Fuyuhiko Motoi

Despite advances in multidisciplinary treatment, recurrence remains a major clinical challenge in refractory cancers. Many patients have residual tumor after neoadjuvant chemotherapy (NAC), and clinical outcomes among patients without a pathological complete response (non-pCR) are heterogeneous. The spatial relationships between residual tumor cells and surrounding stromal cells may provide information for further prognostic stratification. In this review, we discuss histology-based spatial analysis (HSA) of surgical specimens, with particular attention to pancreatic ductal adenocarcinoma. We describe four steps that connect existing biological, histological, and clinical findings. First, intercellular distances and local cell numbers are compared to identify candidate partner cells. Second, functional and molecular studies examine their interactions with tumor cells, including effects on survival and drug resistance. Third, HSA of immunostained patient specimens measures the number, size, and localization of foci containing cell relationships supported by these studies. Fourth, these measurements are evaluated in relation to recurrence and survival, alongside established clinicopathological factors. This approach uses archival surgical specimens to connect biological findings with patient outcomes. Its value for prognostic stratification after NAC requires validation in large clinical cohorts.

Background: Anthracycline (A) and taxane (T)-based therapies improve breast cancer survival, with guidelines strongly recommending these regimens and dose-dense approaches. However, the real-world maintenance of optimal dose intensity, a critical prognostic factor, remains unclear. We aimed to clarify the current treatment situation regarding relative dose intensity (RDI), with a secondary focus on safety. Methods: In this retrospective observational study, we analyzed big data from the DATuM IDEA® electronic medical record database of the Japan Medical Association Medical Information Management Organization, collected from 1 206 955 individuals across 53 medical institutions throughout Japan over 57 months since 2019. We focused on women with primary breast cancer receiving adriamycin/cyclophosphamide (AC), epirubicin/cyclophosphamide (EC), or docetaxel/cyclophosphamide chemotherapy (TC). Results: Analysis included 1989 women who received at least two courses of AC, EC, or TC perioperatively. Patients received 2-weekly adriamycin/cyclophosphamide (ddAC) (n = 207), 3-weekly AC (AC q3w) (n = 177), 2-weekly epirubicin/cyclophosphamide (ddEC) (n = 269), 3-weekly EC (EC q3w) (n = 684), and TC (n = 652). Pegfilgrastim was administered to 98% of ddAC/ddEC, 38% of AC q3w, 42% of EC q3w, and 74% of TC patients. Grade 4 neutropenia (incidences >20%) was observed in AC q3w patients aged ≥65 years (22.6%) and in TC patients of any age (27.6%). RDI remained >95% in all groups. Conclusions: RDI was high in all groups. Clinicians should be cautious when administering AC q3w therapy owing to the high likelihood of patients developing Grade 4 neutropenia. For TC, a slightly lower pegfilgrastim administration rate and >20% Grade 4 neutropenia suggest the need for appropriate pegfilgrastim use.

Neoadjuvant treatment (NAT) for pancreatic cancer has been shown to reduce mortality risk, with carbohydrate antigen (CA)19-9 response indicating survival

Purpose Machine learning (ML) is a method of creating models by learning latent patterns and features from collected data to predict and classify new unknown data. We constructed an ML model to predict postoperative complications using various pre- and intraoperative factors from electronic medical records and examined its prediction accuracy. Methods Data of 617 patients who underwent major organ resection were included in this study. Patient information was collected from the medical records. Consequently, we created Dataset 1, which included all of the data, and Dataset 2, which was adjusted for the factors. The ML models were applied to the two datasets, and the performances of the ML models were compared. Results In Dataset 1, the Logistic Regression model showed the best performance, with correct predictions of serious postoperative complications (accuracy), area under the receiver operating characteristic curve (AUROC), and area under the precision–recall curve (AUPRC) values of 0.798, 0.671, and 0.374, respectively. The random forest (RF) model performed best in Dataset 2, with accuracy, AUROC, and AUPRC values of 0.855, 0.725, and 0.412, respectively. Conclusions The RF model performed well in predicting serious postoperative complications of gastrointestinal surgery. Further studies are required to improve the accuracy of this ML model for clinical applications.

Background/Objectives: Carbon-ion radiotherapy (CIRT) is now covered by Japan’s health insurance for patients with hepatocellular carcinoma (HCC) tumors measuring ≥4 cm. However, no studies have compared intrahepatic control between CIRT and hepatectomy in these patients. Methods: We retrospectively analyzed intrahepatic control in 51 patients with HCC tumors ≥4 cm. Among them, 38 underwent CIRT (60 Gy in four fractions), while 13 underwent systematic hepatectomy. Intrahepatic recurrence was classified as local or intrahepatic distant. We evaluated local, distant, and total intrahepatic control rates at 1 and 2 years. Results: In the CIRT group, the local control rates at 1 and 2 years were 81.5% and 76.3%, whereas the intrahepatic distant control rates were 68.5% and 63.2% (p = 0.0495), respectively. Among patients aged p = 0.0100), with similar trends in local (92.3% vs. 63.2%, p = 0.0381) and distant control (78.9% vs. 47.3%, p = 0.0259). Conclusions: CIRT may be as effective as hepatectomy for HCC tumors ≥4 cm in patients aged <80 years, but its efficacy declines in older patients, warranting age-tailored strategies.

