A virtual audit system for intensity-modulated radiation therapy credentialing in Japan Clinical Oncology Group clinical trials: A pilot study.

PURPOSE: The Medical Physics Working Group of the Radiation Therapy Study Group at the Japan Clinical Oncology Group is currently developing a virtual audit system for intensity-modulated radiation therapy dosimetry credentialing. The target dosimeters include films and array detectors, such as ArcCHECK (Sun Nuclear Corporation, Melbourne, Florida, USA) and Delta4 (ScandiDos, Uppsala, Sweden). This pilot study investigated the feasibility of our virtual audit system using previously acquired data. METHODS: We analyzed 46 films (32 and 14 in the axial and coronal planes, respectively) from 29 institutions. Global gamma analysis between measured and planned dose distributions used the following settings: 3%/3 mm criteria (the dose denominator was 2 Gy), 30% threshold dose, no scaling of the datasets, and 90% tolerance level. In addition, 21 datasets from nine institutions were obtained for array evaluation. Five institutions used ArcCHECK, while the others used Delta4. Global gamma analysis was performed with 3%/2 mm criteria (the dose denominator was the maximum calculated dose), 10% threshold dose, and 95% tolerance level. The film calibration and gamma analysis were conducted with in-house software developed using Python (version 3.9.2). RESULTS: The means ± standard deviations of the gamma passing rates were 99.4 ± 1.5% (range, 92.8%-100%) and 99.2 ± 1.0% (range, 97.0%-100%) in the film and array evaluations, respectively. CONCLUSION: This pilot study demonstrated the feasibility of virtual audits. The proposed virtual audit system will contribute to more efficient, cheaper, and more rapid trial credentialing than on-site and postal audits; however, the limitations should be considered when operating our virtual audit system.

Assessment of using a gamma index analysis for patient-specific quality assurance in Japan.

PURPOSE: The Task Group 218 (TG-218) report was published by the American Association of Physicists in Medicine in 2018, recommending the appropriate use of gamma index analysis for patient-specific quality assurance (PSQA). The paper demonstrates that PSQA for radiotherapy in Japan appropriately applies the gamma index analysis considering TG-218. MATERIALS/METHODS: This survey estimated the acceptance state of radiotherapeutic institutes or facilities in Japan for the guideline using a web-based questionnaire. To investigate an appropriate PSQA of the facility-specific conditions, we researched an optimal tolerance or action level for various clinical situations, including different treatment machines, clinical policies, measurement devices, staff or their skills, and patient conditions. The responded data were analyzed using principal component analysis (PCA) and multidimensional scaling (MDS). The PCA focused on factor loading values of the first contribution over 0.5, whereas the MDS focused on mapped distances among data. RESULTS: Responses were obtained from 148 facilities that use intensity-modulated radiation therapy (IMRT), which accounted for 42.8% of the probable IMRT use in Japan. This survey revealed the appropriate application of the following universal criteria for gamma index analysis from the guideline recommendation despite the facility-specific variations (treatment machines/the number of IMRT cases/facility attributes/responded [representative] expertise or staff): (a) 95% pass rate, (b) 3% dose difference and 2-mm distance-to-agreement, and (c) 10% threshold dose. Conditions (a)-(c) were the principal components of the data by the PCA method and were mapped in a similar distance range, which was easily clustered from other gamma index analytic factors by the MDS method. Conditions (a)-(c) were the universally essential factors for the PSQA in Japan. CONCLUSION: We found that the majority of facilities using IMRT in each region of Japan complied with the guideline and conducted PSQA with deliberation under the individual facility-specific conditions.

A 54 Gy in three fractions of stereotactic body radiotherapy using CyberKnife for T1b-2aN0M0 pathologically confirmed non-small cell lung cancer.

