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Abstract The relative frequency of primary cutaneous lymphoma (PCL) subtypes shows wide variation across different geographical regions. This retrospective study was conducted in a tertiary referral center located in Korea to describe the relative frequency, demographics, survival outcomes, and temporal trend in PCL. A total of 627 PCL cases diagnosed between January 1994 and December 2022 were included. The majority of PCL cases (87.2%) were of T-/NK-cell lineage (CTCL), while the remaining cases (12.8%) were B-cell lineage lymphomas (CBCL). The prevalence of mycosis fungoides (MF) in CTCL increased significantly over time, while other CTCL subtypes, including primary cutaneous extranodal NK/T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma (SPTCL), decreased in frequency. Notably, the prevalence of CD4-positive small/medium T-cell lymphoproliferative disorder showed a substantial increase over time. Primary cutaneous marginal zone lymphoma was consistently the commonest CBCL subtype. Survival analysis demonstrated that CTCL had a more favorable 5-year overall survival (OS) than CBCL. OS rate of MF, SPTCL, and primary cutaneous peripheral T-cell lymphoma, NOS improved significantly over time. This study provides comprehensive insights into the dynamic change in the relative frequency and overall survival of PCL subtypes over time.

Abstract Background The B7-H3 protein, encoded by the CD276 gene, is a member of the B7 family of proteins and a transmembrane glycoprotein. It is highly expressed in various solid tumors, such as lung and breast cancer, and has been associated with limited expression in normal tissues and poor clinical outcomes across different malignancies. Additionally, B7-H3 plays a crucial role in anticancer immune responses. Antibody-drug conjugates (ADCs) are a promising therapeutic modality, utilizing antibodies targeting tumor antigens to selectively and effectively deliver potent cytotoxic agents to tumors. Methods In this study, we demonstrate the potential of a novel B7-H3-targeting ADC, ITC-6102RO, for B7-H3-targeted therapy. ITC-6102RO was developed and conjugated with dHBD, a soluble derivative of pyrrolobenzodiazepine (PBD), using Ortho Hydroxy-Protected Aryl Sulfate (OHPAS) linkers with high biostability. We assessed the cytotoxicity and internalization of ITC-6102RO in B7-H3 overexpressing cell lines in vitro and evaluated its anticancer efficacy and mode of action in B7-H3 overexpressing cell-derived and patient-derived xenograft models in vivo. Results ITC-6102RO inhibited cell viability in B7-H3-positive lung and breast cancer cell lines, inducing cell cycle arrest in the S phase, DNA damage, and apoptosis in vitro. The binding activity and selectivity of ITC-6102RO with B7-H3 were comparable to those of the unconjugated anti-B7-H3 antibody. Furthermore, ITC-6102RO proved effective in B7-H3-positive JIMT-1 subcutaneously xenografted mice and exhibited a potent antitumor effect on B7-H3-positive lung cancer patient-derived xenograft (PDX) models. The mode of action, including S phase arrest and DNA damage induced by dHBD, was confirmed in JIMT-1 tumor tissues. Conclusions Our preclinical data indicate that ITC-6102RO is a promising therapeutic agent for B7-H3-targeted therapy. Moreover, we anticipate that OHPAS linkers will serve as a valuable platform for developing novel ADCs targeting a wide range of targets.

Abstract Introduction Non‐small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation has a higher incidence of brain metastases than wild‐type EGFR mutations. Osimertinib, a third‐generation EGFR tyrosine kinase inhibitor (TKI), targets both EGFR‐TKI sensitizing and T790M‐resistance mutations and has a higher brain penetration rate relative to first‐ and second‐generation EGFR‐TKIs. Therefore, osimertinib has become a preferred first‐line therapy for advanced EGFR mutation‐positive NSCLC. However, lazertinib, an emerging EGFR‐TKI, has shown higher selectivity toward EGFR mutations and improved penetration of the blood–brain barrier compared to osimertinib in preclinical studies. This trial will evaluate the efficacy of lazertinib as a first‐line therapy in patients with EGFR mutation‐positive NSCLC who have brain metastases, with or without additional local therapy. Methods This is a single‐center, open‐label, single‐arm phase II trial. A total of 75 patients with advanced EGFR mutation‐positive NSCLC will be recruited. Eligible patients will receive oral lazertinib 240 mg, once daily until disease progression or intolerable toxicity is detected. Patients with moderate to severe symptoms related to brain metastasis will simultaneously receive local therapy for the brain. The primary endpoints are progression‐free survival and intracranial progression‐free survival. Discussion Lazertinib, in combination with local therapy for the brain, if necessary, is expected to improve the clinical benefit in advanced EGFR mutation‐positive NSCLC with brain metastases, as a first‐line treatment.

