BACKGROUND: Small-field dosimetry plays a pivotal role in stereotactic body radiation therapy (SBRT), where high-precision dose delivery is essential. In multi-institutional clinical trials, quality assurance (QA) becomes increasingly critical due to the variability in linear accelerator (linac) output calibration and treatment planning system (RTPS) configurations. Conventional relative dose factor, which assess relative dose outputs, lack absolute dose information and thus cannot verify the consistency of linac calibration or monitor unit (MU)-to-dose conversion across institutions. These limitations may compromise treatment quality and undermine the integrity of clinical trials. Therefore, an enhanced QA method that incorporates absolute dosimetry is required. PURPOSE: This study introduces and implements a novel credentialing procedure for small-field dosimetry in SBRT clinical trials using the absorbed dose per MU, expressed in cGy/MU. By integrating absolute dose information into the verification process, this method aims to evaluate both linac output calibration and small-field modeling accuracy across institutions. METHODS: A nationwide dosimetric survey was conducted involving 545 beams from 120 institutions participating in Japan Clinical Oncology Group (JCOG) trials. Treatment plans were created in each institution's RTPS by prescribing 10 Gy to the isocenter for square field sizes of 2 × 2 to 10 × 10 cm2. Doses were calculated at depths of 5 and 10 cm in a virtual water phantom under a fixed source-to-surface distance of 90 cm. The absorbed dose per MU values were calculated and compared against multicenter averages stratified by linac type and beam energy. A ±3% tolerance criterion was applied for credentialing. Institutions with deviations were contacted and corrective actions were taken as needed. RESULTS: Of the 545 beams analyzed, 97.8% met the ±3% tolerance criteria. Discrepancies in the ten beams were attributed to small-field beam modeling errors or incorrect RTPS MU-to-dose settings, which were subsequently corrected through feedback. Although variations were observed between the dose calculation algorithms and RTPSs, the differences were within 0.6%, 0.4%, and 1.6%, respectively. The credentialing process proved robust in standardizing dose calculations for clinical trial participation. CONCLUSION: The proposed absorbed dose per MU-based method enables comprehensive small-field dosimetry evaluation by incorporating absolute dose verification into the credentialing process. This approach effectively identifies calibration inconsistencies that are not detectable using traditional relative dose factor methods. Its application across a large cohort of institutions demonstrated high accuracy and inter-institutional consistency, reinforcing its utility as a practical QA tool in SBRT clinical trials. By enhancing standardization in RTPS performance and linac output verification, this method strengthens the foundation of safe and reliable SBRT implementation in multi-center clinical research.

Stereotactic radiosurgery (SRS) involves steep dose gradients and small irradiation fields, which makes ensuring irradiation accuracy extremely important. While general semiconductor array detectors are reusable and cost-effective, their wide detector spacing results in insufficient spatial resolution. The aim of this study is to establish a novel patient-specific quality assurance (PSQA) method for single-isocenter multiple-target SRS volumetric modulated arc therapy (SIMT-SRS-VMAT) that can evaluate dose distribution with the same accuracy as radiochromic film by virtually narrowing the detector spacing by combining measurement with a general semiconductor array detector and translational movement of the treatment couch. Single-field plans with a single target and SIMT-SRS-VMAT plans with two targets were created for 1 cm lesions. Measurements using MapCHECK2 (Sun Nuclear, Melbourne, FL, USA) were combined with couch movement to synthesize measurement data at virtual detector spacings of 5, 4, 3, 2, and 1 mm. Root mean square error (RMSE) was used to evaluate profile shape accuracy, and γ analysis was used to evaluate dose distribution agreement. At virtual detector spacings of 10 mm, 5 mm, 4 mm, 3 mm, 2 mm, 1 mm, and with radiochromic film, the RMSE values in SIMT-SRS-VMAT were 8.02% ± 0.34%, 2.16% ± 0.07%, 1.60% ± 0.08%, 1.48% ± 0.17%, 1.32% ± 0.10%, 1.38% ± 0.03%, and 1.25% ± 0.02%, respectively. The RMSE decreased as the detector spacing narrowed, resulting in profile shapes comparable to those obtained with radiochromic film. In γ analysis, setting the virtual detector spacing to 5 mm enabled analysis covering the entire dose range, and the γ pass rate was comparable to EBT4 (Ashland Inc., Wayne, NJ, USA) for all tolerances. This study established a novel method of verification of dose distribution with the same accuracy as film, combining measurement with a general semiconductor array detector and translational movement of the treatment couch. With this approach, specialized high-resolution SRS array detectors and disposable radiochromic film are not needed, making SRS PSQA less costly and manpower-intensive.

BACKGROUND AND PURPOSE: Oligometastatic disease represents limited metastatic burden, and local ablative therapies such as stereotactic body radiotherapy (SBRT) may improve survival. However, inter-institutional variability in target segmentation and treatment planning can compromise treatment quality. This study aimed to evaluate the segmentation variability and dose distribution quality of SBRT in oligometastatic settings using a multi-institutional dummy run approach. METHODS AND MATERIALS: Sixty-nine institutions were provided with two anonymized cases of adrenal and spine metastases to delineate targets and organs at risk (OARs) and create intensity-modulated radiotherapy plans following a protocol. Variability was quantified using the Dice similarity coefficient (DSC), Hausdorff distance, and mean distance to agreement. Plan qualities were assessed using the Paddick conformity index, modified gradient index, and a new three-dimensional conformity-gradient index (3D-CGI). Knowledge-based planning (KBP) was applied to explore potential improvements in OAR sparing. RESULTS: All submitted plans met protocol dose constraints. However, substantial segmentation variability was observed, particularly for the spine case. Among 136 plans, 79% demonstrated acceptable conformity and dose gradients, with 3D-CGI < 6 correlating with favorable distributions. Mean DSC was 0.93 for the clinical target volume and 0.76 for the cauda equina, which showed the highest variability. KBP reduced OAR doses for the adrenal case but showed limited impact for the spine case. CONCLUSIONS: Although dose constraints were achieved, segmentation variability remained substantial, particularly for the cauda equina in the spine case. These findings emphasize inter-institutional differences and the need for standardization and tools to improve SBRT consistency.

PURPOSE: The aim of this study was to investigate the prognostic impact of thoracic extra-regional lymph node metastasis (M1b-LYM, determined by the 12th edition of the Japanese Classification of Esophageal Cancer) in definitive radiotherapy for esophageal squamous cell carcinoma. METHODS: Eighty-six consecutive patients who underwent definitive radiotherapy for esophageal squamous cell carcinoma between 2017 and 2022 at our institute were included in this retrospective study. Progression-free survival (PFS), overall survival (OS), distant metastasis (DM), and loco-regional recurrence (LR) were compared between patients with and without M1b-LYM using Kaplan-Meier or cumulative incidence function analysis. RESULTS: Among the 86 patients, 15 had M1b-LYM metastasis (the M1b( +) group) and 71 had no M1b-LYM metastasis (the M1b(-) group). The median follow-up period was 38 months. The 2-year PFS, OS, cumulative incidence of DM, and cumulative incidence of LR for the M1b(-) group versus M1b( +) group were 41% vs 20% (p = 0.129), 58% vs 47% (p = 0.172), 31% vs 33% (p = 0.906), and 31% vs 60% (p = 0.0369), respectively. Multivariate analysis showed that M1b( +) was associated with higher LR (p = 0.0350), T stage was associated with poorer PFS (p = 0.0138), and omitting chemotherapy was associated with poorer PFS (p = 0.0160) and OS (p < 0.01). CONCLUSION: The presence of thoracic extra-regional lymph node metastasis was associated with poor loco-regional control but not distant metastasis or survival in esophageal squamous cell carcinoma patients after definitive radiotherapy. TRIAL REGISTRATION NUMBER: This study was retrospectively registered on 21 June 2024 (R06-053).

