Combination chemotherapy for older patients with unresectable biliary tract cancer: a prospective observational study using propensity-score matched analysis (JON2104-B).

Background: Systemic chemotherapy with gemcitabine plus S-1 (GEM + S-1), GEM + CDDP plus S-1 (GEM + CDDP + S-1), or gemcitabine plus cisplatin (GEM + CDDP) is standard treatment for advanced biliary tract cancer (aBTC). We aimed to evaluate the efficacy and safety of combination chemotherapy in older patients with aBTC.

Methods: This multicenter prospective observational study (JON2104-B, UMIN000045156) included patients aged ≥ 70 years with aBTC.

Risk Stratification Using DIPSS and Splenomegaly in Myelofibrosis Treated with Pre-Transplant JAK inhibitors.

The Dynamic International Prognostic Scoring System for primary myelofibrosis (DIPSS) has been reported to predict transplant outcomes in myelofibrosis (MF) patients. Recently, the pre-transplant use of JAK inhibitors has become common in clinical practice, but it is unclear whether DIPSS is also useful for predicting transplant outcomes for these patients. In this study, we compared the prognostic impact of DIPSS between MF patients with and without pre-transplant Ruxolitinib therapy.

Outcomes of FOLFIRINOX versus gemcitabine plus nab-paclitaxel in patients with early recurrent pancreatic cancer after adjuvant S-1 treatment: A propensity score-matched analysis.

Background: Oral fluoropyrimidine, S-1 is the standard adjuvant chemotherapy for patients with resected pancreatic cancer (PC) in Japan. Patients experiencing early recurrence are typically treated with 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine plus nab-paclitaxel (GnP), which are commonly used in patients with advanced PC. However, no clinical studies have compared these regimens in this particular population.

[Exploring leadership and promoting career development for female physicians].

Based on the Women Physicians' Career Symposium at the 86th Annual Meeting of the Japanese Society of Hematology, this paper explores career development and leadership among female physicians. A career encompasses not only one's professional life but also the entirety of one's life, as highlighted by Schein's concept of the "career anchor" and Hall's "protean career" theory. The discussion also emphasizes the importance of sustaining careers while navigating life events such as childbirth and childcare, alongside addressing the need to overcome unconscious bias.

[Successful management of cardiac arrest due to cytokine release syndrome following chimeric antigen receptor T-cell therapy for multiple myeloma].

A 58-year-old woman received chimeric antigen receptor T-cell (CAR-T) therapy for triple-class refractory multiple myeloma. Following CAR-T infusion, she developed severe cytokine release syndrome (CRS) and was promptly admitted to the intensive care unit (ICU). Subsequently, she developed immune effector cell-associated neurotoxicity syndrome (ICANS), and then progressed to cardiac arrest.

Amino acid-dependent TSC2 dephosphorylation by lysosome-PP2A regulates mTORC1 signaling transduction.

The mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, composed of amino acid (AA)-sensing (Ragulator/LAMTOR-Rag) and growth factor (GF)-sensing (AKT-TSC1/2-Rheb) axes, pivotally regulates intracellular anabolism and catabolism. mTORC1 deregulation is associated with various metabolic diseases, including cancer and diabetes. As a key regulator of nutrient signaling, mTORC1 integrates a variety of nutrient signals.

Body composition as a predictive factor for chemotherapy-induced peripheral neuropathy and dose-limiting toxicity in patients with endometrial cancer undergoing carboplatin and paclitaxel.

Objective: This study investigated whether lean body mass could predict the incidence of dose-limiting toxicity and chemotherapy-induced peripheral neuropathy in patients with endometrial cancer treated with carboplatin-paclitaxel.

Methods: This retrospective study included patients with endometrial cancer who underwent carboplatin-paclitaxel after primary surgery. Lean body mass was calculated using an approximation formula based on abdominal computed tomography images.

Neoadjuvant palbociclib in women with operable, hormone receptor-positive breast cancer.

The addition of a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor to endocrine therapy augments biological response in breast cancer. This phase III randomized, double-blind study evaluated the efficacy of adding palbociclib to neoadjuvant endocrine therapy (NET) for operable, hormone receptor-positive human epidermal growth factor receptor-2 (HER2)-negative breast cancer. Patients randomly received 16 weeks of endocrine therapy (letrozole for post-menopausal and tamoxifen plus ovarian function suppression for pre/peri-menopausal patients) plus palbociclib or placebo.

Survival After Fertility-Preserving Hormonal Therapy vs Hysterectomy for Early-Stage Endometrial Cancer.

Importance: As the number of young women with early-stage endometrial cancer is increasing, there is growing interest in use of progesterone-based therapy to allow fertility preservation.

Objective: To ascertain the long-term survival of premenopausal women with clinical stage I endometrial cancer treated primarily with fertility-preserving hormonal therapy compared with hysterectomy.