Hypofractionated radiotherapy schedules provide higher per-fraction radiation doses delivered in fewer fractions than conventional schedules. This novel delivery method is supported by a large body of clinical trial evidence across various cancer sites in both curative and palliative settings. Hypofractionation is associated with benefits such as lower costs, improved patient access and increased treatment precision, which has led to its inclusion in various treatment guidelines. Despite this, utilization is not uniform across cancer sites and geographic regions due to reasons such as reimbursement models, nuances in healthcare systems, and professional culture. Key factors to ensure patients benefit from access to high quality radiotherapy include publishing clinical evidence, cross-country collaboration to fill knowledge gaps, reviewing reimbursement models, and improving patient advocacy in treatment decision-making.

Abstract Metastatic colorectal cancer (CRC) remains a substantial problem for mortality and requires screening and early detection efforts to increase survival. Epithelial-mesenchymal transition (EMT) and circulation of tumor cells in the blood play important roles in metastasis. To identify a novel target for metastasis of CRC, we conducted a gene microarray analysis using extracted RNA from the blood of preclinical models. We found that NCK-associated protein 1 (NCKAP1) was significantly increased in the blood RNA of patient-derived xenograft (PDX) models of colon cancer. In the NCKAP1 gene knockdown-induced human colon cancer cell lines HCT116 and HT29, there was a reduced wound healing area and significant inhibition of migration and invasion. As the result of marker screening for cytoskeleton and cellular interactions, CRC treated with siRNA of NCKAP1 exhibited significant induction of CDH1 and phalloidin expression, which indicates enhanced adherent cell junctions and cytoskeleton. In HCT116 cells with a mesenchymal state induced by TGFβ1, metastasis was inhibited by NCKAP1 gene knockdown through the inhibition of migration, and there was increased CTNNB1 expression and decreased FN expression. We established metastasis models for colon cancer to liver transition by intrasplenic injection shRNA of NCKAP1-transfected HCT116 cells or by implanting tumor tissue generated with the cells on cecal pouch. In metastasis xenograft models, tumor growth and liver metastasis were markedly reduced. Taken together, these data demonstrate that NCKAP1 is a novel gene regulating EMT that can contribute to developing a diagnostic marker for the progression of metastasis and new therapeutics for metastatic CRC treatment.

Abstract Purpose This study aimed to investigate the differences in characteristics, clinical stages, treatment modalities, and survival outcomes in patients with non‐small‐cell lung cancer (NSCLC) based on sex differences using Korean nationwide registry data. Methods We analyzed the data of 8650 patients diagnosed with NSCLC between 2014 and 2017, obtained from the Korean Association for Lung Cancer Registry (KALC‐R). The Cox proportional hazard model was used to define the differences in survival based on sex. Propensity score matching was used to adjust for differences between men and women. Results Of a total of 10 943 patients, 8650 (79.1%) were diagnosed with NSCLC, of whom 68.7% were men and 31.3% were women. For NSCLC, the median age was higher (69.0 vs. 67.0, p