PURPOSE: This study aimed to assess the potential of prognostic factors including consolidation tumor ratio (CTR) on treatment outcomes in patients with clinical stage 0-IA non-small cell lung cancer (NSCLC) undergoing stereotactic body radiotherapy (SBRT). METHODS: The analysis included data of 63 patients with 67 lesions of clinical stage 0-IA NSCLC treated with SBRT. According to the Union for International Cancer Control 8th edition, the following tumor stages were observed: Tis, 3; T1mi, 2; T1a, 11; T1b, 29; and T1c, 22. The prescribed dose was 48 (range, 42-52) Gy in four fractions. RESULTS: The median follow-up was 29.3 (range: 2.4-120.5) months. The five-year local control (LC), overall survival, and progression-free survival (PFS) rates were 89.4%, 60.3%, and 40.5%, respectively. Squamous cell carcinoma (Sq) and Dmax < 125 GyBED10 for planning target volume (PTV) were associated with a worse LC (p = 0.001 and 0.017, respectively). Patients with Sq, T1b-c, CTR > 0.25, PTV ≥ 30 cm3 tumors were associated with worse PFS than those with non-Sq, ≤ cT1a, CTR ≤ 0.25, PTV < 30 cm3 tumors (p = 0.049, 0.004, 0.038, and 0.004, respectively). No recurrences, metastases, or deaths were found in patients with CTR ≤ 0.25 (n = 5). CONCLUSION: In patients with stage 0-IA lung cancer treated with SBRT, tumors classified as ≤ T1a showed a better PFS than T1b-c. NSCLC with a low CTR of ≤ 0.25 seemed to have a low risk of recurrence after SBRT.

BACKGROUND: For delivering high radiation doses to pancreatic tumors, organ motion management is indispensable; however, studies on this are limited. We aimed to evaluate the efficacy and safety of dynamic tumor tracking (DTT) moderately hypofractionated intensity-modulated radiotherapy (IMRT) in patients with locally advanced pancreatic cancer (LAPC). METHODS: Patients with histological confirmation for LAPC were included. A linac system, which was mounted with a gimbal function, was used for DTT-IMRT. The prescribed dose was 48 Gy in 15 fractions. The primary endpoint was the 1-year rate of freedom from locoregional progression (FFLP). RESULTS: DTT-IMRT was successfully administered in 25 patients enrolled from four institutions. The median range of respiratory motion during DTT-IMRT was 9.8 mm (range: 3.5-27.3 mm), and the median tracking accuracy was 2.6 mm (range: 0.7-5.2 mm). With a median follow-up period of 13.9 months, the 1-year FFLP rate was 75.3% (lower limit of one-sided 80% confidence interval [CI]: 60.2%), which satisfied the predetermined primary endpoint. One-year locoregional progression-free survival, progression-free survival, and overall survival were 56.0% (95% CI: 34.8%-72.7%), 44.0% (95% CI: 24.5%-61.9%), and 60.0% (95% CI: 38.4%-76.1%), respectively. Regarding nonhematologic toxicities, grade 3 acute gastrointestinal (GI) toxicity was observed in two patients (8%), and two patients (8%) each experienced grade 3 late GI and non-GI toxicities. No grade 4 or 5 nonhematologic toxicities were observed. CONCLUSIONS: DTT moderately hypofractionated IMRT shows preferable locoregional control without significant toxicity in patients with LAPC. TRIAL REGISTRATION: UMIN000017521.

BACKGROUND AND PURPOSE: This study aims to externally validate a predictive model for distant metastasis (DM) with computed tomography (CT)-based radiomics features in prospectively enrolled non-small-cell lung cancer patients undergoing dynamic tumor-tracking stereotactic body radiation therapy (DTT-SBRT). MATERIALS AND METHODS: The study collected retrospective data from 567 patients across 11 institutions as the training dataset and prospectively enrolled 42 patients from four institutions as the external test dataset. Four clinical features were collected, and 944 CT-based radiomic features were extracted from gross tumor volumes. After standardization and feature selection, DM predictive models were developed using fine and gray regression (FG) and random survival forest (RSF), incorporating clinical and radiomic features, and their combinations within the training dataset. Then, the model was applied to the test dataset, dividing patients into high- and low-risk groups based on medians of risk scores. Model performance was assessed using the concordance index (C-index), and the statistical significance between groups was evaluated using Gray's test. RESULTS: In the training dataset, 122 of 567 patients (21.5%) developed DM, compared to 9 of 42 patients (21.4%) in the test dataset. In the test dataset, the C-indices of the clinical, radiomics, and hybrid models with FG were 0.559, 0.544, and 0.560, respectively, whereas those with RSF were 0.576, 0.604, and 0.627, respectively. The hybrid model with RSF, which exhibited the best predictive performance of all models, identified 7 of 23 patients (30.4%) as high risk and 2 of 19 patients (10.5%) as low risk for DM incidence in the test dataset (p = 0.116). CONCLUSION: Although predictive models for DM lack significance when applied to prospectively enrolled cases undergoing DTT-lung SBRT, the model with RSF exhibits a consistent capacity to effectively classify patients at a high risk of developing DM.

BACKGROUND AND PURPOSE: Symptomatic radiation pneumonitis (SRP) is a complication of thoracic stereotactic body radiotherapy (SBRT). As visual assessments pose limitations, artificial intelligence-based quantitative computed tomography image analysis software (AIQCT) may help predict SRP risk. We aimed to evaluate high-resolution computed tomography (HRCT) images with AIQCT to develop a predictive model for SRP. MATERIALS AND METHODS: AIQCT automatically labelled HRCT images of patients treated with SBRT for stage I lung cancer according to lung parenchymal pattern. Quantitative data including the volume and mean dose (Dmean) were obtained for reticulation + honeycombing (Ret + HC), consolidation + ground-glass opacities, bronchi (Br), and normal lungs (NL). After associations between AIQCT's quantified metrics and SRP were investigated, we developed a predictive model using recursive partitioning analysis (RPA) for the training cohort and assessed its reproducibility with the testing cohort. RESULTS: Overall, 26 of 207 patients developed SRP. There were significant between-group differences in the Ret + HC, Br-volume, and NL-Dmean in patients with and without SRP. RPA identified the following risk groups: NL-Dmean ≥ 6.6 Gy (high-risk, n = 8), NL-Dmean < 6.6 Gy and Br-volume ≥ 2.5 % (intermediate-risk, n = 13), and NL-Dmean < 6.6 Gy and Br-volume < 2.5 % (low-risk, n = 133). The incidences of SRP in these groups within the training cohort were 62.5, 38.4, and 7.5 %; and in the testing cohort 50.0, 27.3, and 5.0 %, respectively. CONCLUSION: AIQCT identified CT features associated with SRP. A predictive model for SRP was proposed based on AI-detected Br-volume and the NL-Dmean.

BACKGROUND: Differences in radiation-induced lymphopenia and prognosis between methods of radiotherapy (RT) for brain metastases remain unclear. METHODS: In this retrospective analysis of patients who underwent whole-brain radiotherapy (WBRT) or stereotactic radiosurgery/radiotherapy (SRS/SRT) for brain metastases, baseline total lymphocyte count (TLC) data were obtained within 2 weeks before RT initiation. Follow-up TLC data were evaluated at 0-2, 2-4, and 4-8 weeks after RT completion. Persistent lymphopenia was defined as <800/μL at any time point. RESULTS: Overall, 138 RT courses in 128 patients were eligible (94 WBRT; 44 SRS/SRT). In the WBRT courses, the median baseline TLC was 1325/μL (IQR: 923-1799). Follow-up TLC decreased significantly to 946/μL (626-1316), 992/μL (675-1291), and 1075/μL (762-1435) (p < 0.001). SRS/SRT courses showed no significant TLC decrease. Multivariate analysis revealed female sex, prior RT, baseline TLC < 800/μL, and WBRT use were significantly associated with persistent lymphopenia. In the WBRT group, overall survival was significantly different between those with and without persistent lymphopenia (median, 2.6 and 6.1 months; p < 0.001). However, there was no significant difference in survival in the SRS/SRT group (p = 0.60). CONCLUSION: This study suggests SRS/SRT might be preferable for lymphocyte preservation in brain metastasis patients.

BACKGROUND: Surgery is the standard care for patients with early-stage lung cancer, and stereotactic body radiation therapy is an option for those who are medically inoperable or refuse surgery. Medical developments in diagnostic and therapeutic strategies would prolong prognosis of patients with cancer. The number of patients with multiple cancers has also increased. Duplex primary malignant neoplasms are the most common, and triple or more primary malignant neoplasms were extremely rare. This is the first case of sextuple primary malignant neoplasms with lung cancer. CASE PRESENTATION: We report a case of two courses of stereotactic body radiation therapy for an 88-year-old Japanese male patient with six primary cancers in five organs. Cancers were detected in the thyroid, prostate, esophagus, bladder, and lungs. He also had a history of angina pectoris and had undergone percutaneous coronary intervention. Although he was capable of undergoing surgery for lung cancers, he refused it because he had experienced many invasive treatments, such as surgeries and percutaneous coronary intervention. In January 2020, the first stereotactic body radiation therapy was performed for the adenocarcinoma in the right lung. In March 2022, the second stereotactic body radiation therapy was performed for the nodule of the left lung. Although he complained of mild dyspnea after the first stereotactic body radiation therapy, we did not use steroids because his peripheral oxygen saturation was within the normal range. He had pleural effusion, cardiac dilatation, and pericardial effusion 2 months after the second stereotactic body radiation therapy, which improved with the use of compression stockings. CONCLUSION: A total of 43 and 17 months have passed since the first and second stereotactic body radiation therapy, respectively, there is no local recurrence and the patient can walk independently. We safely performed stereotactic body radiation therapy twice for our older patient with metachronous early-stage lung cancers. If another new tumor is detected, stereotactic body radiation therapy would be a good treatment option for the functional preservation of organs.