OBJECTIVE: Optimal dose-fractionation regimen of stereotactic body radiotherapy for peripheral early-stage non-small cell lung cancer remains unclear. We retrospectively investigated outcomes of stereotactic body radiotherapy using CyberKnife at 54 Gy in three fractions in 26 patients (median age: 76 years) with pathologically confirmed T1b-T2aN0M0 non-small cell lung cancer. METHODS: A 54 Gy in three fractions was prescribed to cover the 99% of gross tumor volume. We estimated cumulative local control, progression-free survival and overall survival rates (Kaplan-Meier method), and toxicity (Common Toxicity Criteria for Adverse Events, version 5.0). RESULTS: All the tumors were located at peripheral area of lung. Mean distance from chest wall to tumor was 6.5 mm (range: 0-32 mm). The patients' pathological diagnoses were: adenocarcinoma: n = 18, squamous cell carcinoma: n = 7 and non-small cell carcinoma: n = 1. Their stages were T1b: n = 9, T1c: n = 14 and T2a: n = 3. Median follow-up was 24 months (range: 6-54). Cumulative 2-year effect rates were local control: 100%, progression-free survival 70% and overall survival: 92%. Twenty patients developed grade one radiation pneumonitis, but grade 2 or greater radiation pneumonitis was not observed. CONCLUSIONS: We found CyberKnife-stereotactic body radiotherapy for pathologically confirmed T1b-T2aN0M0 non-small cell lung cancer to be effective and safe. However, these results should be validated with a larger patient cohort and prospective follow-up monitoring.

Development of an HDR-BT QA tool for source position verification.

PURPOSE: This study aimed to develop a high-dose-rate brachytherapy (HDR-BT) quality assurance (QA) tool for verification of source positions, and to report on its effectiveness. METHODS: We fabricated a cuboid phantom measuring 30 × 30×3 cm3 with spaces to embed Fletcher-Williamson tandem and ovoid applicators. Lead-based, cylindrically shaped radiopaque markers, which scatter radiation and blacken the Gafchromic® RTQA2 films placed on the applicators, were inserted into the phantom to determine the applicator tip and reference source positions. A three-dimensional image-guided brachytherapy (3D-IGBT) plan was generated, and the source positions on the film and radiation treatment planning system (RTPS) were verified with the tool. Source position errors were evaluated as the distance in the applicator axis direction between the source position and the center position of two radiopaque marker pairs. RESULTS: Source position errors on the film and RTPS were in good agreement with one another and were all within 0.5 mm for all applicators. Offset values of each applicator were in good agreement with the value determined in treatment planning (6 mm). The expanded measurement uncertainty of our QA tool was estimated to be 0.87 mm, with a coverage factor k of 2. CONCLUSIONS: Our new HDR-BT QA tool developed for comprehensive source position verification will be useful for cross checking actual source positions and planned source positions on the RTPS.

A prospective multicentre feasibility study of stereotactic body radiotherapy in Japanese patients with spinal metastases.

OBJECTIVE: Stereotactic body radiotherapy has emerged as an attractive alternative to conventional radiotherapy for spinal metastases. However, it has limitations, including the need for advanced techniques and specific adverse effects. The present trial aimed to validate the feasibility and safety of stereotactic body radiotherapy in Japanese patients with spinal metastases. METHODS: Patients with one or two spinal metastases received stereotactic body radiotherapy of 24 Gy in two fractions. The primary endpoint was the proportion of severe adverse effects (≥ grade 3) in patients within 6 months after spine stereotactic body radiotherapy. Adverse effects were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. The treatment protocol was considered feasible and tolerable if the proportion of severe adverse effects was 10% or less. RESULTS: Overall, 20 spinal segments in 20 patients who registered between March 2014 and October 2015 were included. Minor and major deviations were observed in the planning of 2 and 0 cases, respectively. The treatment completion rate was 100%. The median follow-up after registration was 24.5 (range: 1-61) months. Although four patients experienced acute grade 2 adverse effects, no grade 3 or higher adverse effects were observed within 6 months after spine stereotactic body radiotherapy. Vertebral compression fractures were observed in two patients (14 and 16 months after stereotactic body radiotherapy). The local control and pain response rates at 6 months were 100 and 83%, respectively. CONCLUSION: This study demonstrated the feasibility and safety of spine stereotactic body radiotherapy in Japanese patients with spinal metastases.