Abstract Background Immunotherapy has been administered to many patients with non-small-cell lung cancer (NSCLC). However, only few studies have examined toxicity in patients receiving an immune checkpoint inhibitor (ICI) after concurrent chemoradiotherapy (CCRT). Therefore, we performed a retrospective study to determine factors that predict radiation pneumonitis (RP) in these patients. Methods We evaluated the size of the planning target volume, mean lung dose (MLD), and the lung volume receiving more than a threshold radiation dose (VD) in 106 patients. The primary endpoint was RP ≥ grade 2, and toxicity was evaluated. Results After CCRT, 51/106 patients were treated with ICI. The median follow-up period was 11.5 months (range, 3.0–28.2), and RP ≥ grade 2 occurred in 47 (44.3%) patients: 27 and 20 in the ICI and non-ICI groups, respectively. Among the clinical factors, only the use of ICI was associated with RP (p = 0.043). Four dosimetric variables (MLD, V20, V30, and V40) had prognostic significance in univariate analysis for occurrence of pneumonitis (hazard ratio, p-value; MLD: 2.3, 0.009; V20: 2.9, 0.007; V30: 2.3, 0.004; V40: 2.5, 0.001). Only V20 was a significant risk factor in the non-ICI group, and MLD, V30, and V40 were significant risk factors in the ICI group. The survival and local control rates were superior in the ICI group than in the non-ICI group, but no significance was observed. Conclusions Patients receiving ICI after definitive CCRT were more likely to develop RP, which may be related to the lung volume receiving high-dose radiation. Therefore, several factors should be carefully considered for patients with NSCLC.

Abstract Purpose Data are lacking regarding pulmonary rehabilitation (PR) programs in patients with lung cancer receiving radiation therapy. This study aimed to confirm the feasibility of an outpatient‐based PR program in lung cancer patients during radiation therapy. Methods A retrospective chart review was performed of 40 patients with lung cancer who had undergone radiation therapy between July and December 2019. The patients received an outpatient‐based PR program for a total of eight sessions two times weekly comprising 60 min per session. Feasibility was assessed based on the completion rate, adverse events, and satisfaction with the PR program. Functional evaluations using 6‐min walk and grip strength tests were conducted before and after PR. Patient quality of life was assessed by the EORTC QLQ‐C30 questionnaire before and after PR. Results The completion rate for the PR program was 72.5% among the 40 patients. No adverse events related to PR were reported. The overall satisfaction was 5.7 ± 1.1 on a seven‐point Likert scale in all participants. The mean 6‐min walk test distance increased significantly from 419.1 to 446.2 m. The improvement in grip strength in the dominant hand after PR was not significant. The social functioning score in the EORTC QLQ‐C30 improved significantly. Conclusion The results of this study showed the feasibility without serious adverse effects of a 4‐week outpatient‐based PR program for lung cancer patients undergoing outpatient‐based radiation therapy. This program might improve patient physical function and quality of life.

Background Radiotherapy is a common treatment option for lung or esophageal cancer, particularly when surgery is not feasible for patients with poor lung function. However, radiotherapy can affect pulmonary function and thereby induce pneumonitis or pneumonia, which can be fatal in patients with respiratory impairment. The purpose of this study is to evaluate if reductions in pulmonary function after radiotherapy can be minimized through simultaneous pulmonary rehabilitation (PR). Methods In this matched case control study, we retrospectively analyzed patients who had undergone radiotherapy for thoracic malignant disease between January 2018 and June 2019. We analyzed results from pulmonary function tests and 6-minute walking tests (6MWT) conducted within the six months before and after radiotherapy treatment. Results In total, results from 144 patients were analyzed, with 11 of the patients receiving PR and radiotherapy simultaneously. Of the 133 patients in the control group, 33 were matched with 11 patients in the PR group. Changes in forced expiratory volume in one second (FEV1) and FEV1/forced vital capacity were significantly different between the PR group and the matched control group (240 mL vs. −10 mL, p=0.017 and 5.5% vs. 1.0%, p=0.038, respectively). The median distance of 6MWT in the PR group also increased significantly, from 407.5 m to 493.0 m after radiotherapy (p=0.017). Conclusion Simultaneous PR improved pulmonary function, particularly in measures of FEV1, and exercise capacity for patients with lung or esophageal cancer even after radiotherapy treatment. These findings may provide an important base of knowledge for further large population studies with long-term follow-up analysis in the identification of the PR’s effects during thoracic radiotherapy.