PURPOSE: The Lung-mol graded prognostic assessment (GPA) system predicts the prognosis of patients with brain metastases (BM) from non-small cell lung cancer (NSCLC) separately for adenocarcinoma and non-adenocarcinoma. This study aimed to validate the Lung-molGPA system using a cohort of patients in our institution who received radiotherapy for BM. MATERIALS AND METHODS: Three hundred and thirty-nine patients with NSCLC who received their first course of radiotherapy for BM were included in the analysis. Among them, 65 received their second course of radiotherapy for BM. Data on sex, age, Karnofsky performance status (KPS), extracranial metastases (ECM), number of BM, histological type, and gene mutations were collected according to the Lung-molGPA system. We examined the validity of the scores assigned to the factors included in the Lung-molGPA system, separately for adenocarcinoma and non-adenocarcinoma. In addition, we validated the Lung-molGPA system to predict survival during both the first and second courses of radiotherapy. RESULTS: The factors in the Lung-molGPA were significantly associated with survival, except for age in non-adenocarcinoma with marginal significance. Regarding discrimination ability, the C-indices were 0.65 and 0.69 for adenocarcinoma and non-adenocarcinoma, respectively, in the first course of radiotherapy for BM, while those in the second course were 0.62 and 0.74, respectively. Survival prediction by Lung-molGPA was almost consistent with actual survival in the first course of radiotherapy, except for the score of 0-1.0 in both histologies and 2.5-3.0 in non-adenocarcinoma. In the second course of radiotherapy, median survival could be predicted for some patients with adenocarcinoma. CONCLUSIONS: Our study confirms the validity of Lung-molGPA for the estimation of median survival based on patient characteristics at the time of initiation of radiotherapy for patients in the first course of radiotherapy and shows that it may be applicable to patients with adenocarcinoma in the second course of radiotherapy.

Surgery is the standard treatment for stage I non-small cell lung cancer (NSCLC); however, no clear randomized trial demonstrates its superiority to stereotactic body radiotherapy (SBRT) regarding survival. We aimed to retrospectively evaluate the treatment outcomes of SBRT in operable patients with stage I NSCLC using a large Japanese multi-institutional database to show real-world outcome. Exactly 399 patients (median age 75 years; 262 males and 137 females) with stage I (IA 292, IB 107) histologically proven NSCLC (adenocarcinoma 267, squamous cell carcinoma 96, others 36) treated at 20 institutions were reviewed. SBRT was prescribed at a total dose of 48-70 Gy in 4-10 fractions. The median follow-up period was 38 months. Local progression-free survival rates were 84.2% in all patients and 86.1% in the T1, 78.6% in T2, 89.2% in adenocarcinoma, and 70.5% in squamous cell subgroups. Overall 3-year survival rates were 77.0% in all patients: 90.7% in females, 69.6% in males, and 41.2% in patients with pulmonary interstitial changes. Fatal radiation pneumonitis was observed in two patients, all of whom had pulmonary interstitial changes. This real-world evidence will be useful in shared decision-making for optimal treatment, including SBRT for operable stage I NSCLC, particularly in older patients.

The emergence of an aging society and technological advances have made radiotherapy, especially stereotactic body radiotherapy (SBRT), a common alternative to surgery for elderly patients with early stage non-small-cell lung cancer (NSCLC). Carbon-ion radiotherapy (CIRT) is also an attractive treatment option with potentially lower toxicity for elderly patients with comorbidities. We compared the clinical outcomes of the two modalities using Japanese multicenter data. SBRT (n = 420) and single-fraction CIRT (n = 70) data for patients with stage I NSCLC from 20 centers were retrospectively analyzed. Contiguous patients ≥ 80 years of age were enrolled, and overall survival (OS), disease-specific survival (DSS), local control (LC), and adverse event rates were compared. The median age was 83 years in both groups and the median follow-up periods were 28.5 and 42.7 months for SBRT and CIRT, respectively. The 3-year OS, DSS, and LC rates were 76.0% vs. 72.3% (p = 0.21), 87.5% vs. 81.6% (p = 0.46), and 79.2% vs. 78.2% (p = 0.87), respectively, for the SBRT vs. CIRT groups. Regarding toxicity, 2.9% of the SBRT group developed grade ≥ 3 radiation pneumonitis, whereas none of the CIRT group developed grade ≥ 2 radiation pneumonitis. SBRT and CIRT in elderly patients showed similar survival and LC rates, although CIRT was associated with less severe radiation pneumonitis.

BACKGROUND AND PURPOSE: This prospective multicenter phase II study aimed to evaluate the safety and efficacy of dynamic tumor tracking (DTT) stereotactic body radiotherapy (SBRT) with real-time monitoring of liver tumors using a gimbal-mounted system. MATERIALS AND METHODS: Patients with < 4 primary or metastatic liver tumors with diameters ≤ 50 mm and expected to have a respiratory motion of ≥ 10 mm were eligible. The prescribed dose was 40 Gy in five fractions. The primary endpoint was local control (LC) at 2 years. The secondary endpoints were overall survival (OS), progression-free survival (PFS), treatment-related toxicity, and tracking accuracy. RESULTS: Between September 2015 and March 2019, 48 patients (48 lesions) with a median age of 74 years were enrolled from four institutions. Of these, 39 were diagnosed with hepatocellular carcinoma and nine with metastatic liver cancer. The median tumor diameter was 17.5 mm. DTT-SBRT was successfully performed in all patients; the median treatment time was 28 min/fraction. The median follow-up period was 36.5 months. The 2-year LC, OS, and PFS rates were 98.0 %, 88.8 %, and 55.1 %, respectively. Disease progression was observed in 33 (68.8 %) patients. One patient (0.2 %) had local recurrence, 31 (64.6 %) developed new hepatic lesions outside the irradiation field, and nine (18.8 %) had distant metastases (including overlap). Grade 3 late adverse events were observed in seven patients (14.5 %). No grade 4 or 5 treatment-related toxicity was observed. The median tracking accuracy was 2.9 mm. CONCLUSION: Employing DTT-SBRT to treat liver tumors results in excellent LC with acceptable adverse-event incidence.

Stereotactic body radiotherapy (SBRT), a type of external beam radiotherapy, yields local control of hepatocellular carcinoma (HCC) at rates as high as 90%. SBRT has been recognized as an alternative therapy for patients for whom standard modalities such as surgery (resection or transplantation) or ablation are deemed unsuitable. SBRT has the potential to improve the prognosis of HCC, as it can be used as an adjunct to other treatment modalities. The assessment of post-SBRT images of the treated tumor and surrounding normal liver tissue requires special attention. Future research is warranted to determine how best to use SBRT versus other therapies and how to combine them.

PURPOSE: The feasibility of a deep learning-based markerless real-time tumor tracking (RTTT) method was retrospectively studied with orthogonal kV X-ray images and clinical tracking records acquired during lung cancer treatment. METHODS: Ten patients with lung cancer treated with marker-implanted RTTT were included. The prescription dose was 50 Gy in four fractions, using seven- to nine-port non-coplanar static beams. This corresponds to 14-18 X-ray tube angles for an orthogonal X-ray imaging system rotating with the gantry. All patients underwent 10 respiratory phases four-dimensional computed tomography. After a data augmentation approach, for each X-ray tube angle of a patient, 2250 digitally reconstructed radiograph (DRR) images with gross tumor volume (GTV) contour labeled were obtained. These images were adopted to train the patient and X-ray tube angle-specific GTV contour prediction model. During the testing, the model trained with DRR images predicted GTV contour on X-ray projection images acquired during treatment. The predicted three-dimensional (3D) positions of the GTV were calculated based on the centroids of the contours in the orthogonal images. The 3D positions of GTV determined by the marker-implanted RTTT during the treatment were considered as the ground truth. The 3D deviations between the prediction and the ground truth were calculated to evaluate the performance of the model. RESULTS: The median GTV volume and motion range were 7.42 (range, 1.18-25.74) cm3 and 22 (range, 11-28) mm, respectively. In total, 8993 3D position comparisons were included. The mean calculation time was 85 ms per image. The overall median value of the 3D deviation was 2.27 (interquartile range: 1.66-2.95) mm. The probability of the 3D deviation smaller than 5 mm was 93.6%. CONCLUSIONS: The evaluation results and calculation efficiency show the proposed deep learning-based markerless RTTT method may be feasible for patients with lung cancer.

