Optimizing smartphone psychotherapy for depressive symptoms in patients with cancer: Multiphase optimization strategy using a decentralized multicenter randomized clinical trial (J-SUPPORT 2001 Study).

AIM: Patients with cancer experience various forms of psychological distress, including depressive symptoms, which can impact quality of life, elevate morbidity risk, and increase medical costs. Psychotherapy and pharmacotherapy are effective for reducing depressive symptoms among patients with cancer, but most patients prefer psychotherapy. This study aimed to develop an efficient and effective smartphone psychotherapy component to address depressive symptom. METHODS: This was a decentralized, parallel-group, multicenter, open, individually randomized, fully factorial trial. Patients aged ≥20 years with cancer were randomized by the presence/absence of three cognitive-behavioral therapy (CBT) skills (behavioral activation [BA], assertiveness training [AT], and problem-solving [PS]) on a smartphone app. All participants received psychoeducation (PE). The primary outcome was change in the patient health questionnaire-9 (PHQ-9) total score between baseline and week 8. Secondary outcomes included anxiety. RESULTS: In total, 359 participants were randomized. Primary outcome data at week 8 were obtained for 355 participants (99%). The week 8 PHQ-9 total score was significantly reduced from baseline for all participants by -1.41 points (95% confidence interval [CI] -1.89, -0.92), but between-group differences in change scores were not significant (BA: -0.04, 95% CI -0.75, 0.67; AT: -0.16, 95% CI -0.87, 0.55; PS: -0.19, 95% CI -0.90, 0.52). CONCLUSION: As the presence of any of the three intervention components did not contribute to a significant additive reduction of depressive symptoms, we cannot make evidence-based recommendations regarding the use of specific smartphone psychotherapy.

Impact of the perioperative assessment of deglutition on postoperative respiratory complications in elderly patients undergoing gastrectomy for gastric cancer.

PURPOSE: To investigate the association between perioperative deglutition screening and postoperative respiratory complications (PRCs) in elderly patients undergoing gastrectomy for gastric cancer. METHODS: We analyzed data from 86 patients with gastric cancer (aged ≥ 70 years) who underwent gastrectomy between October, 2016 and November, 2018. Videofluoroscopic swallowing examinations (VFSEs) were performed before and after surgery. We examined the association of these results with postoperative respiratory complications, as well as the relationships between demographic, operative, and swallowing function assessment data. RESULTS: PRCs were identified in 16 patients. The results of pre- and postoperative VFSE showed abnormalities in 28 and 32 patients, respectively. Multivariate analysis revealed that abnormalities in the postoperative VFSEs were strongly associated with the development of PRCs (P = 0.002). The findings of this analysis suggests that ventilatory impairment, a Charlson comorbidity index score ≥ 3, and an open surgical approach are independent risk factors for PRCs. CONCLUSION: This is the first study to demonstrate the efficacy of perioperative assessment of swallowing function using VFSE for predicting PRCs in elderly patients undergoing gastrectomy for gastric cancer.

Clinical experience of treatment of immunocompromised individuals with persistent SARS-CoV-2 infection based on drug resistance mutations determined by genomic analysis: a descriptive study.

