Six Sigma method was used to identify failure modes, establish quality control checks, and re-evaluate these checks 1 year after clinical implementation.