Chemoradiotherapy followed by consolidation durvalumab (CCRT+D) improves survival in patients with stage III non-small-cell lung cancer (NSCLC). We compared recurrence patterns and survival in the CCRT+D and CCRT cohorts. We conducted a multicenter, retrospective study in Japan. Patients who received CCRT for stage III NSCLC were included in this study. Of 178 eligible patients, 136 were in the CCRT+D and 42 were in the CCRT cohorts. Locoregional recurrence (LR), LR plus distant metastases (DM), and DM were observed in 20.6%, 8.8%, 27.9% of the CCRT+D, and 26.2%, 16.7% and 33.3% of the CCRT cohorts, respectively. In-field recurrence was the most common LR pattern in both cohorts. Squamous cell carcinoma and PD-L1 expression < 1%, and female sex and EGFR mutations were significantly associated with an increased risk of LR and DM. In patients with any risk factors for LR, the incidence of LR was similar in the CCRT+D and CCRT (39.5% vs 45.5%). The 24 month progression-free survival (PFS) and overall survival (OS) were 40.3% and 69.4% in the CCRT+D and 24.7% and 61.0% in the CCRT cohorts, respectively. Poor performance status and no consolidation durvalumab were significantly associated with shorter PFS. There was a significant difference in PFS between the CCRT+D and CCRT in the propensity score-matched cohort (HR = 0.51, P = 0.005). In conclusion, consolidation durvalumab decreased both LR and DM, and significantly improved PFS. However, in-field recurrence was still a major problem, as well as DM.

We applied two propensity score-based analyses to simultaneously compare three treatment modalities-stereotactic body radiotherapy (SBRT), lobectomy, or sublobar resection (SLR)-for stage I non-small cell lung cancer (NSCLC), with the aim of clarifying the average treatment effect (ATE) and formulating a risk-adapted approach to treatment selection. A retrospective review of 823 patients aged ≥65 years who underwent SBRT, lobectomy, or SLR for stage I NSCLC was conducted. The following two analyses using machine learning-based propensity scores were performed: (i) propensity score weighting (PSW) to assess the ATE in the entire cohort, and (ii) propensity score subclassification (PSS) to evaluate treatment effects of subgroups. PSW showed no significant difference in the 5-year overall survival (OS) between SBRT and SLR (60.0% vs 61.2%; P = 0.70) and significant difference between SBRT and lobectomy (60.0% vs 77.6%; P = 0.026). Local (LR) and distant recurrence (DR) rates were significantly lower in lobectomy than in SBRT, whereas there was no significant difference between SBRT and SLR. PSS identified four subgroups with different patient characteristics: lobectomy-oriented (5-year cumulative incidences of non-lung cancer death, 7.5%), SLR-oriented (14.2%), SBRT-oriented (23.8%) and treatment-neutral subgroups (16.1%). Each subgroup showed different survival trends regarding the three treatments. The ATE of SBRT was not significantly different from that of SLR, but it was inferior to lobectomy. Four subgroups with different risks of non-lung cancer death and different survival trends for each treatment were identified. These would help decision-making for patients with stage I NSCLC.

Prophylactic cranial irradiation (PCI) is recommended for patients with limited-stage small-cell lung cancer (LS-SCLC) who respond well to initial treatment. However, PCI is often omitted because of its potential neurotoxicity in the era of modern diagnostic imaging devices. In the present study, we aimed to investigate the risk factors for brain metastasis (BM) in patients eligible for PCI and who may benefit more from it. Patients with LS-SCLC who responded well to definitive thoracic chemoradiotherapy were included in the present study. Competing risk regression was used to identify factors associated with BM, and the Kaplan-Meier method was used to assess overall survival (OS). Between 2004 and 2017, 62 patients were eligible for PCI and were analyzed. Of these, 38 (61.3%) underwent PCI. Overall, 17 patients (27.4%) developed BM, with a 2-year cumulative incidence of 22.8%. Multivariate analysis (MVA) revealed that pretreatment elevated pro-gastrin-releasing peptide (ProGRP) levels were associated with an increased risk for BM (HR, 7.96, P = 0.0091). PCI tended to reduce the risk of BM (HR, 0.33; P = 0.051). The use of PCI was associated with improved OS in patients with ProGRP levels > 410 pg/mL (P = 0.008), but not in those with ProGRP ≤ 410 pg/mL (P = 0.9). Pretreatment ProGRP levels may be useful in predicting the development of BM in patients with LS-SCLC who achieved a good response to initial therapy and to determine which patients should undergo PCI.

Prophylactic cranial irradiation (PCI) is recommended for patients with limited-stage small-cell lung cancer (LS-SCLC) who respond well to initial treatment. However, PCI is often omitted because of its potential neurotoxicity in the era of modern diagnostic imaging devices. In the present study, we aimed to investigate the risk factors for brain metastasis (BM) in patients eligible for PCI and who may benefit more from it. Patients with LS-SCLC who responded well to definitive thoracic chemoradiotherapy were included in the present study. Competing risk regression was used to identify factors associated with BM, and the Kaplan–Meier method was used to assess overall survival (OS). Between 2004 and 2017, 62 patients were eligible for PCI and were analyzed. Of these, 38 (61.3%) underwent PCI. Overall, 17 patients (27.4%) developed BM, with a 2-year cumulative incidence of 22.8%. Multivariate analysis (MVA) revealed that pretreatment elevated pro-gastrin-releasing peptide (ProGRP) levels were associated with an increased risk for BM (HR, 7.96, P = 0.0091). PCI tended to reduce the risk of BM (HR, 0.33; P = 0.051). The use of PCI was associated with improved OS in patients with ProGRP levels > 410 pg/mL (P = 0.008), but not in those with ProGRP ≤ 410 pg/mL (P = 0.9). Pretreatment ProGRP levels may be useful in predicting the development of BM in patients with LS-SCLC who achieved a good response to initial therapy and to determine which patients should undergo PCI.

The spread through air spaces (STAS) is recognized as a negative prognostic factor in patients with early-stage lung adenocarcinoma. The present study aimed to develop a machine learning model for the prediction of STAS using peritumoral radiomics features extracted from preoperative CT imaging. A total of 339 patients who underwent lobectomy or limited resection for lung adenocarcinoma were included. The patients were randomly divided (3:2) into training and test cohorts. Two prediction models were created using the training cohort: a conventional model based on the tumor consolidation/tumor (C/T) ratio and a machine learning model based on peritumoral radiomics features. The areas under the curve for the two models in the testing cohort were 0.70 and 0.76, respectively (P = 0.045). The cumulative incidence of recurrence (CIR) was significantly higher in the STAS high-risk group when using the radiomics model than that in the low-risk group (44% vs. 4% at 5 years; P = 0.002) in patients who underwent limited resection in the testing cohort. In contrast, the 5-year CIR was not significantly different among patients who underwent lobectomy (17% vs. 11%; P = 0.469). In conclusion, the machine learning model for STAS prediction based on peritumoral radiomics features performed better than the C/T ratio model.

PURPOSE Clear evidence indicating whether surgery or stereotactic body radiation therapy (SBRT) is best for non–small-cell lung cancer (NSCLC) is lacking. SBRT has many advantages. We used artificial neural networks (NNs) to predict treatment outcomes for patients with NSCLC receiving SBRT, aiming to aid in decision making. PATIENTS AND METHODS Among consecutive patients receiving SBRT between 2005 and 2019 in our institution, we retrospectively identified those with Tis–T4N0M0 NSCLC. We constructed two NNs for prediction of overall survival (OS) and cancer progression in the first 5 years after SBRT, which were tested using an internal and an external test data set. We performed risk group stratification, wherein 5-year OS and cancer progression were stratified into three groups. RESULTS In total, 692 patients in our institution and 100 patients randomly chosen in the external institution were enrolled. The NNs resulted in concordance indexes for OS of 0.76 (95% CI, 0.73 to 0.79), 0.68 (95% CI, 0.60 to 0.75), and 0.69 (95% CI, 0.61 to 0.76) and area under the curve for cancer progression of 0.80 (95% CI, 0.75 to 0.84), 0.72 (95% CI, 0.60 to 0.83), and 0.70 (95% CI, 0.57 to 0.81) in the training, internal test, and external test data sets, respectively. The survival and cumulative incidence curves were significantly stratified. NNs selected low-risk cancer progression groups of 5.6%, 6.9%, and 7.0% in the training, internal test, and external test data sets, respectively, suggesting that 48% of patients with peripheral Tis–4N0M0 NSCLC can be at low-risk for cancer progression. CONCLUSION Predictions of SBRT outcomes using NNs were useful for Tis–4N0M0 NSCLC. Our results are anticipated to open new avenues for NN predictions and provide decision-making guidance for patients and physicians.

