To describe changes in Japanese clinical trial regulations after the implementation of the Clinical Trials Act in April 2018.
First, how to apply multiple regulations after the enforcement of ...Clinical Trials Act was described. Second, the changes in the number of clinical trials in the National Cancer Center Hospital under each regulation were compared before and after the implementation of Clinical Trials Act. Third, new requirements imposed by Clinical Trials Act and their influences were discussed.
In April 2018, Clinical Trials Act was enacted and academic clinical trials were classified into the following three categories: (i) investigator-initiated registration-directed trial under the Pharmaceuticals and Medical Devices Act; (ii) clinical trial under Clinical Trials Act; and (iii) clinical trial under the Ethical Guidelines. While 90% (205/227) of interventional studies were conducted under the Ethical Guidelines before the implementation of Clinical Trials Act in 2018, 46% (94/204) were subject to Clinical Trials Act in 2019 at the National Cancer Center Hospital. Under the Clinical Trials Act, investigators receive a scientific/ethical review by a certified review board (CRB). The identification of investigators in charge is mandated and they are required to submit the conflict of interest management plan to CRB. After the CRB review, the principal investigator must submit the trial plan to the government, and the content is uploaded to the newly established clinical trial registry site, the Japan Registry of Clinical Trials.
The enforcement of the new Clinical Trials Act was supposed to improve the reliability of academic clinical trials in Japan; however, the financial and administrative burden may reduce clinical trial activity in the years to come.
To evaluate, in Japan Clinical Oncology Group study 0403, the safety and efficacy of stereotactic body radiation therapy (SBRT) in patients with T1N0M0 non-small cell lung cancer (NSCLC).
Eligibility ...criteria included histologically or cytologically proven NSCLC, clinical T1N0M0. Prescribed dose was 48 Gy at the isocenter in 4 fractions. The primary endpoint was the percent (%) 3-year overall survival. The threshold % 3-year survival to be rejected was set at 35% for inoperable patients, whereas the expected % 3-year survival was 80% for operable patients.
Between July 2004 and November 2008, 169 patients from 15 institutions were registered. One hundred inoperable and 64 operable patients (total 164) were eligible. Patients' characteristics were 122 male, 47 female; median age 78 years (range, 50-91 years); adenocarcinomas, 90; squamous cell carcinomas, 61; others, 18. Of the 100 inoperable patients, the % 3-year OS was 59.9% (95% confidence interval 49.6%-68.8%). Grade 3 and 4 toxicities were observed in 10 and 2 patients, respectively. No grade 5 toxicity was observed. Of the 64 operable patients, the % 3-year OS was 76.5% (95% confidence interval 64.0%-85.1%). Grade 3 toxicities were observed in 5 patients. No grade 4 and 5 toxicities were observed.
Stereotactic body radiation therapy for stage I NSCLC is effective, with low incidences of severe toxicity. This treatment can be considered a standard treatment for inoperable stage I NSCLC. This treatment is promising as an alternative to surgery for operable stage I NSCLC.
Full text
Available for:
GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
Objective The study objective was to evaluate the long-term survival of patients with radiographically determined noninvasive lung adenocarcinomas. Methods A prospective, multi-institutional study on ...image diagnosis to define early (noninvasive) adenocarcinomas of the lung (Japan Clinical Oncology Group 0201) has shown that a consolidation/tumor ratio on thin-section computed tomography 0.25 or less in cT1a (≤2.0 cm) could be used as a better radiologic criterion for a noninvasive pathology than a consolidation/tumor ratio 0.50 or less in cT1a-b (≤3.0 cm). From the prognostic viewpoints, these criteria were evaluated for 545 patients with adenocarcinoma who underwent lobectomy and lymph node dissection. Results The subjects consisted of 233 men and 312 women with a median age of 62 years. The median follow-up period among overall patients was 7.1 years (range, 0-8.5 years). The overall and relapse-free 5-year survivals of the overall patients were 90.6% and 84.7%, respectively. When a consolidation/tumor ratio 0.5 or less in cT1a-b was used as a cutoff, the 5-year overall survivals of radiologic noninvasive (121 patients, 22.2%) and invasive (424 patients, 77.8%) adenocarcinomas were 96.7% and 88.9%, respectively, and the difference was statistically significant ( P < .001, log-rank test). With the use of a consolidation/tumor ratio 0.25 or less in cT1a, the 5-year overall survivals of radiologic noninvasive (35 patients, 12.1%) and invasive (254 patients, 87.9%) adenocarcinomas were 97.1% and 92.4%, respectively, and the difference was not statistically significant ( P = .259). Conclusions The radiologic criteria of a consolidation/tumor ratio 0.25 or less in cT1a (≤2.0 cm) and 0.50 in cT1a-b (≤3.0 cm) were both able to define a homogeneous group of patients with an excellent prognosis before surgery.