Malignant melanoma of the nasal cavity treated with stereotactic radiotherapy using CyberKnife: report of 2 cases.

Radiotherapy with high doses per fraction may have the potential to control radioresistant tumors, such as malignant melanoma. Here we report 2 cases with malignant melanoma of the nasal cavity treated with hypofractionated stereotactic radiotherapy using CyberKnife®.

Japanese structure survey of high-precision radiotherapy in 2012 based on institutional questionnaire about the patterns of care.

OBJECTIVE: The purpose of this study was to clarify operational situations, treatment planning and processes, quality assurance and quality control with relevance to stereotactic radiotherapy, intensity-modulated radiotherapy and image-guided radiotherapy in Japan. METHODS: We adopted 109 items as the quality indicators of high-precision radiotherapy to prepare a questionnaire. In April 2012, we started to publicly open the questionnaire on the website, requesting every institution with radiotherapy machines for response. The response ratio was 62.1% (490 out of 789 institutions responded). RESULTS: Two or more radiotherapy technologists per linear accelerator managed linear accelerator operation in ∼90% of the responded institutions while medical physicists/radiotherapy quality managers were engaged in the operation in only 64.9% of the institutions. Radiotherapy certified nurses also worked in only 18.4% of the institutions. The ratios of the institutions equipped for stereotactic radiotherapy of lung tumor, intensity-modulated radiotherapy and image-guided radiotherapy were 43.3, 32.6 and 46.8%, respectively. In intensity-modulated radiotherapy planning, radiation oncologists were usually responsible for delineation while medical physicists/radiotherapy quality managers or radiotherapy technologists set up beam in 33.3% of the institutions. The median time required for quality assurance of intensity-modulated radiotherapy at any site of brain, head and neck and prostate was 4 h. Intensity-modulated radiotherapy quality assurance activity had to be started after clinical hours in >60% of the institutions. CONCLUSIONS: This study clarified one major issue in the current high-precision radiotherapy in Japan. A manpower shortage should be corrected for high-precision radiotherapy, especially in the area relevant to quality assurance/quality control.

Validation of nomogram-based prediction of survival probability after salvage re-irradiation of head and neck cancer.

OBJECTIVE: Treatment outcomes after salvage re-irradiation in patients with recurrent head and neck cancer vary widely due to heterogeneous patient characteristics, and it is difficult to evaluate optimal re-irradiation schedules. This study aimed to validate a nomogram, originally developed by Tanvetyanon et al., used to predict the survival probability of patients with recurrent head and neck cancer after re-irradiation. METHODS: Twenty-eight patients with recurrent head and neck cancer who underwent salvage re-irradiation between June 2007 and November 2011 were evaluated. The median total dose used for initial radiotherapy was 60 Gy (range, 22-72). Re-irradiation sites included the nasopharynx or Rouviere's node (n = 14), external ear (n = 4), neck lymph node (n = 3) and other sites (n = 7). Overall survival after re-irradiation was calculated using the Kaplan-Meier method, and the 2-year survival probability was estimated using Tanvetyanon's nomogram. RESULTS: Twenty-two patients were treated with stereotactic body radiotherapy using a median total dose of 30 Gy (range, 15-40) in 1-7 fractions and six patients were treated with conventional external beam radiotherapy using 45 Gy (range, 23.4-60) in 10-30 fractions. The 2-year overall survival was 21.7% (95% confidence interval: 9.3-41.3), and the 2-year survival probability was 16.8% (95% confidence interval: 9.9-23.6). The 2-year overall survival in 20 patients with unfavorable prognosis (median 2-year survival probability, 5.5%) and in 8 patients with favorable prognosis (median 2-year survival probability, 45%) were 11.0 and 45.7%, respectively (P = 0.05). CONCLUSIONS: Our findings show that Tanvetyanon's nomogram accurately estimates the survival probability in patients with recurrent head and neck cancer after re-irradiation.

Learning curve of lung dose optimization in intensity-modulated radiotherapy for locally advanced non-small cell lung cancer.

