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Background: To integrate radiomics and dosiomics features from multiple regions in the radiation pneumonia (RP grade ≥ 2) prediction for esophageal cancer (EC) patients underwent radiotherapy (RT)., Methods: Total of 143 EC patients in the authors' hospital (training and internal validation: 70%:30%) and 32 EC patients from another hospital (external validation) underwent RT from 2015 to 2022 were retrospectively reviewed and analyzed. Patients were dichotomized as positive (RP+) or negative (RP-) according to CTCAE V5.0. Models with radiomics and dosiomics features extracted from single region of interest (ROI), multiple ROIs and combined models were constructed and evaluated. A nomogram integrating radiomics score (Rad_score), dosiomics score (Dos_score), clinical factors, dose-volume histogram (DVH) factors, and mean lung dose (MLD) was also constructed and validated., Results: Models with Rad_score_Lung&Overlap and Dos_score_Lung&Overlap achieved a better area under curve (AUC) of 0.818 and 0.844 in the external validation in comparison with radiomics and dosiomics models with features extracted from single ROI. Combining four radiomics and dosiomics models using support vector machine (SVM) improved the AUC to 0.854 in the external validation. Nomogram integrating Rad_score, and Dos_score with clinical factors, DVH factors, and MLD further improved the RP prediction AUC to 0.937 and 0.912 in the internal and external validation, respectively., Conclusion: CT-based RP prediction model integrating radiomics and dosiomics features from multiple ROIs outperformed those with features from a single ROI with increased reliability for EC patients who underwent RT., (© 2024. The Author(s).)

Purpose: To investigate the feasibility and performance of deep learning (DL) models combined with plan complexity (PC) and dosiomics features in the patient-specific quality assurance (PSQA) for patients underwent volumetric modulated arc therapy (VMAT)., Methods: Total of 201 VMAT plans with measured PSQA results were retrospectively enrolled and divided into training and testing sets randomly at 7:3. PC metrics were calculated using house-built algorithm based on Matlab. Dosiomics features were extracted and selected using Random Forest (RF) from planning target volume (PTV) and overlap regions with 3D dose distributions. The top 50 dosiomics and 5 PC features were selected based on feature importance screening. A DL DenseNet was adapted and trained for the PSQA prediction., Results: The measured average gamma passing rate (GPR) of these VMAT plans was 97.94% ± 1.87%, 94.33% ± 3.22%, and 87.27% ± 4.81% at the criteria of 3%/3 mm, 3%/2 mm, and 2%/2 mm, respectively. Models with PC features alone demonstrated the lowest area under curve (AUC). The AUC and sensitivity of PC and dosiomics (D) combined model at 2%/2 mm were 0.915 and 0.833, respectively. The AUCs of DL models were improved from 0.943, 0.849, 0.841 to 0.948, 0.890, 0.942 in the combined models (PC + D + DL) at 3%/3 mm, 3%/2 mm and 2%/2 mm, respectively. A best AUC of 0.942 with a sensitivity, specificity and accuracy of 100%, 81.8%, and 83.6% was achieved with combined model (PC + D + DL) at 2%/2 mm., Conclusions: Integrating DL with dosiomics and PC metrics is promising in the prediction of GPRs in PSQA for patients underwent VMAT., (© 2023. The Author(s).)

Background: The development of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has dramatically improved the prognosis of patients with EGFR-mutant non-small-cell lung cancer (NSCLC). The purpose of this study is to investigate the clinical outcome with or without EGFR-TKI resistance before WBRT and the sequence between EGFT-TKIs and whole brain radiotherapy (WBRT) of EGFR-mutant NSCLC patients who developed multiple brain metastases (BMs)., Patients and Methods: Three hundred forty-four EGFR-mutant NSCLC patients with multiple BMs were reviewed. Enrolled patients were divided into TKI-naïve group and TKI-resistant group. The intracranial progression-free survival (PFS) and overall survival (OS) were analyzed via the Kaplan-Meier method., Results: For patients with multiple BMs treated by WBRT, the median intracranial PFS and OS were longer in the TKI-naïve group than those in the TKI-resistant group, but there were no statistically significant between two groups (Intracranial PFS: 7.7 vs. 5.4 months, p = 0.052; OS: 11.2 vs. 9.2 months, p = 0.106). For patients with Lung-molGPA 0-2, no significant differences in median intracranial PFS (6.2 vs. 5.2 months, p = 0.123) and OS (7.8 vs. 6.7 months, p = 0.514) between TKI-naïve and TKI-resistant groups. For patients with Lung-molGPA 2.5-4, intracranial PFS: 12.8 vs. 10.1 months; OS: 23.3 vs. 15.3 months., Conclusions: Our study found that there were no difference in intracranial PFS and OS in all patients between the two groups of TKI-naïve and TKI-resistant. But for patients in subgroup of Lung-molGPA 2.5-4, there were a better intracranial PFS and OS in TKI-naïve group.

