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Background: Adjuvant chemotherapy is the conventional treatment for stage II and III gastric cancer(GC). Postoperative doublet chemotherapy has consistently shown improved survival outcomes in advanced-stage GC patients compared to single-agent regimens. Triplet regimens have shown significant survival benefits in the perioperative settings. This retrospective study evaluated the efficacy and safety of paclitaxel/S-1/oxaliplatin (PSOX) compared to S-1/oxaliplatin (SOX) as postoperative adjuvant chemotherapy in stage II-III GC patients following D2 gastrectomy. Methods: A retrospective review was conducted on patients with histologically confirmed stage II-III gastric cancer who underwent D2 gastrectomy at Jiangsu Cancer Hospital, categorizing them into two groups. A total of 75 patients were included in PSOX group and 81 patients in the SOX group between April 2018 and August 2021. Patients in PSOX group received paclitaxel (120 mg/m2), oxaliplatin (100 mg/m2) and S-1 (80 − 60 mg/d) per cycle, while those patients in SOX group were administrated oxaliplatin (130 mg/m2) and S-1 (80–120 mg/d) per cycle. Patients from both groups were matched in a 1:1 ratio using propensity scores to assess differences in disease-free survival (DFS) and safety. Results: The 3-year DFS rate was 78.2% for the PSOX group and 74.0% for the SOX group (P = 0.355), with a hazard ratio for peritoneal relapse of 0.287 (95% CI, 0.090–0.915; P = 0.035). Subgroup analysis indicated that stage IIIC GC patients in the PSOX group had a higher DFS rate than those in the SOX group(P = 0.032). Grade 3 or 4 adverse events, as per the National Cancer Institute Common Toxicity Criteria, such as leucopenia (10.6% vs. 4.5%), neutropenia (10.6% vs. 9.1%), nausea/vomiting (4.5% vs. 3.0%), and diarrhea (4.5% vs. 3.0%) were relatively common in the PSOX group compared to the SOX group, with no statistically significant differences between the two groups. Conclusion: Our findings suggested that adjuvant PSOX chemotherapy offers superior survival benefits compared to the SOX regimen in patients with staged IIIC GC after D2 gastrectomy. The incidence of adverse events with PSOX chemotherapy was comparable to that of SOX chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: S-1, an oral multicomponent capsule containing tegafur, gimeracil, and potassium oxonate, has demonstrated efficacy in various tumor types. This study aimed to assess the pharmacokinetics, bioequivalence (BE), and safety of a newly developed generic S-1 capsule compared to the original brand-name formulation in Chinese cancer patients under fasting and fed conditions. Methods: A multicenter, randomized, open-label, single-dose, double-cycle crossover study was conducted in Chinese cancer patients. The study involved 120 subjects, with 60 assigned to the fasting group and another 60 to the fed group. In each study cycle, subjects were randomly assigned toreceive either the reference or test S-1 capsule at a 7-day interval. Blood samples were collected for analysis within 48 h after ingestion. The plasma concentrations of tegafur, 5-fluorouracil, gimeracil, and potassium oxonate were determined by liquid chromatography–tandem mass spectrometry (LC-MS/MS). The main pharmacokinetic (PK) parameters were calculated using the non-compartmental approach. BE was assessed through geometric mean ratios (GMRs) between the two formulations and their respective 90% confidence intervals (CIs). The safety of the two formulations was also evaluated. Results: The pharmacokinetics of the two formulations were similar under both fasting and fed conditions. The 90% CIs of the GMRs for the maximum observed serum concentration (Cmax), AUC0-t, and AUC0- ∞ ratios were observed to lie within the BE acceptance range of 80%–125%. Both formulations of the S-1 capsule exhibited similar adverse events (AEs), primarily including decreased white blood cell count and hypertension. These AEs were generally mild and transient. The safety profiles of the two formulations were found to be good and comparable, with no serious adverse events (SAEs) reported. Conclusion: The newly developed generic S-1 and reference formulations exhibit comparable PK in Chinese cancer patients in the fasting and fed state. The formulations of S-1 showed good tolerability and a similar safety profile. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/index.html, identifier CTR20171562. [ABSTRACT FROM AUTHOR]

