Tomonori Mizutani

Predictors of non-neoplastic lesions in lung tumours showing ground-glass opacity on thin-section computed tomography based on a multi-institutional prospective study

OBJECTIVES Peripheral small lung tumours (LTs) showing ground-glass opacity (GGO) tend to be treated without preoperative histological diagnosis due to difficulty in obtaining tissue samples. Exclusion of non-neoplastic lesions (NNLs) is essential when considering non-surgical treatment such as stereotactic radiotherapy. Here, we sought to determine preoperative factors associated with NNLs in peripheral LTs using data from a prospective study that investigated the efficacy of lesser pulmonary resection (JCOG0804/WJOG4507L). METHODS The key eligibility criteria of the study were as follows: (i) peripherally located definitive or suspected LC with maximum diameter ≤2 cm and (ii) radiological non-invasive tumour with consolidation/tumour ratio (CTR) of ≤0.25 based on thin-section computed tomography (CT). Among all the resected LTs, incidences of NNL and precancerous lesions were examined. Also, logistic regression analysis was conducted to investigate the predictors of NNL using maximum tumour dimension (≤1 cm/>1 cm) and CTR (0/>0) as an explanatory variable. RESULTS Between May 2009 and April 2011, 333 patients were prospectively enrolled from 51 institutions into the study. Among 333 patients, 345 LTs were included in the analysis. There were 314 (91.0%) LCs, 17 (4.9%) precancerous lesions and 14 (4.1%) non-cancerous lesions. Maximum tumour dimension ≤1 cm was identified as a significant predictor of NNLs with logistic regression analysis. There were 10 (8.6%) NNLs in 116 LT ≤1 cm, but 4 (1.7%) NNLs in 229 LTs >1 cm. CONCLUSIONS NNLs were found in only 4.1% of peripheral LTs with GGO. However, when the tumour diameter was ≤1 cm, ∼10% were NNLs, necessitating a histological diagnosis when non-surgical treatment was considered.

A Phase III study of oral steroid administration versus local steroid injection therapy for the prevention of esophageal stricture after endoscopic submucosal dissection (JCOG1217, Steroid EESD P3)

A randomized Phase III trial commenced in Japan in September 2014. Endoscopic local steroid injection has been commonly used and considered acceptable as the current standard treatment for the prevention of esophageal stricture after endoscopic submucosal dissection for superficial esophageal cancer. The purpose of this study is to confirm the superiority of prophylactic oral steroid administration following endoscopic submucosal dissection in terms of stricture-free survival over endoscopic local steroid injection for patients with superficial esophageal cancer. A total of 360 patients will be accrued from 35 Japanese institutions within 2.5 years. The primary endpoint is stricture-free survival, and the secondary endpoints are the number of endoscopic balloon dilations for 12 weeks after endoscopic submucosal dissection, adverse events, serious adverse events and the proportion of patients with dysphagia score ≤1 at 12 weeks after endoscopic submucosal dissection. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000015064 (http://www.umin.ac.jp/ctr/index.htm).

Intensive vs. Standard Post-Operative Surveillance in High-Risk Breast Cancer Patients (INSPIRE): Japan Clinical Oncology Group Study JCOG1204

This Phase III trial aims to determine the superiority of intensive follow-up to standard follow-up in terms of overall survival in high-risk breast cancer patients, who are expected to have recurrence rates of over 30% within 5 years after surgery. Eligible patients are randomized either to the intensive follow-up group or to the standard follow-up group; the former will undergo physical examination, bone scintigraphy, chest computed tomography, abdominal computed tomography, brain magnetic resonance imaging/computed tomography and frequent tumor marker evaluations, whereas the latter will undergo physical examination at the same frequency and tumor markers will be evaluated once a year. Mammography once a year is planned for both groups. The primary endpoint is overall survival. Patient accrual was started in November 2013. A total of 1700 patients will be enrolled for 3 years and followed up for 7 years after closure of accrual. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000012429.

