Potential for expanding indications and curability criteria of endoscopic resection for early gastric cancer in elderly patients: results from a Japanese multicenter prospective cohort study.

BACKGROUND AND AIMS: Evidence for endoscopic resection (ER) in elderly patients with early gastric cancer (EGC) is limited. We assessed its clinical outcomes, and explored new indications and curability criteria. METHODS: We analyzed data from a Japanese multicenter prospective cohort study. Patients aged ≥75 years with EGC treated with ER were included. We classified "eCuraC-2 (corresponding to noncurative ER, defined in the Japanese gastric cancer treatment guidelines)" into "elderly-high (EL-H)" (>10% estimated metastatic risk) and "elderly-low (EL-L)" (≤10%). RESULTS: In total, 3,371 patients with 3,821 EGCs were included; endoscopic submucosal dissection (ESD) was the prominent treatment choice. Among them, 3,586 lesions met the guidelines' ER indications and 235 did not. The proportions of en bloc and R0 resections and perforations were 98.9%, 94.4%, and 0.8%, respectively, in EGCs within the indications. In EGCs beyond the indications, they were 99.5%, 85.4%, and 5.9%, respectively, for lesions diagnosed as ≤3 cm, and 96.0%, 64.0%, and 18.0% for those >3 cm. Curative ER ("eCuraA/B") and EL-L were observed in 83.6% and 6.2% of lesions within the indications, respectively, and in 44.2% and 16.8% of lesions <3 cm beyond the indications, respectively. The 5-year cumulative gastric cancer death rates following eCuraA/B and EL-H were 0.3% (95% CI, 0.2-0.6) and 3.5% (2.0-5.7), respectively. Following EL-L, the rate was 0.9% (0.2-3.5) even without subsequent treatment. CONCLUSIONS: Usefulness of ESD for elderly EGC patients was confirmed by their clinical outcomes. Lesions ≤3 cm and EL-L emerged as new ER indication and curability criterion, respectively.

Risk factors for intraoperative and delayed perforation related with gastric endoscopic submucosal dissection.

BACKGROUND AND AIM: Perforation is one of the most important complications of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Several studies have examined risk factors for intraoperative and delayed perforations, but most were retrospective analyses with small numbers of patients. METHODS: This study represents a secondary analysis of a Japanese multicenter prospective cohort study. We investigated the factors associated with each type of perforation using 9015 patients with 9975 EGCs undergoing ESD between July 2010 and June 2012. RESULTS: Intraoperative perforation occurred in 198 patients (2.2%) with 203 lesions (2.0%), necessitating emergency surgery for four lesions (0.04% [2.0%, 4/203]). Delayed perforation occurred in another 37 patients (0.4%) with 42 lesions (0.4%), requiring emergency surgery for 12 lesions (0.12% [28.6%, 12/42]). Factors showing significant independent correlations with intraoperative perforation were upper or middle third of the stomach; remnant stomach or gastric tube; procedure time ≥100 min; tumor size >35 mm; body mass index (BMI) < 18.5 kg/m2; and ≥72 years. Factors showing significant independent correlations with delayed perforation were procedure time ≥60 min; BMI < 18.5 kg/m2; ≥75 years; ulceration; and tumor size >20 mm. Intraoperative perforation occurred most frequently at the greater curvature in the upper third of the stomach (7.9%), whereas delayed perforation occurred most frequently at the greater curvature in the middle third (1.2%). CONCLUSION: This multicenter prospective cohort study clarified the risk and risk factors of intraoperative and delayed perforation related to ESD for EGCs, providing information to help endoscopists reduce perforation.

Prediction of patient-specific quality assurance for volumetric modulated arc therapy using radiomics-based machine learning with dose distribution.