Background: S-1 monotherapy had previously been widely used as a second-line treatment for pancreatic cancer (PC) after gemcitabine-based chemotherapy mainly in Japan. Based on the results of the NAPOLI-1 trial, the recommended second-line therapy is now liposomal irinotecan plus fluorouracil/folinic acid (nal-IRI + 5-FU/LV). However, there have been no studies comparing nal-IRI + 5-FU/LV therapy with S-1 monotherapy. Methods: The main objective of this study was to compare overall survival (OS) in patients treated with nal-IRI + 5-FU/LV and those treated with S-1 monotherapy as second-line treatments, using the inverse probability of treatment weighting (IPTW) method. This study was conducted in 31 institutions participating in Japan Oncology Network in Hepatobiliary and Pancreas. To minimize potential biases due to the retrospective design, IPTW analysis was performed with multiple imputation, and imputed IPTW-adjusted hazard ratios and corresponding 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model and combined into pooled estimates. Results: A total of 463 metastatic PC patients were enrolled in this study (257 in the S-1 monotherapy group and 206 in the nal-IRI + 5-FU/LV group). The median OS was 7.50 months (95% CI 4.18–12.69 months) in the nal-IRI + 5-FU/LV group and 5.72 months (95% CI 2.76–10.79 months) in the S-1 monotherapy group. In the IPTW-adjusted Cox proportional hazards model, nal-IRI + 5-FU/LV was associated with a significant OS benefit (pooled IPTW-adjusted hazard ratio, 0.779; 95% CI 0.399—0.941; p = 0.025). Conclusion: These findings support the use of nal-IRI + 5-FU/LV as standard second-line treatment for PC patients after gemcitabine-based chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to compare outcomes and adverse events between three-dimensional conformal radiation therapy (3D-CRT) and intensity-modulated radiation therapy (IMRT) in patients undergoing long-course neoadjuvant radiation therapy (NA-RT) for locally advanced rectal adenocarcinoma (LARC). Methods: We retrospectively analyzed a total of 47 consecutive patients who received NA-RT for LARC between January 2011 and September 2022. Seven and 40 patients were diagnosed with clinical stages II and III, respectively. The prescribed dose per fraction was 1.8 Gy for total doses of 45 or 50.4 Gy. Seventeen and 30 patients received 3D-CRT and IMRT, respectively. NA-RT was delivered with concurrent chemotherapy of oral administration of S-1. Results: Planned NA-RT was completed without any treatment interruption in 43 of the 47 patients. Two patients experienced treatment interruption, and two patients discontinued due to grade ≥ 3 toxicities. No significant differences were observed between patients receiving 3D-CRT and IMRT in local control, progression-free survival, and overall survival (P = 0.488, 0.259, and 0.636, respectively). Patients receiving IMRT showed significantly fewer non-hematological grade ≥ 2 acute toxicities than those receiving 3D-CRT (33.3% vs. 70.6%, P = 0.018). In addition, patients who received IMRT tended to have less intestinal toxicity of grade ≥ 2 than those who received 3D-CRT (P = 0.057). Conclusion: IMRT significantly reduced grade ≥ 2 acute toxicities without compromising oncologic outcomes compared to 3D-CRT. Therefore, IMRT may be considered as a current standard treatment in the total neoadjuvant therapy era. [ABSTRACT FROM AUTHOR]

