Difference in target dose distributions between Acuros XB and collapsed cone convolution/superposition and the impact of the tumor locations in clinical cases of stereotactic ablative body radiotherapy for lung cancer.

Objectives: The objective of the study is to analyze the difference in target dose distributions between Acuros XB (AXB) and collapsed cone convolution (CCC)/superposition and the impact of the tumor locations in clinical cases of stereotactic ablative body radiotherapy (SABR) for lung cancer. Materials and Methods: Ninety-six patients underwent SABR for lung cancers Kyushu University Hospital from 2014 to 2017. We recalculated clinical plans originally calculated by AXB using CCC with the identical monitor units (MUs) and beam arrangements. We calculated the following dosimetric parameters: maximum dose (Dmax), minimum dose (Dmin), homogeneity index (HI), conformity index (CI), and D95 of the planning target volume (PTV). We investigated the difference between the results of two calculations and examined the impact of tumor location. Moreover, we determined the target central dose using a thorax phantom and assessed the calculation accuracy of the two algorithms for each fraction. Results: CCC significantly overestimated the dose to PTV, compared to AXB (P < 0.05). The mean differences of Dmax, Dmin, and D95 were 1.17, 1.95, and 1.85 Gy, respectively. The mean differences of HI and CI were 0.02 and - 0.06. Dmin, HI, and D95 had significant correlations with the tumor location, and the difference was greater when the PTV was included the chest wall (P < 0.05). The discrepancy between the calculated and irradiated dose was 2.48% for CCC, whereas it was 0.14% for AXB. Conclusions: We demonstrated that CCC significantly overestimated the dose to PTV relative to AXB in clinical cases of lung SABR.

Concurrent chemoradiotherapy with cisplatin + S-1 versus cisplatin + other third-generation agents for locally advanced non-small-cell lung cancer: a meta-analysis of individual participant data.

BACKGROUND: For decades, concurrent chemo-radiotherapy with cisplatin-based regimen has been a standard therapy for locally advanced stage III non-small-cell lung cancer (NSCLC). We conducted individual-participant-data (IPD) meta-analyses to compare S-1/cisplatin versus other third-generation anti-cancer medications plus cisplatin regimens with the goal of determining whether or not S-1/cisplatin was the ideal choice for treatment accompanied by radiotherapy (RT). METHODS: A thorough search was performed using multiple electronic databases. We integrated the IPD of each trial and analyzed the resulting meta-database. The primary endpoint was the overall survival (OS), and the secondary endpoints included the progression-free survival (PFS), objective response rate (ORR), toxicities, and treatment delivery. Subgroup analyses were conducted based on baseline characteristics. Statistical analyses were stratified by trials. RESULTS: Three randomized control trials (WJOG5008L study, SPECTRA study, and TORG1018 study) were found. Of the 316 patients enrolled in those studies, 159 received S-1/cisplatin (SP), and 157 were assigned to other combination chemotherapy. The median OS for the SP arm was 48.2 months, and that of the non-SP arm was 42.4 months. The combined hazard ratio (HR) for the OS was 0.895 (95% confidence interval [CI] 0.638-1.256), and no heterogeneity was noted among the trials (test for heterogeneity, p = 0.87; I2 = 0). The median PFS for the SP and non-SP arms was 12.8 and 14.0 months, respectively. The corresponding HR for the PFS was 1.022 (95% CI 0.776-1.347), and there was evidence of moderate heterogeneity among the trials (test for heterogeneity, p = 0.16; I2 = 0.46). The ORRs were 69.7% (95% CI 62.1-76.7%) and 70.9% (95% CI 63.7-78.1%) in the SP and non-SP arms, respectively. The toxicity profile showed that SP caused significantly fewer instances of grade 3-4 leukopenia and neutropenia than non-SP regimens. CONCLUSION: No marked differences were detected in the OS, PFS, or ORR between the SP and non-SP arms. SP had significantly less myelosuppression and better treatment compliance as a chemotherapy regimen for concurrent chemoradiation in locally advanced NSCLC than non-SP regimens.

