The Cancer Institute Hospital

In this nationwide retrospective study, we sought to evaluate the oncologic and functional outcomes and safety of transoral surgery (TOS) for hypopharyngeal and laryngeal squamous cell carcinomas in Japan and to clarify the appropriate indications for various TOS modalities. Data were obtained from the Head and Neck Cancer Registry of Japan. Patients who underwent transoral or endoscopic resection between 2011 and 2016 were selected. Detailed clinical information was collected from 55 institutions using web-based case report forms. Surgical modalities analyzed included endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), endoscopic laryngopharyngeal surgery (ELPS), transoral laser microsurgery (TLM), and transoral videolaryngoscopic surgery (TOVS). In total, 1825 patients were included (hypopharyngeal cancer, 62.5 %; laryngeal cancer, 37.5 %). Most cases (77.5 %) were T1 or lower, and 90.8 % were Stage II or earlier. TLM is predominantly used for glottic cancers, ELPS/ESD for superficial hypopharyngeal lesions, and TOVS for more advanced tumors, reflecting distinct indications for each modality. The 5-year disease-specific survival (DSS), recurrence-free survival (RFS), and overall survival (OS) were 97.1 %, 84.3 %, and 85.4 %, respectively. The laryngeal preservation rate was 98.2 %. Tracheostomy was performed in 5.0 % of cases, mainly for airway protection; major complications, including pneumonia (2.4 %), hemorrhage (1.1 %), fistula formation (0.4 %), and vocal cord fixation (2.6 %), occurred in <3 % of patients. Postoperative functional outcomes were favorable, with persistent dysphagia (Functional Outcome Swallowing Scale stage ≥ 3) in 1.6 % and tube feeding dependence in 1.8 %. Non-robot-assisted TOS demonstrated excellent oncologic control and functional preservation of the larynx with low complication rates in early-stage hypopharyngeal and laryngeal cancers. Each surgical modality has distinct indications depending on the tumor site, depth of invasion, and institutional expertise. These findings support the use of TOS as a safe and effective treatment option for selected patients. Further procedural standardization and data accumulation are required to refine the indications and facilitate their broader adoption in clinical practice.

BackgroundA Japanese phase 2 trial of encorafenib plus binimetinib met the primary endpoint of the centrally assessed objective response rate in patients with unresectable BRAF V600E-mutated thyroid cancer. Consequently, encorafenib plus binimetinib has been approved in Japan. We present the health-related quality of life (HR-QoL) outcomes from the trial.MethodsThe multicenter, open-label, uncontrolled phase 2 trial enrolled patients with unresectable locally advanced or metastatic BRAF V600E-mutated thyroid cancer. HR-QoL score, one of the secondary endpoints, was assessed using the EORTC QLQ-C30 and QLQ-THY34 at baseline and during follow-up. The minimal important change (MIC) threshold was set at 10 points.ResultsWe enrolled 22 patients with BRAF V600E-mutated thyroid cancer. The median follow-up was 11.5 months. Completion rates for the questionnaires were 100% (22 of 22 patients) at baseline and 68% (15 of 22) at week 20. Until week 20, changes from baseline were below MIC at most time points in 29 of all 32 domains in QLQ-C30 and QLQ-THY34. In the other 3 domains, patients showed tendencies toward improvement (social support and appetite loss) or deterioration (joint pain) for consecutive time points. Patients with anaplastic thyroid cancer showed tendencies toward improvement for swallowing, restlessness, body image, and discomfort in the head and neck, from the first assessment after the initial treatment.ConclusionThe combination therapy of encorafenib plus binimetinib for unresectable BRAF V600E-mutated thyroid cancer was associated with generally maintained HR-QoL. Considering the efficacy and safety data from the trial, the regimen may provide clinical benefits while maintaining HR-QoL.