BACKGROUND: Intensity-modulated radiotherapy (IMRT) has been increasingly used for patients with locally advanced non-small cell lung cancer (LA-NSCLC). However, there are some barriers to implementing IMRT for LA-NSCLC, including the complexity of treatment plan optimization. This study aimed to evaluate the learning curve of lung dose optimization in IMRT for LA-NSCLC and identify the factors that affect the degree of achievement of lung dose optimization. METHODS: We retrospectively evaluated 40 consecutive patients with LA-NSCLC who received concurrent chemoradiotherapy at our institution. These 40 patients were divided into two groups: 20 initially treated patients (earlier group) and 20 subsequently treated patients (later group). Patient and tumor characteristics were compared between the two groups. The dose-volume parameter ratio between the actually delivered IMRT plan and the simulated three-dimensional conformal radiotherapy plan was also compared between the two groups to determine the learning curve of lung dose optimization. RESULTS: The dose-volume parameter ratio for lung volume to receive more than 5 Gy (lung V5) and mean lung dose (MLD) significantly decreased in later groups. The spread of the beam path and insufficient optimization of dose coverage of planning target volume (PTV) might cause poor control of lung V5, MLD. CONCLUSIONS: A learning curve for lung dose optimization was observed with the accumulation of experience. Appropriate techniques, such as restricting the beam path and ensuring dose coverage of PTV during the optimization process, are essential to control lung dose in IMRT for LA-NSCLC.

Results of computer tomography-based adaptive brachytherapy in combination with whole-pelvic- and central-shielding-external beam radiotherapy for cervical cancer.

PURPOSE: To evaluate treatment results and investigate predictors of local control. METHODS AND MATERIALS: In this retrospective study of 236 patients with cervical cancer, we administered CT-based adaptive brachytherapy (BT) in combination with whole- pelvic (WP)- and central shielding (CS)- external beam radiotherapy (EBRT) with or without chemotherapy. The study cohort comprised patients with cervical cancer treated with definitive radiotherapy (RT) or concurrent chemoradiotherapy between June 2013 and March 2019. Local control (LC), overall survival (OS), and late toxicity were evaluated. Predictive factors for LC were analyzed by univariate and multivariate analyses. RESULTS: Median doses of WP- and CS-EBRT and BT were 30.6 GyEQD2, 19.8 GyEQD2, and 40.3 GyEQD2, respectively. The 3-year LC rates for T1b2, T2a, T2b, T3b, and T4 were 100%, 100%, 97.3%, 86.9%, and 91.7%, respectively (p = 0.346). The 3-year OS for Stages IB, IIB, IIIB, IIIC, and IVA were 100%, 94.8%, 82.5%, 81.7%, and 74.6%, respectively (p = 0.037). Rates of Grade 3-4 gastrointestinal and genitourinary toxicities were 3.8% and 1.7%, respectively. Multivariate analysis showed that T3-4, nonsquamous cell histology, and high-risk clinical target volume (CTVHR) D90 of BT < 36GyEQD2 were independently associated with significantly poorer LC. CONCLUSIONS: The combination of WP- and CS-EBRT and CT-based IGBT with or without concurrent chemotherapy produced favorable LC outcomes with low rates of late toxicities for patients with small or medium-sized tumors. However, LC was less favorable for patients who had large T3 disease, and the use of CS requires caution in these patients.

High-dose stereotactic body radiotherapy using CyberKnife® for stage I peripheral lung cancer: a single-center retrospective study.