A multi-institutional randomized phase III trial comparing postoperative radiotherapy to observation after adjuvant chemotherapy in patients with pathological N2 Stage III non-small cell lung cancer: Japan Clinical Oncology Group Study JCOG1916 (J-PORT study).

The standard treatment for pathological N2 Stage III non-small cell lung cancer with negative surgical margins in Japan is cisplatin-based adjuvant chemotherapy. However, recent studies suggest that the addition of thoracic radiotherapy after adjuvant chemotherapy prolongs survival. While thoracic radiotherapy is considered to prolong survival by improving locoregional control, it is known to increase radiation-induced adverse events. We began a randomized controlled trial in January 2021 in Japan to confirm the superiority of radiotherapy over observation after adjuvant chemotherapy in pathological N2 Stage III non-small cell lung cancer patients with negative surgical margins. We aim to accrue 330 patients from 47 institutions over 5 years. The primary endpoint is relapse-free survival; the secondary endpoints are overall survival, proportion of patients completing radiotherapy in the radiotherapy arm, early adverse events, late adverse events in the radiotherapy arm, serious adverse events and local recurrence.

Phase 2 Study of Nimotuzumab in Combination With Concurrent Chemoradiotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer.

BACKGROUND: We evaluated the tolerability and efficacy of nimotuzumab, a humanized IgG1 monoclonal anti-epidermal growth factor receptor antibody, with concurrent chemoradiotherapy in patients with unresectable locally advanced non-small-cell lung cancer. PATIENTS AND METHODS: In this multicenter, single-arm, open-label, phase 2 trial conducted in Japan (JapicCTI-090825), patients received thoracic radiotherapy (60 Gy, 2 Gy per fraction, 6 weeks) and four 4-week cycles of chemotherapy (day 1, cisplatin 80 mg/m2; days 1 and 8, vinorelbine 20 mg/m2). Nimotuzumab 200 mg was administrated weekly for 16 weeks. The primary endpoint was treatment completion rate, defined as the percentage of patients completing 60 Gy of radiotherapy within 8 weeks, 2 cycles of chemotherapy, and at least 75% of the required nimotuzumab dose during the initial 2-cycle concurrent chemoradiotherapy period. RESULTS: Of 40 patients enrolled, 39 received the study treatment, which was well tolerated, with a completion rate of 87.2%. Thirty-eight patients completed 60 Gy of radiotherapy within 8 weeks. Infusion reaction, grade 3 or higher rash, grade 3 or higher radiation pneumonitis, or grade 4 or higher nonhematologic toxicity were not observed. The objective response rate was 69.2%. The median progression-free survival (PFS) and 5-year PFS rate were 508 days and 29.0%, respectively. The 5-year PFS rate in patients with non-squamous cell carcinoma (n = 23) was 13.7% and in patients with squamous cell carcinoma (n = 16) was 50.0%. The 5-year overall survival rate was 58.4%. CONCLUSION: Addition of nimotuzumab to the concurrent chemoradiotherapy regimen was well tolerated and showed potential for treating patients with locally advanced non-small-cell lung cancer, particularly squamous cell carcinoma.

Japanese structure survey of radiation oncology in 2012.

This paper describes the ongoing structure of radiation oncology in Japan in terms of equipment, personnel, patient load and geographic distribution to identify and overcome any existing limitations. From March 2013 to August 2016, the Japanese Society for Radiation Oncology conducted a questionnaire based on the Japanese national structure survey of radiation oncology in 2012. Data were analyzed based on the institutional stratification by the annual number of new patients treated with radiotherapy per institution. The estimated annual numbers of new and total (new plus repeat) patients treated with radiation were 213 000 and 251 000, respectively. Additionally, the estimated cancer incidence was 865 238 cases with ~24.6% of all newly diagnosed patients being treated with radiation. The types and numbers of treatment devices actually used included linear accelerator (LINAC; n = 864), telecobalt (n = 0), Gamma Knife (n = 44), 60Co remote afterloading system (RALS; n = 23) and 192Ir RALS (n = 130). The LINAC system used dual-energy functions in 651 units, 3D conformal radiotherapy functions in 759 and intensity-modulated radiotherapy (IMRT) functions in 466. There were 792 Japan Radiological Society/Japanese Society for Radiation Oncology-certified radiation oncologists, 1061.6 full-time equivalent (FTE) radiation oncologists, 2124.2 FTE radiotherapy technologists, 181.3 FTE medical physicists, 170.9 FTE radiotherapy quality managers and 841.5 FTE nurses. The frequency of IMRT use significantly increased during this time. In conclusion, the Japanese structure of radiation oncology has clearly improved in terms of equipment and utility although there was a shortage of personnel in 2012.