BACKGROUND: The efficacy of antiviral drugs that neutralize antibody drugs and fight against SARS-COV-2 is reported to be attenuated by genetic mutations of the virus in vitro. When B-cell immunocompromised patients are infected with SARS-COV-2, the infection can be prolonged, and genetic mutations can occur during the course of treatment. Therefore, for refractory patients with persistent COVID-19 infection, genomic analysis was performed to obtain data on drug resistance mutations as a reference to determine which antiviral drugs and antibody therapies might be effective in their treatment. METHODS: This was a descriptive analysis with no controls. Patients were diagnosed as having COVID-19, examined, and treated in the Kansai Medical University General Medical Center between January 2022 and January 2023. The subjects of the study were B-cell immunocompromised patients in whom genome analysis of SARS-CoV-2 was performed. RESULTS: During the study period, 984 patients with COVID-19 were treated at our hospital. Of those, 17 refractory cases underwent genomic analysis. All 17 patients had factors related to immunodeficiency, such as malignant lymphoma or post-organ transplantation. Eleven patients started initial treatment for COVID-19 at our hospital, developed persistent infection, and underwent genomic analysis. Six patients who were initially treated for COVID-19 at other hospitals became persistently infected and were transferred to our hospital. Before COVID-19 treatment, genomic analysis showed no intrahost mutations in the NSP5, the NSP12, and the RBD regions. After COVID-19 treatment, mutations in these regions were found in 12 of 17 cases (71%). Sixteen patients survived the quarantine, but one died of sepsis. CONCLUSIONS: In genomic analysis, more mutations were found to be drug-resistant after COVID-19 treatment than before COVID-19 treatment. Although it was not possible to demonstrate the usefulness of genome analysis for clinical application, the change of the treatment drug with reference to drug resistance indicated by genomic analysis may lead to good outcome of immunocompromised COVID-19 patients.

Prognostic awareness in Japanese patients with advanced cancer: a follow-up cohort study.

BACKGROUND: Patients with advanced cancer have been reported to be more likely to receive goal-concordant care if they have accurate prognostic awareness. However, many patients do not have this awareness. This study aimed to examine the prognostic awareness among Japanese patients with advanced cancer. METHODS: This single-center, follow-up cohort study included Japanese patients with advanced cancer who received chemotherapy at Tohoku University Hospital between January 2015 and January 2016. Patients were surveyed at enrollment and followed up for clinical events for 5 years thereafter. We compared (i) the patients' prognostic awareness with both actual survival time and physician's prediction of survival and (ii) physician's prediction of survival time with actual survival. Factors associated with accurate prognostic awareness were identified by univariate analysis. RESULTS: Of the 133 patients eligible for the study, 57 patients were analyzed. Only 10 (17.5%) patients had accurate prognostic awareness. Forty-three patients (75.4%) were optimistic about their prognosis; >80% of patients were more optimistic than their physicians about their prognosis. The physicians' predictions were accurate in for patients (37.5%). Accurate prognostic awareness was associated with physician's explanation of the prognosis and patients' perception of a good death. CONCLUSIONS: A majority of the patients with advanced cancer in this study had prognostic awareness that was more optimistic in comparison with their actual survival, and most were more optimistic than their physicians about their prognosis. Further research is needed to develop programs to facilitate the discussion of life expectancy with patients in a manner that is consistent with their preferences.

Prevalence of opioid-induced adverse events across opioids commonly used for analgesic treatment in Japan: a multicenter prospective longitudinal study.

PURPOSE: Although opioids have been shown to be effective for cancer pain, opioid-induced adverse events (AEs) are common. To date, little is known about the differences in risks of AEs by opioid type. This study was performed to compare the prevalence of AEs across opioids commonly used for analgesic treatment in Japan. METHODS: This study was conducted as a preplanned secondary analysis of a multicenter prospective longitudinal study of inpatients with cancer pain who received specialized palliative care for cancer pain relief. We assessed daily AEs until termination of follow-up. We rated the severity of AEs based on the Common Terminology Criteria for Adverse Events version 5.0. We computed adjusted odds ratios for each AE (constipation, nausea and vomiting, delirium, and drowsiness) with the following variables: opioid, age, sex, renal dysfunction, and primary cancer site. RESULTS: In total, 465 patients were analyzed. Based on the descriptive analysis, the top four most commonly used opioids were included in the analysis: oxycodone, hydromorphone, fentanyl, and tramadol. With respect to the prevalence of AEs among all analyzed patients, delirium (n = 25, 6.3%) was the most frequent, followed by drowsiness (n = 21, 5.3%), nausea and vomiting (n = 19, 4.8%), and constipation (n = 28, 4.6%). The multivariate logistic analysis showed that no single opioid was identified as a statistically significant independent predictor of any AE. CONCLUSION: There was no significant difference in the prevalence of AEs among oxycodone, fentanyl, hydromorphone, and tramadol, which are commonly used for analgesic treatment in Japan.