BACKGROUND: This retrospective study was performed to evaluate the efficacy and toxicity of high-dose stereotactic body radiotherapy (SBRT) using a CyberKnife® for patients with stage I peripheral non-small cell lung cancer (NSCLC). METHODS: Ninety-six patients with stage I peripheral NSCLC who were treated with SBRT using a CyberKnife® from August 2010 to June 2019 were identified and included in this study. Local control (LC), local progression-free survival (LPFS), progression-free survival (PFS), overall survival (OS), and late toxicity were evaluated. Potential risk factors associated with LC, LPFS, PFS, or OS were investigated by univariate analyses. RESULTS: Data of 96 patients were examined. The prescribed dose to the tumor was 54 Gy in 3 fractions in 91 patients and 60 Gy in 3 fractions in 5 patients. The median follow-up duration was 27 months. The 2-year LC, LPFS, PFS, and OS rates were 97%, 88%, 84%, and 90%, respectively. The T factor was significantly correlated with LC, LPFS, and PFS. The 2-year LC rate for patients with T1a/T1b and T1c/T2a disease was 100% and 90%, respectively (p < 0.05), and the 2-year PFS rate for the corresponding patients was 95% and 65%, respectively (p < 0.001). One patient (1%) developed grade 3 radiation pneumonitis. CONCLUSIONS: High-dose SBRT using a CyberKnife® for stage I peripheral NSCLC produced favorable treatment outcomes with acceptable late toxicity. Further studies are needed to improve the treatment outcomes for patients with T1c/T2a disease.

Simple method for evaluating achievement degree of lung dose optimization in individual patients with locally advanced non-small cell lung cancer treated with intensity modulated radiotherapy.

BACKGROUND: In this study, we developed a simple method for evaluating achievement degree of lung dose optimization in individual patients with locally advanced non-small cell lung cancer (NSCLC) treated with intensity modulated radiotherapy (IMRT). METHODS: Data of 28 patients with stage IIB to IIIC NSCLC were retrospectively analyzed. All patients were treated with IMRT and a simulated three-dimensional conformal radiotherapy (3D-CRT) plan created for them. Dose-volume parameters of lung were analyzed for their correlation with radiation pneumonitis (RP). RESULTS: Over a median follow-up of 14 months, grade 1 pneumonitis was diagnosed in 14 patients (50%), grade 2 pneumonitis in 11 (39%), and grade 3 pneumonitis in one (4%). Two patients did not develop pneumonitis. None of the patients developed grade 4 or 5 pneumonitis. Regarding dose-volume parameter ratios between IMRT and simulated 3D-CRT, receiver operating characteristic analysis showed that mean lung dose (MLD)IMRT /MLD3D-CRT had the largest area under curve (0.750). Cumulative 6-month incidences of grade 2 or greater RP were 78.4% versus 19.5% (MLDIMRT /MLD3D-CRT, ≥1.0 or less); this difference was significant (p < 0.05). CONCLUSIONS: We found that cutoff values for dose volume parameter ratios significantly predict grade 2 or greater RP. We believe that these parameter ratios could be useful in assisting evaluation of achievement degree of lung dose optimization in IMRT for LA-NSCLC.

A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using multicatheter interstitial brachytherapy: clinical results with a median follow-up of 60 months.

BACKGROUND: We carried out the first multi-institutional prospective study on accelerated partial breast irradiation (APBI) via multicatheter interstitial brachytherapy in a shorter period for early breast cancer in Japan. METHODS: Patient eligibility criteria included positive hormone receptors, tumors ≤ 3 cm and TNM stage pN0M0. After breast-conserving surgery (Japanese cylindrical resection) and histological confirmation of negative surgical margins and the absence of lymph node metastasis, applicator implantation was performed either postoperatively or intraoperatively. High-dose-rate brachytherapy of 36 Gy in 6 fractions was delivered. RESULTS: Forty-six patients from six institutions received this treatment regimen, and the median follow-up time was 60 months (range 57-67 months). The median resected breast tissue volume was 81 cm3 (range 28-260 cm3). No Grade 4 late sequela, local recurrence nor death due to breast cancer were observed. Grade 2-3 sequelae such as rib fracture (2%), soft tissue necrosis (9%), fibrosis (20%), and breast pain (9%) were observed. The resected breast tissue volumes of the patients who had Grade ≥ 2 fibrosis and Grade < 2 fibrosis were 105.9 ± 32.3 cm3 and 76.3 ± 45.6 cm3, respectively, p = 0.02. The overall cosmetic outcome score of Excellent/Good was 74% at 60 months after APBI. Grade ≥ 1 fibrosis was observed in 44% and 92% of patients who scored Excellent/Good and Fair/Poor, respectively, p = 0.004. CONCLUSIONS: This study showed excellent local control and survival results with minimal late sequelae.