The uncertainties of four-dimensional computed tomography (4DCT), also called as residual motion artefacts (RMA), induced from irregular respiratory patterns can degrade the quality of overall radiotherapy. This study aims to quantify and reduce those uncertainties. A comparative study on quantitative indicators for RMA was performed, and based on this, we proposed a new 4DCT sorting method that is applicable without disrupting the current clinical workflow. In addition to the default phase sorting strategy, both additional amplitude information from external surrogates and the quantitative metric for RMA, investigated in this study, were introduced. The comparison of quantitative indicators and the performance of the proposed sorting method were evaluated via 10 cases of breath-hold (BH) CT and 30 cases of 4DCT. It was confirmed that N-RMSD (normalised root-mean-square-deviation) was best matched to the visual standards of our institute's regime, manual sorting method, and could accurately represent RMA. The performance of the proposed method to reduce 4DCT uncertainties was improved by about 18.8% in the averaged value of N-RMSD compared to the default phase sorting method. To the best of our knowledge, this is the first study that evaluates RMA indicators using both BHCT and 4DCT with visual-criteria-based manual sorting and proposes an improved 4DCT sorting strategy based on them.

Abstract Human epidermal growth factor receptor 2 (HER2) is overexpressed in breast and gastric cancers and this causes poor clinical outcomes. Although both T‐DM1 and Enhertu are approved as an HER2‐targeting antibody‐drug conjugate (ADC), the effects of these drugs are still not satisfactory to eradicate diverse tumors expressing HER2. To address this shortfall in HER2‐targeted therapeutics, an elaborate cleavable linker is created and a novel HER2‐targeting ADC composed with trastuzumab and monomethyl auristatin F, which is being investigated in a phase 1 clinical trial and is referred to as LegoChem Bisciences‐ADC (LCB‐ADC). LCB‐ADC displays a higher cytotoxic potency than T‐DM1 and it also has a higher G2/M arrest ratio. In animal studies, LCB‐ADC produces noticeable tumor growth inhibition compared with trastuzumab or T‐DM1 in an HER2 high‐expressing N87 xenograft tumor. Especially, LCB‐ADC shows good efficacy in terms of suppressing tumor growth in a patient‐derived xenograft (PDX) model of HER2‐positive gastric cancer as well as in T‐DM1‐resistant models such as HER2 low‐expressing HER2 low expressing JIMT‐1 xenograft tumor and PDX. Collectively, the results demonstrate that LCB‐ADC with the elaborate linker has a higher efficacy and greater biostability than its ADC counterparts and may successfully treat cancers that are nonresponsive to previous therapeutics.

Abstract Background Systemic inflammation plays a critical role in cancer progression and oncologic outcomes in cancer patients. We investigated whether preoperative inflammatory biomarkers, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil to lymphocyte ratio (NLR), could be surrogate biomarkers for predicting overall survival (OS) in soft tissue sarcoma (STS) patients treated with surgery and postoperative radiotherapy. Methods A series of 99 patients who presented with localized extremity STS were retrospectively reviewed. The preoperative CRP levels, ESR, and NLR were evaluated for associations with OS, disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS). Cutoff values for CRP, ESR, and NLR were derived from receiver-operating characteristic curve analysis. Results Elevated CRP (> 0.14 mg/dL), ESR (> 15 mm/h), and NLR (> 1.95) levels were seen in 33, 44, and 45 patients, respectively. Of these three inflammatory biomarkers, elevated CRP and ESR were associated with a poorer OS (CRP: P = 0.050; ESR: P = 0.001), DFS (CRP: P = 0.023; ESR: P = 0.003), and DMFS (CRP: P = 0.015; ESR: P = 0.001). By multivariate analysis, an elevated ESR was found to be an independent prognostic factor for OS (HR 3.580, P = 0.025) and DMFS (HR 3.850, P = 0.036) after adjustment for other established prognostic factors. Conclusions The preoperative ESR level is a simple and useful surrogate biomarker for predicting survival outcomes in STS patients and might improve the identification of high-risk patients of tumor relapse in clinical practice.