Updated Survival Data for a Phase I/II Study of Carboplatin plus Nab-Paclitaxel and Concurrent Radiotherapy in Patients with Locally Advanced Non-Small Cell Lung Cancer.

LESSONS LEARNED: Updated survival data for a phase I/II study of carboplatin plus nab-paclitaxel and concurrent radiotherapy were collected. In the group of 58 patients who were enrolled at 14 institutions in Japan, the median overall survival was not reached and the 2-year overall survival rate was 66.1% (95% confidence interval, 52.1%-76.8%). Results reveal encouraging feasibility and activity for this regimen. BACKGROUND: We report the updated survival data for a phase I/II study of carboplatin plus nab-paclitaxel (nab-P/C) and concurrent radiotherapy (CRT) in patients with locally advanced non-small cell lung cancer (NSCLC). METHODS: Individuals between 20 and 74 years of age with unresectable NSCLC of stage IIIA or IIIB and a performance status of 0 or 1 were eligible for the study. Patients received weekly nab-paclitaxel at 50 mg/m2 for 6 weeks together with weekly carboplatin at an area under the curve (AUC) of 2 mg/ml/min and concurrent radiotherapy with 60 Gy in 30 fractions. This concurrent phase was followed by a consolidation phase consisting of two 3-week cycles of nab-paclitaxel (100 mg/m2 on days 1, 8, and 15) plus carboplatin (AUC of 6 on day 1). After the treatment, patients were observed off therapy. The primary endpoint of the phase II part of the study was progression-free survival (PFS). RESULTS: Between October 2014 and November 2016, 58 patients were enrolled at 14 institutions in Japan, with 56 of these individuals being evaluable for treatment efficacy and safety. At the median follow-up time of 26.0 months (range, 4.0-49.6 months), the median overall survival (OS) was not reached (95% confidence interval [CI], 25.3 months to not reached) and the 2-year OS rate was 66.1% (95% CI, 52.1%-76.8%). The median PFS was 11.8 months (95% CI, 8.2-21.0 months), and the 2-year PFS rate was 35.9% (95% CI, 23.1%-48.9%). Subgroup analysis according to tumor histology or patient age revealed no differences in median PFS or OS. Long-term follow-up of toxicities did not identify new safety signals, and no treatment-related deaths occurred during the study period. CONCLUSION: Concurrent chemoradiation with nab-P/C was safe and provided a long-term survival benefit for patients with locally advanced NSCLC.

Japanese Structure Survey of Radiation Oncology in 2011.

We evaluated the evolving structure of radiation oncology in Japan in terms of equipment, personnel, patient load and geographic distribution to identify and overcome any existing limitations. From March 2012 to August 2015, the Japanese Society for Radiation Oncology conducted a questionnaire based on the Japanese national structure survey of radiation oncology in 2011. Data were analyzed based on the institutional stratification by the annual number of new patients treated with radiotherapy per institution. The estimated annual numbers of new and total (new plus repeat) patients treated with radiation were 211 000 and 250 000, respectively. Additionally, the estimated cancer incidence was 851 537 cases with approximately 24.8% of all newly diagnosed patients being treated with radiation. The types and numbers of treatment devices actually used included linear accelerator (LINAC; n = 836), telecobalt (n = 3), Gamma Knife (n = 46), 60Co remote afterloading system (RALS; n = 24), and 192Ir RALS (n = 125). The LINAC system used dual-energy functions in 619 units, 3D conformal radiotherapy functions in 719 and intensity-modulated radiotherapy (IMRT) functions in 412. There were 756 JRS or JASTRO-certified radiation oncologists, 1018.5 full-time equivalent (FTE) radiation oncologists, 2026.7 FTE radiotherapy technologists, 149.1 FTE medical physicists, 141.5 FTE radiotherapy quality managers and 716.3 FTE nurses. The frequency of IMRT use significantly increased during this time. To conclude, although there was a shortage of personnel in 2011, the Japanese structure of radiation oncology has clearly improved in terms of equipment and utility.