PURPOSE: We sought to develop machine learning models to predict the results of patient-specific quality assurance (QA) for volumetric modulated arc therapy (VMAT), which were represented by several dose-evaluation metrics-including the gamma passing rates (GPRs)-and criteria based on the radiomic features of 3D dose distribution in a phantom. METHODS: A total of 4,250 radiomic features of 3D dose distribution in a cylindrical dummy phantom for 140 arcs from 106 clinical VMAT plans were extracted. We obtained the following dose-evaluation metrics: GPRs with global and local normalization, the dose difference (DD) in 1% and 2% passing rates (DD1% and DD2%) for 10% and 50% dose threshold, and the distance-to-agreement in 1-mm and 2-mm passing rates (DTA1 mm and DTA2 mm) for 0.5%/mm and 1.0%.mm dose gradient threshold determined by measurement using a diode array in patient-specific QA. The machine learning regression models for predicting the values of the dose-evaluation metrics using the radiomic features were developed based on the elastic net (EN) and extra trees (ET) models. The feature selection and tuning of hyperparameters were performed with nested cross-validation in which four-fold cross-validation is used within the inner loop, and the performance of each model was evaluated in terms of the root mean square error (RMSE), the mean absolute error (MAE), and Spearman's rank correlation coefficient. RESULTS: The RMSE and MAE for the developed machine learning models ranged from <1% to nearly <10% depending on the dose-evaluation metric, the criteria, and dose and dose gradient thresholds used for both machine learning models. It was advantageous to focus on high dose region for predicating global GPR, DDs, and DTAs. For certain metrics and criteria, it was possible to create models applicable for patients' heterogeneity by training only with dose distributions in phantom. CONCLUSIONS: The developed machine learning models showed high performance for predicting dose-evaluation metrics especially for high dose region depending on the metric and criteria. Our results demonstrate that the radiomic features of dose distribution can be considered good indicators of the plan complexity and useful in predicting measured dose evaluation metrics.

Long-term Survival After Endoscopic Resection For Gastric Cancer: Real-world Evidence From a Multicenter Prospective Cohort.

BACKGROUND & AIMS: We aimed to clarify the long-term outcomes of endoscopic resection (ER) for early gastric cancers (EGCs) based on pathological curability in a multicenter prospective cohort study. METHODS: We analyzed the long-term outcomes of 9054 patients with 10,021 EGCs undergoing ER between July 2010 and June 2012. Primary endpoint was the 5-year overall survival (OS). The hazard ratio for all-cause mortality was calculated using the Cox proportional hazards model. We also compared the 5-year OS with the expected one calculated for the surgically resected patients with EGC. If the lower limit of the 95% confidence interval (CI) of the 5-year OS exceeded the expected 5-year OS minus a margin of 5% (threshold 5-year OS), ER was considered to be effective. Pathological curability was categorized into en bloc resection, negative margins, and negative lymphovascular invasion: differentiated-type, pT1a, ulcer negative, ≤2 cm (Category A1); differentiated-type, pT1a, ulcer negative, >2 cm or ulcer positive, ≤3 cm (Category A2); undifferentiated-type, pT1a, ulcer negative, ≤2 cm (Category A3); differentiated-type, pT1b (SM1), ≤3 cm (Category B); or noncurative resections (Category C). RESULTS: Overall, the 5-year OS was 89.0% (95% CI, 88.3%-89.6%). In a multivariate analysis, no significant differences were observed when the hazard ratio of Categories A2, A3, and B were compared with that of A1. In all the pathological curability categories, the lower limit of the 95% CI for the 5-year OS exceeded the threshold 5-year OS. CONCLUSION: ER can be recommended as a standard treatment for patients with EGCs fulfilling Category A2, A3, and B, as well as A1 (UMIN Clinical Trial Registry, UMIN000005871).

Curative Management After Endoscopic Resection for Esophageal Squamous Cell Carcinoma Invading Muscularis Mucosa or Shallow Submucosal Layer-Multicenter Real-World Survey in Japan.

