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This article discusses a prospective cohort study that examined the use of circulating tumor DNA (ctDNA) as a biomarker to predict failure patterns and the efficacy of consolidation immunotherapy in patients with locally advanced non-small-cell lung cancer (LA-NSCLC) who received chemoradiotherapy (CRT). The study found that dynamic ctDNA levels could predict failure patterns and identify patients who may benefit from consolidation immunotherapy. Patients with decreased ctDNA levels after CRT had a higher risk of distant metastasis but showed more benefit from immunotherapy, while patients with increased ctDNA levels had a higher risk of both local-regional and distant failure and also showed benefit from immunotherapy. The study suggests that ctDNA testing could be used to personalize treatment decisions and improve outcomes for LA-NSCLC patients. [Extracted from the article]

In this study, we explore the diagnostic value of a novel PET/CT imaging tracer that specifically targets fibroblast activation protein (FAP), 18F-NOTA-FAPI, in a radiation induced lung damage (RILD) rat model. High focal radiation (40, 60, or 90 Gy) was administered to a 5-mm diameter area of the right lung in Wistar rats for evaluation of RILD induction. Lung tissues exposed to 90 Gy radiation were scanned with 18F-NOTA-FAPI PET/CT and with 18F-FDG. Dynamic 18F-NOTA-FAPI PET/CT scanning was performed on day 42 post-irradiation. After in vivo scanning, lung cryosections were prepared for autoradiography, hematoxylin and eosin (HE) and immunohistochemical (IHC) staining. An animal model of RILD was established and validated by histopathological analysis. On 18F-NOTA-FAPI PET/CT, RILD was first observed on days 42, 35 and 7 in the 40, 60 and 90 Gy groups, respectively. After treatment with 90 Gy, 18F-NOTA-FAPI uptake in an area of RILD emerged on day 7 (0.65 ± 0.05%ID/ml) and reappeared on day 28 (0.81 ± 0.09%ID/ml), remaining stable for 4–6 weeks. Autoradiography and HE staining IHC staining revealed that 18F-NOTA-FAPI accumulated mainly in the center of the irradiated area. IHC staining confirmed the presence of FAP+ macrophages in the RILD area, while FAP+ fibroblasts were observed in the peripheral area of irradiated lung tissue. 18F-NOTA-FAPI represents a promising radiotracer for in vivo imaging of RILD in a dose- and time-dependent manner. Noninvasive imaging of FAP may potentially aiding in the clinical management of radiotherapy patients. [ABSTRACT FROM AUTHOR]

The purpose of this work was to determine the actual dose received by normal tissues during four‐dimensional radiation therapy (4DRT) composed of ten phases of four‐dimensional computer tomography (4DCT) images. The analysis was performed by tracking the hepatocellular carcinoma SBRT. Data were acquired from the tracking of each phase with the beam aperture for 28 hepatocellular carcinoma patients, and the data were used to generate a cumulative plan, which was compared to a three‐dimensional (3D) plan formed from a merged target volume based on 4DCT images in a radiation treatment planning system (TPS). The change in normal tissue dose was evaluated in the plan using the parameters V5, V10, V15, V20, V25, V30, V35, and V40 (volumes receiving 5, 10, 15, 20, 25, 30, 35, and 40 Gy, respectively) in the dose‐volume histogram for the liver; the mean dose was analyzed for the following tissues: liver, left kidney, and right kidney. The maximum dose was analyzed for the following tissues: bowel, duodenum, esophagus, stomach, and heart. There was a significant difference in the dose between the 4D planning target volume (PTV) (average 115.71 cm3) and ITV (169.86 cm3). The planning objective was for 95% of the volume of the PTV to be covered by the prescription dose, but the mean dose for the liver, left kidney and right kidney had an average decrease of 23.13%, 49.51%, and 54.38%, respectively. The maximum dose for the bowel, duodenum, esophagus, stomach, and heart had an average decrease of 16.77%, 28.07%, 24.28%, 4.89%, and 4.45%, respectively. Compared to 3D RT, the radiation volume for the liver V5, V10, V15, V20, V25, V30, V35, and V40 using the 4D plans had a significant decrease (P ﹤ 0.05). The 4D method creates plans that permit sparing of the normal tissues more than the commonly used ITV method, which delivers the same dosimetric effects to the target. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to experimentally assess the dosimetric impact of leaf interdigitation using different inverse treatment strategies for representative tumour sites and to identify the situations in which leaf interdigitation can benefit these tumour sites.Material and Methods: Sixty previously treated patients (15 nasopharyngeal carcinoma (NPC), 15 multiple brain metastasis (MBM), 15 cervical cancer and 15 prostate cancer) were re-planned for volumetric modulated arc therapy (VMAT), sliding window IMRT (dMLC) and step-and-shoot IMRT (ssIMRT) with and without leaf interdigitation. Various dosimetric variables, such as PTV coverage, OARs sparing, delivery efficiency and planning time, were evaluated for each plan. In addition, a protocol developed by our group was applied to identify the situations in which leaf interdigitation can achieve benefits in clinical practice.Results: Leaf interdigitation produced few benefits in PTV homogeneity for the MBM VMAT plans and NPC ssIMRT plans. For OARs, sparing was equivalent with and without leaf interdigitation. Leaf interdigitation showed an increase in MUs for dMLC plans and a decrease in MUs for ssIMRT plans. Leaf interdigitation resulted in an increase in segments for dMLC plans and a decrease in segments for NPC and MBM ssIMRT plans. For beam on time, leaf interdigitation showed an increase in MBM dMLC, NPC ssIMRT and prostate ssIMRT plans. In addition, leaf interdigitation saved planning time for VMAT and dMLC plans but increased planning time for ssIMRT plans.Conclusion: Leaf interdigitation does not improve plan quality when performing inverse treatment strategies, regardless of whether the target is simple or complex. However, it influences the delivery efficiency and planning time. Based on these observations, our study suggests that leaf interdigitation should be utilized when performing MBM VMAT plans and NPC ssIMRT plans. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to identify risk factors associated with symptomatic radiation pneumonitis (RP, Grade ≥ 2) following immunotherapy preceding thoracic radiotherapy (ICI-TRT) and establish safe dose constraints., Patients and Methods: This retrospective study enrolled patients diagnosed with non-small-cell lung cancer (NSCLC) who underwent thoracic radiotherapy (TRT) following immune checkpoint inhibitors (ICIs) treatment. The primary endpoint was the occurrence of symptomatic RP (Grade ≥ 2), as defined by the Common Terminology Criteria for Adverse Events version 5.0. Clinical and lung dosimetric parameters were analyzed to determine their associations with symptomatic RP. Dosimetric parameters included mean lung dose (MLD) and the percentage of lung volume receiving ≥10 Gy (V10), ≥20 Gy (V20), ≥30 Gy (V30), and ≥40 Gy (V40). Receiver operating characteristic curves were used to predict the risk of developing symptomatic RP to establish optimal threshold values for each dosimetric predictor., Results: Among the 118 patients included, the incidence of symptomatic RP was 25.4%. Tumor locations, intervals between immunotherapy and radiotherapy, and MLD, V10, V20, V30, and V40 were identified as independent risk factors for symptomatic RP. The area under the curve (AUC) values for MLD, V10, V20, V30, and V40 were 0.788 (95% confidence interval [CI] 0.704-0.873), 0.789 (95% CI 0.705-0.874), 0.791 (95% CI 0.706-0.876), 0.784 (95% CI 0.697-0.871), and 0.749 (95% CI 0.656-0.842), respectively. The optimal threshold values for MLD, V10, V20, V30, and V40 were 9.7 Gy, 26.3%, 15.9%, 13.3%, and 8.6%, respectively. These thresholds are lower than current guideline recommendations, and maintaining dosimetric parameters below these values resulted in a cumulative symptomatic RP incidence of <12%., Conclusion: The recommended dose thresholds for MLD, V10, V20, V30, and V40 are lower than the current guidelines, underscoring the importance of radiotherapy planning to minimize symptomatic RP occurrence in patients receiving ICI-TRT., Competing Interests: The authors declare that this study was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (© 2024 Wang et al.)

