Clinical utility of Todai OncoPanel in the setting of approved comprehensive cancer genomic profiling tests in Japan.

Comprehensive cancer genome profiling (CGP) has been nationally reimbursed in Japan since June 2019. Less than 10% of the patients have been reported to undergo recommended treatment. Todai OncoPanel (TOP) is a dual DNA-RNA panel as well as a paired tumor-normal matched test. Two hundred patients underwent TOP as part of Advanced Medical Care B with approval from the Ministry of Health, Labour and Welfare between September 2018 and December 2019. Tests were carried out in patients with cancers without standard treatment or when patients had already undergone standard treatment. Data from DNA and RNA panels were analyzed in 198 and 191 patients, respectively. The percentage of patients who were given therapeutic or diagnostic recommendations was 61% (120/198). One hundred and four samples (53%) harbored gene alterations that were detected with the DNA panel and had potential treatment implications, and 14 samples (7%) had a high tumor mutational burden. Twenty-two samples (11.1%) harbored 30 fusion transcripts or MET exon 14 skipping that were detected by the RNA panel. Of those 30 transcripts, 6 had treatment implications and 4 had diagnostic implications. Thirteen patients (7%) were found to have pathogenic or likely pathogenic germline variants and genetic counseling was recommended. Overall, 12 patients (6%) received recommended treatment. In summary, patients benefited from both TOP DNA and RNA panels while following the same indication as the approved CGP tests. (UMIN000033647).

Evaluating the impact of regulatory action on denosumab-induced hypocalcaemia in Japan.

WHAT IS KNOWN AND OBJECTIVE: Since its introduction in April 2012, denosumab has been administered to approximately 7,300 patients as of August 2012, and 32 cases of serious hypocalcaemia after denosumab administration, including two deaths, have been reported in Japan. A Dear Healthcare Professional Letter of Rapid Safety Communication ('Blue letter') was released to warn about the risks of hypocalcaemia associated with denosumab. The goal of this study therefore was to measure the impact of regulatory action on denosumab-induced hypocalcaemia in Japan by using an electronic medical information database (MID). METHODS: We used two different aggregated data sets based on MIDs (data sets one and two). The patients studied were those who were newly prescribed denosumab or zoledronic acid between April 2012 and September 2014. We assessed four indicators: (a) the proportion of patients with calcium supplementation at the initial denosumab treatment, (b) the proportion of patients who underwent a serum calcium test, (c) the average number of serum calcium tests performed and (d) the prevalence of hypocalcaemia. All indices were aggregated by every 3 months. To evaluate the impact of regulatory action, we used difference in difference (DID) analysis. RESULTS AND DISCUSSION: The proportion of patients with calcium supplementation at the initial denosumab treatment increased year by year in both data sets. The average number of serum calcium tests increased year by year in data set two. There was a significant difference in the prevalence of hypocalcaemia in data set two. This suggests that the estimate of impact of the regulatory action may vary according to the database. In DID analysis, however, significant influences of the regulatory action on combination use with a calcium supplement were detected in both data sets. WHAT IS NEW AND CONCLUSION: There was a significant influence on combination use of denosumab with vitamin D and/or calcium supplement in both data sets. That there was no apparent increase in the prevalence of denosumab-induced hypocalcaemia, suggests that the regulatory action had an impact in the clinical setting studied. Such regulatory actions may play an important role in the promotion of drug safety.

Comparisons of perioperative outcomes and costs between open and laparoscopic radical prostatectomy: a propensity-score matching analysis based on the Japanese Diagnosis Procedure Combination database.

We compared perioperative outcomes and costs between open and laparoscopic radical prostatectomy for prostate cancer. The Japanese Diagnosis Procedure Combination database, including cases from 2007 to 2010, was used by one-to-one propensity-score matching. The following items were compared: complication rate; homologous and autologous transfusion rate; first cystography day and cystography repeat rate; anesthesia time; postoperative length of stay; and costs. Multivariate analyses were carried out by including age, Charlson Comorbidity Index, T stage, hospital volume and hospital academic status as variables. As a result, among 15 616 open and 1997 laparoscopic radical prostatectomies, 1627 propensity-score matched pairs were generated. The laparoscopic approach showed a better overall complication rate (3.4% vs 5.0%), homologous transfusion rate (3.3% vs 9.2%), autologous transfusion rate (44.9% vs 79.3%), first cystography day (mean 6th vs 7th day), mean postoperative length of stay (mean 11 vs 13 days), and cost without surgery and anesthesia (mean $7965 vs $9235; all P < 0.001). Anesthesia time was longer (mean 345 vs 285 min) and total cost was higher (mean $14 980 vs $12 356) for the laparoscopic approach (both P < 0.001). The secondary cystography rates were comparable between the groups (18.3% vs 15.7%, P = 0.144). The multivariate analyses showed similar trends. In conclusion, these findings confirm several benefits of laparoscopy over open approach for radical prostatectomy.

In-hospital outcomes and cost assessment between bipolar versus monopolar transurethral resection of the prostate.

PURPOSE: We compared the in-hospital outcomes between bipolar and monopolar transurethral resection of the prostate (B-TURP and M-TURP, respectively) on a real-world practice using a large database. PATIENTS AND METHODS: Patients who underwent TURP were extracted from the Diagnosis Procedure Combination database, which is a case-mix administrative claims database in Japan. TURP procedures were classified into M-TURP and B-TURP groups according to intraoperative use or nonuse of D-sorbitol solution, respectively, which is the only nonelectrolyte bladder irrigation fluid for M-TURP available in Japan. To exclude causality among autologous and homologous transfusion events, we confined eligible hospitals to those in which no autologous blood preparation was undertaken for TURP and whose annual surgical caseloads were 15 cases or more. Multivariate analyses were conducted for homologous transfusion, postoperative complications, operative time, postoperative length of stay, and total costs. RESULTS: There were 5155 M-TURP and 1531 B-TURP patients identified. The results for M-TURP vs B-TURP (effect sizes were evaluated with reference to M-TURP) were 2.3% vs 1.3% for transfusion (odds ratio [OR]=0.54; P=0.013), 3.3% vs 1.7% for postoperative complications (OR=0.46; P<0.01), 98 vs 116 minutes for operative time (20.5% increase; P<0.001), 8.65 vs 8.45 days for postoperative stay (3.6% reduction; P=0.003), and $6103 vs $6062 for cost (1.7% reduction; P=0.018). CONCLUSION: B-TURP had significantly lower rates of transfusion and postoperative complications, but a longer operative time. The impacts of B-TURP on shortening the hospital stay and lowering the costs were of little clinical significance.