INTRODUCTION: Curative management after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC), which invades the muscularis mucosa (pMM-ESCC) or shallow submucosal layer (pSM1-ESCC), has been controversial. METHODS: We identified patients with pMM-ESCC and pSM1-ESCC treated by ER. Outcomes were the predictive factors for regional lymph node and distant recurrence, and survival data were based on the depth of invasion, lymphovascular invasion (LVI), and additional treatment immediately after ER. RESULTS: A total of 992 patients with pMM-ESCC (n = 749) and pSM1-ESCC (n = 243) were registered. According to the multivariate Cox proportional hazards analysis, pSM1-ESCC (hazard ratio = 1.88, 95% confidence interval 1.15-3.07, P = 0.012) and LVI (hazard ratio = 6.92, 95% confidence interval 4.09-11.7, P < 0.0001) were associated with a risk of regional lymph node and distant recurrence. In the median follow-up period of 58.6 months (range 1-233), among patients with risk factors (pMM-ESCC with LVI or pSM1-ESCC), the 5-year overall survival rates, relapse-free survival rates, and cause-specific survival rates of patients with additional treatment were significantly better than those of patients without additional treatment; 85.4% vs 61.5% ( P < 0.0001), 80.5% vs 53.3% ( P < 0.0001), and 98.5% vs 93.1% ( P = 0.004), respectively. There was no difference in survival rate between the chemoradiotherapy and surgery groups. DISCUSSION: pSM1 and LVI were risk factors for metastasis after ER for ESCC. To improve the survival, additional treatment immediately after ER, such as chemoradiotherapy or surgery, is effective in patients with these risk factors.

Deep learning-based detection and classification of multi-leaf collimator modeling errors in volumetric modulated radiation therapy.

PURPOSE: The purpose of this study was to create and evaluate deep learning-based models to detect and classify errors of multi-leaf collimator (MLC) modeling parameters in volumetric modulated radiation therapy (VMAT), namely the transmission factor (TF) and the dosimetric leaf gap (DLG). METHODS: A total of 33 clinical VMAT plans for prostate and head-and-neck cancer were used, assuming a cylindrical and homogeneous phantom, and error plans were created by altering the original value of the TF and the DLG by ± 10, 20, and 30% in the treatment planning system (TPS). The Gaussian filters of σ = 0.5 $\sigma = 0.5$ and 1.0 were applied to the planar dose maps of the error-free plan to mimic the measurement dose map, and thus dose difference maps between the error-free and error plans were obtained. We evaluated 3 deep learning-based models, created to perform the following detections/classifications: (1) error-free versus TF error, (2) error-free versus DLG error, and (3) TF versus DLG error. Models to classify the sign of the errors were also created and evaluated. A gamma analysis was performed for comparison. RESULTS: The detection and classification of TF and DLG error were feasible for σ = 0.5 $\sigma = 0.5$ ; however, a considerable reduction of accuracy was observed for σ = 1.0 $\sigma = 1.0$ depending on the magnitude of error and treatment site. The sign of errors was detectable by the specifically trained models for σ = 0.5 $\sigma = 0.5$ and 1.0. The gamma analysis could not detect errors. CONCLUSIONS: We demonstrated that the deep learning-based models could feasibly detect and classify TF and DLG errors in VMAT dose distributions, depending on the magnitude of the error, treatment site, and the degree of mimicked measurement doses.

Advanced diagnostic endoscopy in the upper gastrointestinal tract: Review of the Japan Gastroenterological Endoscopy Society core sessions.

We held four upper gastrointestinal tract advanced diagnostic endoscopy sessions from the 89th to the 92nd Congress of the Japan Gastroenterological Endoscopy Society. The most common region addressed was the stomach in 25 presentations, followed by the esophagus in 23, duodenum in five, and other in one. Looking at techniques discussed, the most common image enhancement method discussed was narrowband imaging in 29 presentations, blue laser imaging, and linked color imaging (LCI) in 10 each, dual red imaging in three, and autofluorescence imaging in one. Furthermore, there were presentations of new techniques such as M-Chromo-LCI and acetic acid-indigo carmine mixture LCI. There were also six presentations regarding probe-based confocal laser endomicroscopy, and one of endocytoscopy techniques. We also saw presentations of images of gastric subepithelial tumors within the submucosa, 3D endoscopy, the development of computer-aided detection systems for early cancers, and fluorescent imaging.

Esophagogastric complications in radiofrequency and cryoballoon catheter ablation of atrial fibrillation.