Background: Prophylactic cranial irradiation (PCI) is indicated for limited-stage small cell lung cancer (LS-SCLC) with good response to chemoradiotherapy (CRT). However, brain metastasis (BM) developed in LS-SCLC before PCI is not rare. In this study, we comprehensively investigated the features of pre-PCI BMs, aiming to explore the potential of PCI optimization for LS-SCLC., Methods: One-hundred-ten LS-SCLC patients achieving clinical complete remission after definitive CRT with contrast-enhanced cranial magnetic resonance imaging (MRI) at baseline and immediately before PCI were included. The time trend and risk factors for pre-PCI BM were evaluated. Several radiological features, including numbers, sizes, and locations of pre-PCI BMs, were investigated to explore the technical feasibility of stereotactic radiotherapy and hippocampal-avoidance (HA) PCI., Results: Twenty-four (21.8%) of the LS-SCLC patients harbored pre-PCI BM, all except one were asymptomatic. CRT duration (CRT-D) was the only independent risk factor for pre-PCI BM. The pre-PCI BM rate gradually increased in line with a growing time interval between treatment initiation and pre-PCI MRI. Pre-PCI BM and prolonged CRT-D were both correlated with worse overall survival. Of 129 pre-PCI intracranial lesions, 2 (1.5%) were in the HA region. Eight of the 24 (33.3%) pre-PCI BM patients were ineligible for stereotactic radiotherapy., Conclusion: Our findings suggest that PCI is still of importance in LS-SCLC, and MRI evaluation before PCI is indispensable. Investigations are warranted to explore the possibility of moving PCI up to before CRT completion in LS-SCLC patients with prolonged CRT-D. HA-PCI could be considered to reduce neurotoxicity.

Background: Despite development of several next-generation tyrosine kinase inhibitors (TKIs), crizotinib remains one of the first-line treatment options for advanced ALK-positive NSCLC and is widely used in situations where next-generation TKIs aren't yet approved or economically inaccessible. However, the pattern of failure and clinical value of radiotherapy in metastatic crizotinib-treated ALK-mutant lung cancer, with or without baseline brain metastases (BBM), are largely unknown., Methods: Consecutive crizotinib-treated NSCLC patients with adequate imaging and measurable disease were retrospectively enrolled. Disease progression in original sites (primary/metastatic), new sites, or both, are classified as original failure (OF), distant failure (DF) and ODF, respectively. Progression free survival, from crizotinib initiation to the first disease progression, and from that to the second disease progression, were calculated as PFS1 and PFS2., Results: Ninety-three patients were identified. With a median follow up of 22.0 (range, 2.0-72.0) months, 52 patients had crizotinib-treatment failure. The frequencies of OF, ODF, and DF, were 50.0, 26.9, and 23.1%, respectively. Histology, primary tumor size and presence of BBM, were independently associated with OF, using competing risks analyses. The brain was the most common site of initial disease progression. Patients with BBM had a significant higher possibility developing multiple-progressive lesions in the brain (p = 0.002). Importantly, four of the ten patients who had baseline oligo-metastatic cranial disease but didn't receive upfront brain radiation, developed multiple-progressive disease in the brain. Brain radiation before crizotinib could alter the disease failure patterns and improve PFS1 among patients with BBM (p = 0.006). Extracranial radiation was efficient in controlling symptoms but it was not associated with PFS1 (p = 0.223), and the majority of patients were eligible for salvage radiotherapy upon disease progression to crizotinib. By the time of data cut-off, 28 patients had second disease progression, with a median PFS2 of 7.0 (95% CI 5.4-8.6) months and salvage radiotherapy significantly prolonged PFS2 (p = 0.003). Additionally, patients receiving any radiotherapy during their treatment course had a significant longer overall survival (p = 0.048)., Conclusions: Among patients with baseline oligo-metastatic brain lesions which are suitable for stereotactic radiosurgery, upfront brain radiotherapy provides considerable clinical benefits. While, extracranial radiation may be deferred in asymptomatic patients with multiple-metastatic lesions.