BACKGROUND AND PURPOSE: This study aimed to evaluate the safety and efficacy of dynamic tumor tracking-stereotactic body radiotherapy (DTT-SBRT) for lung tumors. MATERIALS AND METHODS: Patients with cStage I primary lung cancer or metastatic lung cancer with an expected range of respiratory motion of ≥10 mm were eligible for the study. The prescribed dose was 50 Gy in four fractions. A gimbal-mounted linac was used for DTT-SBRT delivery. The primary endpoint was local control at 2 years. RESULTS: Forty-eight patients from four institutions were enrolled in this study. Forty-two patients had primary non-small-cell lung cancer, and six had metastatic lung tumors. DTT-SBRT was delivered for 47 lesions in 47 patients with a median treatment time of 28 min per fraction. The median respiratory motion during the treatment was 13.7 mm (range: 4.5-28.1 mm). The motion-encompassing method was applied for the one remaining patient due to the poor correlation between the abdominal wall and tumor movement. The median follow-up period was 32.3 months, and the local control at 2 years was 95.2% (lower limit of the one-sided 85% confidence interval [CI]: 90.3%). The overall survival and progression-free survival at 2 years were 79.2% (95% CI: 64.7%-88.2%) and 75.0% (95% CI: 60.2%-85.0%), respectively. Grade 3 toxicity was observed in one patient (2.1%) with radiation pneumonitis. Grade 4 or 5 toxicity was not observed. CONCLUSION: DTT-SBRT achieved excellent local control with low incidences of severe toxicities in lung tumors with respiratory motion.

To evaluate the reproducibility of dose-based radiomic (dosiomic) features between dose-calculation algorithms for lung stereotactic body radiation therapy (SBRT). We analyzed 105 patients with early-stage non-small cell lung cancer who underwent lung SBRT between March 2011 and December 2017. Radiation doses of 48, 60, and 70 Gy were prescribed to the isocenter in 4-8 fractions. Dose calculations were performed using X-ray voxel Monte Carlo (XVMC) on the iPlan radiation treatment planning system (RTPS). Thereafter, the radiation doses were recalculated using the Acuros XB (AXB) and analytical anisotropic algorithm (AAA) on the Eclipse RTPS while maintaining the XVMC-calculated monitor units and beam arrangements. A total of 6808 dosiomic features were extracted without preprocessing (112 shape, 144 first-order, and 600 texture features) or with wavelet filters to eight decompositions (1152 first-order and 4800 texture features). Features with absolute pairwise concordance correlation coefficients-|CCcon|-values exceeding or equaling 0.85 were considered highly reproducible. Subgroup analyses were performed considering the wavelet filters and prescribed doses. The numbers of highly reproducible first-order and texture features were 34.8%, 26.9%, and 31.0% for the XVMC-AXB, XVMC-AAA, and AXB-AAA pairs, respectively. The maximum difference between the mean |CCcon| values was 0.70 and 0.11 for the subgroup analyses of wavelet filters and prescribed dose, respectively. The application of wavelet filter-based dosiomic analyses may be limited when using different types of dose-calculation algorithms for lung SBRT.

BACKGROUND: In infrared reflective (IR) marker-based hybrid real-time tumor tracking (RTTT), the internal target position is predicted with the positions of IR markers attached on the patient's body surface using a prediction model. In this work, we developed two artificial intelligence (AI)-driven prediction models to improve RTTT radiotherapy, namely, a convolutional neural network (CNN) and an adaptive neuro-fuzzy inference system (ANFIS) model. The models aim to improve the accuracy in predicting three-dimensional tumor motion. METHODS: From patients whose respiration-induced motion of the tumor, indicated by the fiducial markers, exceeded 8 mm, 1079 logfiles of IR marker-based hybrid RTTT (IR Tracking) with the gimbal-head radiotherapy system were acquired and randomly divided into two datasets. All the included patients were breathing freely with more than four external IR markers. The historical dataset for the CNN model contained 1003 logfiles, while the remaining 76 logfiles complemented the evaluation dataset. The logfiles recorded the external IR marker positions at a frequency of 60 Hz and fiducial markers as surrogates for the detected target positions every 80-640 ms for 20-40 s. For each logfile in the evaluation dataset, the prediction models were trained based on the data in the first three quarters of the recording period. In the last quarter, the performance of the patient-specific prediction models was tested and evaluated. The overall performance of the AI-driven prediction models was ranked by the percentage of predicted target position within 2 mm of the detected target position. Moreover, the performance of the AI-driven models was compared to a regression prediction model currently implemented in gimbal-head radiotherapy systems. RESULTS: The percentage of the predicted target position within 2 mm of the detected target position was 95.1%, 92.6% and 85.6% for the CNN, ANFIS, and regression model, respectively. In the evaluation dataset, the CNN, ANFIS, and regression model performed best in 43, 28 and 5 logfiles, respectively. CONCLUSIONS: The proposed AI-driven prediction models outperformed the regression prediction model, and the overall performance of the CNN model was slightly better than that of the ANFIS model on the evaluation dataset.

PURPOSE: Stereotactic body radiation therapy (SBRT) can be easily used for patients with tumors in various organs and is a promising local therapy for eradicating tumors in cancer patients. There is a rising clinical need for increasing knowledge of oligometastases in the treatment of multiple pulmonary tumors. This study aimed to explore the predictive factors for symptomatic radiation pneumonitis (RP) after SBRT for multiple pulmonary oligometastases or synchronous primary lung cancer (SPLC). METHODS AND MATERIALS: A total of 38 consecutive patients who had 2 or more pulmonary oligometastases (n = 21) or SPLC (n = 17) and who were treated with SBRT were investigated. Patient characteristics, tumor characteristics, and details of radiation therapy were retrospectively collected from a clinical database. The association between RP of grade 2 or worse (grade 2+ RP) and clinical or dosimetric factors was assessed using logistic regression analyses. RESULTS: The tumors presented ipsilaterally in 24 patients and bilaterally in 14 patients. During the median follow-up period of 4.9 years, grade 2+ RP, grade 2 RP, and grade 3 RP were observed in 9 patients (23.7%), 7 patients (18.4%), and 2 patients (5.3%), respectively. The mean lung dose (MLD) and the volume of the normal lung receiving ≥5 Gy (lung V5Gy) were significantly associated with grade 2+ RP (P = .023 and P = .012, respectively). The logistic model showed that 20% and 50% of the predicted probability of grade 2+ RP were 6.1 Gy and 9.1 Gy for MLD and 31.6 % and 42.8% for lung V5Gy, respectively. CONCLUSION: Although further investigation is required to validate the metrics and establish reliable dose constraints, the dose-volume metrics for the normal lung could be predictive of the development of grade 2+ RP after SBRT for multiple pulmonary oligometastases or SPLCs.

BACKGROUND/AIM: Treatment options for unresectable cholangiocarcinoma are limited. The aim of the study was to evaluate the clinical outcomes of definitive external-beam radiation therapy (EBRT) for patients with unresectable cholangiocarcinoma. PATIENTS AND METHODS: Patients with unresectable primary cholangiocarcinoma, or local recurrent cholangiocarcinoma after primary surgery, without distant metastasis who received definitive EBRT (≥45 Gy) between January 2006 and December 2020 at our Institution were analyzed retrospectively. EBRT was basically performed using conventional fractionation (1.8-2 Gy per fraction). Prophylactic nodal irradiation was not performed. RESULTS: A total of 21 consecutive patients were analyzed: 7 primary and 14 recurrent cases. The median age was 70 (range=38-85) years at initiation of EBRT. A median dose of 54 (range=45-60) Gy comprising 1.8 (range=1.8-3) Gy per fraction was administered to the primary/recurrent local tumor site. The median follow-up period was 21.6 months. The 2-year overall survival, cause-specific survival, progression-free survival, and local recurrence-free rates were 35.7, 35.7, 16.1, and 32.7%, respectively. Long-term local control (>2 years after EBRT) was achieved in 19.0%. Grade 3 toxicities related to EBRT were observed in 4.8% (duodenum hemorrhage). No grade 4 or higher toxicities were observed. CONCLUSION: Definitive EBRT for unresectable cholangiocarcinoma was feasible and achieved long-term local control in a subset of patients. As the avoidance of local recurrence may lead to the benefits of prolonging biliary patency and subsequently alleviating the need for an invasive procedure for biliary drainage, EBRT could be one sustainable therapeutic option for patients with unresectable cholangiocarcinoma.

