Japanese journal of clinical oncology最新文献

Background: Despite advancements in treatment options for metastatic urothelial carcinoma (mUC), therapeutic choices remain limited for patients with disease refractory to platinum-based chemotherapy (PBC) and immune checkpoint inhibitors (ICIs). Enfortumab vedotin (EV) has demonstrated significant efficacy in later lines of therapy for mUC; however, its organ-specific responses remain uncertain.

Methods: We conducted a retrospective study of 69 patients with mUC who received EV following treatment with PBC and ICIs. Efficacy was assessed using Response Evaluation Criteria in Solid Tumors, with organ-specific response rates (OSRR) and organ-specific disease control rates (OSCR) calculated across different metastatic sites. Multivariate Cox regression analysis was performed to identify independent predictors of disease progression and survival.

Results: The median progression-free survival (PFS) was 8.3 months, whereas the median overall survival (OS) was 18.0 months. The objective response rate (ORR) was 53.6%, and the disease control rate (DCR) was 82.6%. OSCR was ≥70% across all metastatic sites, confirming the broad efficacy of EV. Liver metastases exhibited the highest OSRR at 66.7%, whereas bone metastases had the lowest OSRR at 12.5%. Tumor burden reduction was significantly lower in bone metastases compared to other metastatic sites. Disease progression was predominantly observed at target lesions, with a median time to progression of 3 months. Eastern Cooperative Oncology Group performance status and serum C-reactive protein levels were identified as significant independent predictors of PFS and OS.

Conclusion: EV exhibited favorable organ-specific tumor responses in mUC, with particularly high efficacy against liver metastasis. However, response rates were lower in bone metastases. No significant differences in organ-specific overall survival were observed.

Objectives: To evaluate outcomes of early-stage nonsmall cell lung cancer (NSCLC) patients in relation to patient and hospital factors.

Summary background data: Results of randomized controlled trials (RCTs) may not be applicable to daily practice.

Methods: Outcomes of patients who had undergone curative surgery for node-negative NSCLC were retrospectively evaluated. They were either participants in an RCT (JCOG0707) or those excluded from it. "Excluded patients" were either ineligible to ("ineligible cohort") or eligible but did not participate ("eligible cohort") in the RCT. Correlations between hospital volume, study forwardness, and patient outcomes were also analyzed.

Results: A total of 5921 patients, 917 in JCOG0707, were evaluated. The overall survival (OS) of the eligible cohort (n = 2616) was similar to the JCOG0707 cohort with an adjusted hazard ratio (aHR) of 1.01 (P = .90), while that of the ineligible cohort (n = 2388) was significantly worse, with an aHR of 1.67 (P < .0001). Both deaths from lung cancer and from other causes led to the inferior outcome. The OS of patients in the ineligible cohort, excluded from the trial due solely to the presence of concomitant malignancy (n = 704), was significantly worse than OS in the eligible cohort, but disease-specific survivals were not significantly different. Hospital volume did not affect OS (high vs low: aHR 0.91, P = .13), but high-volume hospitals had lower "other-cause" mortality (aHR 0.79, P = .02).

Conclusions: RCT-ineligible patients had worse OS, and their excess mortalities are mainly attributed to nonlung-cancer-specific deaths.

The GLOW and SPOTLIGHT trials have demonstrated the efficacy of chemotherapy plus zolbetuximab for HER2-negative, claudin-18 isoform 2 (CLDN18.2)-positive unresectable advanced or recurrent gastric cancer (AGC)/gastroesophageal junction cancer. However, data on adverse events in real-world clinical practice are still insufficient. Specifically, gastritis and protein-losing enteropathy (PLE), which were not evident in either trials, are not generally recognized. This paper reports on the notable clinical course and examination findings of two cases of PLE observed in patients with unresectable AGC who were administered zolbetuximab. Case 1 involved a 66-year-old woman with HER2-negative, CLDN18.2-positive unresectable advanced gastric cancer (cT4aN1M1) with peritoneal dissemination. As a fifth-line treatment, she underwent combination therapy with capecitabine, oxaliplatin, and zolbetuximab (CAPEOX + Zolbe). Case 2 involved a 58-year-old woman with HER2-negative, CLDN18-positive gastric cancer (pT1aN3bM1) with extra-regional lymph node metastasis. After undergoing robot-assisted distal gastrectomy, she commenced CAPEOX + Zolbe therapy. In both cases, following the initiation of CAPEOX + Zolbe therapy, serum albumin levels decreased from 3.5 g/dL pre-treatment to 2.2 g/dL. Upper gastrointestinal endoscopy revealed diffuse redness and edema of the gastric mucosa. Pathological histological examination of the gastric mucosal biopsy also revealed findings consistent with PLE. A technetium-99m-labeled human serum albumin scintigraphy demonstrated leakage of Tc-99m albumin into the gastrointestinal tract, leading to a diagnosis of PLE. In the two cases we experienced, we observed gastritis and PLE caused by zolbetuximab. These adverse events are not widely recognized among clinicians. However, when hypoalbuminemia occurs during zolbetuximab administration, this diagnosis should be considered.