INTRODUCTION: Direct comparison studies about the incidence of esophagogastric complications between radiofrequency (RF) and cryoballoon (CB) catheter ablation (CA) for atrial fibrillation (AF) have been scarce. We sought to elucidate the relationship between the pulmonary vein isolation (PVI) modalities and esophagogastric complications. METHODS: The study population consisted of 254 patients who underwent CA for AF from November 2017 to October 2018. Finally, 160 patients were enrolled and divided into the RF and CB groups. Esophageal ulcers, gastric hypomotility, and exfoliative esophagitis detected by esophagogastroduodenoscopy were defined as esophagogastric complications in this study. RESULTS: The median age was 68 years old, with 34% being females. Esophagogastric complications were observed in 42.5% of patients who underwent CA. According to the detailed esophagogastric complications, the RF group had a higher prevalence of esophageal ulcers than the CB group (19% vs. 0%, p < .0001). There was no significant difference between the two groups regarding gastric hypomotility and exfoliative esophagitis (18% vs. 28%; p = .15 and 16% vs. 21%; p = .42, respectively). CONCLUSION: Asymptomatic esophagogastric complications were common in CA for AF. The incidence of esophageal ulcers was higher in the RF group than in the CB group, whereas the other esophagogastric complications did not significantly differ.

A retrospective 5-year survival analysis of surgically resected gastric cancer cases from the Japanese Gastric Cancer Association nationwide registry (2001-2013).

BACKGROUND: The nationwide registry of the Japanese Gastric Cancer Association collected data of surgically resected cases of gastric cancer between 2001 and 2013. These retrospective analyses aimed to delineate tumor characteristics, surgical history, and survival distribution. METHODS: Data from 254,706 patients with primary gastric cancer were included. The 5-year survival rates were calculated for various subsets of prognostic factors. RESULTS: The number of patients over 70 years old increased from 2001 to 2013. The frequency with which laparoscopic gastrectomy was opted for increased dramatically (from 3.5 to 40.8%) in 13 years. We focused on the patients registered between 2010 and 2013, for whom data collection was based on the 3rd edition of the Japanese classification and guidelines. Five-year overall survival (OS) rate among 92,305 patients with resected tumors was 70.6%. The 5-year OS rates of patients with pathological stage IA, IB, IIA, IIB, IIIA, IIIB, IIIC, and IV disease were 89.6%, 83.2%, 77.6%, 68.1%, 59.3%, 45.6%, 29.9%, and 14.0%, respectively. CONCLUSION: Our detailed analysis highlights the historical changes in outcomes of surgically treated gastric malignancies in Japan, and provides robust dataset for future analysis.

Safety and feasibility of laparoscopic and endoscopic cooperative surgery for duodenal neoplasm: a retrospective multicenter study.

BACKGROUND: A delayed perforation can often occur after endoscopic treatment for duodenal neoplasms and may be fatal due to leakage of pancreatic and bile juices. We aimed to evaluate the feasibility and safety of laparoscopic and endoscopic cooperative surgery for duodenal neoplasms (D-LECS) in a multicenter, retrospective study. METHODS: The clinical characteristics and surgical outcomes of 206 patients with duodenal neoplasms in whom D-LECS had initially been attempted at one of 14 institutions were reviewed retrospectively. RESULTS: Of the 206 patients, 63 (30.6 %), 128 (62.1 %), and 15 patients (7.3 %) had lesions at the bulb, second portion, and third portion of the duodenum, respectively. The rates of en bloc and R0 resections during D-LECS were 96.1 % and 95.1 %, respectively. Intraoperative and delayed perforations occurred in 10 (4.9 %) and 5 patients (2.4 %), respectively. No cases of recurrence were observed. Surgical duration of ≥ 180 minutes was an independent risk factor for postoperative complications. CONCLUSIONS: The results revealed that D-LECS was performed with oncological safety and technical feasibility.

Factors for unsuccessful endoscopic hemostasis in patients with severe peptic ulcer bleeding.