Randomized phase III trial of adjuvant therapy with locoregional interferon beta versus surgery alone in stage II/III cutaneous melanoma: Japan Clinical Oncology Group Study (JCOG1309, J-FERON)

Randomized phase III trial (JCOG1309) has been started to confirm the superiority of adjuvant therapy with locoregional interferon beta over surgery alone in overall survival for patients with stage II/III cutaneous melanoma.

Prognostic value of Lung Cancer Subscale in older patients with advanced non-small cell lung cancer: An integrated analysis of JCOG0207 and JCOG0803/WJOG4307L (JCOG1414A)

OBJECTIVE The Lung Cancer Subscale (LCS) of the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire is commonly used for evaluating lung cancer-specific symptoms. The objective of this study was to elucidate the prognostic value of the LCS in older patients with advanced non-small cell lung cancer (NSCLC). MATERIAL AND METHODS We conducted an integrated analysis of data from two randomized phase III trials (JCOG0207, JCOG0803/WJOG4307L) including patients aged 70 years or older with advanced NSCLC to evaluate the prognostic value of LCS scores at baseline (Aim 1) and for symptom improvement (an increase in LCS of two points or more during treatment) (Aim 2). Multivariable analyses for survival, adjusted for baseline factors, were performed using a stratified Cox regression model with treatment regimen as a stratum. RESULTS A total of 327 patients were included in the analysis for Aim 1 and 373 patients for Aim 2. Approximately 70% of patients were aged 75 or older. In Aim 1, use of descriptive statistics determined a cutoff point for baseline LCS score of 21. Multivariable analysis showed that higher baseline LCS was associated with favorable overall survival (OS) (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.52-0.89) and progression-free survival (HR: 0.68; 95% CI: 0.52-0.89). In Aim 2, symptom improvement was not associated with favorable OS (HR: 0.97; 95% CI: 0.72-1.23). CONCLUSION It is recommended to consider baseline LCS scores while determining treatment strategies for older patients with advanced NSCLC.

A randomized Phase III trial of lobe-specific vs. systematic nodal dissection for clinical Stage I–II non-small cell lung cancer (JCOG1413)

In January 2017, the Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group commenced a randomized Phase III trial to confirm the clinical benefit of lobe-specific nodal dissection for clinical Stage I-II non-small cell lung cancer. The primary endpoint is overall survival, and the main objective is to confirm the non-inferiority of lobe-specific in comparison to systematic nodal dissection with regard to lobectomy. The secondary endpoints are relapse-free survival, %local recurrence, %regional lymph node recurrence, operation time, blood loss, length of hospitalization, duration of chest tube placement and adverse events. A total of 1700 patients will be accrued from 44 Japanese institutions within 5 years. This study is the first and large prospective trial to evaluate whether the difference in the area of nodal dissection affects the overall survival of patients with relatively early-stage non-small cell lung cancer. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000025530.

A phase III trial to confirm modified S-1 adjuvant chemotherapy for pathological stage II/III vulnerable elderly gastric cancer patients who underwent gastric resection (JCOG1507, BIRDIE)

Adjuvant chemotherapy with S-1 is a standard treatment for patients with stage II/III gastric cancer after D2 gastrectomy; however, this is not uniformly applicable in older patients. The Stomach Cancer Study Group of the Japan Clinical Oncology Group conducted a questionnaire survey on older patients aged ≥80 years and revealed wide heterogeneity among older patients of similar chronological age. This randomized trial aims to confirm the superiority of modified S-1 treatment (reduced initial dose of S-1 by ≥ 1 level compared with the standard dose) versus surgery alone in vulnerable older (≥80 years old) patients with pathological stage II/III gastric cancer after curative resection. A total of 370 patients will be enrolled from 62 institutions over 4.5 years. The primary endpoint of this study is overall survival. This trial has been registered in the UMIN Clinical Trials Registry with code UMIN000025742 [http://www.umin.ac.jp/ctr/index.htm].