Practical guidelines of online MR-guided adaptive radiotherapy.

The first magnetic resonance (MR)-guided radiotherapy system in Japan was installed in May 2017. Implementation of online MR-guided adaptive radiotherapy (MRgART) began in February 2018. Online MRgART offers greater treatment accuracy owing to the high soft-tissue contrast in MR-images (MRI), compared to that in X-ray imaging. The Japanese Society for Magnetic Resonance in Medicine (JSMRM), Japan Society of Medical Physics (JSMP), Japan Radiological Society (JRS), Japanese Society of Radiological Technology (JSRT), and Japanese Society for Radiation Oncology (JASTRO) jointly established the comprehensive practical guidelines for online MRgART. These guidelines propose the essential requirements for clinical implementation of online MRgART with respect to equipment, personnel, institutional environment, practice guidance, and quality assurance/quality control (QA/QC). The minimum requirements for related equipment and QA/QC tools, recommendations for safe operation of MRI system, and the implementation system are described. The accuracy of monitor chamber and detector in dose measurements should be confirmed because of the presence of magnetic field. The ionization chamber should be MR-compatible. Non-MR-compatible devices should be used in an area that is not affected by the static magnetic field (outside the five Gauss line), and their operation should be checked to ensure that they do not affect the MR image quality. Dose verification should be performed using an independent dose verification system that has been confirmed to be reliable through commissioning. This guideline proposes the checklists to ensure the safety of online MRgART. Successful clinical implementation of online MRgART requires close collaboration between physician, radiological technologist, nurse, and medical physicist.

Multi-Institutional Study of End-to-End Dose Delivery Quality Assurance Testing for Image-Guided Brachytherapy Using a Gel Dosimeter.

PURPOSE: To quantify dose delivery errors for high-dose-rate image-guided brachytherapy (HDR-IGBT) using an independent end-to-end dose delivery quality assurance test at multiple institutions. The novelty of our study is that this is the first multi-institutional end-to-end dose delivery study in the world. MATERIALS AND METHODS: The postal audit used a polymer gel dosimeter in a cylindrical acrylic container for the afterloading system. Image acquisition using computed tomography, treatment planning, and irradiation were performed at each institution. Dose distribution comparison between the plan and gel measurement was performed. The percentage of pixels satisfying the absolute-dose gamma criterion was reviewed. RESULTS: Thirty-five institutions participated in this study. The dose uncertainty was 3.6% ± 2.3% (mean ± 1.96σ). The geometric uncertainty with a coverage factor of k = 2 was 3.5 mm. The tolerance level was set to the gamma passing rate of 95% with the agreement criterion of 5% (global)/3 mm, which was determined from the uncertainty estimation. The percentage of pixels satisfying the gamma criterion was 90.4% ± 32.2% (mean ± 1.96σ). Sixty-six percent (23/35) of the institutions passed the verification. Of the institutions that failed the verification, 75% (9/12) had incorrect inputs of the offset between the catheter tip and indexer length in treatment planning and 17% (2/12) had incorrect catheter reconstruction in treatment planning. CONCLUSIONS: The methodology should be useful for comprehensively checking the accuracy of HDR-IGBT dose delivery and credentialing clinical studies. The results of our study highlight the high risk of large source positional errors while delivering dose for HDR-IGBT in clinical practices.

Feasibility of intensity modulated radiotherapy with involved field radiotherapy for Japanese patients with locally advanced non-small cell lung cancer.