Simple Detection and Culture of Circulating Tumor Cells from Colorectal Cancer Patients Using Poly(2-Methoxyethyl Acrylate)-Coated Plates.

Here we aimed to establish a simple detection method for detecting circulating tumor cells (CTCs) in the blood sample of colorectal cancer (CRC) patients using poly(2-methoxyethyl acrylate) (PMEA)-coated plates. Adhesion test and spike test using CRC cell lines assured efficacy of PMEA coating. A total of 41 patients with pathological stage II-IV CRC were enrolled between January 2018 and September 2022. Blood samples were concentrated by centrifugation by the OncoQuick tube, and then incubated overnight on PMEA-coated chamber slides. The next day, cell culture and immunocytochemistry with anti-EpCAM antibody were performed. Adhesion tests revealed good attachment of CRCs to PMEA-coated plates. Spike tests indicated that ~75% of CRCs from a 10-mL blood sample were recovered on the slides. By cytological examination, CTCs were identified in 18/41 CRC cases (43.9%). In cell cultures, spheroid-like structures or tumor-cell clusters were found in 18/33 tested cases (54.5%). Overall, CTCs and/or growing circulating tumor cells were found in 23/41 CRC cases (56.0%). History of chemotherapy or radiation was significantly negatively correlated with CTC detection (p = 0.02). In summary, we successfully captured CTCs from CRC patients using the unique biomaterial PMEA. Cultured tumor cells will provide important and timely information regarding the molecular basis of CTCs.

Is spiritual well-being related to survival time of inpatients with advanced cancer? An East Asian cohort study.

OBJECTIVES: It has been suggested that psychosocial factors are related to survival time of inpatients with cancer. However, there are not many studies examining the relationship between spiritual well-being (SWB) and survival time among countries. This study investigated the relationship between SWB and survival time among three East Asian countries. METHODS: This international multicenter cohort study is a secondary analysis involving newly admitted inpatients with advanced cancer in palliative care units in Japan, South Korea, and Taiwan. SWB was measured using the Integrated Palliative Outcome Scale (IPOS) at admission. We performed multivariate analysis using the Cox proportional hazards model to identify independent prognostic factors. RESULTS: A total of 2,638 patients treated at 37 palliative care units from January 2017 to September 2018 were analyzed. The median survival time was 18.0 days (95% confidence interval [CI] 16.5-19.5) in Japan, 23.0 days (95% CI 19.9-26.1) in Korea, and 15.0 days (95% CI 13.0-17.0) in Taiwan. SWB was a significant factor correlated with survival in Taiwan (hazard ratio [HR] 1.27; 95% CI 1.01-1.59; p = 0.04), while it was insignificant in Japan (HR 1.10; 95% CI 1.00-1.22; p = 0.06), and Korea (HR 1.02; 95% CI 0.77-1.35; p = 0.89). SIGNIFICANCE OF RESULTS: SWB on admission was associated with survival in patients with advanced cancer in Taiwan but not Japan or Korea. The findings suggest the possibility of a positive relationship between spiritual care and survival time in patients with far advanced cancer.

[A Case of Hepatic Encephalopathy Caused by Portal Vein Thrombosis after Surgery for Perihilar Cholangiocarcinoma].