Assessment of the anatomical position of point B and the relationship between point B dose and the dose delivered to pelvic lymph nodes in CT-based high-dose-rate brachytherapy for uterine cervical cancer.

PURPOSE: To examine the anatomical position of point B and the relationship between the dose at point B and the dose delivered to the pelvic lymph nodes in computed tomography (CT)-based brachytherapy for cervical cancer. MATERIAL AND METHODS: Forty-nine cervical cancer patients were treated at Kyushu University Hospital. For all cases, planning CT images obtained after the applicator insertion were imported to an Oncentra Brachy (Elekta AB, Stockholm, Sweden), and points A (dose prescription, 6 Gy) and points B were set according to the Manchester method. The pelvic lymph node regions (external iliac, internal iliac, and obturator) were contoured, and the anatomic positions of 98 points B in 49 patients were examined. Dose volume histogram (DVH) parameters (D100, D90, D50, D2cc, D1cc, and D0.1cc) were calculated for each lymph node region and compared with the point B dose. RESULTS: The mean bilateral dose to point B was 1.70 ±0.18 Gy, and 26 (27%) of 98 points B were not located in any pelvic lymph node regions. The DVH analysis indicated a low degree of correlation overall, and all values were significantly different from point B doses (p < 0.05), except for D0.1cc of the external iliac node (p = 0.0594) and D1cc of the internal iliac node (p = 0.0711). CONCLUSIONS: We investigated the anatomical location of point B in patients with cervical cancer who underwent brachytherapy, and the DVH analysis revealed that the point B dose was a poor surrogate for the dose delivered to the pelvic lymph nodes.

Dose evaluation indices for total body irradiation using TomoDirect with different numbers of ports: A comparison with the TomoHelical method.

TomoDirect has been reported to have some advantages over TomoHelical in delivering total body irradiation (TBI). This study aimed to investigate the relationships between the number of ports and the dose evaluation indices in low-dose TBI in TomoDirect mode using 2-12 ports and to compare these data with those for the TomoHelical mode in a simulation study. Thirteen patients underwent low-dose TBI in TomoHelical mode from June 2015 to June 2016. We used the same computed tomography data sets for these patients to create new treatment plans for upper-body parts using TomoDirect mode with 2-12 beam angles as well as TomoHelical mode. The prescription was 4 Gy in two equal fractions. For the TomoDirect data, we generated plans with 2-12 ports with approximately equally spaced angles; the modulation factor, field width, and pitch were 2.0, 5.0 cm, and 0.500, respectively. For the TomoHelical plans, the modulation factor, field width, and pitch were 2.0, 5.0 cm, and 0.397, respectively. D2, D98, D50, and the homogeneity index (HI) were evaluated to compare TomoDirect plans having 2-12 ports with the TomoHelical plan. Using TomoDirect plans, D2 with four ports or fewer, D98 with 10 ports or fewer, D50 with four ports or fewer and HI with five ports or fewer showed statistically significantly worse results than the TomoHelical plan. With the TomoDirect plans, D2 with seven ports or more, D50 with eight ports or more, and HI with eight ports or more showed statistically significant improvement compared with the TomoHelical plan. All of the dose evaluation indices of the TomoDirect plans showed a tendency to improve as the number of ports increased. TomoDirect plans showed statistically significant improvement of D2, D50, and HI compared with the TomoHelical plan. Therefore, we conclude that TomoDirect can provide better dose distribution in low-dose TBI with TomoTherapy.

Japanese structure survey of radiation oncology in 2010.