Design, Setting, And Participants: This cohort study used data from the National Cancer Database to identify female patients aged 18 to 49 years with clinical stage I, grade 1 to 2, endometrioid endometrial cancer diagnosed from 2004 through 2020.

Subsequent primary cancer incidence in cervical cancer survivors: insights from a comprehensive cohort study utilizing combined Japanese population-based cancer registries.

Objective: This study aimed to evaluate the incidence of subsequent primary cancer (SPC) among cervical cancer survivors in Japan.

Methods: Data from the cancer registries of Osaka, Kanagawa, and Miyagi prefectures were combined. The cohort included individuals diagnosed with invasive and in situ cervical cancer between 1980 and 2010, with the SPC incidence evaluated until 2015.

Overexpression of Nuclear Factor of Activated T-cells (NFAT) Transcription Factors Drives Chemoresistance and Poor Outcomes in Pancreatic Cancer.

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies with high recurrence and poor survival (5-year survival rate: approximately 10%) despite curative resection. Identifying molecular drivers of PDAC recurrence remains a significant challenge. PDAC is characterized by dense stromal hyperplasia that may influence tumor cell-specific gene expression.

Electronic Patient-Reported Outcome Quality of Life Score in Japanese Patients With Pancreatic Cancer on Second-Line Chemotherapy: A Multicenter Observational Study.

Introduction: Patients' QoL scores during chemotherapy are generally measured during hospital visits. However, patients frequently recover from AEs before hospital arrival. This study continuously assessed each chemotherapy's impact on patients' QoL scores during hospital visits and at home using an electronic device (ePRO).

Dasatinib is superior to imatinib in adult Ph + ALL: a propensity score-matched analysis of pooled JALSG trial data.

This study compared dasatinib and imatinib in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). Using pooled data from three JALSG prospective trials (Ph + ALL202, Ph + ALL208, Ph + ALL213), we analyzed outcomes for 206 patients aged 15-64 years treated with dasatinib (n = 74) or imatinib (n = 132) in combination with chemotherapy. We applied propensity score matching (1:1) and inverse probability of treatment weighting to minimize selection bias and balance baseline characteristics.

Clinical outcomes and prognostic factors of adjuvant radiotherapy for vulvar cancer: a Japanese Gynecologic Oncology Group nationwide survey study.

This study aimed to analyze the clinical outcomes and prognostic factors of postoperative adjuvant radiotherapy (RT) for vulvar cancer based on a retrospective Japanese nationwide survey. Data were collected from 108 institutions for patients diagnosed with vulvar cancer between January 2001 and December 2010. Patients with histologically confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma who underwent curative surgery and adjuvant radiotherapy were included in this study.

Impact of Population Size and Aging on the Efficiency of Cancer Screening in Japanese Municipalities: Insights from Data Envelopment Analysis.

Background: Improving cancer screening participation is increasingly important. However, insufficient medical and financial resources have been reported to hinder program implementation; therefore, enhancing program efficiency is crucial. Although demographic factors have been reported to correlate with public health program efficiency, it remains unclear whether this applies to cancer screening.

First-Line Lenvatinib plus Pembrolizumab for Hepatocellular Carcinoma: Post hoc Analysis of Japanese Patients from the Phase 3 LEAP-002 Trial.

Introduction: The phase 3 LEAP-002 study (NCT03713593) of advanced hepatocellular carcinoma (HCC) suggested improved antitumor activity of lenvatinib plus pembrolizumab versus lenvatinib alone with manageable safety, although overall survival (OS) and progression-free survival (PFS) did not reach prespecified statistical significance. This post hoc analysis assessed efficacy and safety in Japanese patients.

Methods: Patients with advanced HCC without prior systemic treatment were randomly assigned 1:1 to receive 8 mg (body weight <60 kg) or 12 mg (body weight ≥60 kg) oral lenvatinib once daily plus 200 mg intravenous pembrolizumab or placebo every 3 weeks for up to 35 cycles.

Pembrolizumab Plus Chemotherapy Versus Chemotherapy as Perioperative Therapy in Locally Advanced Gastric and Gastroesophageal Junction Cancer: Final Analysis of the Randomized, Phase III KEYNOTE-585 Study.

We report results of the final analysis of overall survival (OS) and patient-reported outcomes from the phase III KEYNOTE-585 (ClinicalTrials.gov identifier: NCT03221426) study. Participants with previously untreated, locally advanced, resectable gastric and gastroesophageal junction (G/GEJ) cancer were enrolled into the main (n = 804) and fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT; n = 203) cohorts, and randomly assigned 1:1 to neoadjuvant and adjuvant pembrolizumab plus chemotherapy or placebo plus chemotherapy.

Has early mortality following single-unit unrelated cord blood transplantation improved in recent years? A nationwide registry data analysis from 2003 to 2022 in Japan.

