Japanese journal of clinical oncology最新文献

Radical lobectomy, proposed as a curative treatment for lung cancer in 1960, has long been regarded as the standard surgical approach. The findings of two phase III randomized controlled trials comparing limited resection versus lobectomy for non-small cell lung cancer (NSCLC) ≤2 cm have challenged the long-standing evidence supporting lobectomy as the universal surgical option for all patients with lung cancer. The Japanese clinical oncology group (JCOG) and West Japan Oncology Group (WJOG) (JCOG0802/WJOG4607L) demonstrated both the non-inferiority and superiority of segmentectomy, while the Cancer and Leukemia Group B trial (CALGB140503) conducted by the Alliance for Clinical Trials in Oncology in North America, confirmed the non-inferiority of limited resection, including wedge resection for NSCLC measuring ≤2 cm. As both trials demonstrated non-inferiority of limited resection in NSCLC ≤2 cm, their results are often summarized together. However, patient background, radiological findings, prognosis, and extent of resection differ significantly between the two trials and should be interpreted with caution. Previous trials have demonstrated that preserving lung parenchyma helps maintain pulmonary function and improves patient prognosis by enabling appropriate management of subsequent malignancy or other diseases. Limited resection, including segmentectomy, is currently the standard of care for early-stage NSCLC. The JCOG and WJOG are conducting trials to determine whether the indications for limited resection can be expanded to include patients with NSCLC >2 cm or those with stage I NSCLC. This review article outlines the results of previous trials, provides an overview of ongoing trials, and discusses prospects for limited resection.

Objective: Definitive chemoradiotherapy (CRT) is a treatment strategy for localized esophageal squamous cell carcinoma (ESCC). Herein, we aimed to evaluate clinical outcomes of definitive CRT for ESCC.

Methods: We reviewed 127 patients who received definitive CRT for localized ESCC at our institution between January 2004 and December 2022. All patients received elective nodal irradiation with concurrent chemotherapy, primarily comprising cisplatin and 5-fluorouracil, during radiotherapy. Seventeen patients (13%) received intensity-modulated radiation therapy (IMRT) only, and 16 patients (13%) were treated with IMRT as a boost. The median total dose was 61.4 Gy. Approximately 80% of the patients had clinical stage III or higher disease. We analyzed overall survival (OS), progression-free survival (PFS), locoregional recurrence rate (LRR), prognostic factors, and adverse events.

Results: The median follow-up period was 13 months for all patients and 22 months for survivors. The 2-year OS, PFS, and LRR were 40.4%, 27.1%, and 30.8%, respectively. The overall complete response rate was 40.2%. On multivariate analysis, clinical stage 0-III (non-T4) (P < .001) and the use of IMRT (P = .034) were significantly associated with better OS. Pulmonary toxicity was significantly lower in the IMRT group (P = .049).

Conclusions: IMRT for localized ESCC may improve prognosis and reduce pulmonary toxicity.

Background: The Geriatric-8 (G8) is used for the functional status of older adult patients with cancer. However, its role in treatment decision-making for gynecological malignancies has not been established.

Methods: We retrospectively analyzed the data of 180 women aged ≥75 years with gynecological malignancies who underwent initial treatment at our institution between January 2019 and December 2023. Pre-treatment G8 scores were assessed and patients were categorized as fit (G8 > 14) or frail (G8 ≤ 14). Associations between the G8 score and patient background, disease characteristics, treatment options, and treatment tolerability were examined.

Results: Of the 180 women, 53 (29.4%) were classified as fit and 127 (70.6%) as frail. Frail patients required long-term care (P = .008) and used anticoagulants more frequently than fit patients (P = .019). Median G8 scores were highest in endometrial cancer (14) and lowest in vulvar cancer (10). Best supportive care (8) and neoadjuvant chemotherapy (10) had lower G8 scores than surgery and concurrent chemoradiotherapy (14) (P < .001). Postoperative complications occurred in 10/96 surgical cases; these cases had lower scores than those without complications (12 vs. 14, P = .044). During chemotherapy, median scores were lower in women with ≥ grade 3 (12 vs. 14, P = .008) and grade ≥ 4 adverse events (10 vs. 14, P = .002).

Conclusions: The G8 score is associated with patient background, cancer type, and treatment options, and is associated with treatment tolerability in women aged ≥75 years with gynecological malignancies.

Background: Efficacy of available treatments for liposarcoma (LPS), including dedifferentiated liposarcoma (DDLPS) is limited, and detailed real-world clinical data for patients with LPS treated in Japan are scarce. We used the MASTER KEY Registry Database to evaluate the clinical characteristics and outcomes of patients with advanced/metastatic LPS treated with systemic antineoplastic therapy in Japan.