Palliative interventional radiology (IR) procedures are effective for managing refractory cancer pain, but their real-world utilization—including procedural volume, physicians’ perceptions, and barriers to implementation—remains unclear. This study aimed to assess the current implementation of these procedures in Japan and to explore IR physicians’ perceptions and barriers. A nationwide cross-sectional survey was conducted among 1,087 board-certified IR physicians in Japan from February to March 2020. A self-administered questionnaire assessed current practice for three procedures (celiac plexus/splanchnic nerve block [nerve block], percutaneous vertebroplasty/osteoplasty [bone augmentation], and transcatheter arterial embolization [TAE]), perceived effectiveness, willingness to perform in the future, and demographics. Barriers to implementation, which were predefined as questionnaire items, were evaluated using univariable and multivariable logistic regression analyses. A total of 554 valid responses were obtained (response rate: 51.1%). Although all respondents were board-certified IR physicians, 52.5% reported diagnostic imaging as their primary practice, and 35.0% were dedicated to IR. Implementation rates were 18.1% for nerve block, 22.6% for bone augmentation, and 51.4% for TAE. Lack of adequate training was the most consistent barrier across all procedures, along with delayed referrals, lack of confidence, limited case volume, time constraints, institutional resource limitations, and insufficient evidence. Perceived effectiveness was high (81.2% for nerve block, 83.1% for bone augmentation, and 62.1% for TAE), whereas willingness to perform was lower (50.2%, 48.4%, and 66.0%). Implementation of palliative IR procedures in Japan remains limited, despite the high perceived effectiveness among IR physicians. Lack of adequate training was the most consistent barrier across all procedures, suggesting that greater availability of training opportunities may help narrow the gap between perceived benefit and actual practice. These findings highlight a clinically important mismatch: procedures viewed as effective for refractory cancer pain are not reaching patients who might benefit from them.

Abstract Background: We are conducting an ongoing project using archival tissue samples from primary breast cancer cases treated with surgery alone at our institution, without any adjuvant systemic therapy. Tissue microarrays (TMAs) have been constructed, and various protein expressions are being re-evaluated using contemporary immunohistochemical techniques. This treatment-naïve cohort provides a unique opportunity to assess the intrinsic prognostic significance of biomarker expression, free from the confounding effects of systemic therapy. Androgen receptor (AR) is a steroid hormone receptor expressed in a subset of breast cancers and has attracted growing interest as a potential prognostic and therapeutic marker. Forkhead-box protein A1 (FOXA1) is a pioneer transcription factor known to act as a super-enhancer of the estrogen receptor (ER), playing a crucial role in mammary gland development. It is well established as a favorable prognostic marker in ER-positive, HER2-negative breast cancer. In recent years, however, FOXA1 expression has also been reported in other subtypes, including ER-negative tumors, although its clinical significance in these contexts remains uncertain. Whether FOXA1 functions primarily as a true prognostic marker or rather as a surrogate for endocrine responsiveness remains an open question. In this study, we report the results of immunohistochemical analyses for AR and FOXA1 in a treatment-naïve historical cohort, aiming to clarify their intrinsic prognostic relevance across breast cancer subtypes. Methods: We retrospectively analyzed primary breast cancer cases operated on at our institution between 1979 and 1982, from which TMAs were constructed by sampling three representative areas of the invasive tumor component. All pathological features, including immunohistochemical markers, were re-evaluated using current standardized protocols. Clinical outcomes were obtained from institutional records. Results: Among 935 eligible cases, 758 were available for AR and FOXA1 immunohistochemical evaluation. Subtype distribution based on ER and HER2 status was as follows: ER+/HER2− (n = 538, 71.3%), ER+/HER2+ (n = 47, 6.2%), ER−/HER2+ (n = 74, 9.8%), and ER−/HER2− (n = 96, 12.7%), comparable to current subtype frequencies. Using a 10% cutoff for positivity, AR expression was observed in 69.1% of ER+/HER2−, 57.5% of ER+/HER2+, 44.6% of ER−/HER2+, and 16.7% of ER−/HER2− tumors. In survival analysis, strong AR expression was significantly associated with improved distant recurrence-free survival (DRFS) (p = 0.0239). FOXA1 expression, using the same cutoff, was detected in 96.4% of ER+/HER2−, 100% of ER+/HER2+, 92.9% of ER−/HER2+, and 23.2% of ER−/HER2− tumors. Notably, FOXA1 was expressed in a subset of ER-negative tumors. FOXA1 expression was not significantly associated with DRFS, including in ER-positive tumors. In the ER−/HER2− subtype, although no significant difference in DRFS was observed based on Kaplan-Meier analysis, among patients who experienced recurrence, those with FOXA1-positive tumors had a significantly longer disease-free interval (DFI) (p = 0.0005). Conclusion: In this historical cohort of breast cancer patients untreated with adjuvant therapy, strong AR expression was significantly associated with improved DRFS. FOXA1 was expressed across all intrinsic subtypes and, contrary to previous reports, did not demonstrate prognostic significance in ER-positive tumors in the absence of systemic therapy. These findings suggest that FOXA1 may be more reflective of endocrine responsiveness rather than intrinsic tumor aggressiveness. The observation that FOXA1-positive tumors had a longer DFI suggests a potential role in late recurrence, particularly in ER-negative subtypes, and warrants further investigation. Citation Format: Y. Inoue, T. Osako, M. Akiya, T. Chiba, Y. Haruyama, U. Nakadaira, J. Masuda, Y. Kimura, A. Iesato, M. Nishimura, Y. Ozaki, T. Maeda, N. Uehiro, N. Yamashita, T. Kobayashi, T. Sakai, T. Takano, T. Ueno. Androgen receptor and FOXA1 in breast cancer: Prognostic insights from a treatment-naïve historical cohort [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-01-12.