OBJECTIVES: Although the first approach for peptic ulcer bleeding is endoscopic hemostasis, quick determination of a hemostatic strategy is important in patients with vitals indicating shock. However, the unsuccessful factors for endoscopic treatment have yet to be sufficiently examined. We aimed to investigate the factors for unsuccessful endoscopic hemostasis in severe peptic ulcer bleeding. MATERIALS AND METHODS: Unsuccessful factors were retrospectively investigated in 150 eligible patients who underwent endoscopic hemostasis for shock-presenting peptic ulcer bleeding at our critical care center between April 2007 and March 2021. RESULTS: There were 123 and 27 cases of successful and unsuccessful endoscopic hemostasis, respectively. Causative diseases included gastric ulcer bleeding in 124 patients (82.7%) and duodenal ulcer bleeding in 26 patients (17.3%). Shock index (SI) (1.46 vs. 1.60) (p = .013), exposed blood vessel diameter (1.4 mm vs. 3.1 mm) (p < .001) identified on contrast-enhanced computed tomography (CE-CT), duodenal ulcer bleeding (p = .012), and Forrest classification Ia (p = .004) were extracted as independent factors for unsuccessful endoscopic hemostasis. In receiving operating curve analysis, when the cut-off value for the SI was set at 1.53, the sensitivity and specificity were 70.4% and 63.4%, respectively. When the cut-off value for the exposed blood vessel diameter was set at 1.9 mm, these were 88.9% and 83.7%, respectively. CONCLUSIONS: When these factors (SI ≥ 1.53, exposed blood vessel diameter ≥1.9 mm identified on CE-CT, duodenal ulcer bleeding, and Forrest Ia) are present in patients with severe peptic ulcer bleeding, non-endoscopic hemostasis, such as interventional radiology (IVR) and surgery, should be considered.

Surgically treated gastric cancer in Japan: 2011 annual report of the national clinical database gastric cancer registry.

BACKGROUND: The National Clinical Database (NCD) nationwide registry program of gastric cancer started in 2018. The purpose of this study was to report the treatment results of the NCD registry in the form of treatment results of the real world in Japan. METHODS: Patients' characteristics, tumor features, treatments, and outcomes were collected using a web-based data entry system. We analyzed the initial NCD database for data on surgically treated gastric cancer patients in 2011. RESULTS: A total of 30,257 patients with malignant gastric tumors were enrolled by the NCD registry program from 501 hospitals in all 47 prefectures. Of these, the status of data entry was not approved in 8.8% of the registered data, and follow-up information was missing in 1.2% of the approved cases. Excluding 1777 cases, which were not resected for primary gastric cancer, 25,306 resected cases included 44.4% of stomach surgeries recorded in the NCD. The 5 year survival rate of the resected cases was 71.3% and the operative mortality rate was 0.41%. The stage-specific 5 year survival rates were as follows: 89.6% for stage IA, 83.8% for stage IB, 77.3% for stage IIA, 69.1% for stage IIB, 58.7% for stage IIIA, 44.1% for stage IIIB, 30.1% for stage IIIC, and 13.4% for stage IV. CONCLUSIONS: The NCD gastric cancer registry program demonstrated validity for database construction. The gastric cancer registry is expected to become a nationwide registry with the dissemination of data entry system and method in the NCD.

A nonrandomized, single-arm confirmatory trial of expanded endoscopic submucosal dissection indication for undifferentiated early gastric cancer: Japan Clinical Oncology Group study (JCOG1009/1010).

BACKGROUND: While endoscopic submucosal dissection (ESD) is recognized as a minimally invasive standard treatment for differentiated early gastric cancers (EGCs), it has not been indicated for undifferentiated EGC (UD-EGC) because of a relatively high risk of lymph node metastasis (LNM). However, patients with surgically resected mucosal (cT1a) UD-EGC ≤ 2 cm in size with no lymphovascular invasion or ulceration are reported to be at a very low risk of LNM. This multicenter, single-arm, confirmatory trial was conducted to evaluate the efficacy and safety of ESD for UD-EGC. METHODS: The key eligibility criteria were endoscopically diagnosed cT1a/N0/M0, single primary lesion, size ≤ 2 cm, no ulceration and histologically proven components of undifferentiated adenocarcinoma on biopsy. Based on the histological findings after ESD, additional gastrectomy was indicated if the criteria for curative resection were not satisfied. The subjects of the primary analysis were patients with UD-EGC as the dominant component. The primary endpoint was 5-year overall survival (OS) of patients with UD-EGC. RESULTS: Three hundred 46 patients were enrolled from 49 institutions. The proportion of en bloc resection was 99%. No ESD-related Grade 4 adverse events were noted. Delayed bleeding and intraoperative and delayed perforation occurred in 25 (7.3%), 13 (3.8%), and 6 (1.7%) patients, respectively. Among the 275 patients who were the subjects of the primary analysis, curative resection was achieved in 195 patients (71%), and 5-year OS was 99.3% (95% CI: 97.1-99.8). CONCLUSIONS: ESD can be a curative and less invasive treatment for UD-EGC for patients meeting the eligibility criteria of this study.