A female in her 70s underwent right hepatectomy with resection of caudate lobe and extrahepatic bile duct for perihilar cholangiocarcinoma(T2aN0M0, Stage Ⅱ: Biliary Cancer Treatment Regulations, 7th edition). On the 4th postoperative day, the patient had impaired consciousness, which worsened to almost coma on the 5th postoperative day. On the same day, a blood test showed high ammonia level, thus the state was thought to be hepatic encephalopathy. Contrast -enhanced CT on the same day showed thrombus from the main trunk of the portal vein to the remnant left branch, narrowing of the lumen of the vessel. Simultaneously, enlarged portosystemic shunt in the pelvic floor due to portal hypertension induced by the thrombosis. Plasmapheresis was performed, and anticoagulation with sodium heparin and antithrombin Ⅲ were started. Then, the portal vein thrombus was reduced, and encephalopathy was improved. She was discharged from the hospital on postoperative day 48. She was treated with edoxaban as an outpatient, and anticoagulation therapy was terminated after a CT scan 6 months after surgery, which confirmed no recurrence of thrombus. She is now alive without recurrence of thrombus or tumor for about 2 years after the surgery.

[A Case of Rectal Cancer in Which Total Pelvic Organ Excision Could Be Avoided by TNT Therapy and Robotic Surgery].

The patient is a 50s year old man. He visited his local doctor with complaints of anal pain and bloody stools, and a rectal examination revealed a tumor on the anterior wall of the rectal canal. CT imaging showed tumors invading the prostate, urethra, and anorectal muscles, and a 3 mm-sized nodule was found in the lungs. The patient was diagnosed as cT4bN1M1a, Stage Ⅳ, and total neoadjuvant chemotherapy was planned as preoperative treatment. The 5 Gy×5 times radiation therapy followed by 5 courses of CAPOX plus BEV as preoperative chemotherapy and CAPOX. CAPOX was administered. After completion of treatment, the colonoscopy showed PR, and MRI showed clear boundary between the prostate and tumor but invasion into the anorectal muscles; CT showed no lung metastasis, and preoperative diagnosis was ycT4bN0M0, ycStage Ⅱ. Robotic-assisted rectal amputation and left lateral lymph node dissection were performed under general anesthesia. Pathologically, the patient was diagnosed as ycT4bN0M0, Stage Ⅱ, and the efficacy was determined as TRG 1(AJCC). Vertical dissection was negative and radical resection was possible.

[A Case of Rectal Cancer with Enlarged Lateral Lymph Nodes Treated with Total Neoadjuvant Therapy and Robotic Surgery].

A 70s woman with advanced rectal cancer(AV 3 cm, type 2)was diagnosed as cT3N2M1a, Stage Ⅳ(UICC, TNM 8th) and underwent total neoadjuvant therapy(TNT)consisted of preoperative 5 Gy×5 short course RT followed by 5 courses of CAPOX plus BEV and CAPOX. Post-treatment endoscopy revealed nearCR, MRI failed to identify the primary tumor, and the mesenteric and lateral lymph node enlargement had disappeared. The patient underwent robot-assisted low anterior resection, bilateral lymph node dissection, and temporary ileal colostomy. Postoperative pathological findings were ypT0N0M0, Stage 0, and the efficacy evaluation was TRG 0(AJCC)with no residual tumor including lateral lymph nodes. The patient was discharged on the 16th day without any postoperative complications and is currently alive 6 months postoperatively without recurrence.

[A Case of Locally Advanced Sigmoid Colon Cancer Invading the Urinary Bladder Treated with Neoadjuvant Chemotherapy and Robot Assisted Urinary Bladder-Conserving Surgery].

We report a case of 72s male with locally advanced sigmoid colon cancer. Colonoscopy revealed an advanced sigmoid colon cancer(AV 15 cm, type 2, semi-peripheral, deeper than T3). He was diagnosed as cT4bN2M0, cStage Ⅲc(Japanese Classification of Colorectal, appendiceal, and, Carcinoma, 9th edition), and was given chemotherapy as preoperative treatment. He was treated with CAPOX plus BEV as neoadjuvant chemotherapy. Preoperative diagnosis was ycT4bN0M0, ycStage Ⅱc. The robot assisted high anterior resection and partial bladder resection were performed. The bladder was sutured under robotic assistance. The residual bladder capacity was 100 mL. Postoperative diagnosis was ypT0N0M0, ypStage 0, TRG 0 (AJCC). We experienced a case of neoadjuvant chemotherapy for rectosigmoid colon cancer with bladder invasion, which resulted in pCR.