<title>Abstract</title> Purpose This study was conducted to confirm the actual opioid conversion ratios (CRs) and opioid rotation ratios (ORRs) in clinical practice in Japan. Methods A cross-sectional survey was conducted between March 7th to 20th, 2024, targeting palliative care physicians and pharmacists in the following three societies: Japanese Society for Palliative Medicine, Japanese Society for Pharmaceutical Palliative Care and Sciences, and Japanese Association of Supportive Care in Cancer. The primary endpoint was to determine the CRs and ORRs used by participants, which were measured in the survey. Results 433 responses (68.1% physicians and 31.9% pharmacists) were received. 30.3% conducted &gt; 30 opioid rotations in the past 6 months. For most CRs and ORRs obtained from all the participants, values for the median, first quartile, third quartile, and mode were consistent. Among groups of professions and number of opioid rotations frequency, there were no differences in the median opioid ratios involving morphine, hydromorphone and oxycodone. However, there were significant differences in the ORRs involving intravenous (IV) fentanyl, specifically in the rotation ratios between IV fentanyl and IV morphine. Conclusion There was great consistency in the CRs and ORRs used by physicians and pharmacists in palliative care in Japan. This would suggest that education on the ratios is well established for medical professionals in Japan.

In cancer patients, malnutrition worsens postoperative outcomes, with increased complications and poor prognosis. We aimed to update the impact of malnutrition, as defined by the Global Leadership Initiative on Malnutrition (GLIM) criteria, on postoperative outcomes in patients with gastroenterological cancer after curative resection. We identified observational studies published from inception to April 2, 2025. A systematic review and random-effects meta-analysis were performed on studies including adult patients (age > 18 years) with gastroenterological cancer who received surgical treatment and had nutritional status assessments based on GLIM criteria. The primary outcomes were overall survival (OS) and overall postoperative complications, which were defined as events with a Clavien-Dindo (CD) grade ≥ II that occurred within 30 days after surgery. Hazard ratios and relative risk ratios for OS and postoperative complications, respectively, with 95% confidence intervals were pooled. The protocol has been published in PROSPERO (CRD42023434267). Twenty-five studies (28 reports comprising 10 942 patients) were included in the qualitative and quantitative syntheses. Compared with the absence of malnutrition, GLIM-defined malnutrition probably worsens OS (hazard ratio: 1.88, 95% concordance interval: 1.62-2.18, certainty of the evidence: low) and increases postoperative complications (relative risk ratio: 1.57, 95% concordance interval: 1.34-1.84, certainty of the evidence: low). The risk of bias in each study was moderate or high. GLIM-defined malnutrition probably worsens OS and increases the risk of postoperative complications in patients with gastroenterological cancer after surgery.