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Gaps in colonoscopy skills among endoscopists, primarily due to experience, have been identified, and solutions are critically needed. Hence, the development of a real-time robust detection system ...for colorectal neoplasms is considered to significantly reduce the risk of missed lesions during colonoscopy. Here, we develop an artificial intelligence (AI) system that automatically detects early signs of colorectal cancer during colonoscopy; the AI system shows the sensitivity and specificity are 97.3% (95% confidence interval CI = 95.9%-98.4%) and 99.0% (95% CI = 98.6%-99.2%), respectively, and the area under the curve is 0.975 (95% CI = 0.964-0.986) in the validation set. Moreover, the sensitivities are 98.0% (95% CI = 96.6%-98.8%) in the polypoid subgroup and 93.7% (95% CI = 87.6%-96.9%) in the non-polypoid subgroup; To accelerate the detection, tensor metrics in the trained model was decomposed, and the system can predict cancerous regions 21.9 ms/image on average. These findings suggest that the system is sufficient to support endoscopists in the high detection against non-polypoid lesions, which are frequently missed by optical colonoscopy. This AI system can alert endoscopists in real-time to avoid missing abnormalities such as non-polypoid polyps during colonoscopy, improving the early detection of this disease.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In metastatic or recurrent cervical cancer, cisplatin-based chemotherapy is standard. The JCOG0505 randomized phase III trial evaluated the clinical benefits of carboplatin-based regimen.
Eligible ...patients had metastatic or recurrent cervical cancer and had ≤ one platinum-containing treatment and no prior taxane. Patients were randomly assigned either to conventional paclitaxel plus cisplatin (TP; paclitaxel 135 mg/m(2) over 24 hours on day 1 and cisplatin 50 mg/m(2) on day 2, repeated every 3 weeks) or paclitaxel plus carboplatin (TC; paclitaxel 175 mg/m(2) over 3 hours and carboplatin area under curve 5 mg/mL/min on day 1, repeated every 3 weeks). Primary end point was overall survival (OS). Planned sample size was 250 patients to confirm the noninferiority of TC versus TP with the threshold hazard ratio (HR) of 1.29.
Between February 2006 and November 2009, 253 patients were enrolled. The HR of OS was 0.994 (90% CI, 0.79 to 1.25; noninferiority P = .032 by stratified Cox regression). Median OS was 18.3 months with TP versus 17.5 months with TC. Among patients who had not received prior cisplatin, OS was shorter with TC (13.0 v 23.2 months; HR, 1.571; 95% CI, 1.06 to 2.32). One treatment-related death occurred with TC. Proportion of nonhospitalization periods was significantly longer with TC (P < .001).
TC was noninferior to TP and should be a standard treatment option for metastatic or recurrent cervical cancer. However, cisplatin is still the key drug for patients who have not received platinum agents.
A randomized Phase III trial was commenced to confirm the clinical benefit of lobe-specific nodal dissection in comparison to systematic nodal dissection for clinical Stage I–II non-small cell lung ...cancer.
Abstract
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.
Since treatment efficacy of cisplatin- or carboplatin-based chemotherapy in the first-line treatment of small-cell lung cancer (SCLC) remains contentious, a meta-analysis of individual patient data ...was performed to compare the two treatments.
A systematic review identified randomized trials comparing cisplatin with carboplatin in the first-line treatment of SCLC. Individual patient data were obtained from coordinating centers of all eligible trials. The primary end point was overall survival (OS). All statistical analyses were stratified by trial. Secondary end points were progression-free survival (PFS), objective response rate (ORR), and treatment toxicity. OS and PFS curves were compared by using the log-rank test. ORR was compared by using the Mantel-Haenszel test.
Four eligible trials with 663 patients (328 assigned to cisplatin and 335 to carboplatin) were included in the analysis. Median OS was 9.6 months for cisplatin and 9.4 months for carboplatin (hazard ratio HR, 1.08; 95% CI, 0.92 to 1.27; P = .37). There was no evidence of treatment difference between the cisplatin and carboplatin arms according to sex, stage, performance status, or age. Median PFS was 5.5 and 5.3 months for cisplatin and carboplatin, respectively (HR, 1.10; 95% CI, 0.94 to 1.29; P = .25). ORR was 67.1% and 66.0%, respectively (relative risk, 0.98; 95% CI, 0.84 to 1.16; P = .83). Toxicity profile was significantly different for each of the arms: hematologic toxicity was higher with carboplatin, and nonhematologic toxicity was higher with cisplatin.