Background Radiation pneumonitis is one of the most harmful and clinically significant complications of radiotherapy. This study investigated the benefits of nebulized acetylcysteine for lung cancer patients diagnosed with radiation pneumonitis after radiotherapy. Methods We prospectively enrolled and followed 25 patients with radiation pneumonitis who used nebulized acetylcysteine three times a day for 12 weeks. We also reviewed the medical records of 106 control patients who had undergone radiotherapy for lung cancer but had not used acetylcysteine. We evaluated the effects of nebulized acetylcysteine by comparing visits 1 and 4 among nebulizer users and by comparing the acetylcysteine group with the control group. Results Twenty‐five acetylcysteine group patients and 101 control group patients were included in the analyses. The mean patient‐rated severity score associated with sputum production decreased in the acetylcysteine group between visits 1 and 4 (from 1.10 to 0.95; P = 0.08). None of the patients used additional expectorant agents after using nebulized acetylcysteine and critical adverse events were not reported. The acetylcysteine group had a shorter mean duration of expectorant use among patients whose radiation pneumonitis required steroid therapy and covered > 10% of a single lung field on computed tomography (37.2 vs. 78.1 days, respectively; P = 0.07). Conclusions The beneficial effects of nebulized acetylcysteine for patients with radiation pneumonitis included relieving sputum severity and minimizing expectorant use, especially in severe cases. Further investigation is required to clarify and expand on the benefits of nebulized acetylcysteine for patients with radiation pneumonitis.

Background: A multimodal approach is the standard treatment for desmoplastic small round cell tumor (DSRCT); however, many patients are diagnosed with inoperable disease, which leaves chemotherapy as the only treatment option. There are limited data on the effectiveness of palliative chemotherapy, especially when used after first-line treatment. Here, we evaluated the clinical outcomes of patients with DSRCT treated with multiple lines of chemotherapy. Methods: We reviewed medical records of 14 patients with pathologically confirmed DSRCT at Asan Medical Center between 2004 and 2018. Results: The median age at diagnosis was 25, with males comprising 92.9% of patients. All patients had inoperable disease at presentation and received chemotherapy as the initial treatment. Four patients (28.6%) were treated with surgery, and complete resection was achieved in 1 patient. Median overall survival (OS) was 23.9 months, and 1-, 2-, and 3-year survival rates were 92.9%, 48.6%, and 19.5%, respectively. In patients receiving first- (N = 14), second- (N = 10), and third-line (N = 8) chemotherapy, median time-to-progression was 9.9, 3.5, and 2.5 months, respectively, and the disease control rates were 100%, 88.9%, and 75.0%, respectively. Factors associated with longer OS in the univariable analysis were ⩽2 metastatic sites at presentation (27.0 vs 14.7 months; P = .024) and surgery with intended complete resection (43.5 vs 20.1 months; P = .027). Conclusions: Although advanced DSRCT may initially respond to chemotherapy after first-line treatment, the response becomes less durable as the disease progresses. Individualized treatment decisions focused on palliation should be made.

Abstract Background Combined stereotactic body radiotherapy (SBRT) for lung lesions and conventional radiotherapy (CRT) for nodal areas may be more effective than CRT alone in patients with locally advanced lung cancer. Methods This study included 21 patients with small primary lung tumors distant from the regional nodal areas. The SBRT dose was 40–60 Gy in 4 fractions. CRT doses were 66 Gy in 30 fractions for non-small cell lung cancer and 52.5 Gy in 25 fractions for small cell lung cancer. Results The median follow-up duration was 12 months, and the median survival was 13 months. The 1 year overall survival, local recurrence-free survival, and distant metastasis-free survival rates were 60.5, 84.8, and 62.1%, respectively. Two patients experienced in-field local recurrence combined with out-field regional recurrence and/or distant failure. The major recurrence pattern was distant failure (crude incidence, 43%). Three patients aged ≥79 years experienced grade ≥ 3 acute radiation pneumonitis, and one also had idiopathic interstitial pneumonia. Conclusion The combination of SBRT for the lung lesion and CRT for the nodal region seems to be effective and safe for lung malignancies. However, patients older in age and/or with underlying pulmonary disease require stricter lung dose constraints.