Marital status has been proposed as a promising prognostic factor in many malignancies, including non-small-cell lung cancer (NSCLC). However, its prognostic value is still unclear for individual non-surgical treatments for stage I NSCLC. This study investigated the prognostic value of marital status in patients with early-stage NSCLC treated with stereotactic body radiotherapy (SBRT). Patients with early-stage NSCLC treated with SBRT between January 2003 and March 2014 at our institute were enrolled, and marital status at the time of SBRT was investigated. Propensity score matching (PSM) was applied to reduce potential selection bias between the married and unmarried groups. Two hundred and forty patients (median age 77 years; 152 married, 87 unmarried) were analyzed. The unmarried included higher proportions of the elderly, women, never smokers, and those with decreased pulmonary function compared to the married. PSM identified 53 matched pairs of married and unmarried patients, with no significant difference in patient background parameters. The 5-year overall survival (OS) was 52.8% and 46.9% in the married and unmarried groups, respectively (P = 0.26). There was no significant difference in NSCLC death or non-NSCLC death between the two groups (P = 0.88 and 0.30, respectively). There was no significant difference in OS between married and unmarried male patients (n = 85, 5-year OS, 52.6% vs. 46.0%; P = 0.42) and between married and unmarried female patients (n = 21, 54.5% vs. 50.0%; P = 0.44). In conclusion, marital status was not associated with OS in patients receiving SBRT for early-stage NSCLC.

Purpose: Patients undergoing radiotherapy often have their skin marked. Previous studies on skin markings examined the durability and physical effects of the markings, but no study has focused on patients' emotional experiences toward the markings. This study aimed to clarify how patients undergoing radiotherapy feel about skin markings, as well as factors that affect patients' emotional experiences. Patients and Methods: We conducted a cross-sectional study using a self-administered questionnaire and medical records. Participants were patients aged ≥20 years undergoing cancer radiotherapy at a designated cancer care hospital. The primary outcome was the level of uncomfortable emotions toward skin markings, and the secondary outcome was the level of favorable ratings on skin markings. To examine factors related to uncomfortable emotions, ordinal logistic regression analysis was performed. Results: Questionnaire forms were distributed to 153 patients, and responses were collected from 132 (86%). Among 108 patients included in the analysis, 56% (59/105, excluding 3 who did not answer this question) responded that they were uncomfortable with skin markings. The proportion of patients who favorably rated skin markings was 63% (59/93, excluding 15 who did not answer this question). No factors were significantly associated with the primary outcome. Conclusion: Many patients accepted skin markings with resignation, as they understood the necessity of the markings in their treatment. Medical staff should understand the emotional experiences of patients toward skin markings and take sufficient care to ensure that they are provided with explanations, including the impact of skin markings on their daily lives, as well as a sense of security that treatment is being performed in a precise manner.

PURPOSE: The purpose of this study was to assess the impact of local recurrence (LR) on cause-specific death (CSD) in patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). A dynamic prediction model that incorporated LR as a time-dependent covariate was used. METHODS AND MATERIALS: This study included 535 stage I (cT1-T2aN0M0) NSCLC patients treated with SBRT from two institutions. We developed a landmark dynamic prediction model to estimate the probability of a CSD. This model determined the probability of surviving for an additional 3 years at different prediction time points during follow-up, given the history of recurrence status. The baseline covariates included in the model were age, sex, T stage, and histology, while the time-dependent covariates were LR and regional and/or distant recurrence (RDR) status. RESULTS: Overall, 137 patients (25.6%) died of lung cancer within a median follow-up of 4.1 years. Of the 195 patients who developed recurrence, 28, 125, and 42 patients had LR only, RDR only, and both, respectively. The landmark model showed that older age, advanced T stage, LR, and RDR were significantly associated with an increased risk of subsequent CSD. Among these covariates, LR (odds ratio [OR], 8.5; 95% confidence interval [CI], 6.0-12.0; P < .001) and RDR (OR, 11.6; 95% CI, 9.1-14.9; P < .001) demonstrated strong effects on CSD within 3 years after the prediction time points. The dynamic prediction provided information on the probability of future CSD according to individual recurrence status during follow-up. CONCLUSIONS: Dynamic prediction using the landmark model showed that LR had a substantial impact on subsequent CSD, which was comparable to that of RDR. This result supports the notion that strategies to improve local control are reasonable.

This study sought to develop and validate a prognostic model for non-lung cancer death (NLCD) in elderly patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Patients aged ≥65 diagnosed with NSCLC (Tis-4N0M0), tumor diameter ≤5 cm and SBRT between 1998 and 2015 were retrospectively registered from two independent institutions. One institution was used for model development (arm D, 353 patients) and the other for validation (arm V, 401 patients). To identify risk factors for NLCD, multiple regression analysis on age, sex, performance status (PS), body mass index (BMI), Charlson comorbidity index (CCI), tumor diameter, histology and T-stage was performed on arm D. A score calculated using the regression coefficient was assigned to each factor and three risk groups were defined based on total score. Scores of 1.0 (BMI ≤18.4), 1.5 (age ≥ 5), 1.5 (PS ≥2), 2.5 (CCI 1 or 2) and 3 (CCI ≥3) were assigned, and risk groups were designated as low (total ≤ 3), intermediate (3.5 or 4) and high (≥4.5). The cumulative incidences of NLCD at 5 years in the low, intermediate and high-risk groups were 6.8, 23 and 40% in arm D, and 23, 19 and 44% in arm V, respectively. The AUC index at 5 years was 0.705 (arm D) and 0.632 (arm V). The proposed scoring system showed usefulness in predicting a high risk of NLCD in elderly patients treated with SBRT for NSCLC.

Solid-organ transplant recipients require long-term immunosuppressants to prevent graft rejection. However, immunosuppressant use increases the risk of malignancy. Radiotherapy can be a treatment option for patients who are medically inoperable or refuse surgery; however, whether the irradiation of transplanted organs is safe remains unclear. We present two patients with malignancies that developed in transplanted organs and were treated with dynamic tumor-tracking (DTT) stereotactic body radiation therapy (SBRT). The first patient underwent transplantation owing to liver cirrhosis caused by hepatitis C virus and subsequently developed hepatocellular carcinoma in the donated liver. There was no evidence of recurrence 12 months post-treatment, and liver function enzyme levels did not deviate from their pre-SBRT baselines. The second patient had a solitary tongue cancer metastasis in a transplanted lung; she also had a history of interstitial pneumonia caused by scleroderma. Six weeks after DTT-SBRT, she developed grade 3 radiation pneumonitis but recovered with oral steroids; she experienced no tumor recurrence after 14 months, although her respiratory function was worse than it was pre-SBRT owing to post-transplant rejection. DTT-SBRT is thus feasible for treating tumors that arise in transplanted lungs and livers.

Intensity-modulated radiotherapy (IMRT) is now regarded as an important treatment option for patients with locally advanced pancreatic cancer (LAPC). To reduce the underlying tumor motions and dosimetric errors during IMRT as well as the burden of respiratory management for patients, we started to apply a new treatment platform of the dynamic tumor dynamic tumor-tracking intensity-modulated radiotherapy (DTT-IMRT) using the gimbaled linac, which can swing IMRT toward the real-time tumor position under patients' voluntary breathing. Between June 2013 and March 2015, ten patients were treated, and the tumor-tracking accuracy and the practical benefits were evaluated. The mean PTV size in DTT-IMRT was 18% smaller than a conventional ITV-based PTV. The root-mean-squared errors between the predicted and the detected tumor positions were 1.3, 1.2, and 1.5 mm in left-right, anterior-posterior, and cranio-caudal directions, respectively. The mean in-room time was 24.5 min. This high-accuracy of tumor-tracking with reasonable treatment time are promising and beneficial to patients with LAPC.