[A Case of Conversion Surgery after Chemotherapy for Locally Advanced Unresectable Rectal Cancer].

We report a case of locally advanced rectal cancer that could not be curatively resected, in which the patient underwent conversion surgery after chemotherapy. The patient is a 70-year-old woman. She came to our hospital with a chief complaint of lower abdominal pain, and a close examination revealed rectal cancer with invasion of the external iliac artery and pelvic wall. She was treated with mFOLFOX6 plus cetuximab for locally advanced rectal cancer that was not amenable to surgical resection. After 11 courses of chemotherapy, significant shrinkage of the tumor was observed, and robot assisted laparoscopic high-anterior resection was performed. The patient didn't relapse at 12 months after surgery without adjuvant chemotherapy.

[A Case of Single Hole Ileal Resection for Ascendiry Colon Cancer with Ureterocutaneous Fistula in the Right Lower Abdomen].

The patient is a 70s woman. She underwent cystectomy for bladder cancer 6 years ago and had a ureterocutaneous fistula in the right lower abdomen. After colonoscopy for positive fecal occult blood, a type 1 elevated lesion was found in the ascending colon, which was diagnosed as a well-differentiated adenocarcinoma on biopsy. Surgery was performed with a single hole. The approach from the right lower abdomen, where the ureterocutaneous fistula and ureter are located, was avoided, and the approach from the hepatic flexure of the transverse colon was used first. After the right colon was mobilized, the large mesh adhesions around the ureter were carefully dissected, and the right ureter was identified and preserved, extending from the lateral ascending colon to the abdominal wall. The ileal artery was dissected at the root and after dissection of the D3 lymph node, the intestine was dissected and anastomosed extracorporeally. The operative time was 246 minutes with small amount of blood loss. The patient was discharged on the 6th postoperative day without any postoperative complications. The pathology result was pT3N0M0, pStage Ⅱa, and radical resection had been performed. The patient is currently undergoing recurrence-free follow-up.

[A Case of Pathological Complete Response for MSI-High Locally Advanced Unresectable Transverse Colon Cancer Treated with Nivolumab plus Ipilimumab Combination Therapy].

74-year-old woman was diagnosed with locally advanced unresectable transverse colon cancer. She started CAPOX therapy as first-line therapy after ileostomy. After second course, MSI-high was detected, so nivolumab plus ipilimumab combination therapy was started as second-line therapy. After 4 courses of combination therapy, she was judged to be in partial response and surgery was performed. Histopathological diagnosis of the surgical specimen showed complete response, and she is still alive without recurrence 15 months after surgery.

[A Case of Response to Pembrolizmab in Unresectable MSI-High Transverse Colon Cancer].

A 80s man was diagnosed circulated type 2 colon cancer at the transverse colon, and pathological findings was adenocarcinoma( por1). Genomic findings were microsatellite instability-high(MSI-H), all RAS wild type and BRAFV600E mutated. Contrast-enhanced CT showed an enlarged lymph nodes(#221, #222, #223, #214)along the middle colic and superior mesenteric artery. Clinical diagnosis was a locally advanced unresectable transverse colon cancer, cT4aN3M1a(LYM), cStage Ⅳa. Drug therapy with pembrolizumab was prescribed. Six months later, contrast-enhanced CT and PET demonstrated remarkable shrinkage of the primary tumor and lymph nodes except 2 peri-colic enlarged lymph nodes. Primary lesion turned almost undetectable, however the biopsy demonstrated residual tumor. Two months later, CT showed that the residual lymph nodes had also disappeared.

[A case of repeated severe hypoglycemia caused by accidental ingestion of sulfonylurea in an elderly patient].