Abstract Background To evaluate the role of radiotherapy (RT) as an adjuvant or definitive treatment in primary tracheal adenoid cystic carcinoma (ACC) for local tumor control and survival. Methods A retrospective chart review was performed in 22 patients treated with adjuvant or definitive RT for primary tracheal ACC at a single center between November 1994 and December 2008. Results Thirteen and 9 patients received adjuvant and definitive RT, respectively. Microscopic residual disease after surgery was pathologically reported in 11 patients. The median RT dose was 59.4 Gy for adjuvant and 74.4 Gy for definitive RT. The overall response rate for definitive RT was 77.8%. Six patients in the definitive RT group exhibited local progression (LP), whereas 14 patients in both groups exhibited distant metastasis. The most common recurrence site in cases of treatment failure was the lung parenchyma. The median follow-up duration was 123 months, and the 10-year overall survival (OS) rate was 54.2%. Although LP was the most common cause of death (4 patients), two-thirds of the patients treated with definitive RT lived for >5 years. The 5-year and 10-year LP-free survival (LPFS) rates in the definitive RT group were 66.7 and 26.7%, respectively. Patients with higher RT dose by brachytherapy boost had good 5-year OS, 83.3%, and showed no local progression till 5-years. Most of the RT-induced side-effects were mild and tolerable, but 2 patients died of tracheal stenosis without any tumor recurrence. Conclusions Adjuvant RT may be suitable for controlling microscopic residual disease, whereas definitive RT may yield appropriate long-term survival in >50% patients with unresectable tracheal ACC. Dose escalation should be considered to warrant long-term survival in definitive RT.

PurposeThis study aimed to evaluate the dosimetric accuracy of respiratory gated volumetric modulated arc therapy (VMAT) for lung stereotactic body radiation therapy (SBRT) under simulation conditions similar to the actual clinical situation using patient-specific lung phantoms and realistic target movements.MethodsSix heterogeneous lung phantoms were fabricated using a 3D-printer (3DISON, ROKIT, Seoul, Korea) to be dosimetrically equivalent to actual target regions of lung SBRT cases treated via gated VMAT. They were designed to move realistically via a motion device (QUASAR, Modus Medical Devices, Canada). Using the lung phantoms and a homogeneous phantom (model 500-3315, Modus Medical Devices), film dosimetry was performed with and without respiratory gating for VMAT delivery (TrueBeam STx; Varian Medical Systems, Palo Alto, CA, USA). The measured results were analyzed with the gamma passing rates (GPRs) of 2%/1 mm criteria, by comparing with the calculated dose via the AXB and AAA algorithms of the Eclipse Treatment Planning System (version 10.0.28; Varian Medical Systems).ResultsGPRs were greater than the acceptance criteria 80% for all film measurements with the stationary and homogeneous phantoms in conventional QAs. Regardless of the heterogeneity of phantoms, there were no significant differences (p > 0.05) in GPRs obtained with and without target motions; the statistical significance (p = 0.031) was presented between both algorithms under the utilization of heterogeneous phantoms.ConclusionsDosimetric verification with heterogeneous patient-specific lung phantoms could be successfully implemented as the evaluation method for gated VMAT delivery. In addition, it could be dosimetrically confirmed that the AXB algorithm improved the dose calculation accuracy under patient-specific simulations using 3D printed lung phantoms.