Background: Metastatic colorectal cancer (mCRC) remains a significant clinical challenge, particularly for patients who have failed standard first- and second-line therapies. Despite advancements in targeted therapies, options for third-line treatments are limited, with current regimens such as regorafenib, fruquintinib, and TAS-102 demonstrating modest efficacy. The RS regimen, combining raltitrexed and S-1, has shown improved objective response rates (ORR) and progression-free survival (PFS) compared to standard therapies. Fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, has also demonstrated efficacy in heavily pretreated mCRC patients, including those resistant to prior anti-VEGF therapies. Combining these agents in the RSF regimen leverages complementary mechanisms of action to address resistance and improve outcomes. Methods: This multicenter, prospective, single-arm, open-label Phase II clinical trial evaluates the efficacy and safety of the RSF regimen in mCRC patients who have failed first- and second-line therapies. Eligible patients will receive S-1 orally (14 days), raltitrexed intravenously (day 1), and fruquintinib orally (14 days) in a 21-day cycle. The primary endpoint is ORR, assessed using RECIST v1.1 criteria. Secondary endpoints include PFS, overall survival (OS), disease control rate (DCR), and quality of life (QoL). Safety will be monitored per NCI-CTCAE v4.0 criteria. Discussion: The RSF regimen represents a novel approach to third-line treatment in mCRC, integrating chemotherapy and targeted therapy to enhance tumor response while managing toxicity. By leveraging complementary mechanisms of action, this study aims to optimize therapeutic outcomes in heavily pretreated patients. Further clinical research is essential to validate efficacy, safety, and potential biomarkers for patient selection. Trial registration: ClinicalTrials.gov identifier: NCT06427005, registered on 19 June 2024. [ABSTRACT FROM AUTHOR]

Background: Interstitial pneumonia is a group of pathologies affecting the pulmonary interstitium, characterized by interstitial fibrosis and extensive alveolar consolidation. This disease can extend to the surrounding blood vessels and pulmonary interstitium, sometimes affecting the entire lung, resulting in functional limitations, including restrictive ventilatory defect, impaired gas exchange, and hypoxemia. Severe interstitial pneumonia can lead to death. Antitumor drugs can induce interstitial pneumonia. Sintilimab is an immune checkpoint inhibitor, a recombinant fully human immunoglobulin G-type programmed death protein-1 monoclonal antibody inhibitor. S-1 is a compound preparation consisting of gimeracil, oteracil potassium, and ftorafur. There have been cases of interstitial pneumonia caused by treatment with sintilimab or S-1 in clinical settings, but no cases of interstitial pneumonia caused by treatment with a combination of sintilimab and S-1 have been reported. Case report: A patient diagnosed with gastric cancer underwent nine courses of treatment using a chemotherapy regimen of combined oxaliplatin S-1., Due to severe bone marrow suppression and gastrointestinal adverse reactions, the treatment was switched to sintilimab in combination with S-1therapy., This change resulted in the development of interstitial pneumonia, as revealed by non-contrast chest Computed Tomography scans. Following a review of blood test results and a multidisciplinary consultation, we suspect that the interstitial pneumonia may have been caused either by Sintilimab alone or by the combined effects of sintilimab and S-1. The treatment was discontinued, and after receiving adequate glucocorticoid therapy, the pulmonary lesions showed slight improvement. Conclusion: This case provides a clinical reference, indicating that prior touse of sintilimab in combination with S-1 antitumor regimen, a comprehensive baseline assessment should be conducted, including blood routine examination, enzyme tests, and pulmonary imaging examination, with close monitoring of the patient's pulmonary condition. If drug-induced lung injury is suspected, the medication should be discontinued immediately, and appropriate treatment should be initiated promptly. [ABSTRACT FROM AUTHOR]