Knowledge of the imaging doses delivered to patients and accurate dosimetry of the radiation to organs from various imaging procedures is becoming increasingly important for clinicians. The purposes of this study were to calculate imaging doses delivered to the organs of lung cancer patients during real-time tumor tracking (RTTT) with three-dimensional (3D), and four-dimensional (4D) cone-beam computed tomography (CBCT), using Monte Carlo techniques to simulate kV X-ray dose distributions delivered using the Vero4DRT. Imaging doses from RTTT, 3D-CBCT and 4D-CBCT were calculated with the planning CT images for nine lung cancer patients who underwent stereotactic body radiotherapy (SBRT) with RTTT. With RTTT, imaging doses from correlation modeling and from monitoring of imaging during beam delivery were calculated. With CBCT, doses from 3D-CBCT and 4D-CBCT were also simulated. The doses covering 2-cc volumes (D2cc) in correlation modeling were up to 9.3 cGy for soft tissues and 48.4 cGy for bone. The values from correlation modeling and monitoring were up to 11.0 cGy for soft tissues and 59.8 cGy for bone. Imaging doses in correlation modeling were larger with RTTT. On a single 4D-CBCT, the skin and bone D2cc values were in the ranges of 7.4-10.5 cGy and 33.5-58.1 cGy, respectively. The D2cc from 4D-CBCT was approximately double that from 3D-CBCT. Clinicians should Figure that the imaging dose increases the cumulative doses to organs.

Purpose: To estimate the maximum tolerated dose (MTD) and to determine the recommended dose (RD) of stereotactic body radiation therapy (SBRT) for peripheral T2N0M0 non-small cell carcinoma (NSCLC) with target volume (PTV) < 100 cc. Materials and methods: The continual reassessment method (CRM) was used to determine the dose level that patients should be assigned to and to estimate the MTD. Dose limiting toxicity (DLT) was grade 3 radiation pneumonitis (RP) within 180 days after the start of SBRT, grade 2 RP was used as a surrogate DLT. The RD was equal to the MTD. The dose was prescribed at D95 of the PTV. Results: Fifteen patients were accrued. Only 1 experienced grade 2 RP at 60 Gy in 4 fractions. It was difficult to fulfill the dose constraints at 60 Gy in 4 fractions, and the maximum dose level assigned by CRM was changed to 55 Gy in 4 fractions. The lower limit of 95% of the credible interval exceeded the adjacent level, and the RD was determined as 55 Gy in 4 fractions. Conclusions: The RD of SBRT for peripheral T2N0M0 NSCLC with PTV < 100 cc was determined to be 55 Gy in 4 fractions.

PURPOSE: To estimate the maximum tolerated dose (MTD) and to determine the recommended dose (RD) of stereotactic body radiation therapy (SBRT) for peripheral T2N0M0 non-small cell carcinoma (NSCLC) with target volume (PTV) &lt; 100cc. MATERIALS AND METHODS: The continual reassessment method (CRM) was used to determine the dose level that patients should be assigned to and to estimate the MTD. Dose limiting toxicity (DLT) was grade 3 radiation pneumonitis (RP) within 180days after the start of SBRT, grade 2 RP was used as a surrogate DLT. The RD was equal to the MTD. The dose was prescribed at D95 of the PTV. RESULTS: Fifteen patients were accrued. Only 1 experienced grade 2 RP at 60Gy in 4 fractions. It was difficult to fulfill the dose constraints at 60Gy in 4 fractions, and the maximum dose level assigned by CRM was changed to 55Gy in 4 fractions. The lower limit of 95% of the credible interval exceeded the adjacent level, and the RD was determined as 55Gy in 4 fractions. CONCLUSIONS: The RD of SBRT for peripheral T2N0M0 NSCLC with PTV&lt;100cc was determined to be 55Gy in 4 fractions.

We report a case presenting with severe thrombocytopenia following multidisciplinary treatment for malignant pleural mesothelioma. The patient was a 68-year-old man, who suffered from radiation pneumonitis during intensity-modulated radiation therapy, after right extra-pleural pneumonectomy and chemotherapy with cisplatin and pemetrexed for right malignant pleural mesothelioma. We discontinued the radiotherapy and administered glucocorticoid. Approximately 1 month later, the platelet count markedly decreased to 2×10³/μL, and he frequently required platelet transfusion. Subsequently, he developed cytomegalovirus (CMV) antigenemia, and we administered ganciclovir, which successfully reduced the level of CMV antigens. However, the platelet count did not increase. Bone marrow examination showed slight hypocellularity with a normal megakaryocyte count. Hence, we treated the thrombocytopenia as immune thrombocytopenic purpura by administering intravenous immunoglobulin. Afterwards, the platelet recovery was poorer than we had expected despite the administration of an oral thrombopoietin receptor agonist. Taking into account the thrombocytopenia developing during glucocorticoid treatment and the poor response to medication, multiple factors such as bone marrow dysfunction due to chemotherapy and/or radiation, drugs, and CMV infection were possibly associated with the thrombocytopenia.

We are developing an innovative dynamic tumor tracking irradiation technique using gold markers implanted around a tumor as a surrogate signal, a real-time marker detection system, and a gimbaled X-ray head in the Vero4DRT. The gold markers implanted in a normal organ will produce uncertainty in the dose calculation during treatment planning because the photon mass attenuation coefficient of a gold marker is much larger than that of normal tissue. The purpose of this study was to simulate the dose variation near the gold markers in a lung irradiated by a photon beam using the Monte Carlo method. First, the single-beam and the opposing-beam geometries were simulated using both water and lung phantoms. Subsequently, the relative dose profiles were calculated using a stereotactic body radiotherapy (SBRT) treatment plan for a lung cancer patient having gold markers along the anterior-posterior (AP) and right-left (RL) directions. For the single beam, the dose at the gold marker-phantom interface laterally along the perpendicular to the beam axis increased by a factor of 1.35 in the water phantom and 1.58 in the lung phantom, respectively. Furthermore, the entrance dose at the interface along the beam axis increased by a factor of 1.63 in the water phantom and 1.91 in the lung phantom, while the exit dose increased by a factor of 1.00 in the water phantom and 1.12 in the lung phantom, respectively. On the other hand, both dose escalations and dose de-escalations were canceled by each beam for opposing portal beams with the same beam weight. For SBRT patient data, the dose at the gold marker edge located in the tumor increased by a factor of 1.30 in both AP and RL directions. In clinical cases, dose escalations were observed at the small area where the distance between a gold marker and the lung tumor was ≤ 5 mm, and it would be clinically negligible in multibeam treatments, although further investigation may be required.

72歳男。肺腺癌の単発肝転移で径36mmであった。腫瘍位置の参照として腫瘍近傍に金マーカー(Visicoil)を経皮的に留置し、毎回の治療前に腹壁の赤外線反射マーカーとVisicoil間の相関モデルを作成した。治療中は腹壁のマーカー位置に基づいて照射ビームのヘッドを制御して動体追尾照射を施行し、同時にX線透視でVisicoilの位置をモニタリングした。処方線量は56Gy/4frであり、特に問題なく終了した。治療時間は平均38.5分であり従来の照射法(15-30分)より延長していたが、計画標的体積は従来法と比較して133.3mlから85.6mlへ低減し、正常肝の平均線量も14.3Gyから11.5Gyへ低減した。治療終了後5ヵ月現在、腫瘍は縮小傾向にあり、良好に制御できている。

当科でI期非小細胞肺癌に対し体幹部定位放射線治療(SBRT)を施行した66例の治療成績について検討した。その結果、治療後5年の時点で19例が無病生存中であったが、その後の経過観察により4例(21.1%)に晩期再発、2例(10.5%)に二次肺癌が認められた。再発4例の再発時期は6年4ヵ月〜9年1ヵ月で、再発形式は局所単独再発が2例、遠隔転移(脳)1例、局所再発+遠隔転移(肺)1例であった。局所再発の1例はゲフィチニブ投与を試みたが肝障害にて数ヵ月で中止し、他の3例は無治療であった。1例は心不全と腎不全で死亡し、他の3例は原病死した。二次肺癌はそれぞれ9年2ヵ月、10年2ヵ月で認め、前者は追加治療を現在検討中、後者は無治療にて経過観察中で、いずれも生存中である。

Objectives: Total laryngectomy is still the standard treatment for locally advanced laryngeal cancer, particularly T4, although chemoradiotherapy has been developed for advanced head and neck cancers for organ preservation. At the Comprehensive Cancer Center of Kyoto University, both a head and neck surgeon and a radiation oncologist discuss the possibility of larynx preservation treatment even for locally advanced laryngeal cancers. The current preliminary study reports on the potential of larynx preservation treatment using induction chemotherapy for locally advanced laryngeal cancer.
Materials and Methods: The Comprehensive Cancer Center of Kyoto University was established in 2008, and 52 new cases with laryngeal cancer including seven cases with T3 or T4 cancer have been treated between 2008 and 2011. A retrospective chart review was performed to examine the efficacy of larynx preservation treatment in the T3/4 cases.
Results: Six cases were treated by larynx preservation regimen, while a supraglottic T4 case was treated by total laryngectomy because of comorbidity. Of the six cases, a glottis T3 case was treated with hyperfractionated radiotherapy, and the five other cases were treated by induction chemotherapy of TPF. Induction chemotherapy led to CR in one case and PR in three cases. Grade 5 toxicity occurred in one case. Chemoradiotherapy following induction chemotherapy was applied in two cases, while larynx preservation surgery was performed in two cases. All cases that completed larynx preservation treatment have demonstrated preservation of the larynx without recurrence during the follow-up period of 1 to 3 years (mean 2 years).
Conclusion: Although the number of patients and follow-up period are not sufficient, the current preliminary data suggest the possibility of larynx preservation treatment for locally advanced laryngeal cancers using induction chemotherapy followed by concurrent chemoradiotherapy (IMRT) or laryngeal preservation surgery.