This prospective study examined whether imaging results obtained using the tracer 18 F-AlF-NOTA-fibroblast activation protein inhibitor (FAPI)-04 (denoted as 18 F-FAPI-04) in PET/CT can predict the short-term outcome in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) treated with concurrent chemoradiotherapy (CCRT). Methods: The 18 enrolled LA-ESCC patients underwent 18 F-FAPI-04 PET/CT scanning before CCRT. The SUV max , SUV mean , SUV peak , metabolic tumor volume, and total lesion fibroblast activation protein expression of the primary tumor were recorded. Additionally, the SUV max of the primary tumor and SUV mean of normal tissue (muscle and blood) were measured, and their ratios were denoted as target-to-background ratios (TBR muscle and TBR blood ). Patients were classified as responders or nonresponders according to RECIST (version 1.1), and variables were compared between the 2 groups. Results: The TBR blood , TBR muscle , and SUV mean were significantly higher in nonresponders than in responders (all P < 0.05). Receiver-operating-characteristic curve analysis identified TBR blood (area under the curve [AUC], 0.883; P = 0.008), TBR muscle (AUC, 0.896; P = 0.006) and SUV mean (AUC, 0.870; P = 0.010) as significant predictors of the response to CCRT, with cutoffs of 10.68, 10.95, and 6.88, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were also determined for TBR blood (100.0%, 72.7%, 66.7%, 88.9%, and 77.8%, respectively), TBR muscle (100.0%, 72.7%, 66.7%, 88.9%, and 77.8%, respectively), and SUV mean (85.7%, 81.8%, 75.0%, 90.0%, and 83.3%, respectively). On univariate logistic regression analysis, TBR blood ( P = 0.026), TBR muscle ( P = 0.036), SUV mean ( P = 0.045), and tumor site ( P = 0.032) were significantly correlated with the short-term outcome. On multivariable logistic regression analysis, TBR blood ( P = 0.046) was an independent prognostic factor for short-term outcome. Conclusion: A higher baseline TBR blood on 18 F-FAPI-04 PET/CT scans was associated with a poor response to CCRT in LA-ESCC patients, and thus, TBR blood may be useful for screening LA-ESCC patients before CCRT treatment., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

In this study, we explore the diagnostic value of a novel PET/CT imaging tracer that specifically targets fibroblast activation protein (FAP), 18 F-NOTA-FAPI, in a radiation induced lung damage (RILD) rat model. High focal radiation (40, 60, or 90 Gy) was administered to a 5-mm diameter area of the right lung in Wistar rats for evaluation of RILD induction. Lung tissues exposed to 90 Gy radiation were scanned with 18 F-NOTA-FAPI PET/CT and with 18 F-FDG. Dynamic 18 F-NOTA-FAPI PET/CT scanning was performed on day 42 post-irradiation. After in vivo scanning, lung cryosections were prepared for autoradiography, hematoxylin and eosin (HE) and immunohistochemical (IHC) staining. An animal model of RILD was established and validated by histopathological analysis. On 18 F-NOTA-FAPI PET/CT, RILD was first observed on days 42, 35 and 7 in the 40, 60 and 90 Gy groups, respectively. After treatment with 90 Gy, 18 F-NOTA-FAPI uptake in an area of RILD emerged on day 7 (0.65 ± 0.05%ID/ml) and reappeared on day 28 (0.81 ± 0.09%ID/ml), remaining stable for 4-6 weeks. Autoradiography and HE staining IHC staining revealed that 18 F-NOTA-FAPI accumulated mainly in the center of the irradiated area. IHC staining confirmed the presence of FAP+ macrophages in the RILD area, while FAP+ fibroblasts were observed in the peripheral area of irradiated lung tissue. 18 F-NOTA-FAPI represents a promising radiotracer for in vivo imaging of RILD in a dose- and time-dependent manner. Noninvasive imaging of FAP may potentially aiding in the clinical management of radiotherapy patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qin, Wang, Liu, Duan, Cheng, Mu, Jia, Wei and Yuan.)