Ken Masuda

A 67‐year‐old patient with metastatic lung adenocarcinoma harboring a HER2 V659E mutation received trastuzumab deruxtecan (T‐DXd) as second‐line treatment. The V659E mutation is a rare alteration located in the transmembrane domain of HER2. The antitumor effect observed in this patient was comparable to that reported in a previous phase 2 trial, in which most patients had mutations in the kinase domain. Here, we present the detailed clinical course and discuss the findings from a molecular biological perspective.

Background: Schlafen 11 (SLFN‐11) has been identified as a sensitizer of tumor cells to DNA‐damaging agents. However, the relationship between SLFN‐11 expression and clinical outcomes in patients with small cell lung cancer (SCLC) remains unexplored. Thus, we aimed to evaluate the impact of SLFN‐11 expression on survival in patients with limited‐stage (LS) SCLC.Methods: We conducted a retrospective review of data from patients pathologically diagnosed with LS‐SCLC post‐surgery between January 2008 and December 2018. SLFN‐11 expression was assessed using immunohistochemistry in tissue microarrays and scored using a histology (H)‐score (range: 0–300).Results: Overall, 86 patients were included in the analysis with a median H‐score of 43 for SLFN‐11 expression. Among the patients, 44 had high SLFN‐11 expression (provisionally defined as H‐score ≥ 43). No significant differences in clinical profiles were observed between the two groups (high and low SLFN expression). The median survival durations were not reached (NR; 95% confidence interval [CI]: 65.1 months to NR) and 33.5 months (95% CI: 24.2 months to NR) for patients with high and low SLFN‐11 expression, respectively (hazard ratio [HR]: 0.40, 95% CI: 0.19–0.81; p = 0.012). Among patients who relapsed post‐surgery (n = 21), the median survival durations were 22.0 (95% CI: 7.6–44.9 months) and 8.1 (95% CI: 1.8–24.6 months) months in patients with high and low SLFN‐11 expression, respectively (HR: 0.22, 95% CI: 0.06–0.84; p = 0.026).Conclusions: High SLFN‐11 expression is associated with relatively longer survival in patients with LS‐SCLC in both those undergoing surgery and those who have relapsed.

Background: Pemetrexed is used for the chemotherapy of advanced thymoma. Exceptional responses of thymoma to pemetrexed treatment are not frequently observed. The underlying genetic mechanism of the exceptional responses remains unclear. We used whole-exome sequencing to explore the specific genomic aberrations that lead to an extreme and durable response. Methods: Whole-exome sequencing using NovaSeq6000 (150 bp paired-end sequencing) was performed on nine formalin-fixed paraffin-embedded tissues from patients with advanced thymomas treated with pemetrexed (two exceptional responders and seven typical responders). Results: We identified 284 somatic single-nucleotide variants (SNVs; 272 missense, 8 missense/splice-site, 3 stop-gain, and 1 stop-gain/splice-site), 34 insertions and deletions (Indels; 33 frameshift and one splice region), and 21 copy number variations (CNVs; 15 gains and six losses). No difference in the number of SNVs variants and distribution of deleterious Indels was observed between the exceptional and typical responders. Interestingly, arm-level chromosomal CNVs (15 gains and six losses) were detected in four patients, including an exceptional responder. The highest number of arm-level CNVs was observed in an exceptional responder. Conclusion: Exceptional responders to pemetrexed for metastatic thymomas may be characterized by arm-level CNVs. Further, whole-genome and RNA sequencing studies should be performed.

Purpose: Paracentesis is among the most widely utilised treatments for Malignant ascites (MA). However, paracentesis in patients with MA has the potential to be associated with life-shortening effects. Thus, this study aimed to investigate whether paracentesis affected the duration of survival in such patients.Methods: We performed a post-hoc analysis of a prospective multicenter observational study investigating the dying process and end-of-life care in patients with terminal cancer, admitted to 23 palliative care units in Japan. Survival duration was compared between patients who did (paracentesis group) and did not undergo paracentesis (non-paracentesis group). We used inverse probability of treatment weighting (IPTW) to control for baseline covariates between groups.Results: Among the 1,896 initially enrolled patients, 568 with ascites were included in the study cohort. Eighty-five (15.0%) patients underwent paracentesis. The primary tumor site was the pancreas (51.9%, n=295), followed by the gastrointestinal tract (22.7%, n=129). Non-adjusted median durations of survival were 22 days (95% confidence interval [CI]: 16–25) and 12 days (95% CI: 11–13) in the paracentesis and non-paracentesis groups, respectively (hazard ratio [HR]: 0.69, 95% CI: 0.54–0.88; p=0.003). The IPTW-adjusted median survival durations were 22 (95% CI: 16–25) and 16 days (95% CI: 12–22) in the paracentesis and non-paracentesis groups, respectively (HR: 0.89, 95% CI: 0.64–1.24; p=0.492). No serious adverse events occurred in the paracentesis group.Conclusions: Paracentesis does not negatively affect the survival of patients with cancer and MA and can be a standard treatment in palliative care settings.