BACKGROUND/AIMS:Retroperitoneal liposarcoma (RPLS) is characterized by high recurrence rates after complete resection. Existing prognostic models such as Sarculator and modified Glasgow Prognostic Score (mGPS), rely on postoperative data or are not specific to early recurrence, limiting their utility for preoperative decision-making. This study aimed to develop and validate a simple preoperative scoring system to predict early recurrence after curative-intent resection of RPLS. METHODS:A single-center institutional database was retrospectively reviewed to identify 90 consecutive patients who underwent curative-intent resection for primary RPLS between 2010 and 2024. Early recurrence was defined as recurrence within 2 years after surgery. Preoperative clinical, histological, and serum biochemical variables were associated with early recurrence were combined to develop a simple preoperative risk score. Its ability to predict early recurrence-free survival (RFS) was evaluated using receiver operating characteristic (ROC) analysis and compared with the mGPS and Sarculator-based risk estimates. RESULTS:During a median follow-up of 36 months, 44 patients (49%) developed recurrence. Multivariable analysis identified three independent predictors of early recurrence: dedifferentiated liposarcoma, serum albumin <3.5 g/dL, and high-sensitivity C-reactive protein ≥0.07 mg/dL. Based on these independently associated preoperative factors, Histology-Albumin-C-reactive protein (HAC) score was developed. The HAC score showed good discrimination for 2-year RFS, with an area under the ROC curve (AUC) of 0.79. This was higher than the AUC for the mGPS (0.63) and Sarculator (0.72). CONCLUSION:The HAC score is a novel tool based solely on preoperative factors that effectively predicts early recurrence after RPLS resection. The score may support patient counseling, referral to specialist sarcoma centers, surgical planning, and consideration of neoadjuvant treatment or closer postoperative surveillance.

Biliary tract cancer (BTC) exhibits a poor prognosis and limited responses to current therapeutic strategies. While surgical resection followed by adjuvant S-1 therapy is the standard curative treatment for BTC, long-term postoperative remission is hardly achieved. Therefore, more effective perioperative strategies are urgently needed. Here, we show that an immune-cold tumor microenvironment (TME) in KRAS-mutated BTC correlated with resistance to postoperative adjuvant S-1 therapy. Surgically resected tumor specimens were collected from 31 BTC patients who received adjuvant S-1 therapy after surgery and were subjected to integrated immunogenomic analysis, including multiplexed immunohistochemistry staining and whole-exome sequencing. The analysis revealed a strong correlation between limited CD8⁺ T cell and antigen-presenting cell (APC) infiltration into the TME and KRAS mutations in BTC. In addition, the distances between tumor cells and APCs, as well as between APCs and CD8⁺ T cells, were significantly greater in the TME of KRAS-mutated BTC than in that of KRAS wild-type BTC. These findings indicate that interactions between effector T cells and APCs were impaired in the TME of KRAS-mutated BTC, thereby disrupting antitumor immune responses. Furthermore, wild-type KRAS and abundant CD8⁺ T cells and APCs correlated with a favorable prognosis following adjuvant S-1 therapy for BTC. Altogether, we propose a novel immunogenomic-based biomarker for optimizing perioperative chemotherapy for BTC.