Purpose: Body weight loss after surgery for gastric cancer is related to S-1 compliance and it also affects the prognosis. However, it is unclear whether the preoperative skeletal muscle mass affects S-1 completion for gastric cancer. We investigated the impact of preoperative skeletal muscle mass loss on the completion of S-1 adjuvant chemotherapy for gastric cancer. Methods: We retrospectively analyzed data from 53 patients who underwent curative gastrectomy followed by adjuvant S-1 monotherapy for pStage II–III gastric cancer between 2012 and 2021 at our hospital. The psoas muscle mass index (PMI) was used as the index for preoperative skeletal muscle mass. Results: Thirty-six patients completed S-1 treatment and 17 discontinued treatment. The patients who completed S-1 treatment had a longer overall survival than those who discontinued treatment (log-rank test, p = 0.043). According to a univariate analysis, the patients in the discontinuation group had a significantly lower preoperative body mass index (< 22.9 kg/m2, p = 0.005) and a higher rate of adverse events (grade 2 or higher, p < 0.001) than those in the completion group. According to a multivariate analysis, preoperative PMI (HR 3.563, p = 0.030) was an independent predictive factor for S-1 completion. Conclusion: Preoperative skeletal muscle loss might therefore prevent the completion of adjuvant chemotherapy S-1 in patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Background: It is essential to ensure optimal adherence to adjuvant chemotherapy regimens following gastric cancer surgery. However, treatment intensity for S-1 as adjuvant chemotherapy has not as yet been compared between minimally invasive (MI) and open (Open) surgery. Methods: We retrospectively compared dose modification of adjuvant S-1 between MI and Open surgery in patients undergoing R0 gastrectomy for gastric or esophago-gastric junction cancer at the Cancer Institute Hospital Tokyo, Japan, during the period from 2012 to 2022, and receiving S-1 for pStage II or S-1 plus docetaxel for pStage III as adjuvant chemotherapy. Propensity score matching (PSM) was conducted to adjust for possible confounders. Results: In total, 323 patients were initially included. After PSM, 158 patients remained, 79 in each group. The adjuvant chemotherapy completion rates were similar in the two groups. However, the proportion of patients who required S-1 dose reduction was significantly lower in the MI than in the Open group (43.0% vs. 65.8%, p = 0.004). In addition, the MI group had significantly fewer patients requiring suspension of S-1 than the Open group (46.8% vs. 64.6%, p = 0.025). Moreover, the frequency of adverse events of grade ≥ 3 was significantly lower in the MI than in the Open group (17.7% vs. 31.7%, p = 0.042). Conclusions: In adjuvant chemotherapy for gastric cancer, minimally invasive surgery may offer better treatment intensity for oral S-1 administration than open surgery. [ABSTRACT FROM AUTHOR]

Purpose The prognosis for type 4 and large type 3 gastric cancer (GC) is extremely poor, especially in elderly patients (≥ 75 years). To improve the prognosis of these types of GC, we performed a phase I study to determine the recommended dose (RD) of S-1 combined with neoadjuvant radiotherapy. Methods Patients with clinically resectable type 4 and large type 3 GC were enrolled to successive cohorts in a conventional 3 + 3 design. Three dose levels were designed, as follows: level 0: S-1 60 mg/m2/day on Days 1–14; level 1: S-1 80 mg/m2/day on Days 1 –14; level 2: S-1 80 mg/m2/day on Days 1–14 and Days 22–35. The starting dose was level 1. Radiotherapy was delivered at a total dose of 40 Gy in fractions for 4 weeks. Results Ten patients were enrolled from July 2014 to August 2018. Six patients were registered at level 1, and one patient developed a dose limiting toxicity as gastric stenosis (grade 3). Two of four patients enrolled at level 2 developed dose limiting toxicity (inability to receive S-1 for hematological reasons). Therefore, the RD was determined as level 1. All patients underwent the protocol surgery; one patient underwent R1 resection because of positive peritoneal washing cytology. There were no treatment-related deaths, and the pathological response rate was 80%. The 5-year overall- and progression-free survival rates were both 60.0%. Conclusion The RD was determined as level 1. A phase II trial using the RD should be initiated. [ABSTRACT FROM AUTHOR]