The feasibility of intensity modulated radiotherapy (IMRT) with involved field radiotherapy (IFRT) for Japanese patients with locally advanced non-small cell lung cancer (LA-NSCLC) remains unclear. Here we reviewed our initial experience of IMRT with IFRT for Japanese patients with LA-NSCLC to evaluate the feasibility of the treatment. Twenty LA-NSCLC patients who were treated with IMRT with IFRT during November 2019 to October 2020 were retrospectively analyzed. All patients received 60 Gy in 30 fractions of IMRT and were administered concurrent platinum-based chemotherapy. The median patient age was 71 years old and the group included 15 men and 5 women. The patient group included 2 patients with stage IIB, 11 patients with stage IIIA, 5 patients with stage IIIB, and 2 patients with stage IIIC disease. Histological diagnosis was squamous cell carcinoma in 14 patients, adenocarcinoma in 5 patients, and non-small cell lung cancer in 1 patient. The median follow-up period was 8 months. The incidence of grade 3 or greater pneumonitis was 5%, and grade 3 or greater esophagitis was not observed. None of the patients developed regional lymph node, with only recurrence reported so far. These findings indicate that IMRT with IFRT for Japanese patients with LA-NSCLC is feasible in terms of acute toxicity. Further study with a larger number of patients and longer follow-up to clarify the effect of treatment on patient prognosis is required.

Incidence and risk factors for pneumonitis among patients with lung cancer who received immune checkpoint inhibitors after palliative thoracic radiotherapy.

The aim of this study is to analyze the incidence and risk factors for pneumonitis when immune checkpoint inhibitors (ICIs) are combined with palliative thoracic radiotherapy (RT) for lung cancer. We retrospectively evaluated 29 patients with lung cancer who received ICIs after palliative thoracic RT (30 Gy in 10 fractions). Their ICIs were pembrolizumab (n = 17), nivolumab (n = 8) and atezolizumab (n = 4). Median follow-up period was 10 months. The median interval between starting RT and starting ICI was 25 days. Pneumonitis events were grade 1 (n = 10; 34%), grade 2 (n = 4; 14%) and grade 3 (n = 3; 10%). Obstructive pneumonia was significantly associated with grade ≥ 2 pneumonitis (P = 0.036). Age, sex, ICI agent, interval between RT and ICI and history of ICI before RT were not associated with grade ≥ 2 pneumonitis. Tumor volume; Brinkman index; dosimetric factors, such as lung V5, V10, V20, V30 and mean lung dose (MLD); lactate dehydrogenase; and C-reactive protein did not significantly differ between the grade ≤ 1 and grade ≥ 2 pneumonitis groups. Levels of sialylated carbohydrate antigen KL-6 were evaluated in 27 patients before RT; they significantly differed between patients with grade ≤ 2 pneumonitis (mean: 431 U/ml) and those with grade ≥ 3 pneumonitis (mean: 958 U/ml; P < 0.001). Patients who receive ICI after palliative thoracic RT should be carefully followed-up, especially those who have had obstructive pneumonia or high KL-6 levels.

Effect of durvalumab on local control after concurrent chemoradiotherapy for locally advanced non-small cell lung cancer in comparison with chemoradiotherapy alone.

BACKGROUND: Durvalumab after concurrent chemoradiotherapy (CCRT) for locally advanced non-small cell lung cancer (LA-NSCLC) has been found to significantly improve overall survival (OS). However, the effect of durvalumab on local control remains unclear. Here, we evaluated the effect of the durvalumab on local control in comparison with the clinical result of patients treated with CCRT alone. METHODS: A total of 120 LA-NSCLC patients including 76 patients with CCRT alone and 44 patients with CCRT followed by durvalumab were analyzed. Baseline patient characteristics of CCRT alone cohort and durvalumab cohort were compared with student's t test or Mann-Whitney U test for continuous variables and with chi-squared test for categorical variables. Local control (LC), progression free survival (PFS) and OS rates were estimated using the Kaplan-Meier method and compared with the log-rank test. RESULTS: There were 19 patients with stage II disease and 101 patients with stage III disease. Age, sex, histopathological type, T classification, N classification, clinical stage, tumor volume and dose fractionation schedule were not significantly different between the CCRT alone and durvalumab cohorts. The one-year LC rate was significantly higher in the durvalumab cohort (86%) compared with the CCRT alone cohort (62%) (P = 0.005), whereas no significant difference was observed in either PFS (P = 0.864) or OS (P = 0.443) between the CCRT and durvalumab cohorts. CONCLUSIONS: The one-year LC rate was significantly higher in the durvalumab cohort compared with the CCRT alone cohort. Although the follow-up period was too short to draw definitive conclusions, the study revealed that durvalumab might have a significant effect on LC. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Effect of durvalumab on local control after chemoradiotherapy for locally advanced non-small cell lung cancer is unclear WHAT THIS STUDY ADDS: The one-year local control rate of chemoradiotherapy followed by durvalumab was significantly higher compared with chemoradiotherapy alone.