Our meta-analysis of individual patient data suggests no differences in efficacy between cisplatin and carboplatin in the first-line treatment of SCLC, but there are differences in the toxicity profile.
Pathological noninvasiveness needs to be precisely predicted in preoperative radiological examinations of patients with early lung cancer for the application of limited surgery.
Patients with ...clinical T1N0M0 peripheral lung cancer were recruited. Radiological findings of the main tumor were evaluated as to ground-glass opacity with thin-section computed tomography. The primary end point was specificity, i.e., the proportion of patients with radiologically diagnosed invasive lung cancer to patients with pathologically diagnosed invasive lung cancer. The precision-based planned sample size was 450. We expected that the lower limit of the 95% confidence interval (CI) for specificity should be satisfied in ≥97% of patients.
We enrolled 811 patients from 31 institutions between December 2002 and May 2004. The primary end point was evaluated in 545 patients. The specificity and sensitivity for the diagnosis of pathologically diagnosed invasive cancer were 96.4% (161/167, 95% CI: 92.3–98.7%) and 30.4% (115/378, 95% CI: 25.8–35.3%), respectively, i.e., a negative result. Nevertheless, the specificity for lung adenocarcinoma ≤2.0 cm with ≤0.25 consolidation to the maximum tumor diameter was 98.7% (95% CI: 93.2–100.0%), and this criterion could be used to radiologically define early adenocarcinoma of the lung.
Although our predetermined criterion for specificity was not statistically confirmed, radiological diagnosis of noninvasive lung cancer with a thin-section computed tomography scan corresponded well with pathological invasiveness. Radiological noninvasive peripheral lung adenocarcinoma could be defined as an adenocarcinoma ≤2.0 cm with ≤0.25 consolidation.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Improved optical diagnostic technology is needed that can be used by also outside expert centers. Hence, we developed an artificial intelligence (AI) system that automatically and robustly ...predicts the pathological diagnosis based on the revised Vienna Classification using standard colonoscopy images.
Methods
We prepared deep learning algorithms and colonoscopy images containing pathologically proven lesions (56,872 images, 6775 lesions). Four classifications were adopted: revised Vienna Classification category 1, 3, and 4/5 and normal images. The best algorithm—ResNet152—in the independent internal validation (14,048 images, 1718 lesions) was used for external validation (255 images, 128 lesions) based on neoplastic and non-neoplastic classification. Diagnostic performance of endoscopists was compared using a computer-assisted interpreting test.
Results
In the internal validation, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for adenoma (category 3) of 84.6% (95% CI 83.5–85.6%), 99.7% (99.5–99.8%), 90.8% (89.9–91.7%), 89.2% (88.5–99.0%), and 89.8% (89.3–90.4%), respectively. In the external validation, ResNet152’s sensitivity, specificity, PPV, NPV, and accuracy for neoplastic lesions were 88.3% (82.6–94.1%), 90.3% (83.0–97.7%), 94.6% (90.5–98.8%), 80.0% (70.6–89.4%), and 89.0% (84.5–93.6%), respectively. This diagnostic performance was superior to that of expert endoscopists. Area under the receiver-operating characteristic curve was 0.903 (0.860–0.946).
Conclusions
The developed AI system can help non-expert endoscopists make differential diagnoses of colorectal neoplasia on par with expert endoscopists during colonoscopy.
(229/250 words).
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A Phase III study was started in Japan to evaluate the non-inferiority in overall survival of segmentectomy compared with lobectomy in patients with small-sized (diameter ≤2 cm) peripheral non-small ...cell lung cancer, excluding radiologically determined non-invasive cancer. This study began in August 2009, and a total of 1100 patients will be accrued from 71 institutions within 3 years. The primary endpoint is overall survival. The secondary endpoints are post-operative respiratory function, relapse-free survival, proportion of local recurrence, adverse events, proportion of patients who complete segmentectomy, duration of hospitalization, duration of chest tube placement, operation time, blood loss and number of auto-sutures used. This study is one of the first intergroup studies in Japan between the Japan Clinical Oncology Group and the West Japan Oncology Group.
PDF