ObjectiveS-1, an oral multicomponent capsule containing tegafur, gimeracil, and potassium oxonate, has demonstrated efficacy in various tumor types. This study aimed to assess the pharmacokinetics, bioequivalence (BE), and safety of a newly developed generic S-1 capsule compared to the original brand-name formulation in Chinese cancer patients under fasting and fed conditions.MethodsA multicenter, randomized, open-label, single-dose, double-cycle crossover study was conducted in Chinese cancer patients. The study involved 120 subjects, with 60 assigned to the fasting group and another 60 to the fed group. In each study cycle, subjects were randomly assigned toreceive either the reference or test S-1 capsule at a 7-day interval. Blood samples were collected for analysis within 48 h after ingestion. The plasma concentrations of tegafur, 5-fluorouracil, gimeracil, and potassium oxonate were determined by liquid chromatography–tandem mass spectrometry (LC-MS/MS). The main pharmacokinetic (PK) parameters were calculated using the non-compartmental approach. BE was assessed through geometric mean ratios (GMRs) between the two formulations and their respective 90% confidence intervals (CIs). The safety of the two formulations was also evaluated.ResultsThe pharmacokinetics of the two formulations were similar under both fasting and fed conditions. The 90% CIs of the GMRs for the maximum observed serum concentration (Cmax), AUC0-t, and AUC0-∞ ratios were observed to lie within the BE acceptance range of 80%–125%. Both formulations of the S-1 capsule exhibited similar adverse events (AEs), primarily including decreased white blood cell count and hypertension. These AEs were generally mild and transient. The safety profiles of the two formulations were found to be good and comparable, with no serious adverse events (SAEs) reported.ConclusionThe newly developed generic S-1 and reference formulations exhibit comparable PK in Chinese cancer patients in the fasting and fed state. The formulations of S-1 showed good tolerability and a similar safety profile.Clinical Trial Registrationhttp://www.chinadrugtrials.org.cn/index.html, identifier CTR20171562.

BackgroundInterstitial pneumonia is a group of pathologies affecting the pulmonary interstitium, characterized by interstitial fibrosis and extensive alveolar consolidation. This disease can extend to the surrounding blood vessels and pulmonary interstitium, sometimes affecting the entire lung, resulting in functional limitations, including restrictive ventilatory defect, impaired gas exchange, and hypoxemia. Severe interstitial pneumonia can lead to death. Antitumor drugs can induce interstitial pneumonia. Sintilimab is an immune checkpoint inhibitor, a recombinant fully human immunoglobulin G-type programmed death protein-1 monoclonal antibody inhibitor. S-1 is a compound preparation consisting of gimeracil, oteracil potassium, and ftorafur. There have been cases of interstitial pneumonia caused by treatment with sintilimab or S-1 in clinical settings, but no cases of interstitial pneumonia caused by treatment with a combination of sintilimab and S-1 have been reported.Case reportA patient diagnosed with gastric cancer underwent nine courses of treatment using a chemotherapy regimen of combined oxaliplatin S-1., Due to severe bone marrow suppression and gastrointestinal adverse reactions, the treatment was switched to sintilimab in combination with S-1therapy., This change resulted in the development of interstitial pneumonia, as revealed by non-contrast chest Computed Tomography scans. Following a review of blood test results and a multidisciplinary consultation, we suspect that the interstitial pneumonia may have been caused either by Sintilimab alone or by the combined effects of sintilimab and S-1. The treatment was discontinued, and after receiving adequate glucocorticoid therapy, the pulmonary lesions showed slight improvement.ConclusionThis case provides a clinical reference, indicating that prior touse of sintilimab in combination with S-1 antitumor regimen, a comprehensive baseline assessment should be conducted, including blood routine examination, enzyme tests, and pulmonary imaging examination, with close monitoring of the patient’s pulmonary condition. If drug-induced lung injury is suspected, the medication should be discontinued immediately, and appropriate treatment should be initiated promptly.