Results of definitive radiotherapy with concurrent chemotherapy for maxillary sinus carcinomas with neck lymph node metastasis.

The purpose of this study was to describe the results of definitive radiotherapy (RT) with concurrent chemotherapy for maxillary sinus carcinomas (MSCs) with neck lymph node metastasis to clarify its limitation. Local control (LC), progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method and were compared between subgroups using the log rank test. Toxicity was classified using common terminology criteria of adverse events version 5.0. Eighteen patients with inoperable MSC with neck lymph node metastasis including 12 men and 6 women with a median age of 67 years were analyzed. The histologic diagnoses were as follows: 16 patients had squamous cell carcinomas and 2 had other histology. Four patients had stage T3 MSC, 6 had T4a and 8 had T4b. Among 18 patients, 7 received concurrent systemic chemotherapy and 11 received selective arterial chemo-infusion. The median follow-up period was 17 months. The 2-year LC, PFS and OS rates for the entire cohort were 34, 31 and 46%, respectively. No significant differences were observed for LC, PFS and OS rates between systemic chemotherapy and selective arterial chemo-infusion cohorts. Grade 3 or higher acute toxicity, including both non-hematological and hematological, was observed in nine patients (50%), while no grade 3 or higher late toxicity was observed. In conclusion, we described the results of definitive RT for MSCs with neck lymph node metastasis. Local recurrence of primary tumor was a frequent pattern of failure and it should be addressed in future study.

A comparison of the respiratory signals acquired by different respiratory monitoring systems used in respiratory gated radiotherapy.

PURPOSE: Respiratory monitoring systems are used to detect the respiratory phase of patients during the planning and administration of respiratory gated radiotherapy by using four-dimensional computed tomography (4DCT) or 4D positron-emission tomography/CT (4DPET/CT) and the linear accelerator (linac), respectively. Generally, identical respiratory monitoring systems are used for 4DCT, 4DPET/CT, and linac. However, different systems are sometimes used in combination because the accessibility of the respiratory monitoring systems may differ by manufacturer. The combined use of different respiratory monitoring systems in phase-based gating is of concern because the differences in the timing of tags (end-respiration signals algorithmically determined by the respiratory monitoring system), defined by the two systems, may result in phase differences, The purpose of this study is to estimate this difference and evaluate its effect on 4DCT data. METHODS: Ten patients (seven men and three women) with a median age of 75 yr (range: 57-84 yr) were treated by gated stereotactic body radiation therapy between April and December 2009. Two types of respiratory monitoring systems--RPM (Varian Medical Systems) and AZ-733V (Anzai MEDICAL)--were placed on the abdominal surface of the patients, and the respiratory signals were acquired by both systems. The relationship between the amplitude peak and the tag obtained by each respiratory system was analyzed for each patient. Further, the 4DCT images were reconstructed by using the signals obtained from both the RPM and the AZ-733V systems, and the tumor volumes and the tumor centroid positions in the craniocaudal plane were analyzed for each patient. RESULTS: The correlation factor between the respiratory signals from the RPM system and AZ-733V system was 0.990 (range: 0.940-0.994). The amplitude peak of the RPM system corresponded well with that of the AZ-733V system. The median +/- standard deviation of the phase difference for all the patients ranged from -4.3 +/- 7.1% to 3.5 +/- 2.2%. In the case of some patients, differences were noted between the two systems in the estimation of the tumor centroid position and tumor shape. CONCLUSIONS: The estimation of the position of the tumor centroid and tumor shape may vary with the use of different respiratory monitoring systems. This implies that it is preferable to use the same respiratory monitoring system with 4DCT, 4DPET-CT, and linac.