The concept and definition of combined hepatocellular-cholangiocarcinoma (cHCC-CCA), an extremely rare condition accounting for only 1% of all primary liver cancers, has shifted in recent years. The latest World Health Organization Classification (fifth edition) includes two types of cHCC-CCAs, (i) the classical type described in the previous edition, which contains a mixture of distinctly differentiated components of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) and (ii) intermediate cell carcinoma wherein all cells comprising the tumor express both hepatocellular and cholangiocellular features. However, the pathogenesis of cHCC-CCA, including its origins, remains controversial even among experts. Treatment strategies for cHCC-CCA in clinical practice have been determined based on imaging findings, tumor markers, and pathologically predominant tumor components for either HCC or ICC, suggesting that cHCC-CCA has yet to be been established as an independent disease entity. As with HCC and ICC, the treatment strategy for HCC-CCA involves initially considering resectability. Although systemic therapy has been considered for patients unsuitable for local treatment, no prospective clinical trials have evaluated the efficacy and safety of systemic therapy for cHCC-CCA, which could explain the lack of a standard of care. In recent years, however, studies have demonstrated the efficacy of immune checkpoint inhibitors for HCC and ICC, with therapeutic results having been reported for cHCC-CCA. Hence, further accumulation of cases is expected to facilitate the establishment of a consensus on treatment strategies in the near future.

Objective: This study aimed to assess the oncological outcomes of the subtype of urothelial carcinoma (SUC), including divergent differentiation and histologic subtype, in comparison with those of pure urothelial carcinoma (PUC) in nonmuscle-invasive bladder cancer.

Methods: We retrospectively evaluated patients who were initially treated with transurethral resection of the bladder tumor (TURBT) between March 2005 and August 2020 at a single institution. Patients with PUC and SUC were compared in terms of recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS).

Results: Out of 853 enrolled patients, 783 (91.8%) and 70 (8.2%) had PUC and SUC, respectively. SUC presence was significantly associated with old age, tumor size (≥3 cm), higher pT1 rate, high grade, concomitant carcinoma in situ, and lymphovascular invasion. RFS rates after TURBT did not significantly differ between the PUC and SUC groups. With a median follow-up period of 66 months (interquartile range, 38-103 months), the rates and median time of progression to muscle invasion were 6.9% and 22.5 months in the PUC group, and 22.9% and 10.0 months in the SUC group. Moreover, the incidence of progression to metastasis was 4.6% and 15.7% in the PUC and SUC groups, respectively. The 5-year PFS rates (64.5% and 81.9%, P < .001) and 5-year OS rates (71.7% and 86.2%, P = .009) were lower in the SUC group than in the PUC group. On multivariate analysis, SUC presence independently predicted progression to muscle invasion and metastasis.

Conclusion: At initial TURBT diagnosis, we must pay more attention to higher progression risk of SUC than that of PUC in nonmuscle-invasive bladder cancer.

Background: JCOG1113 is a randomized phase III trial that showed non-inferiority of gemcitabine plus S-1 to gemcitabine plus cisplatin in patients with advanced biliary tract cancer. Assessment of inter-institutional heterogeneity in chemotherapy contributes to confirm generalizability and reliability of the study itself. However, there have been no studies conducted to assess the heterogeneity among participating centers in randomized phase III trials for biliary tract cancer.

Methods: The objective of this post-hoc analysis was to assess the inter-institutional heterogeneity in the overall survival and progression-free survival of patients with advanced biliary tract cancer treated with first-line chemotherapy in the JCOG1113 trial. The heterogeneity in the overall survival and progression-free survival was assessed according to three factors: hospital volume, experience in medical oncology and experience in biliary intervention. A total of 300 advanced biliary tract cancer patients were analyzed. There were no statistically significant trends observed between hospital volume, experience in medical oncology, or experience in biliary intervention and overall survival (hospital volume: adjusted trend P value = 0.6796; experience in medical oncology: adjusted trend P value = 0.4092; experience in biliary intervention: adjusted trend P value = 0.6112). Similarly, no statistically significant trends were observed between these factors and progression-free survival (hospital volume: adjusted trend P value = 0.3000; experience in medical oncology: adjusted trend P value = 0.1108; experience in biliary intervention: adjusted trend P value = 0.2898).

Conclusions: This study revealed no inter-institutional heterogeneity in the overall survival and progression-free survival in the JCOG1113 study population of advanced biliary tract cancer patients.