An 81-year-old man was being treated with oral medication for chronic heart failure and epilepsy. He had no history of diabetes, cirrhosis, or gastric surgery. He was admitted to our hospital due to disturbance of consciousness. His blood glucose level was 6 mg/dl, with a relatively high insulin level (14.4 µU/ml). Computed tomography and a 48 h fasting test showed no signs of insulinoma. There were no signs of reactive hypoglycemia, insulin autoimmune syndrome, or adrenal insufficiency. His wife had been taking medication for diabetes, including sulfonylurea. She had dementia, and he managed her medication. Since his medication was found in his wife's medicine box, we considered the possibility that he might have taken sulfonylurea by mistake. We asked his daughter to manage their medicine. However, one month later, he was admitted to our hospital again with severe hypoglycemia. His wife's HbA1c value and estimated glomerular filtration rate were 6.9% and 30 ml/min/1.73 m2. We asked his wife's home doctor to stop sulfonylurea prescription, and the hypoglycemia did not recur, with his wife's level of HbA1c remaining stable.Elderly individuals and patients with an impaired renal function are prone to hypoglycemia from sulfonylurea. In elderly households, there is a possibility of accidental ingestion of oral hypoglycemic agents by other family members living with the patient. It is therefore necessary to understand and manage the medications of family members living together. It is also important to avoid prescribing medications with a high risk of hypoglycemia to elderly patients.

Sequential Administration of XPO1 and ATR Inhibitors Enhances Therapeutic Response in TP53-mutated Colorectal Cancer.

BACKGROUND & AIMS: Understanding the mechanisms by which tumors adapt to therapy is critical for developing effective combination therapeutic approaches to improve clinical outcomes for patients with cancer. METHODS: To identify promising and clinically actionable targets for managing colorectal cancer (CRC), we conducted a patient-centered functional genomics platform that includes approximately 200 genes and paired this with a high-throughput drug screen that includes 262 compounds in four patient-derived xenografts (PDXs) from patients with CRC. RESULTS: Both screening methods identified exportin 1 (XPO1) inhibitors as drivers of DNA damage-induced lethality in CRC. Molecular characterization of the cellular response to XPO1 inhibition uncovered an adaptive mechanism that limited the duration of response in TP53-mutated, but not in TP53-wild-type CRC models. Comprehensive proteomic and transcriptomic characterization revealed that the ATM/ATR-CHK1/2 axes were selectively engaged in TP53-mutant CRC cells upon XPO1 inhibitor treatment and that this response was required for adapting to therapy and escaping cell death. Administration of KPT-8602, an XPO1 inhibitor, followed by AZD-6738, an ATR inhibitor, resulted in dramatic antitumor effects and prolonged survival in TP53-mutant models of CRC. CONCLUSIONS: Our findings anticipate tremendous therapeutic benefit and support the further evaluation of XPO1 inhibitors, especially in combination with DNA damage checkpoint inhibitors, to elicit an enduring clinical response in patients with CRC harboring TP53 mutations.

Efficacy of platinum agents for stage III non-small-cell lung cancer following platinum-based chemoradiotherapy: a retrospective study.

BACKGROUND: Platinum-based chemoradiotherapy is the standard treatment for unresectable stage III non-small-cell lung cancer (NSCLC). However, few studies have evaluated the efficacy of subsequent chemotherapy for relapsed NSCLC following platinum-based chemoradiotherapy. This study aimed to evaluate the efficacy of platinum-doublet chemotherapy as a second-line treatment for patients with unresectable stage III NSCLC. METHODS: We retrospectively evaluated patients with unresectable stage III NSCLC treated with cytotoxic chemotherapy following platinum-based chemoradiotherapy who were registered in a nationwide registry NSCLC database. Patients were divided into the platinum-doublet chemotherapy (platinum) group and single-agent chemotherapy (non-platinum) group based on the type of second-line chemotherapy. RESULTS: The platinum group (n = 119) showed significantly better overall survival (OS) than the non-platinum group (n = 201) (median OS: 21.5 vs. 10.5 months, hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.40-0.73, p < 0.001). OS from the beginning of chemoradiotherapy was also significantly better in the platinum group than in the non-platinum group (median OS: 34.9 vs. 21.8 months, HR: 0.58, 95% CI: 0.43-0.79, p = 0.001). In the multivariate analysis, platinum-doublet chemotherapy as second-line therapy, female sex, clinical stage IIIA, and duration of ≥ 8.6 months from the beginning of first-line therapy to the beginning of second-line therapy were associated with significantly better OS. CONCLUSION: Platinum-doublet chemotherapy as a second-line therapy may prolong survival in unresectable stage III NSCLC patients following platinum-based chemoradiotherapy. Thus, re-administration of platinum agents may be a promising treatment for unresectable stage III NSCLC treated with platinum-based chemoradiotherapy.