Usefulness of endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma in elderly patients: a single-center retrospective cohort study.

BACKGROUND: The effectiveness of endoscopic treatment for superficial esophageal squamous cell carcinoma in the elderly is unclear. METHODS: We retrospectively studied efficacy and safety of endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma in 358 patients at our hospital from July 2005 to December 2018. Patients were divided into elderly (≥75 years) and young (≤74 years) groups. Efficacy was evaluated based on overall survival and disease-specific survival, whereas safety was investigated based on the frequency of endoscopic submucosal dissection-related adverse events. RESULTS: The median observation period was 50 months. The elderly group comprised 111 patients, and young group comprised 247 patients. In the elderly and young groups, 76 (68.5%) and 159 (64.4%) underwent curative resection (P = 0.450), 8 (7.2%) and 34 (13.8%) underwent non-curative resection plus additional treatment and 12 (10.8%) and 15 (6.0%) underwent follow-up, respectively. The frequency of additional treatment for non-curative resection was significantly lower in the elderly group (P = 0.023). The 3-year overall survival of the elderly and young groups was 85.6 and 94.1%, respectively (P = 0.003). The 3-year disease-specific survival of the elderly and young groups was 98.4 and 98.5% (P = 0.682), respectively. The frequency of endoscopic submucosal dissection-related adverse events did not differ significantly between the groups (P = 0.581). The Charlson Comorbidity Index ≥2 was an independent prognostic factor for survival in the elderly group (P = 0.010; hazard ratio, 5.570; 95% confidence interval, 1.519-20.421). CONCLUSIONS: Endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma in elderly patients is as safe as that for young patients. The evaluation of Charlson Comorbidity Index was considered to help estimate the prognosis of elderly patients.

Determinant Factors on Differences in Survival for Gastric Cancer Between the United States and Japan Using Nationwide Databases.

BACKGROUND: Although the incidence and mortality have decreased, gastric cancer (GC) is still a public health issue globally. An international study reported higher survival in Korea and Japan than other countries, including the United States. We examined the determinant factors of the high survival in Japan compared with the United States. METHODS: We analysed data on 78,648 cases from the nationwide GC registration project, the Japanese Gastric Cancer Association (JGCA), from 2004-2007 and compared them with 16,722 cases from the Surveillance, Epidemiology, and End Results Program (SEER), a United States population-based cancer registry data from 2004-2010. We estimated 5-year relative survival and applied a multivariate excess hazard model to compare the two countries, considering the effect of number of lymph nodes (LNs) examined. RESULTS: Five-year relative survival in Japan was 81.0%, compared with 45.0% in the United States. After controlling for confounding factors, we still observed significantly higher survival in Japan. Among N2 patients, a higher number of LNs examined showed better survival in both countries. Among N3 patients, the relationship between number of LNs examined and differences in survival between the two countries disappeared. CONCLUSION: Although the wide differences in GC survival between Japan and United States can be largely explained by differences in the stage at diagnosis, the number of LNs examined may also help to explain the gaps between two countries, which is related to stage migration.

Radiobiological evaluation considering setup error on single-isocenter irradiation in stereotactic radiosurgery.