切除不能肝細胞癌で，下大静脈腫瘍栓（5例）および門脈腫瘍栓（6例）の病勢コントロール目的に放射線治療（総線量39-60 Gy）を行った計11例を対象とし腫瘍栓に対する放射線治療の効果，腫瘍栓の無増悪期間，有害事象を検討した．腫瘍栓に対する前治療は11例中10例に肝動脈注入化学療法が行われていた．下大静脈腫瘍栓に対する有効性はCR 1例 PR 2例 SD 2例（奏効率60％）であったのに対し，門脈腫瘍栓ではPR 1例 SD 4例 PD 1例（奏効率16.7％）であった．放射線治療開始日からの生存期間中央値は下大静脈腫瘍栓症例で401日（141-612日），門脈腫瘍栓症例で374日（136-469日）であった．有害事象としては1例に放射線性肺臓炎を認めたが軽快した．放射線治療に伴う治療関連死は認めなかった．切除不能，肝動注不応腫瘍栓に対する放射線照射は，特に下大静脈腫瘍栓の病勢コントロールに有用である可能性が示唆された．

患者は12歳男児。頸部リンパ節腫脹、難聴にて上咽頭癌と診断された。化学放射線併用療法に反応するも3ヵ月後に原発巣の再増大を認めた。Cisplatin、5-FU、docetaxelによる追加化学療法を行い完全寛解に至り、2年以上が経過した現在も完全寛解を維持している。治療中に再増大した症例に対し、追加化学療法が奏功し長期に寛解を維持している事は今後の治療戦略を考える上で参考になると考えられた。

＜Headline＞ 1 放射線治療のおもな適応は、早期肺がんに対する体幹部定位放射線治療、局所進行がんに対する化学放射線療法および転移がんに対する緩和照射である。転移性脳腫瘍の治療にあたっては、予後に応じた治療法選択が必要である。2 体幹部定位放射線治療は、標準手術不能のI期症例においては標準治療に位置づけられる。高齢などの理由で手術を希望されない場合や、医学的な理由で縮小手術しか耐容できない症例においても検討される 3 局所進行がんに対する化学放射線療法では、プラチナ製剤を含む2剤以上の化学療法とともに放射線治療60Gy以上の投与が標準治療とされる 4 体幹部定位放射線治療および強度変調放射線治療は、近年肺がんへの適用が広がっている。前者は優れた局所制御、後者は有害事象の低減を得るのに有用である。陽子線治療の肺がんにおける有用性は今後の検討課題である。(著者抄録)

【会議の開催】第5回全体会議：2019年4月13日、第6回全体会議：2019年11月22日、メール会議随時開催 【既存多施設研究の遂行】1.有転移性肺癌患者におけるNivolumabと定位放射線治療の併用の安全性試験（NIVOSTLUC-I)、2.保険外臓器腫瘍に対する定位放射線治療の観察研究、3.有転移性腎癌多発患者におけるNivolumabと定位放射線治療の併用の有無による治療効果の差についての比較研究（NIVOIGERCC)（phase II/III） 【新規多施設研究の検討】1.中枢型IA（UICC 7版）期非小細胞肺癌に対する高精度少分割放射線治療の多施設前向き登録、2.III期非小細胞肺癌の従来型化学放射線療法後の残存腫瘍に対する定位放射線治療 【各分担研究者による臨床試験継続】1. 保険適応外臓器に対する定位放射線治療の調査研究、観察研究、 2. 有転移性前立腺癌の定位照射のI/II相臨床試験、アンケート調査、 3. (1) M1前立腺癌, (2) 前立腺癌放射線治療後局所再発, (3) 前立腺癌術後マクロ再発に対する救済 定位放射線治療、 4. 膵臓癌に対する定位放射線治療、5. 子宮頸癌に対する定位放射線治療、6. 婦人科がんのPALN孤発転移へ の定位放射線治療)、7. 直腸がん術後の吻合部以外の再発（仙骨前面の軟部組織）への定位放射線治療、8. 乳癌 の根治的照射としてのブースト定位照射、9. リンパ節転移、胆管癌への定位照射、10. オリゴリンパ節転移に対する定位放射線治 療の第II相研究、11. 5cm以上の肝癌・肺癌に対する定位放射線治療 【研究発表】1.腎癌の定位放射線治療成績をまとめた。2.I期非小細胞肺癌の定位放射線治療と手術との比較論文のレビューを論文化した。3.定位放射線治療ｂにおけるマルチリーフコリメータ位置の医学物理的評価を行った。

慢性炎症や筋肉量減少（サルコペニア）が、がん治療後の生存率に関連しているか否かを評価した。早期肺癌の体幹部定位放射線治療症例をおいては、慢性炎症が肺癌死（特に遠隔転移死）に、サルコペニアが非肺癌死に、それぞれ関連することが判明した。局所進行非小細胞肺癌症例においては、治療前に全身炎症所見を認める症例および体格指数が低い（BMI＜18.5）症例で予後不良の傾向にあった。これらの結果に基づくと、従来の年齢や肺癌病期に加えて、慢性炎症およびサルコペニアが重要な予後因子であることを示すことができた。

放射線治療の成績向上には、生物学的画像情報の治療計画への統合と腫瘍や正常臓器の動きへの対応が必要と考えられた。我々は、放射線治療計画における生物・機能画像情報の有用性の評価、腫瘍動体評価と生物・機能画像の4次元化法の確立、および動体追尾SIB-IMRT治療の実現に向けた基盤技術開発の３つの要素に分けて研究を行った。それぞれF-MISO-PETによる低酸素イメージングにおける最適な撮像タイミング、呼吸同期FDG-PETの有用性、４次元線量計算モジュールの開発などの研究成果を挙げた。今後これらの研究成果が放射線治療の高度化と成績向上につながるものと期待される。

早期の非小細胞肺癌に対する定位放射線治療は、高い有効性と安全性から期待の大きい治療法である。重症の放射線肺炎のリスク因子の一つとして肺線維症が挙げられているが、詳細は明らかにされていない。そこで、放射線肺炎との関連が報告されているTGFb1遺伝子上または周辺の多型および、炎症関連遺伝子多型が定位放射線治療後の肺臓炎発症リスクと関連するか検証した。その結果、肺炎症状（CTCEA grade2以上）についてはステロイド使用歴、平均肺線量、遺伝子多型：rs1801270,rs1800470が、CT上の肺炎所見（照射体積外に発生）についてはステロイドの使用歴と遺伝子多型rs1800470が挙げられた。

研究期間を通じて、肝臓癌に対する定位放射線治療の実施フロー（マーカー挿入、治療計画用CT撮像、治療計画と線量計算、動体追尾定位放射線の実施）確立は達成された。これにより肝臓癌の局所治療として定位放射線治療の選択肢を提供できるようになったことは我が国のがん治療にとって大変意義深いと考える。しかしながら、今回の研究期間では十分な症例数を経験できなかったため、もう一つの研究目的である治療後の経過観察手法の確立は達成されなかった。これに関しては今後の課題としたい。

Deformable Registrationソフトウェアと4次元線量分布評価システムを開発した。また、新規に一筆書き照射法を考案し、その有用性を膵臓癌および頭蓋底腫瘍において確認した。さらに、膵臓癌において臓器移動や変形が線量分布に及ぼす影響を評価し、呼吸停止下強度変調放射線治療を開発して第一相線量増加試験を開始するとともに、悪性胸膜中皮腫および頸部食道癌に対する強度変調放射線治療を用いた臨床試験プロトコールをそれぞれ立案し実施中である。

体幹部定位放射線治療は手術不能の早期肺癌患者における治療法として大変な注目を集めている。しかしながら同治療の中枢存在型肺癌に対する適応は確立したものではない。今回中枢存在型肺癌に対する定位放射線治療の実現に向けた基礎的検討を行った。具体的には、局所制御に関する線量効果関係、治療期間中の腫瘍移動量、線量計算アルゴリズム、固定精度の評価を行った。また、中枢存在型肺癌に対する定位放射線治療の多施設共同プロトコル策定に参画した。