Background: In the era of intensity-modulated radiotherapy (IMRT), the role of additional concurrent chemotherapy (CC) to radiotherapy (RT) after induction chemotherapy (IC) compared to IC followed by RT alone remains unclear for stage II-IVB nasopharyngeal carcinoma (NPC) patients. The aim of this study was to evaluate the efficacy and toxicities of IC/RT and IC/CCRT in the treatment of NPC with volumetric modulated arc therapy (VMAT)., Methods: From January 2012 to March 2016, a total of 217 NPC patients were retrospectively assessed. Of the 217 patients, 139 patients received IC followed by VMAT alone and 78 patients received IC plus CCRT. Overall survival (OS), progression-free survival (PFS) and toxicities were assessed., Results: The 5-year OS, PFS rates were 57.5%, 41.8% and 47.8%, 38.4% for the IC/RT and IC/CCRT arms, respectively, without significant difference in survival between the two groups (both p > 0.05). Multivariate analysis indicated that treatment modality (IC/RT vs. IC/CCRT) was not an independent prognostic factor for OS or PFS. Grade 3-4 leukopenia/neutropenia (3.60% vs. 20.51%, p < 0.001), gastrointestinal disorder (nausea/vomiting/diarrhea, 2.16% vs. 41.03%, p < 0.001), mucositis (29.50% vs. 47.44%, p = 0.01) and xerostomia (34.53% vs. 48.72%, p = 0.04) were more frequent in the IC/ CCRT arm than in the IC/RT arm during VMAT., Conclusions: No significant difference in OS and PFS was observed between IC plus VMAT alone and IC/CCRT in the treatment of stage II-IVB NPC patients, however, more side effects were observed in the IC/CCRT arm.

Objective: The purpose of this study is to investigate the dosimetric advantages of volumetric modulated arc therapy (VMAT) in the treatment of intraocular cancer by comparing it directly with three-dimensional conformal radiotherapy (CRT) and intensity-modulated radiotherapy (IMRT)., Methods: CRT plan, 7f-IMRT plan, and one-arc VMAT plan were generated for 14 intraocular cancer patients. Dosimetric and biological quality indices for target volume and organs at risks (OARs) were evaluated and compared., Results: The target coverage presented by V95 for CRT, IMRT and VMAT were 95.02% ± 0.67%, 95.51% ± 2.25%, and 95.92% ± 3.05%, respectively. The homogeneity index (HI) for CRT, IMRT and VMAT were 0.15 ± 0.05, 0.23 ± 0.05, and 0.23 ± 0.06, respectively. IMRT and VMAT greatly decreased the dose to ipsilateral lens compared with CRT with a D1 of 2972.66 ± 1407.12 cGy, 3317.82 ± 915.28 cGy and 4809.54 ± 524.60 cGy for IMRT, VMAT and CRT, respectively. Similar results were observed for ipsilateral eyeballs. IMRT and VMAT also spared better on brainstem, optical nerves and optical chiasm compared CRT. However, CRT achieved lower dose to the eyeballs compared with IMRT and VMAT. VMAT and IMRT showed mixed results on target coverage and OAR sparing. The average MUs and delivery time of IMRT and VMAT were 531.25 ± 81.21 vs. 400.99 ± 61.49 and 5.05 ± 0.53 vs.1.71 ± 0.69 min, respectively., Conclusions: Although no clear distinction on PTV coverage among CRT, IMRT and VMAT plans was observed in the treatment of intraocular cancer, VMAT and IMRT achieved better homogeneity and conformity for target volume, and delivered fewer doses to ipsilateral lens and eyeballs compared with CRT. However, VMAT and IMRT increased the low dose volume to the contralateral OARs. Although VMAT and IMRT showed mixed results on target coverage and OAR sparing, VMAT decreased MU and delivery time significantly compared with IMRT. VMAT is a promising and feasible external beam radiotherapy technique in the treatment of intraocular cancer patients.