Unrelated single-unit cord blood transplantation (CBT) is a valuable alternative donor source for patients without matched related or unrelated donors. Although initial concerns included limited cell dose, delayed haematopoietic recovery and higher early mortality, advancements in transplant practices may have led to improved outcomes. However, it remains uncertain whether these improvements extend to the most recent years.

Web-Based Video Intervention and Associated Factors for the Uptake of the Catch-Up Human Papillomavirus Vaccination in Japan: Randomized Controlled Trial.

Background: In Japan, the human papillomavirus (HPV) vaccination rate has dropped to nearly zero since the suspension of proactive government recommendations in 2013. Following the termination of vaccination suspension in 2021 and subsequent proactive vaccination recommendation in 2022, it is crucial to promote catch-up vaccinations for those who missed their initial opportunity.

Objective: This study aims to evaluate the effect of video-based informational intervention and explore factors associated with the uptake of catch-up HPV vaccinations among unvaccinated young adult women in Japan.

Automatic segmentation of cone beam CT images using treatment planning CT images in patients with prostate cancer.

Cone-beam computed tomography-based online adaptive radiotherapy (CBCT-based online ART) is currently used in clinical practice; however, deep learning-based segmentation of CBCT images remains challenging. Previous studies generated CBCT datasets for segmentation by adding contours outside clinical practice or synthesizing tissue contrast-enhanced diagnostic images paired with CBCT images. This study aimed to improve CBCT segmentation by matching the treatment planning CT (tpCT) image quality to CBCT images without altering the tpCT image or its contours.

Lymph node dissection as a local control during segmentectomy for small-sized and radiologically solid dominant and pure solid tumors.

Background: Small-sized, peripherally located, and radiologically solid-dominant or pure solid nonsmall cell lung cancer (NSCLC) tumors are related to lymph node metastasis at a certain frequency. The aim of this study is to disclose the validity of lymph node dissection on oncological local control during segmentectomy for such tumors.

Methods: We investigated the clinicopathological findings, the distribution of the involved lymph nodes, the patterns of lymph node recurrences, and the prognosis of 1921 patients with radiologically-determined ≤3 cm-sized, solid-dominant or pure solid NSCLC tumors without clinical lymph node involvement following complete resections with lobectomy (n = 1472) or segmentectomy (n = 449) between 2010 and 2020.

Prognostic implications of MDM2 expression in surgically resected epidermal growth factor receptor mutant lung cancer with pathological lymph node metastasis.

Background: MDM2 protein regulates p53 protein activity; however, the prognostic impact of MDM2 expression in primary lung cancer on patient prognoses is unknown. This study investigated the prognostic implications of MDM2 protein expression among patients with epidermal growth factor receptor mutant (m) lung adenocarcinoma with pathologic lymph node metastases after surgery.

Methods: Immunohistochemical analysis was conducted to determine the MDM2 expression of pN1-N2 m [exon 19 deletion mutation (Ex19) and exon 21 L858R mutation (Ex21)] lung cancer that were surgically resected between January 2010 and December 2020 (n=124).

MiR-200a regulates PD-L1 and predicts response to immune checkpoint inhibitors in advanced non-small cell lung cancer.

Background: The microRNA (miR)-200 family is implicated in regulating the immune checkpoint protein programmed death-ligand 1 (PD-L1), a key factor in lung cancer progression and response to immunotherapy. This study investigates the relationship between miR-200 expression and PD-L1 in non-small cell lung cancer (NSCLC), aiming to clarify its potential as a prognostic biomarker and a therapeutic target in immune checkpoint inhibitor (ICI) treatment for NSCLC.

Methods: RNA sequencing (RNA-seq) data from public databases were analyzed for correlation between miR-200 family expression and PD-L1 levels in lung cancer.

Tasurgratinib (E7090) for cholangiocarcinoma with fibroblast growth factor receptor 2 fusions/rearrangements: a multicenter, open-label, Phase 2 study.

Background: This Phase 2 study (NCT04238715) evaluated the efficacy/safety of tasurgratinib 140 mg daily in patients with cholangiocarcinoma (CCA) and fibroblast growth factor receptor (FGFR) 2 fusions/rearrangements.

Methods: Eligible Japanese and Chinese patients who had surgically unresectable, advanced, or metastatic CCA and had received ≥1 prior gemcitabine-based combination chemotherapy regimen were included and treated with oral tasurgratinib 140 mg daily. The primary endpoint was objective response rate (ORR); the study was considered successful if the lower limit of the ORRs 90% CI was >15%.

Patient and Physician Preferences for Add-On Systemic Therapy to Transarterial Chemoembolization for Hepatocellular Carcinoma in Japan: A Discrete Choice Experiment.

Introduction: Transarterial chemoembolization (TACE) is the primary treatment for intermediate-stage hepatocellular carcinoma (HCC). Synergistic effects are expected by adding recently developed systemic therapies onto TACE. We investigated patient and physician preferences for this treatment approach.