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.

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.

Predicting Adverse Cardiac Events After Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer.

Background: Radiotherapy may cause grade ≥3 cardiac events, necessitating a better understanding of risk factors. The potential predictive role of imaging biomarkers with radiotherapy doses for cardiac event occurrence has not been studied. Objectives: The aim of this study was to establish the associations between cardiac substructure dose and coronary artery calcium (CAC) scores and cardiac event occurrence. Methods: A retrospective cohort analysis included patients with locally advanced non-small cell lung cancer treated with radiotherapy (2006-2018). Cardiac substructures, including the left anterior descending coronary artery, left main coronary artery, left circumflex coronary artery, right coronary artery, and TotalLeft (left anterior descending, left main, and left circumflex coronary arteries), were contoured. Doses were measured in 2-Gy equivalent units, and visual CAC scoring was compared with automated scoring. Grade ≥3 adverse cardiac events were recorded. Time-dependent receiver-operating characteristic modeling, the log-rank statistic, and competing-risk models were used to measure prediction performance, threshold modeling, and the cumulative incidence of cardiac events, respectively. Results: Of the 233 eligible patients, 61.4% were men, with a median age of 68.1 years (range: 34.9-90.7 years). The median follow-up period was 73.7 months (range: 1.6-153.9 months). Following radiotherapy, 22.3% experienced cardiac events, within a median time of 21.5 months (range: 1.7-118.9 months). Visual CAC scoring showed significant correlation with automated scoring (r = 0.72; P < 0.001). In a competing-risk multivariable model, TotalLeft volume receiving 15 Gy (per 1 cc; HR: 1.38; 95% CI: 1.11-1.72; P = 0.004) and CAC score >5 (HR: 2.51; 95% CI: 1.08-5.86; P = 0.033) were independently associated with cardiac events. A model incorporating age, TotalLeft CAC (score >5), and volume receiving 15 Gy demonstrated a higher incidence of cardiac events for a high-risk group (28.9%) compared with a low-risk group (6.9%) (P < 0.001). Conclusions: Adverse cardiac events associated with radiation occur in more than 20% of patients undergoing thoracic radiotherapy within a median time of <2 years. The present findings provide further evidence to support significant associations between TotalLeft radiotherapy dose and cardiac events and define CAC as a predictive risk factor.

Characterization of Metastatic Non-Small Cell Lung Cancer and Oligometastatic Incidence in an Era of Changing Treatment Paradigms.

PURPOSE: Because of the limitations of current staging systems and evolving definitions, there are limited data on oligometastatic non-small cell lung cancer (NSCLC) epidemiology. The purpose of this study was to evaluate metastatic disease burden and the incidence of oligometastatic disease using recent clinical trial eligibility criteria. METHODS AND MATERIALS: A cohort of patients with metastatic NSCLC, diagnosed from 2016 to 2019, were randomly sampled from a curated tumor registry. Definitions for oligometastatic disease were obtained from relevant clinical trials. The Stanford Cancer Institute Research Database was used to identify baseline patient factors, systemic and local therapy, extent and location of metastatic lesions, and survival outcomes. RESULTS: Among 120 patients presenting with metastatic NSCLC, the majority had de novo metastatic disease (75%) with a median of 4 metastatic lesions involving 3 organ systems. Of these, 37.5% would have been eligible for at least 1 oligometastatic trial, with 28.3% meeting criteria for the MD Anderson Cancer Center trial, 20.0% for NRG-LU002, 6.7% for SINDAS, and 16.7% for SABR-COMET. By adding malignant pleural effusions and early progression as exclusionary criteria, only 54.1% of patients with ≤3 synchronous metastases were eligible for consideration of local therapy. Early progression on systemic therapy was associated with worse survival (10.0 vs 42.4 months; P < .001), whereas presence of malignant pleural effusions was not. Of those tumors identified as oligometastatic, 44.4% received local therapy and 28.9% underwent ablative therapy to all sites. There was a trend toward greater overall survival (44.4 vs 24.9 months; P = .055) and progression-free survival (8.0 vs 5.4 months; P = .06) in patients meeting eligibility for at least 1 oligometastatic trial. CONCLUSIONS: Around 48% of patients with metastatic NSCLC had ≤3 metastases at presentation and 28% met clinical trial criteria for oligometastatic disease. Future research is needed to better define the oligometastatic state and identify patients most likely to benefit from local therapy.

Jumping to conclusions: Misdiagnosing radiation induced sarcoma as recurrent breast cancer.

Radiation therapy (RT) induced chondrosarcoma is a rare but important potential complication seen in cancer patients treated with radiation. Although uncommon, these patients tend to have a poor prognosis, so early detection and complete resection are the crucial steps towards survival. We present the case of an 81-year-old breast cancer patient who was treated with RT to the left chest wall. Eight years later, she presented with a growing left chest wall mass, initially thought to represent local breast cancer recurrence. Imaging demonstrated a well-defined mass arising from the left pectoralis major muscle. The mass was excised, and pathology demonstrated chondrosarcoma. We discuss the clinical and radiologic aspects of RT-induced sarcomas with attention to the very rare chondrosarcoma. The aim of this report is to provide a succinct but relevant summary of the diagnostic considerations for RT-induced sarcoma supported by information about epidemiology, clinical diagnostic criteria, and radiation biology to expedite patient workup and ultimately improve patient outcomes.