Purpose: To investigate the feasibility of constant dose rate volumetric modulated arc therapy (CDR-VMAT) in the treatment of nasopharyngeal cancer (NPC) patients and to introduce rotational arc radiotherapy for linacs incapable of dose rate variation., Materials and Methods: Twelve NPC patients with various stages treated previously using variable dose rate (VDR) VMAT were enrolled in this study. CDR-VMAT, VDR-VMAT and mutlicriteria optimization (MCO) VMAT plans were generated for each patient on RayStation treatment planning system with identical objective functions and the dosimetric differences among these three planning schemes were evaluated and compared. Non dosimetric parameters of optimization time, delivery time and delivery accuracy were also evaluated., Results: The planning target volume of clinical target volume (PTV-CTV) coverage of CDR-VMAT was a bit inferior to those of VDR- and MCO-VMAT. The V93 (p=0.01) and V95 (percent volume covered by isodose line) (p=0.04) for CDR-VMAT, VDR-VMAT and MCO-VMAT were 98.74% ± 0.31%, 99.76% ± 0.16%, 99.38% ± 0.43%, and 98.40% ± 0.48%, 99.53% ± 0.28%, 99.07% ±0.52%, respectively. However, the CDR-VMAT showed a better dose homogeneity index (HI) (p=0.01) in PTV-CTV. No significant difference in other target coverage parameters was observed. There was no significant difference in OAR sparing among these three planning schemes except for a higher maximum dose (Dmax) on the brainstem for CDR-VMAT. The brainstem Dmax of CDR-VMAT, VDR-VMAT and MCO-VMAT were 54.26 ± 3.21 Gy, 52.19 ± 1.65 Gy, and 52.79 ± 4.77 Gy, respectively. The average delivery time (p<0.01) and the average percent γ passing rates (p=0.02) of CDR-VMAT, VDR-VMAT and MCO-VMAT were 7.01 ± 0.43 min, 4.75 ± 0.07 min, 4.01 ± 0.28 min, and 95.75% ± 2.57%, 97.65% ± 1.45%, 97.36% ± 2.45%, respectively., Conclusion: CDR-VMAT offers an additional option of rotational arc radiotherapy for linacs incapable of dose rate variation with a lower initial cost. Its plan quality was acceptable but should be thoroughly checked compared with VDR-VMAT and MCO-VMAT in the treatment of NPC.

Objective: To investigate the anatomic and dosimetric variations of volumetric modulated arc therapy (VMAT) in the treatment of nasopharyngeal cancer (NPC) patients based on weekly cone beam CT (CBCT)., Materials and Methods: Ten NPC patients treated by VMAT with weekly CBCT for setup corrections were reviewed retrospectively. Deformed volumes of targets and organs at risk (OARs) in the CBCT were compared with those in the planning CT. Delivered doses were recalculated based on weekly CBCT and compared with the planned doses., Results: No significant volumetric changes on targets, brainstem, and spinal cord were observed. The average volumes of right and left parotid measured from the fifth CBCT were about 4.4 and 4.5 cm3 less than those from the first CBCT, respectively. There were no significant dose differences between average planned and delivered doses for targets, brainstem and spinal cord. For right parotid, the delivered mean dose was 10.5 cGy higher (p = 0.004) than the planned value per fraction, and the V26 and V32 increased by 7.5% (p = 0.002) and 7.4% (p = 0.01), respectively. For the left parotid, the D50 (dose to the 50% volume) was 8.8 cGy higher (p = 0.03) than the planned values per fraction, and the V26 increased by 8.8% (p = 0.002)., Conclusion: Weekly CBCTs were applied directly to study the continuous volume changes and resulting dosimetric variations of targets and OARs for NPC patients undergoing VMAT. Significant volumetric and dosimetric variations were observed for parotids. Replanning after 30 Gy will benefit the protection on parotids.

Background: To investigate the feasibility and benefits of a modified adaptive radiotherapy (ART) by replanning in the initial CT (iCT) with new contours from a repeat CT (rCT) based on CT-CT image fusion for nasopharyngeal cancer (NPC) patients underwent volumetric modulated arc radiotherapy (VMAT)., Materials and Methods: Nine NPC patients underwent VMAT treatment with a rCT at 23rd fraction were enrolled in this study. Dosimetric differences for replanning VMAT plans in the iCT and in the rCT were compared. Volumetric and dosimetric changes of gross tumor volume (GTV) and organs at risk (OARs) of this modified ART were also investigated., Results: No dosimetric differences between replanning in the iCT and in the rCT were observed. The average volume of GTV decreased from 78.83 ± 38.42 cm3 in the iCT to 71.44 ± 37.46 cm3 in the rCT, but with no significant difference (p = 0.42).The average volume of the left and right parotid decreased from 19.91 ± 4.89 cm3 and 21.58 ± 6.16 cm3 in the iCT to 11.80 ± 2.79 cm3 and 13.29 ± 4.17 cm3 in the rCT (both p < 0.01), respectively. The volume of other OARs did not shrink very much. No significant differences on PTVGTV and PTVCTV coverage were observed for replanning with this modified ART. Compared to the initial plans, the average mean dose of the left and right parotid after re-optimization were decreased by 62.5 cGy (p = 0.05) and 67.3 cGy (p = 0.02), respectively, and the V5 (the volume receiving 5 Gy) of the left and right parotids were decreased by 7.8% (p = 0.01) and 11.2% (p = 0.001), respectively. There was no significant difference on the dose delivered to other OARs., Conclusion: Patients with NPC undergoing VMAT have significant anatomic and dosimetric changes to parotids. Repeat CT as an anatomic changes reference and re-optimization in the iCT based on CT-CT image fusion was accurate enough to identify the volume changes and to ensure safe dose to parotids.