We evaluated the evolving structure of radiation oncology in Japan in terms of equipment, personnel, patient load, and geographic distribution to identify and overcome any existing limitations. From March 2011 to June 2013, the Japanese Society for Radiation Oncology conducted a questionnaire based on the Japanese national structure survey of radiation oncology in 2010. Data were analyzed based on the institutional stratification by the annual number of new patients treated with radiotherapy per institution. The estimated annual numbers of new and total (new plus repeat) patients treated with radiation were 211 000 and 251 000, respectively. Additionally, the estimated cancer incidence was 805 236 cases, with ~26.2% of all newly diagnosed patients being treated with radiation. The types and numbers of treatment devices actually used included linear accelerator (LINAC; n = 829), telecobalt (n = 9), Gamma Knife (n = 46), 60Co remote afterloading system (RALS; n = 28), and 192Ir RALS (n = 131). The LINAC system used dual-energy functions in 586 units, three-dimensional conformal radiotherapy functions in 663, and intensity-modulated radiotherapy (IMRT) functions in 337. There were 564 JASTRO-certified radiation oncologists, 959.2 full-time equivalent (FTE) radiation oncologists, 1841.3 FTE radiotherapy technologists, 131.3 FTE medical physicists, 121.5 FTE radiotherapy quality managers, and 649.6 FTE nurses. The frequency of IMRT use significantly increased during this year. To conclude, although there was a shortage of personnel in 2010, the Japanese structure of radiation oncology has clearly improved in terms of equipment and utility.

Phase I/II study of carboplatin plus nab-paclitaxel and concurrent radiotherapy for patients with locally advanced non-small cell lung cancer.

OBJECTIVES: Chemoradiation regimens of greater efficacy are needed for patients with locally advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: In a phase I study, escalating doses of weekly nab-paclitaxel (40 or 50 mg/m2) were administered along with weekly carboplatin at an area under the curve (AUC) of 2 mg mL-1 min and concurrent radiotherapy with 60 Gy in 30 fractions to patients with locally advanced NSCLC. This concurrent phase was followed by a consolidation phase consisting of two 3-week cycles of nab-paclitaxel plus carboplatin. In a phase II study, nab-paclitaxel was administered at the recommended dose (RD) together with carboplatin and radiation. RESULTS: In the phase I study, one of six patients experienced dose-limiting toxicity (leukopenia of grade 3 requiring a second consecutive skip in the administration of weekly chemotherapy) with nab-paclitaxel at 50 mg/m2, which was therefore determined to be the RD. Fifty-six patients treated at the RD were evaluable for safety and efficacy. Common toxicities of grade 3 or 4 in the concurrent phase included leukopenia (60.7%) and neutropenia (28.6%). No treatment-related deaths occurred during the study period. The objective response rate was 76.8% (95% confidence interval [CI], 64.2-85.9%), median progression-free survival was 11.8 months (60% CI, 10.6-16.2 months; 95% CI, 8.2-20.8 months), and median overall survival was not reached. CONCLUSION: Our results reveal encouraging feasibility and activity for concurrent chemoradiation with nab-paclitaxel at 50 mg/m2 and carboplatin at an AUC of 2 in patients with locally advanced NSCLC.

A randomised phase II trial of S-1 plus cisplatin versus vinorelbine plus cisplatin with concurrent thoracic radiotherapy for unresectable, locally advanced non-small cell lung cancer: WJOG5008L.

BACKGROUND: Cisplatin-based chemoradiotherapy is the standard treatment for unresectable, locally advanced non-small-cell lung cancer (NSCLC). This trial evaluated two experimental regimens that combine chemotherapy with concurrent radiotherapy. METHODS: Eligible patients with unresectable stage III NSCLC were randomised to either the SP arm (S-1 and cisplatin) or VP arm (vinorelbine and cisplatin), with early concurrent thoracic radiotherapy of 60 Gy, comprising 2 Gy per daily fraction. The primary endpoint was the overall survival rate at 2 years (2-year overall survival (OS)) (Study ID: UMIN000002420). RESULTS: From September 2009 to September 2012, 112 patients were enroled. Of the 108 eligible patients, the 2-year OS was 75.6% (80% confidence interval (CI), 67-82%) in the SP arm and 68.5% (80% CI: 60-76%) in the VP arm. The hazard ratio (HR) for death between the two arms was 0.85 (0.48-1.49). The median progression-free survival was 14.8 months for the SP arm and 12.3 months for the VP arm with an HR of 0.92 (0.58-1.44). There were four treatment-related deaths in the SP arm and five in the VP arm. CONCLUSIONS: The null hypotheses for 2-year OS were rejected in both arms. The West Japan Oncology Group will employ the SP arm as the investigational arm in a future phase III study.