PURPOSE: We calculated the dosimetric indices and estimated the tumor control probability (TCP) considering six degree-of-freedom (6DoF) patient setup errors in stereotactic radiosurgery (SRS) using a single-isocenter technique. METHODS: We used simulated spherical gross tumor volumes (GTVs) with diameters of 1.0 cm (GTV 1), 2.0 cm (GTV 2), and 3.0 cm (GTV 3), and the distance (d) between the target center and isocenter was set to 0, 5, and 10 cm. We created the dose distribution by convolving the blur component to uniform dose distribution. The prescription dose was 20 Gy and the dose distribution was adjusted so that D95 (%) of each GTV was covered by 100% of the prescribed dose. The GTV was simultaneously rotated within 0°-1.0° (δR) around the x-, y-, and z-axes and then translated within 0-1.0 mm (δT) in the x-, y-, and z-axis directions. D95, conformity index (CI), and conformation number (CN) were evaluated by varying the distance from the isocenter. The TCP was estimated by translating the calculated dose distribution into a biological response. In addition, we derived the x-y-z coordinates with the smallest TCP reduction rate that minimize the sum of squares of the residuals as the optimal isocenter coordinates using the relationship between 6DoF setup error, distance from isocenter, and GTV size. RESULTS: D95, CI, and CN were decreased with increasing isocenter distance, decreasing GTV size, and increasing setup error. TCP of GTVs without 6DoF setup error was estimated to be 77.0%. TCP were 25.8% (GTV 1), 35.0% (GTV 2), and 53.0% (GTV 3) with (d, δT, δR) = (10 cm, 1.0 mm, 1.0°). The TCP was 52.3% (GTV 1), 54.9% (GTV 2), and 66.1% (GTV 3) with (d, δT, δR) = (10 cm, 1.0 mm, 1.0°) at the optimal isocenter position. CONCLUSION: The TCP in SRS for multiple brain metastases with a single-isocenter technique may decrease with increasing isocenter distance and decreasing GTV size when the 6DoF setup errors are exceeded (1.0 mm, 1.0°). Additionally, it might be possible to better maintain TCP for GTVs with 6DoF setup errors by using the optimal isocenter position.

Disability, quality of life, productivity impairment and employer costs of migraine in the workplace.

BACKGROUND: Migraine is the leading cause of days lost due to disability in the world among people less than 50 years of age. There is a paucity of evidence on the impact of migraine and other headache disorders and the cost and productivity losses in the workplace. METHODS: Employee population survey assessed prevalence, characteristics, and disability of headache disorders at a Japanese information technology company. This study was supported by the World Health Organization Western Pacific Region Office and International Headache Society. RESULTS: 2458 (1963men, 495 women) out of 2494 responded to the survey that utilized ICHD-3 beta criteria. Among these, 13% (205 male/123 female) had migraine (M), 53% (1093 male/207 female) had tension-type headache (TTH) and 4% (61 male/27 female) had migraine and TTH (M/TTH). The number of days when productivity at work was reduced by half or more because of headache was significantly higher in migraine compared to TTH. The norm-based scoring of SF-12v2 was significantly lower in M/TTH and M than TTH. The economic loss due to absenteeism for migraine was calculated to be $ 238.3US$/year/person for day-off and 90.2US$/year/person for half-day off using migraine disability assessment score (MIDAS). The economic loss due to presenteeism for migraine was calculated to be $ 375.4US$/year/person using MIDAS and 2217US$/year/person using work productivity and activity impairment questionnaire (WPAI). Furthermore, estimated cost of productivity loss associated with presenteeism using WPAI was calculated at 21.3 billion US$/year in Japan as a whole. CONCLUSIONS: This study revealed a high prevalence and disease burden among employees with migraine that is associated with substantial losses in productivity and employer cost. These results support the development and implementation of workplace programs to improve migraine management in the workplace and reduce the burden and costs associated with lost workplace productivity.

[Nivolumab and Gamma Knife Radiosurgery for a Gastric Cancer Patient with Brain Metastasis-A Case Report].