PURPOSE:To develop a 4D dose reconstruction method and to evaluate the delivered dose in respiratory-gated volumetric modulated arc therapy (VMAT). MATERIALS AND METHODS:A total 112 treatment sessions of gated VMAT for 30 stereotactic body radiotherapy (SBRT) patients (10 lung, 10 liver, and 10 pancreas) were evaluated. For respiratory-gated SBRT, 4DCT was acquired, and the CT data at the end-exhale phase was used for a VMAT plan. The delivered dose was reconstructed using a patient's respiratory motion and machine motion acquired during the beam delivery. The machine motion was obtained from the treatment log file, while the target position was estimated from an external respiratory marker position. The target position was divided into 1-mm position bins, and sub-beams with beam isocenters corresponding to each position bin were created in a motion mimicking plan, reflecting motion data including MLC leaf positions and gantry angle and target position data during beam treatment. The reconstructed 4D dose was compared with the dose of the original plan using these dosimetric parameters; the maximum dose (Dmax) and mean dose (Dmean) of gross target volume (GTV) or organs at risk (spinal cord, esophagus, heart, duodenum, kidney, spinal cord, and stomach). The minimum dose (Dmin) to GTV was also calculated to verify cold spots in tumors. RESULTS:There was no significant difference of dose parameters regard to the GTV in all tumors. For the liver cases, there were significant differences in the Dmax of duodenum (-4.2 ± 1.4%), stomach (-3.5 ± 4.2%), left kidney (-4.1 ± 2.8%), and right kidney (-3.2 ± 1.3%), and in the Dmean of duodenum (-3.8 ± 1.4%), stomach (-3.9 ± 2.2%), left kidney (-3.1 ± 2.8%), and right kidney (-4.1 ± 2.6%). For the pancreas cases, there were significant differences in the Dmax of stomach (2.1 ± 3.0%), and in the Dmean of liver (1.5 ± 0.6%), duodenum (-1.0 ± 1.4%), stomach (2.1 ± 1.6%), and right kidney (-1.3 ± 0.9%). The average gamma pass rates were 97.6 ± 4.8% for lung cases, 99.6 ± 0.5% for liver cases, and 99.5 ± 0.5% for pancreas cases. Most cases showed insignificant dose variation, with gamma pass rates higher than 98%, except for two lung cases with gamma pass rates of 86.9% and 90.6%. The low gamma pass rates showed larger global motion ranges resulting from the baseline shift during beam delivery. CONCLUSION:The actual delivered dose in thoracic and abdominal VMAT under breathing motion was verified by 4D dose reconstruction using typical treatment equipment and software. The proposed method provides a verification method for the actual delivered dose and could be a dosimetric verification QA tool for radiation treatment under various respiratory management techniques.

PURPOSE:To develop a simplified volumetric modulated arc therapy (VMAT) technique for more accurate dose delivery in thoracic stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS:For each of the 22 lung SBRT cases treated with respiratory-gated VMAT, a dose rate modulated arc therapy (DrMAT) plan was retrospectively generated. A dynamic conformal arc therapy plan with 33 adjoining coplanar arcs was designed and their beam weights were optimized by an inverse planning process. All sub-arc beams were converted into a series of control points with varying MLC segment and dose rates and merged into an arc beam for a DrMAT plan. The plan quality of original VMAT and DrMAT was compared in terms of target coverage, compactness of dose distribution, and dose sparing of organs at risk. To assess the delivery accuracy, the VMAT and DrMAT plans were delivered to a motion phantom programmed with the corresponding patients' respiratory signal; results were compared using film dosimetry with gamma analysis. RESULTS:The plan quality of DrMAT was equivalent to that of VMAT in terms of target coverage, dose compactness, and dose sparing for the normal lung. In dose sparing for other critical organs, DrMAT was less effective than VMAT for the spinal cord, heart, and esophagus while being well within the limits specified by the Radiation Therapy Oncology Group. Delivery accuracy of DrMAT to a moving target was similar to that of VMAT using a gamma criterion of 2%/2mm but was significantly better using a 2%/1mm criterion, implying the superiority of DrMAT over VMAT in SBRT for thoracic/abdominal tumors with respiratory movement. CONCLUSION:We developed a DrMAT technique for SBRT that produces plans of a quality similar to that achieved with VMAT but with better delivery accuracy. This technique is well-suited for small tumors with motion uncertainty.