Background Triple-negative breast cancer (TNBC) accounts for approximately 10–20% of all breast cancers and is characterized by aggressive clinical behavior and poor prognosis. Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is associated with a good prognosis. Recently, the addition of pembrolizumab to NAC has improved pCR and overall survival. However, TNBC is biologically heterogeneous, and existing biomarkers, including tumor-infiltrating lymphocytes and PD-L1 provide limited prediction of chemoresistance, leaving an unmet need for markers that could guide integration of immunotherapy in resistant disease. In this study, we aimed to identify biomarkers of chemoresistance in TNBC and characterize their spatial features by integrating transcriptomic and spatial analyses. Methods We retrospectively analyzed 49 TNBC patients treated with anthracycline- and taxane-based NAC at Nagoya University Hospital between 2017 and 2023. Pre-treatment FFPE biopsies from eight patients (pCR n = 4, non-pCR n = 4) were profiled by nCounter gene expression analysis and Xenium spatial transcriptomics. The results were further validated using publicly available datasets, including TCGA. Results No clinicopathological factor was significantly associated with treatment response. nCounter analysis identified reduced expression of immune-related genes and increased expression of proliferation and cell cycle-related genes in non-responders. Spatial transcriptomic profiling revealed greater immune-cell abundance and diversity in the pCR group, with stronger immune-cell and immune-tumor cell interactions. In contrast, the non-pCR group showed enhanced stromal−epithelial interactions and reduced spatial proximity between immune and tumor cells. Cluster-and cell-type resolved analysis identified reduced expression of CD8A and other T-cell associated genes ( CD3E , GZMA ) and cell-cycle genes ( CCNA1 , CCNB1 , E2F3 ) in non-pCR tumors. The inverse spatial relationship between CD8A and LARS suggests as a candidate CD8A−LARS axis linking reduced cytotoxic T-cell presence with altered amino acid metabolism. Conclusions Reduced CD8A and elevated LARS expression in pretreatment TNBC tumors may contribute to chemoresistance through coordinated metabolic reprogramming, immune-cell exclusion, and tumor-cell proliferation. We propose the CD8A - LARS axis as a potential resistance axis warranting functional and prospective validation in independent TNBC cohorts.

BACKGROUND:Indocyanine green (ICG) fluorescence imaging has gained popularity for preventing anastomotic leakage (AL), which was previously evaluated using the Doppler method. However, no study has directly compared the use of Doppler and ICG fluorescence imaging simultaneously. When introducing ICG fluorescence imaging in our department, we also used the conventional Doppler method to confirm the validity of its results. We hypothesized that the length of the available gastric tube might differ depending on the evaluation method potentially affecting the risk of AL and the choice of surgical technique. This study evaluated the usefulness of ICG fluorescence imaging and tested this hypothesis. METHODS:We retrospectively analyzed the data of 248 patients with esophageal cancer who underwent subtotal esophagectomy with gastric tube reconstruction and cervical anastomosis. After excluding 17 cases, 231 patients were included (Doppler-only group, n = 175; Doppler + ICG group, n = 56). In the Doppler + ICG group, changes in the available gastric tube length were evaluated by directly comparing Doppler-based and ICG-based perfusion assessments. To assess the clinical significance of these changes, surgical outcomes, including anastomotic technique and postoperative complications, were compared with those in the Doppler-only group. RESULTS:In the Doppler + ICG group, the available gastric tube length was extended in 37 cases, unchanged in 15 cases, and shortened in 4, showing that extension was significantly more frequent than other changes (p < 0.001). The anastomosis rate with a circular stapler was significantly higher in the Doppler + ICG group (89%) than in the Doppler-only group (61%; p < 0.001). The incidence of Clavien-Dindo grade IIIa AL was significantly lower in the Doppler + ICG group (3.6%) than in the Doppler-only group (15%; p = 0.03). CONCLUSION:By extending the available gastric tube length, ICG fluorescence imaging was associated with a lower incidence of AL compared with the Doppler method, suggesting it has the potential to improve surgical outcomes and patient safety.

Fibroblast growth factor receptors (FGFR) are tyrosine kinases that regulate cellular responses including proliferation, survival, and migration. FGFR fusion genes arose from chromosomal translocations or deletions, lead to ligand-independent constitutive signal activation and contribute to carcinogenesis and cancer progression. FGFR2 fusion genes are identified in 7.4-13.6% of intrahepatic cholangiocarcinoma and 3.6% of perihilar cholangiocarcinoma. They are also reported in colorectal, prostate, and breast cancers, though at lower frequencies. Diagnosis methods are RT-PCR, RNA sequencing, FISH, and NGS. Comprehensive genomic profiling (CGP) tests are available clinically. Three FGFR inhibitors are currently approved. Pemigatinib (approved in 2021) demonstrated a response rate of 35.5%, futibatinib (approved in 2023) showed a response rate of 42%, and tasurgratinib (approved in 2024) achieved a response rate of 30.2%. The most common adverse event is hyperphosphatemia. Alopecia, diarrhea, nail disorders, and retinal detachment are also required attention. Polyclonal on-target resistance to pan-FGFR inhibitors and increasing of FGFR2 kinase domain resistance mutations based on treatment history has been reported. Novel therapeutics, such as highly selective FGFR2 inhibitors and next-generation inhibitors, are developed and are expected to improve prognosis for patients with FGFR2 fusion-positive solid tumors.