Familial adenomatous polyposis (FAP) is an inherited disorder that follows an autosomal dominant inheritance pattern and is caused by a germline pathogenic variant in the APC gene. FAP also has extracolonic manifestations, including osteomas, brain tumors, and congenital hypertrophy of the retinal pigmented epithelium. Desmoid tumor is a rare soft-tissue tumor often associated with FAP. APC is a WNT signal transduction molecule that is abundantly expressed in the central nervous system. The truncation mutations of the APC gene are responsible for FAP. Further, the C-terminal domains of APC associate with proteins such as EB1 and hDLG, which are involved in central nervous system functions. In recent years, several reports have indicated an association between FAP and mental disorders. We have identified a family with FAP that has a cluster of mental disorders. The female probrand experienced FAP and desmoid tumors in her thirties. She underwent a total colectomy and tumor resection. Her genetic test revealed a pathogenic germline pathogenic variant in the APC gene, c.3183_3187del. Her maternal grandmother and great-grandmother had colorectal polyposis. She has some mental disorders, and her son and daughter both have autism spectrum disorder (ASD). It was reported that her younger sister and her two daughters have intellectual disability and symptoms of ASD. For these situations, we found that mental health care is crucial when providing genetic counseling and medical care, especially to younger patients with FAP and carriers of pathological variants of the APC gene.

Background: In Japan, about 70%-80% of cancer deaths occur in hospitals. The actual number of cancer patients who die in hospitals where palliative care is available is not clear. This study aimed to examine whether hospitals where cancer patients died offered palliative care.

Methods: Patients aged ≥20 who died of cancer in 2018 were included. We used the Japanese death records and publicly available data on hospital functions. Cancer death numbers and hospitals were summarized according to hospital function and age group. Logistic regression analysis was performed to examine the death influence in patients with cancer in designated cancer hospitals.

Results: The study included 302 511 patients, and 168 835 patients (55.8%) died in hospitals with palliative care. In hospitals without palliative care, those with 100-199 and 200-499 beds had more deaths than hospitals not in these ranges of beds. Their median number of deaths per year was 17 and 26, respectively. Categorized by the death numbers per hospital without palliative care, hospitals with 20-49 cancer deaths were common. In the designated cancer hospitals, younger patients aged 20-29 had a higher odds ratio (OR) for death (4.28) than those aged 70-79. Blood cancer had a higher OR (2.36) than colorectal and rectal cancer.

Conclusion: Our findings suggest that outreach of palliative care to hospitals with 100-199 or 200-499 beds and 20-49 deaths lacking palliative care could effectively improve end-of-life cancer care.

Objective: To describe standard of care and inform the evolving unmet need among extensive stage small-cell lung cancer (ES-SCLC) patients in Japan since approval of first-line anti-PD-L1 therapies, we describe treatment patterns and overall survival by line of therapy.

Methods: We conducted a descriptive analysis of adult ES-SCLC patients in Japan using de-identified patient data within the MDV database (hospital-based claims) to describe treatment patterns and DeSC database (payer-based claims linked to mortality of municipality records) to describe both treatment patterns and real-world overall survival (rwOS).

Results: The study population of MDV and DeSC cohorts included 6302 and 903 patients, respectively. First-line anti-PD-L1 therapy-based regimens grew since their approval in 2019 and were used in ~35% and ~59% of patients in 2022, in the MDV and DeSC cohorts, respectively. Amrubicin monotherapy was the most common second-line (2 L) regimen before and after 1 L anti-PD-L1 approvals. No clear standard of care was identified in third-line (3 L) and fourth-line (4 L). Median rwOS following 1 L therapy was 10.6 months (95% CI: 9.0, 11.8) and 9.3 months (95% CI: 8.3, 10.3) in patients who did and did not receive anti-PD-L1 therapy, respectively. Following 2 L, 3 L, and 4 L therapy, median rwOS was 6.7 months (95% CI: 5.9, 7.4), 5.5 months (95% CI: 4.4, 6.4), and 4.7 months (95% CI: 3.4, 6.9), respectively.

Conclusions: Anti-PD-L1 therapies have become part of first-line standard of care but survival in treated Japanese ES-SCLC patients remains poor, highlighting the unmet medical need in the post anti-PD-L1 era.

Background: The number of elderly people undergoing surgery for colorectal cancer has been increasing. We examine prognosis, including risks of surgery by age and cancer- and noncancer-related deaths.

Methods: This study retrospectively reviewed 1830 patients who underwent curative resection colorectal surgery. Patients were divided into oldest-old (>85 years old, n = 49), elderly (75-84 years old, n = 637), and young (<75 years old, n = 1144) patient groups.

Results: Physical status was poorer (P < .001), postoperative complications were more frequent (49.0% vs. 20.9% vs. 18.4%; P < .001), and adjuvant chemotherapy was less frequent (0% vs. 44.3% vs. 83.5%; P < .001) as patients got older. Multivariate analysis revealed oldest-old [odds ratio (OR) 4.373, 95% confidence interval (CI) 2.362-8.110; P < .001] as independent predictors of postoperative complications. Elderly patients [hazard ratio (HR) 2.494, 95%CI 1.707-3.642; P < .001], oldest-old patients (HR 5.969, 95%CI 3.229-11.035; P < .001), poor physical status (HR 2.546, 95%CI 1.694-3.827; P < .001), and postoperative complications (HR 1.805, 95%CI 1.252-2.602; P = .001) were predictive factors for noncancer-specific survival.

Conclusions: Elderly patients had many complications and a higher risk of dying from other causes. Surgical risk and general condition must be considered when deciding the appropriateness of surgery and adjuvant therapy.