Objective: This randomized phase II/III study evaluated the superiority of neoadjuvant therapy with gemcitabine plus S-1 over upfront surgery for patients with resectable pancreatic ductal adenocarcinoma (PDAC). Background: PDAC is a leading cause of cancer mortality that urgently requires better treatment. Methods: Patients with resectable PDAC (without arterial abutment) were randomly assigned to upfront surgery or neoadjuvant chemotherapy with gemcitabine (1000 mg/m ² days 1 and 8) and S-1 (40–60 mg orally twice daily, days 1–14 every 3 wk for 2 cycles). Phase II and III primary endpoints were resection rate and overall survival, respectively. UMIN Clinical Trials Registry number: UMIN000009634. Results: Patients (n=364) were enrolled and randomly allocated to upfront surgery (UPS; n=182) or neoadjuvant gemcitabine plus S-1 (NAC-GS; n=182). Patient demographics and tumor characteristics were balanced between groups. Median overall survival in the UPS and NAC-GS groups was 26.6 (95% CI: 21.5, 31.5) and 37.0 (95% CI: 28.6, 43.3) months, respectively. The hazard ratio for mortality in the NAC-GS group compared with the UPS group was 0.73 (95% CI: 0.56, 0.95; P =0.018). Median relapse-free survival in the UPS and NAC-GS groups was 11.3 (95% CI: 9.41, 13.5) and 14.3 (95% CI: 11.7, 17.0) months, respectively. The hazard ratio for relapse in the NAC-GS group compared with the UPS group was 0.77 (95% CI: 0.61, 0.98; P =0.030). Conclusions: The Prep-02/JSAP05 trial results showed that neoadjuvant chemotherapy with gemcitabine plus S-1 significantly extends survival compared with upfront surgery in patients with resectable PDAC.

Background: The effectiveness of intraperitoneal chemotherapy using paclitaxel (i.p.‐PTX) in pancreatic ductal adenocarcinoma (PDAC) patients with peritoneal dissemination remains elusive. The aim of this study is to investigate the clinical outcome of patients treated with i.p.‐PTX combined with systemic chemotherapy compared with current standard chemotherapy including gemcitabine plus nab‐paclitaxel and FOLFIRINOX.Methods: Data of patients with peritoneal dissemination was retrospectively collected and analyzed (i.p.‐PTX, n = 83; control, n = 86). Inverse probability of treatment‐weighted analyses (IPTW) was used to balance baseline characteristics between two groups. Survival curves were estimated using Kaplan–Meier method, and the differences were compared using the log‐rank test.Results: No significant differences were noted in overall survival (14.9 vs. 15.5 months, p = 0.481) and progression free survival (9.5 vs. 9.1 months, p = 0.267) between i.p.‐PTX and the control groups. Nevertheless, i.p.‐PTX (9.9 months) significantly prolonged the median progression‐free survival (PFS) time compared with the control (8.6 months), among the matched patients using IPTW (hazard ratio 0.666, p = 0.041). Moreover, subgroup analysis among the patients whose primary tumor were evaluated either as resectable or borderline resectable disease revealed significantly better overall survival in the i.p.‐PTX group compared with the control group (21.3 vs. 14.7 months, hazard ratio; 0.532, p = 0.033). Conversion surgery was more frequently performed in the i.p.‐PTX group than the control group (24% vs. 4%, p = 0.006).Conclusion: The i.p. PTX regimen prolonged PFS but not overall survival, and subgroup analysis suggested the possibility of survival benefit in patients with occult peritoneal dissemination whose primary tumor was classified as resectable/borderline resectable disease.

Background: Surgical resection is standard treatment for invasive intraductal papillary mucinous carcinoma (IPMC); however, impact of multidisciplinary treatment on survival including postoperative adjuvant therapy (AT), neoadjuvant therapy (NAT), and treatment for recurrent lesions is unclear. We investigated the effectiveness of multidisciplinary treatment in prolonging survival of patients with invasive IPMC.Methods: This retrospective multi‐institutional study included 1183 patients with invasive IPMC undergoing surgery at 40 academic institutions. We analyzed the effects of AT, NAT, and treatment for recurrence on survival of patients with invasive IPMC.Results: Completion of the planned postoperative AT for 6 months improved the overall survival (OS), disease‐specific survival (DSS), and recurrence‐free survival (RFS) of patients with stage IIB and stage III resected invasive IPMC, elevated preoperative carbohydrate antigen 19–9 level, lymphovascular invasion, perineural invasion, serosal invasion, and lymph node metastasis on un‐matched and matched analyses. Of the patients with borderline resectable (BR) invasive IPMC, the OS (p = 0.001), DSS (p = 0.001), and RFS (p = 0.001) of patients undergoing NAT was longer than that of those without on the matched analysis. Of the 484 invasive IPMC patients (40.9%) who developed recurrence after surgery, the OS of 365 patients who received any treatment for recurrence was longer than that of those without treatment (40.6 vs. 22.4 months, p < 0.001).Conclusion: Postoperative AT might benefit selected patients with invasive IPMC, especially those at high risk of poor survival. NAT might improve the survivability of BR invasive IPMC. Any treatment for recurrence after surgery for invasive IPMC might improve survival.