Purpose: This study aimed to assess the real-world clinical outcomes of consolidative durvalumab in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) and to explore the role of radiotherapy in the era of immunotherapy. Materials and Methods: This retrospective study assessed 171 patients with unresectable LA-NSCLC who underwent concurrent chemoradiotherapy (CCRT) with or without consolidative durvalumab at Asan Medical Center between May 2018 and May 2021. Primary outcomes included freedom from locoregional failure (FFLRF), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS). Results: Durvalumab following CCRT demonstrated a prolonged median PFS of 20.9 months (p=0.048) and a 3-year FFLRF rate of 57.3% (p=0.008), compared to 13.7 months and 38.8%, respectively, with CCRT alone. Furthermore, the incidence of in-field recurrence was significantly greater in the CCRT-alone group compared to the durvalumab group (26.8% vs. 12.4%, p=0.027). While median OS was not reached with durvalumab, it was 35.4 months in patients receiving CCRT alone (p=0.010). Patients positive for programmed cell death ligand 1 (PD-L1) expression showed notably better outcomes, including FFLRF, DMFS, PFS, and OS. Adherence to PACIFIC trial eligibility criteria identified 100 patients (58.5%) as ineligible. The use of durvalumab demonstrated better survival regardless of eligibility criteria. Conclusion The use of durvalumab consolidation following CCRT significantly enhanced locoregional control and OS in patients with unresectable LA-NSCLC, especially in those with PD-L1-positive tumors, thereby validating the role of durvalumab in standard care. [ABSTRACT FROM AUTHOR]

Purpose: Surface-guided radiation therapy is an image-guided method using optical surface imaging that has recently been adopted for patient setup and motion monitoring during treatment. We aimed to determine whether the surface guide setup is accurate and efficient compared to the skin-marking guide in prostate cancer treatment. Materials and Methods: The skin-marking setup was performed, and vertical, longitudinal, and lateral couch values (labeled as "M") were recorded. Subsequently, the surface-guided setup was conducted, and couch values (labeled as "S") were recorded. After performing cone-beam computed tomography (CBCT), the final couch values was recorded (labeled as "C"), and the shift value was calculated (labeled as "Gap (M-S)," "Gap (M-C)," "Gap (S-C)") and then compared. Additionally, the setup times for the skin marking and surface guides were also compared. Results: One hundred and twenty-five patients were analyzed, totaling 2,735 treatment fractions. Gap (M-S) showed minimal differences in the vertical, longitudinal, and lateral averages (-0.03 cm, 0.07 cm, and 0.06 cm, respectively). Gap (M-C) and Gap (S-C) exhibited a mean difference of 0.04 cm (p = 0.03) in the vertical direction, a mean difference of 0.35 cm (p = 0.52) in the longitudinal direction, and a mean difference of 0.11 cm (p = 0.91) in the lateral direction. There was no correlation between shift values and patient characteristics. The average setup time of the skin-marking guide was 6.72 minutes, and 7.53 minutes for the surface guide. Conclusion: There was no statistically significant difference between the surface and skin-marking guides regarding final CBCT shift values and no correlation between translational shift values and patient characteristics. We also observed minimal difference in setup time between the two methods. Therefore, the surface guide can be considered an accurate and time-efficient alternative to skin-marking guides. [ABSTRACT FROM AUTHOR]

Purpose: An optimal once-daily radiotherapy (RT) regimen is under investigation for definitive concurrent chemoradiotherapy (CCRT) in limited disease small cell lung cancer (LD-SCLC). We compared the efficacy and safety of dose escalation with intensity-modulated radiotherapy (IMRT). Materials and Methods: Between January 2016 and March 2021, patients treated with definitive CCRT for LD-SCLC with IMRT were retrospectively reviewed. Patients who received a total dose <50 Gy or those with a history of thoracic RT or surgery were excluded. The patients were divided into two groups (standard and dose-escalated) based on the total biologically effective dose (BED, α/β = 10) of 70 Gy. The chemotherapeutic regimen comprised four cycles of etoposide and cisplatin. Results: One hundred and twenty-two patients were analyzed and the median follow-up was 27.8 months (range, 4.4 to 76.9 months). The median age of the patients was 63 years (range, 35 to 78 years) and the majority had a history of smoking (86.0%). The 1- and 3-year overall survival rates of the escalated dose group were significantly higher than those of the standard group (93.5% and 50.5% vs. 76.7% and 33.3%, respectively; p = 0.008), as were the 1- and 3-year freedom from infield failure rates (91.4% and 66.5% vs. 73.8% and 46.9%, respectively; p = 0.018). The incidence of grade 2 or higher acute and late pneumonitis was not significantly different between the two groups (p = 0.062, 0.185). Conclusion: Dose-escalated once-daily CCRT with IMRT led to improved locoregional control and survival, with no increase in toxicity. [ABSTRACT FROM AUTHOR]