Methods: This non-interventional/observational cohort study included patients with LPS, including DDLPS, and well-differentiated LPS (WDLPS), and a history of systemic antineoplastic therapy, enrolled in the MASTER KEY Project Registry Database from 1 May 2017 to 31 December 2022. Outcomes were analysed by type of treatment. Primary outcomes: progression-free survival (PFS); overall survival (OS). Secondary outcomes: overall response rate; disease control rate. Sensitivity analyses (prospective registry subgroup) were performed to minimize immortal time bias.

Results: Since 2017, 100 patients with LPS were prospectively enrolled in the database; of these, 62 had DDLPS and 11 had WDLPS. In patients with LPS, median PFS was 11.1 months after first-line (1 L) pharmacotherapy and 6.9 months after 1 L doxorubicin. In patients with DDLPS, median PFS was 6.9 months after 1 L pharmacotherapy and 4.4 months after 1 L doxorubicin. Median OS after 1 L pharmacotherapy was 45.8 months in patients with LPS, and 40.7 months in those with DDLPS. Median OS in the sensitivity analysis was not reached for patients with LPS and was 13.9 months for the DDLPS subgroup.

Conclusions: These data investigating DDLPS in Japanese patients highlight the poor outcomes and lack of effective treatment options in the real-world clinical practice setting.

RNA therapeutics, including antisense oligonucleotides (ASOs), have emerged as a promising class of drugs, with several already approved for clinical use. To date, most approved ASO-based RNA therapies target non-malignant disorders such as neurodegenerative diseases, and only a single therapy in this class has been approved for cancer. Notably, nearly half of existing RNA therapeutics act by modulating RNA splicing. Given the growing evidence implicating aberrant RNA splicing in cancer pathogenesis, the development of ASO-based therapeutics for oncologic indications is expected to accelerate. More than 250 clinical trials have evaluated oligonucleotide agents targeting diverse cancer-associated molecules, with several showing encouraging early results. In this review, we summarize recent advances in understanding cancer biology relevant to ASO-based therapies and highlight ongoing progress in the development of RNA-targeted approaches for cancer treatment.

Background: Total gastrectomy (TG) is commonly performed as the standard treatment for upper third advanced gastric cancer (AGC). Proximal gastrectomy (PG) may be a potential alternative procedure for upper-third AGC. However, its oncologic safety remains uncertain. This study aimed to compare the long-term outcomes of PG and TG for upper-third AGC and to evaluate the oncological safety of PG.

Methods: We retrospectively analyzed the data of patients who underwent PG or TG for clinical T2-T4aNanyM0 upper-third gastric cancer at six institutions between 2018 and 2022. To minimize selection bias, propensity score matching (PSM) was performed at a 1:1 ratio. The primary endpoint was overall survival (OS).

Results: A total of 208 patients with upper-third AGC were included. After PSM, 104 patients were selected for analysis, with 52 patients in each group. The 3-year OS rates were 81.8% in the PG group and 70.8% in the TG group, with no statistically significant difference between the two groups (P = .167), with a hazard ratio for PG of 0.58 (95% confidence interval, 0.27-1.27; P = .173). Subgroup analysis revealed that the hazard ratio for OS was significantly lower in the PG group than in the TG group among patients with tumor diameters <50 mm.

Conclusions: The long-term survival outcomes of PG and TG for upper-third AGC patients are comparable, suggesting that PG may be an oncologically acceptable option in carefully selected patients.

Background: Triplet therapy with darolutamide, androgen deprivation therapy, and docetaxel (DOC) has emerged as an intensified treatment option for metastatic castration-sensitive prostate cancer (mCSPC). This study evaluated real-world prostate specific antigen (PSA) responses and adverse events (AEs) associated with triplet therapy, with a focus on age-specific differences.

Methods: We performed a retrospective cohort study across six academic institutions in Japan between February 2023 and February 2025. A total of 137 patients with mCSPC who received triplet therapy were analyzed. PSA responses and AEs were assessed, including subgroup analyses by age (<75 vs ≥75 years).