Background: Lacrimation and corneal epithelial damage have been reported in cancer patients receiving chemotherapy with S-1: a combination of tegafur, gimeracil and oteracil potassium. Furthermore, recent studies have revealed that corneal nerves contribute to preservation of ocular surface homeostasis by facilitating protection and healing of corneal epithelium, and by regulating tear secretion. Thus, the adverse effects of S-1 on ocular surface are predicted to involve abnormalities of corneal nerves, as well as the trigeminal ganglion and trigeminal nucleus in the brain stem, where cell bodies of corneal nerves and their central terminals are located. Aims & Objectives: This study investigated the relationship between the toxic effects of S-1 on the ocular surface and neurological alteration of corneal neurons in peripheral and central nervous systems of rats. Method: S-1 (vehicle, 2 or 5 mg/kg) was orally administered to male Wistar rats (6 weeks old) for 28 consecutive days. To evaluate ocular surface pathology, tear volume, corneal epithelial damage and number of blinks were measured every week. At the end of administration period, the corneas were collected; all nerve fibers and peptidergic nerve fibers in the cornea were stained with anti-tublin β III and anti-CGRP antibodies by a whole-mount staining technique. At the same time, the trigeminal ganglia and nuclei were also collected and embedded in paraffin. Expression of GFAP and Iba1 that are neuroinflammation marker were subsequently immunohistochemically visualized using the sections. All images were analyzed using Image J software. Results: Administration of S-1 led to slight increases in the number of blinks and the corneal epithelial damage score, although there was no difference in tear volume between vehicle and S-1 groups. In the cornea, treatments of 2 and 5 mg/kg S-1 for 4 weeks significantly increased the densities of nerve fibers labeled by antitubulin ß III antibody 1.28- and 1.91-fold, respectively. One week after starting S- 1 administration at 5 mg/kg, an increase in nerve density was observed. The ratio of CGRP-positive peptidergic nerves among tubulin β III-positive nerves remained consistent between the vehicle and S-1 groups. In the trigeminal ganglion, the Iba1-positive area in 5 mg/kg S-1 group significantly increased 1.58-fold compared with that in the vehicle group, whereas the GFAP-positive area tended to increase in the 5 mg/kg S-1 group. There was no statistical difference in GFAP- and Iba1-positive area in the trigeminal nucleus. Discussion & Conclusions: Administration of S-1 induced mild corneal damage and abnormality of blink behavior in rats, although ocular symptoms in patients undergoing S-1 chemotherapy are reported to be severe. However, we found that S-1 treatment resulted in significant increases in both total and peptidergic corneal nerves that accompanied by neuroinflammation of the trigeminal ganglion. In future, we will further investigate the relationship between morphological alterations of corneal nerves and epithelial damage, and the neurophysiological changes in corneal nerves under S-1 treatment. [ABSTRACT FROM AUTHOR]

A 71-year-old woman diagnosed with unresectable locally advanced pancreatic cancer was initially treated with gemcitabine and nab-paclitaxel as first-line therapy. The tumor exhibited no significant progression; however, after 12 cycles, the patient developed drug-induced interstitial pneumonia, leading to the discontinuation of gemcitabine and nab-paclitaxel therapy. Following recovery from pneumonia, S-1 therapy was initiated as second-line treatment. During S-1 therapy, she was hospitalized because of impaired consciousness and was subsequently diagnosed with hyperammonemia induced by S-1. Although rarely reported, S-1-induced hyperammonemia is potentially a significant adverse effect. Here, we herein report the case of a patient with pancreatic cancer.