Patterns of radiotherapy infrastructure in Japan and in other countries with well-developed radiotherapy infrastructures.

BACKGROUND: In high-income countries, the number of radiotherapy machine per population reaches a sufficient level. However, the patterns of infrastructure of radiotherapy in high-income countries are not well known. METHODS: Among 29 high-income countries with gross national income of $25,000 or more per capita, we selected 23 countries whose total number of newly diagnosed cancer patients in 2012 was reported in the Organisation for Economic Co-operation and Development Health Statistics 2017. The numbers of radiotherapy centers and teletherapy machines in each of these 23 countries were collected using the Dictionary of Radiotherapy Centers database. RESULTS: The number of cancer patients per teletherapy machine was 452.35-1398.22 (median 711.66) with a three-fold variation, whereas the number of cancer patients per radiotherapy center varied even more widely, from 826.16 to 5159.86 (median 2259.83) with a six-fold variation. The average number of teletherapy machines per radiotherapy center also ranged widely, from 1.24 to 8.29 (median 3.11) with a seven-fold variation. The number of teletherapy machines in each country was almost proportional to that of cancer patients, and the number of teletherapy machines per radiotherapy center was inversely related to the number of radiotherapy centers per cancer patients. The number of teletherapy machines per radiotherapy center in Japan was 1.24, the most fragmented among the high-income countries. The percentage of large radiotherapy centers having three or more teletherapy machines in Japan was the smallest among 23 high-income countries. CONCLUSIONS: Optimization of the radiotherapy infrastructure in Japan should be carefully considered.

Computational analysis of interfractional anisotropic shape variations of the rectum in prostate cancer radiation therapy.

PURPOSE: To analyze the uncertainties of the rectum due to anisotropic shape variations by using a statistical point distribution model (PDM). MATERIALS AND METHODS: The PDM was applied to the rectum contours that were delineated on planning computed tomography (CT) and cone-beam CT (CBCT) at 80 fractions of 11 patients. The standard deviations (SDs) of systematic and random errors of the shape variations of the whole rectum and the region in which the rectum overlapped with the PTV (ROP regions) were derived from the PDMs at all fractions of each patient. The systematic error was derived by using the PDMs of planning and average rectum surface determined from rectum surfaces at all fractions, while the random error was derived by using a PDM-based covariance matrix at all fractions of each patient. RESULTS: Regarding whole rectum, the population SDs were larger than 1.0 mm along all directions for random error, and along the anterior, superior, and inferior directions for systematic error. The deviation is largest along the superior and inferior directions for systematic and random errors, respectively. For ROP regions, the population SDs of systematic error were larger than 1.0 mm along the superior and inferior directions. The population SDs of random error for the ROP regions were larger than 1.0 mm except along the right and posterior directions. CONCLUSIONS: The anisotropic shape variations of the rectum, especially in the ROP regions, should be considered when determining a planning risk volume (PRV) margins for the rectum associated with the acute toxicities.

Exploration of temporal stability and prognostic power of radiomic features based on electronic portal imaging device images.