Results: The median age was 71 years, and 40 patients (29.2%) were aged ≥75 years. Six cycles of DOC were completed at similar rates in patients aged <75 years (66.0%) and ≥ 75 years (57.5%) (P = .435). The median baseline PSA was 298 ng/ml, and 107 patients (78.1%) met the CHAARTED high-volume criteria. At three months, the median [interquartile range] PSA decline was 99.8% [99.0-99.9]; 113 patients (92.6%) achieved a PSA decline >90%, and 35 patients (28.7%) achieved a PSA <0.2 ng/ml. During follow-up, the proportion achieving a PSA nadir <0.2 ng/ml did not differ significantly between patients aged <75 years (63.9%) and ≥ 75 years (55.0%) (P = .341). Grade ≥ 3 AEs occurred in 56 patients (40.9%), including febrile neutropenia in 29 patients (21.2%). The incidence of AEs did not differ significantly by age.

Conclusions: In this real-world cohort, triplet therapy showed substantial PSA declines and acceptable tolerability, with no significant differences in short-term efficacy or safety between patients aged <75 and ≥ 75 years. These findings suggest that chronological age alone should not preclude consideration of triplet therapy in appropriately selected patients.

Accurate histopathological and molecular characterization of lung cancer is essential for optimal treatment selection in the era of precision medicine. While conventional biopsy techniques are widely available and safe, they often yield small tissue samples with crush artifacts that may be insufficient for comprehensive molecular testing. Cryobiopsy has emerged as a promising diagnostic technique that addresses these limitations. For endobronchial and peripheral pulmonary lesions, cryobiopsy demonstrates superior diagnostic yields compared to conventional forceps biopsy, with enhanced capability for molecular diagnostics and programmed death-ligand 1 assessment. Endobronchial ultrasound (EBUS)-guided mediastinal cryobiopsy shows particular promise for lymph node sampling, achieving higher diagnostic yields than EBUS-guided transbronchial needle aspiration, especially for lymphoma and metastatic disease. Moreover, thoracoscopic cryobiopsy provides larger pleural specimens with preserved architecture, improving diagnosis of challenging cases including malignant mesothelioma. The safety profile remains favorable across all applications, with bleeding as the primary complication that is typically manageable with standard techniques. Cryobiopsy represents a significant advancement in thoracic oncology diagnostics, providing high-quality tissue specimens essential for contemporary cancer management.

Oligometastasis is a concept that refers to the condition between localized cancer and widespread distant metastases; however, a consensus on the definition has yet to be reached. Metastasis-directed therapy (MDT) has recently been established to incorporate local therapy, such as radiotherapy and surgery, for distant metastases. Previous trials have proposed the possibility of long-term survival with the administration of MDT for patients with oligometastases. However, the efficacy and safety of MDT have not been sufficiently validated. We are conducting this clinical trial to confirm the superiority of MDT combined with subtype-specific systemic drug therapy over systemic drug therapy alone in patients with oligometastatic breast cancer. Here, "oligometastases" are defined as tumors with a maximum diameter ≤ 3 cm and total number ≤ 3. The primary endpoint is overall survival. We intend to enroll 340 patients from 62 institutions over a 3-year period. This trial has been registered in the Japan Registry of Clinical Trials (jRCTs031230439).

Ribonucleic acid (RNA) modifications, once viewed as static structural features, are now recognized as dynamic regulators of the 'epitranscriptome' that shape RNA fate. In cancer, dysregulation of RNA-modification writers, erasers, and readers reprograms RNA metabolism and translation, promoting tumorigenesis, metastasis, therapy resistance, and immune evasion. Across messenger RNAs, ribosomal RNA (rRNAs), transfer (tRNAs), and diverse non-coding RNAs, aberrant modification patterns drive alternative splicing, generate onco-ribosomes, enforce codon-biased translation, and remodel gene-expression networks in a context-dependent manner. This review summarizes how major RNA modifications-including m6A, m5C, pseudouridine, inosine, and ac4C-and their regulators contribute to cancer biology, together with disease-associated changes in rRNA, tRNA, and regulatory non-coding RNAs. We then discuss emerging diagnostic and prognostic biomarkers, druggable nodes within the epitranscriptomic machinery, and combination strategies that integrate RNA-modification targeting with existing therapies and immunotherapy. Finally, we outline key technologies for mapping RNA modifications, comparing mass spectrometry and NGS-based chemical or antibody-enrichment approaches with the expanding capabilities of nanopore direct RNA sequencing. Recent advances in nanopore direct RNA sequencing technologies, leveraging new chemistry (e.g. RNA004) and deep-learning basecallers (e.g. Dorado), increasingly enable single-molecule, multi-modification profiling, accelerating discovery despite inherent technical challenges. Collectively, biological, clinical, and technological progress is transforming the epitranscriptome into a tractable dimension of cancer biology and a promising source of future biomarkers and RNA-targeted precision therapies.