The nationwide registry of the Japanese Gastric Cancer Association contains data related to the efficacy of adjuvant chemotherapy and prognostic factors across this patient population; elderly patients with advanced resectable gastric cancer are especially prevalent. Here, we analyzed data from 34,931 patients, who were treated between 2011 and 2013 at 421 hospitals in Japan. Although adjuvant chemotherapy was effective overall, 75 years or older elderly patients had a worse prognosis compared to younger patients. The most administered adjuvant chemotherapy was S-1 monotherapy. Adjuvant S-1 monotherapy was also effective for patients with pT1N2, pT1N3, and pT3N0 stage II tumors, as well as patients with other stage II and III malignancies. Independent prognostic factors for poor overall and relapse-free survival in patients at both stage II and stage III were age 75 or older, male, preoperative Eastern Cooperative Oncology Group performance status (ECOG-PS) 1 or more, preoperative renal dysfunction, undifferentiated adenocarcinoma, undergoing total gastrectomy, open laparotomy, no adjuvant chemotherapy, D1 lymphadenectomy, residual tumor R1 or R2, and Clavien-Dindo classification grade II or higher. Age 75 or older, renal dysfunction, ECOG-PS 1 and total gastrectomy were also significant risk factors for postoperative complications and lower compliance with adjuvant chemotherapy. Our analysis also revealed that adjuvant chemotherapy after resection of cancer of gastric remnant and postoperative chemotherapy against CY1 gastric cancer were also effective. We conclude that adjuvant chemotherapy is effective for all stage II and III patients including age 75 or older gastric cancer patients, in addition to distal gastrectomy, proximal gastrectomy, and pylorus-preserving surgery to avoid total gastrectomy may improve surgical outcomes and quality of life for elderly patients., Competing Interests: Yamada Y, Seto Y, Kodera Y, Doki Y, Yoshida K, Kumamaru H, Tachimori H, Sasako M, Katai H, Konno H have no conflicts of interest to disclose. Yoshikawa T has received honoraria from Chugai, Taiho, Daiichi Sankyo, Ono, Medtronic, Bristol- Myers Squibb (BMS), Janssen, AstraZeneca, Intuitive Surgical, Olympus, Astellas, Terumo, research funding from Lilly, and advisory role for MSD. Takeuchi H has received research funding and honoraria from Taiho. Kitagawa Y has received research funding and honoraria from Chugai, Taiho, honoraria from Kyowa Kirin, BMS, Nippon Kayaku, MSD, research funding from Ono, Daiichi Sankyo, Takeda. Muro K has received honoraria from BMS, Ono, MSD, Taiho, Takeda, Daiichi Sankyo, Eli Lilly, and research funding from Astellas, Amgen, Sanofi, Novartis, Parexel International, PRA Health Sciences, Taiho, MSD, Chugai, and Ono. Kabeya Y and Kamada A are employees of IBM Japan. Nagashima K received consulting and advisory fees from SENJU Pharmaceutical, Toray Industries, and Kowa Company. Kakeji Y has received research funding and honoraria from Taiho., (2025, National Center for Global Health and Medicine.)

Background: The recommended treatment for gastric cancer with positive peritoneal cytology (CY1) is primary surgery and S-1 chemotherapy, with 5-year overall survival rates of 24.6%-30.2% reported in previous studies. However, it is unclear whether this strategy is applicable in cases of Type 4 or large Type 3 tumors, which have malignant characteristics and are considered to have different chemosensitivities., Methods: The present study examined the survival of patients who were diagnosed with gastric cancer with CY1, without any other macroscopic distant metastasis, who underwent primary gastrectomy with D2 or more lymph node resection, achieved curative resection except for CY1-positive, and received S-1 postoperative chemotherapy between 2000 and 2017. Patients were divided into the S group (Type 4 or large Type 3 GC) and C group (common GC types)., Results: Among the 352 patients who underwent gastrectomy with CY1, 40 patients were analyzed as the S group and 28 patients as the C group in this study. Both groups were similar in age and ASA-PS, but the S group had more female patients and larger tumors. The median duration of S-1 chemotherapy was 273 days in the S group and 358.5 days in the C group, with similar 1-year continuation rates. The median overall survival of these patients was 24.1 months in the S group and 45.6 months in the C group, with a 5-year survival rate of 23.7% in the S group and 22.0% in the C group. There was no significant difference. Recurrence occurred in 35 patients in the S group and 20 in the C group, with peritoneal metastasis as the most common recurrence site in both groups., Conclusions: Primary surgery and S-1 chemotherapy could be considered a viable treatment option, even for Type 4 or large Type 3 gastric cancer with CY1., (© 2025 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