The prognosis of patients with brain metastasis is very poor. Very few cases of combined treatment with nivolumab(240 mg/body, day 1, q2w, a programmed cell death-1[PD-1]inhibitor)and gamma knife radiosurgery(GKR)(27 Gy/3 Fr) for gastric cancer patients with brain metastasis have been reported. Here, we discuss the case of a 55-year-old man with HER2-positive poorly differentiated gastric adenocarcinoma with multiple bone and intra-abdominal lymph node metastases. After 25 courses of SOX(oxaliplatin 100 mg/m2, day 1, q3w plus S-1 120 mg/day, day 1-14, po, q3w)plus trastuzumab( 6 mg/kg, q3w)treatment, brain metastasis was detected. Subsequently, combined treatment with GKR and nivolumab(8 courses, anti-PD-1 monotherapy)was initiated. Both intra-abdominal and brain lesions decreased in response to this treatment, showing that combined therapy with nivolumab and GKR could be effective for treating gastric cancer patients with brain metastasis.

Randomized study of prevention of gastrointestinal toxicities by nutritional support using an amino acid-rich elemental diet during chemotherapy in patients with esophageal cancer (KDOG 1101).

BACKGROUND: This randomized study was designed to evaluate the clinical effect of an elemental diet during chemotherapy in patients with esophageal cancer. METHODS: The inclusion criteria were as follows: (1) esophageal squamous cell carcinoma, (2) stage IB-IV, (3) schedule to receive docetaxel, cisplatin, and 5-fluorouracil (DCF chemotherapy), (4) 20-80 years old, (5) performance status of 0-2, (6) oral intake ability, and (7) written informed consent. Patients were divided into two groups: the elemental supplementary group and the non-supplementary group. Patients received ELENTAL® (160 g/day) orally 9 weeks after the start of chemotherapy. Primary endpoint was the incidence of grade 2 or higher gastrointestinal toxicity according to the Common Terminology Criteria for Adverse Events, version 4.0. Secondary endpoints were the incidence of all adverse events and the evaluation of nutritional status. RESULTS: Thirty-six patients in the elemental supplementary group and 35 patients in the non-supplementary group were included in the analysis. The incidence of grade 2 or higher gastrointestinal toxicity and all grade 3 or 4 adverse events did not differ significantly between the groups. In the elemental supplementary group, the body weight (p = 0.057), muscle mass (p = 0.056), and blood levels of transferrin (p = 0.009), total amino acids (p = 0.019), and essential amino acids (p = 0.006) tended to be maintained after chemotherapy. CONCLUSION: Nutritional support provided by an amino acid-rich elemental diet was ineffective for reducing the incidence of adverse events caused by DCF chemotherapy in patients with esophageal cancer.

The neurocognitive function change criteria after whole-brain radiation therapy for brain metastasis, in reference to health-related quality of life changes: a prospective observation study.

BACKGROUND: We sought to construct the optimal neurocognitive function (NCF) change criteria sensitive to health-related quality of life (HR-QOL) in patients who have undergone whole-brain radiation therapy (WBRT) for brain metastasis. METHODS: We categorized the patients by the changes of NCF into groups of improvement versus deterioration if at least one domain showed changes that exceeded the cut-off while other domains remained stable. The remaining patients were categorized as stable, and the patients who showed both significant improvement and deterioration were categorized as 'both.' We examined the clinical meaning of NCF changes using the cut-off values 1.0, 1.5, and 2.0 SD based on the percentage of patients whose HR-QOL changes were ≥ 10 points. RESULTS: Baseline, 4-month and 8-month data were available in 78, 41 (compliance; 85%), and 29 (81%) patients, respectively. At 4 months, improvement/stable/deterioration/both was seen in 15%/12%/41%/32% of the patients when 1.0 SD was used; 19%/22%/37%/22% with 1.5 SD, and 17%/37%/37%/9% with 2.0 SD. The HR-QOL scores on the QLQ-C30 functional scale were significantly worse in the deterioration group versus the others with 1.0 SD (p = 0.013) and 1.5 SD (p = 0.015). With 1.5 SD, the HR-QOL scores on the QLQ-BN20 was significantly better in the improvement group versus the others (p = 0.033). However, when 'both' was included in 'improvement' or 'deterioration,' no significant difference in HR-QOL was detected. CONCLUSIONS: The NCF cut-off of 1.5 SD and the exclusion of 'both' patients from the 'deterioration' and 'improvement' groups best reflects HR-QOL changes.