PURPOSE: We aimed to explore the temporal stability of radiomic features in the presence of tumor motion and the prognostic powers of temporally stable features. METHODS: We selected single fraction dynamic electronic portal imaging device (EPID) (n = 275 frames) and static digitally reconstructed radiographs (DRRs) of 11 lung cancer patients, who received stereotactic body radiation therapy (SBRT) under free breathing. Forty-seven statistical radiomic features, which consisted of 14 histogram-based features and 33 texture features derived from the graylevel co-occurrence and graylevel run-length matrices, were computed. The temporal stability was assessed by using a multiplication of the intra-class correlation coefficients (ICCs) between features derived from the EPID and DRR images at three quantization levels. The prognostic powers of the features were investigated using a different database of lung cancer patients (n = 221) based on a Kaplan-Meier survival analysis. RESULTS: Fifteen radiomic features were found to be temporally stable for various quantization levels. Among these features, seven features have shown potentials for prognostic prediction in lung cancer patients. CONCLUSIONS: This study suggests a novel approach to select temporally stable radiomic features, which could hold prognostic powers in lung cancer patients.

Additional radiotherapy following endoscopic submucosal dissection for T1a-MM/T1b-SM esophageal squamous cell carcinoma improves locoregional control.

BACKGROUND: Endoscopic submucosal dissection (ESD) can be used as a less invasive treatment option for superficial esophageal cancer involving the muscularis mucosae (T1a-MM) or upper third of the submucosa (T1b-SM1). Additional treatment after ESD is needed to prevent lymph node metastasis. However, the efficacy of radiotherapy following ESD has not been well evaluated. Moreover, the clinical outcomes of patients with large mucosal defects of the esophagus who received radiotherapy after ESD have not been reported. This study aimed to clarify the efficacy of additional radiotherapy following ESD for esophageal squamous cell cancer involving T1a-MM or T1b-SM1. METHODS: We analyzed twenty-seven patients with pathologically confirmed T1a-MM or T1b-SM1 esophageal squamous cell cancer treated by ESD. Thirteen patients received additional radiotherapy (RT group), and the remaining patients did not (non-RT group). Locoregional control (LRC), overall survival, cause-specific survival, and adverse events including treatment-related esophageal strictures were evaluated. RESULTS: The three-year LRC was significantly better for the RT than the non-RT group (100% vs. 57.8%, respectively; p = 0.022). Chemotherapy following ESD did not improve LRC. Multivariate analysis showed that radiotherapy was an independent prognostic factor for better LRC (p = 0.0022). Contrary to the results in LRC, overall and cause-specific survival were not significantly different between the RT and non-RT groups. A subgroup analysis of patients with mucosal defects involving ≥ 3/4 of the esophageal circumference after ESD showed that LRC of the RT group was better than that of the non-RT group (p = 0.049). Treatment-related esophageal strictures were observed in 2 of 6 patients in the RT group with large mucosal defects after ESD. No patients with mucosal defects involving less than 3/4 of the circumference after ESD developed treatment-related strictures. CONCLUSIONS: Radiotherapy after ESD contributed to better LRC in esophageal squamous cell cancer involving pT1a-MM and pT1b-SM1. Esophageal strictures were observed in some patients with large mucosal defects after ESD. Despite leading to better LRC, radiotherapy after ESD should be undertaken after careful consideration for patients with large mucosal defects after ESD.

Impact of pixel-based machine-learning techniques on automated frameworks for delineation of gross tumor volume regions for stereotactic body radiation therapy.

The aim of this study was to investigate the impact of pixel-based machine learning (ML) techniques, i.e., fuzzy-c-means clustering method (FCM), and the artificial neural network (ANN) and support vector machine (SVM), on an automated framework for delineation of gross tumor volume (GTV) regions of lung cancer for stereotactic body radiation therapy. The morphological and metabolic features for GTV regions, which were determined based on the knowledge of radiation oncologists, were fed on a pixel-by-pixel basis into the respective FCM, ANN, and SVM ML techniques. Then, the ML techniques were incorporated into the automated delineation framework of GTVs followed by an optimum contour selection (OCS) method, which we proposed in a previous study. The three-ML-based frameworks were evaluated for 16 lung cancer cases (six solid, four ground glass opacity (GGO), six part-solid GGO) with the datasets of planning computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT images using the three-dimensional Dice similarity coefficient (DSC). DSC denotes the degree of region similarity between the GTVs contoured by radiation oncologists and those estimated using the automated framework. The FCM-based framework achieved the highest DSCs of 0.79±0.06, whereas DSCs of the ANN-based and SVM-based frameworks were 0.76±0.14 and 0.73±0.14, respectively. The FCM-based framework provided the highest segmentation accuracy and precision without a learning process (lowest calculation cost). Therefore, the FCM-based framework can be useful for delineation of tumor regions in practical treatment planning.