Repeat sentinel lymph node biopsy (re-SLNB) is increasingly performed in patients with ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS). However, evidence on its feasibility and postsurgical lymphatic alterations remains limited. We evaluated the clinical feasibility and drainage patterns of re-SLNB in patients with IBTR who were initially diagnosed with sentinel node-negative (pN0sn) disease but did not undergo axillary lymph node dissection (ALND). We retrospectively reviewed patients who developed IBTR after BCS and sentinel lymph node biopsy (SLNB; pN0sn) at our institution, between January 2000 and December 2019. All patients underwent re-SLNB guided by preoperative radioisotope lymphoscintigraphy; ALND was omitted if re-SLNB was negative. Clinicopathological data were obtained from institutional databases and medical records. Among the 97 eligible patients, 75 (group 1) had sentinel lymph nodes (SLN) identified, retrieved, and confirmed as negative in the ipsilateral axilla, and 22 (group 2) had no SLN identified in the ipsilateral axilla, including those with drainage to alternative basins. In group 1, successful mapping and negative re-SLNB were associated with low axillary recurrence (1.8%) and distant recurrence (4.5%) during a median follow-up of 73 months. Re-SLNB using preoperative radioisotope lymphoscintigraphy is technically feasible in most patients with IBTR and a prior pN0sn status. These findings support re-SLNB as a reliable and less invasive alternative to ALND in appropriately selected patients, suggesting the importance of preoperative lymphatic mapping for surgical planning.

BackgroundChemotherapy selection traditionally relies on tumor tissue of origin. However, since genetic alterations drive tumor behavior, it remains unclear if mutations can better predict response. We hypothesized that genetic aberrations might influence chemotherapy outcomes more than tissue origin.MethodsWe retrospectively analyzed 15,474 Japanese patients with solid tumors who underwent comprehensive genomic profiling (CGP) and received cytotoxic chemotherapy. Genetic alterations and tumor origin were evaluated for objective response rate (ORR) and time to next treatment (TNT). Gene mutations were assessed across five chemotherapy classes: platinum-based, alkylating agents, antimetabolites, microtubule inhibitors, and topoisomerase inhibitors.ResultsGenomic alteration data alone did not surpass organ-based models in predicting response. For platinum-based agents, the gene-only model had an AUC of 0.575 versus 0.604 for the organ-only model. A combined gene-organ model yielded an AUC of 0.618 (P < 0.01). Certain gene-organ interactions were associated with improved outcomes. For example, APC-mutated colorectal cancer showed higher ORR and prolonged TNT (hazard ratio, 0.82; 95% CI, 0.73–0.92; P < 0.001) for platinum-based drugs.ConclusionsWhile genetic alterations alone did not outperform tumor origin as a predictor, incorporating both may improve exploratory predictions of chemotherapy response. These exploratory findings require prospective validation before any clinical application.

PurposeThis study evaluated the safety and preliminary efficacy of zolbetuximab plus chemotherapy in patients with claudin 18 isoform 2 (CLDN18.2)-positive advanced gastric cancer (AGC).MethodsThis single-institutional retrospective study enrolled patients with HER2-negative CLDN18.2-positive AGC who were treated with zolbetuximab plus chemotherapy between July 2024 and August 2025.ResultsThe cohort included 50 patients with a median age of 63 years (range 30–83; 44% male). The primary tumor location was the stomach in 86% of the patients. Meanwhile, 26% of the patients underwent prior gastrectomy. The PD-L1 combined positive score was < 5 in 87% of patients. Among 24 patients with measurable lesions at baseline, the objective response and disease control rates were 66.7% and 87.5%, respectively. After median follow-up of 7.3 months, median progression-free survival and the duration of response were 6.7 [95% confidence interval (CI) 5.3–10.7] and 6.7 months (95% CI 4.7–10.2), respectively. Grade ≥ 3 treatment-emergent adverse events occurred in 62% of the patients, most commonly hypoalbuminemia (22%), neutrophil count decreased (22%) and anorexia (12%). Subsequent treatment was received by 83% of the patients.ConclusionsZolbetuximab plus chemotherapy was administered to real-world patients with CLDN18.2-positive AGC with acceptable safety profiles and showed preliminary antitumor efficacy. Nevertheless, some adverse events warrant careful monitoring.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00432-025-06406-4.