The prognosis for T2N0 glottic squamous cell carcinoma (SCC) is generally favorable, with a 5-year overall survival rate of 79%-96% achieved with radiotherapy (RT), the standard nonsurgical treatment for this condition. However, the local control rate for T2N0 glottic SCC treated with RT remains suboptimal, with a 5-year local control rate of only 65%-80%. Local residual disease or recurrence following RT for T2N0 glottic SCC often leads to difficulties in laryngeal preservation. When total laryngectomy is performed as a salvage surgery in such cases, patients lose their physiological ability to speak. Therefore, improving local control and laryngeal preservation rates through RT could substantially improve the quality of life of these patients. Attempts have been made to combine cytotoxic anticancer agents with RT to achieve better local control in patients with T2N0 glottic SCC. In Japan, several studies have evaluated the effects of combining S-1, an oral fluorinated pyrimidine, with RT in these patients. This review highlights the importance of adding chemotherapy to RT in the treatment of patients with T2N0 glottic SCC., (© The Author(s) 2025. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Patients with large Stage IV gastric cancer (GC) invading the proximal stomach find it difficult to receive not only bypass surgery but also S-1-based chemotherapy. This study aimed to show our treatment results for those GC patients using elementary diet (ED) tubes, which enabled S-1-based chemotherapy and nutrition support., Case Presentation: We evaluated 20 patients (13 men and 7 women; median age 70 years) with large Stage IV GCs (8.7-21.9 cm) invading the proximal stomach, who were admitted due to inability to eat, treated with S-1-based chemotherapy using an ED tube. The duration from the initiation of the chemotherapy to the improvement of oral intake, changes in nutritional status, and disease-specific survival (DSS) were retrospectively investigated. Two of the 20 patients failed to complete even one cycle of chemotherapy due to severe nausea or diarrhea. The other 18 patients improved oral liquid intake after 47.5 ± 18.8 days, and 17 patients improved oral solid food intake after 54.5 ± 19.6 days from the start of chemotherapy. In addition, three patients (16.7%) could receive conversion surgery after improvement of oral intake. The median DSS of those 18 patients was 13.1 months. Serum albumin level and prognostic nutritional index (PNI) were significantly improved after about 1 month of the treatment (both P <0.0001). Improvement of serum albumin level and PNI during the first 1 month of the treatment significantly correlated with better DSS ( P = 0.006, 0.01, respectively)., Conclusions: Given a high oral intake success rate, S-1-based chemotherapy using an ED tube can be a promising treatment option for large Stage IV GC with poor oral intake., Competing Interests: The authors declare that they have no competing interests., (© 2025 The Author(s). Published by Japan Surgical Society.)

In Japan, S-1 is used as adjuvant chemotherapy for pancreatic cancer. Neutropenia during S-1 chemotherapy is reported to be an independent predictor of prolonged survival in patients with advanced gastric cancer. However, this is unclear in pancreatic cancer. This study aimed to examine the effect of severe neutropenia caused by S-1 adjuvant chemotherapy on pancreatic cancer prognosis: overall survival (OS) and recurrence-free survival (RFS), and the potential effect of the duration from surgery to S-1 administration on OS and RFS. This single-center, retrospective, observational study included patients who newly received S-1 adjuvant chemotherapy after curative resection of pancreatic cancer at the Japanese Red Cross Kyoto Daini Hospital between January 1, 2016, and September 30, 2020. Of the 43 patients, 9 had grade 3 or higher neutropenia (G3 group) and had a significantly longer median OS than the other 34 (non-G3 group) did. The median RFS of the G3 group was longer than that of the non-G3 group. The median time from surgery to S-1 administration was significantly shorter in the G3 group than in the non-G3 group. Cox proportional hazards regression analysis revealed that duration from surgery to S-1 administration <51 d (hazard ratio: 0.375, 95% confidence interval: 0.154-0.914, p = 0.031) and occurrence of grade 3 neutropenia (hazard ratio: 0.198, 95% confidence interval: 0.046-0.860, p = 0.031) were significantly associated with prolonged OS. In conclusion, initiating S-1 adjuvant chemotherapy early after surgery and the occurrence of grade 3 neutropenia may improve pancreatic cancer prognosis.