Investigation of interfractional shape variations based on statistical point distribution model for prostate cancer radiation therapy.

PURPOSE: The setup errors and organ motion errors pertaining to clinical target volume (CTV) have been considered as two major causes of uncertainties in the determination of the CTV-to-planning target volume (PTV) margins for prostate cancer radiation treatment planning. We based our study on the assumption that interfractional target shape variations are not negligible as another source of uncertainty for the determination of precise CTV-to-PTV margins. Thus, we investigated the interfractional shape variations of CTVs based on a point distribution model (PDM) for prostate cancer radiation therapy. MATERIALS AND METHODS: To quantitate the shape variations of CTVs, the PDM was applied for the contours of 4 types of CTV regions (low-risk, intermediate- risk, high-risk CTVs, and prostate plus entire seminal vesicles), which were delineated by considering prostate cancer risk groups on planning computed tomography (CT) and cone beam CT (CBCT) images of 73 fractions of 10 patients. The standard deviations (SDs) of the interfractional random errors for shape variations were obtained from covariance matrices based on the PDMs, which were generated from vertices of triangulated CTV surfaces. The correspondences between CTV surface vertices were determined based on a thin-plate spline robust point matching algorithm. The systematic error for shape variations was defined as the average deviation between surfaces of an average CTV and planning CTVs, and the random error as the average deviation of CTV surface vertices for fractions from an average CTV surface. RESULTS: The means of the SDs of the systematic errors for the four types of CTVs ranged from 1.0 to 2.0 mm along the anterior direction, 1.2 to 2.6 mm along the posterior direction, 1.0 to 2.5 mm along the superior direction, 0.9 to 1.9 mm along the inferior direction, 0.9 to 2.6 mm along the right direction, and 1.0 to 3.0 mm along the left direction. Concerning the random errors, the means of the SDs ranged from 0.9 to 1.2 mm along the anterior direction, 1.0 to 1.4 mm along the posterior direction, 0.9 to 1.3 mm along the superior direction, 0.8 to 1.0 mm along the inferior direction, 0.8 to 0.9 mm along the right direction, and 0.8 to 1.0 mm along the left direction. CONCLUSIONS: Since the shape variations were not negligible for intermediate and high-risk CTVs, they should be taken into account for the determination of the CTV-to-PTV margins in radiation treatment planning of prostate cancer.

Computer-assisted framework for machine-learning-based delineation of GTV regions on datasets of planning CT and PET/CT images.

We have proposed a computer-assisted framework for machine-learning-based delineation of gross tumor volumes (GTVs) following an optimum contour selection (OCS) method. The key idea of the proposed framework was to feed image features around GTV contours (determined based on the knowledge of radiation oncologists) into a machine-learning classifier during the training step, after which the classifier produces the 'degree of GTV' for each voxel in the testing step. Initial GTV regions were extracted using a support vector machine (SVM) that learned the image features inside and outside each tumor region (determined by radiation oncologists). The leave-one-out-by-patient test was employed for training and testing the steps of the proposed framework. The final GTV regions were determined using the OCS method that can be used to select a global optimum object contour based on multiple active delineations with a LSM around the GTV. The efficacy of the proposed framework was evaluated in 14 lung cancer cases [solid: 6, ground-glass opacity (GGO): 4, mixed GGO: 4] using the 3D Dice similarity coefficient (DSC), which denotes the degree of region similarity between the GTVs contoured by radiation oncologists and those determined using the proposed framework. The proposed framework achieved an average DSC of 0.777 for 14 cases, whereas the OCS-based framework produced an average DSC of 0.507. The average DSCs for GGO and mixed GGO were 0.763 and 0.701, respectively, obtained by the proposed framework. The proposed framework can be employed as a tool to assist radiation oncologists in delineating various GTV regions.