Changes in depressive symptoms among family caregivers of patients with cancer after bereavement and their association with resilience: A prospective cohort study.

OBJECTIVES: To elucidate changes in depressive symptoms after bereavement and the impact of pre-loss resilience on such changes and on the extent of complicated grief and posttraumatic growth. METHODS: Prospective cohort surveys were provided to family caregivers of patients with cancer in four palliative care units (PCUs) before and after bereavement. Pre-loss Connor-Davidson Resilience Scale scores, pre- and post-loss Patient Health Questionnaire-9 scores, post-loss Brief Grief Questionnaire scores, and the expanded Posttraumatic Growth Inventory scores were determined. RESULTS: Out of 186 bereaved family caregivers, 71 (38.2%) responses were analyzed, among which 47% pre-loss and 15% post-loss responses suggested to be a high risk for major depressive disorder (MDD). Approximately 90% of family caregivers at a high risk for post-loss MDD were already at a high risk for pre-loss MDD. Even after adjustment of the background variables as covariates, the interaction effect between family caregivers' pre-loss depressive symptoms and resilience on post-loss depressive symptoms was observed (F = 7.29; p < 0.01). Moreover, pre-loss resilience was not associated with other bereavement outcome measures. CONCLUSIONS: Among family caregivers of patients with cancer in PCUs, 47% and 15% had high risk for MDD before and after bereavement, respectively. Moreover, pre-loss resilience mitigated post-loss depressive symptoms among family caregivers who had high risk for MDD before bereavement. However, considering the study's small sample size, further research is needed.

First-line therapy in non-small cell lung cancer patients with EGFR activating mutations: a consideration of the clinical position of osimertinib based on the subset of Japanese patients in the FLAURA study.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been established as the standard first-line treatment for patients with previously untreated advanced non-small cell lung cancer (NSCLC) with an EGFR activating mutation. In the FLAURA study, osimertinib, third-generation EGFR-TKI, resulted in significantly longer progression-free survival and overall survival (OS) than first-generation EGFR-TKIs (gefitinib or erlotinib) in patients with previously untreated advanced NSCLC with an EGFR activating mutation. Osimertinib is now widely used as first-line therapy for those patients. In Japanese subset analysis of the FLAURA study, the median progression-free survival was prolonged by osimertinib (19.1 months) relative to gefitinib (13.8 months). However, there was no apparent OS benefit, albeit at the level of an exploratory post-hoc analysis. Although the safety profile in the Japanese subset was generally consistent with the overall population, the incidence of liver enzyme increases in the gefitinib group and that of interstitial lung disease/pneumonitis in the osimertinib group was higher among Japanese patients. There is now an increasing number of first-line treatment options for NSCLC with EGFR mutations, including EGFR-TKIs in combination with platinum-doublet chemotherapy or anti-angiogenic drugs. These combinations show progression-free survival benefits similar to osimertinib regardless of the mutation type. Therefore, a first-line combination regimen followed by osimertinib remains an attractive strategy. We review data from the randomized clinical trials of first-line EGFR-TKIs including a subset of Japanese patients and discuss first-line therapies for patients with NSCLC harbouring EGFR mutations.