BACKGROUND:Left-sided hepatectomy for perihilar cholangiocarcinoma includes conventional left hepatectomy (C-LH; H1234-B), extended left hepatectomy (E-LH; H12345'8'-B-MHV), and left trisectionectomy (LT; H123458-B). The anatomical characteristics of the resected length of the right hepatic duct (RHD) in E-LH remain unclear. This study aimed to characterize the length of the RHD across procedures. METHODS:Patients who underwent left-sided hepatectomy for perihilar tumors between 2015 and 2023 were retrospectively reviewed. The shortest distance between the proximal bile duct stump and left hepatic duct orifice was measured on the resected specimens. The lengths and clinicopathological features of the procedures were compared. RESULTS:In total, 205 patients were included: C-LH (n = 80), E-LH (n = 53), and LT (n = 72). The length of the right anterior hepatic duct was longer in E-LH than that in C-LH (15.2 vs. 13.0 mm, p = 0.006). Similarly, the length of the right posterior hepatic duct increased stepwise from C-LH to E-LH and LT (13.3, 16.6, and 20.0 mm, respectively). CONCLUSIONS:E-LH is an intermediate procedure between C-LH and LT with respect to the resected length of the RHD. The additional bile duct length achieved by E-LH is minimal, and this procedure should be selected primarily to secure the parenchymal margin rather than ductal clearance.

BACKGROUND/PURPOSE:Surgical resection remains the only potentially curative treatment for advanced gallbladder cancer (GBC). However, preoperative diagnosis and staging are often challenging, and the indication for extended resection remains controversial. This study evaluated the feasibility of upfront resection for advanced GBC based on clinical T (cT) staging. METHODS:Patients radiologically diagnosed with cT3 or cT4 GBC at six Japanese centers between 2010 and 2022 were retrospectively analyzed. Resection rate, benign lesions, perioperative outcomes, and overall survival (OS) were compared between the groups. RESULTS:Among 300 patients (cT3, n = 182; cT4, n = 118), 260 (87%) underwent resection. Benign lesions were identified in 21 (8%) patients. Compared with cT3, cT4 tumors had higher rates of extended resection (75% vs. 40%, p < 0.001), exploratory laparotomy (24% vs. 7%, p < 0.001), and postoperative complications (59% vs. 29%, p < 0.001). Postoperative mortality tended to be higher in cT4 patients (7% vs. 3%, p = 0.197), and median OS was significantly shorter (22 vs. 44 months, p < 0.001). CONCLUSIONS:Clinical T staging helps guide treatment planning for advanced GBC. Upfront resection is feasible for cT3 GBC, whereas cT4 disease is associated with extensive surgery and poor outcomes.

OBJECTIVE:To evaluate the prognostic impact of radial margin distance (RMD) in patients with perihilar cholangiocarcinoma (pCCA) and establish clinically relevant cutoff values. BACKGROUND:A positive radial margin is conventionally defined by cancer cell exposure at the transection plane. However, a standardized classification for pCCA has yet to be established. METHODS:pCCA patients who underwent tumor resection between 2005 and 2020 were retrospectively analyzed. The relationships between histologically measured RMDs and long-term outcomes were examined. RESULTS:Among the 658 study patients, the median RMD was 0.4 mm (interquartile range, 0.1-1.1 mm). The hazard for overall survival peaked at an RMD of 0 mm (conventional cutoff), decreased with increasing RMD, and plateaued at approximately 1.0 mm, which was identified as the optimal threshold in rank statistics (|z|, 11.09; P<0.001). On the basis of these findings, patients were categorized into three groups according to their RMDs (0 mm (n=101, 15.3%), >0-<1.0 mm (n=356, 54.1%), and ≥1.0 mm (n=201, 30.5%)); the 5-year cumulative recurrence rates were 83.5%, 68.8%, and 23.9%, respectively (P<0.001), with local recurrence rates of 63.0%, 37.0%, and 11.1%, respectively (P<0.001), and the 5-year overall survival rates were 21.8%, 36.0%, and 78.5%, respectively (P<0.001). Multivariable analysis confirmed that RMDs of 0 mm (hazard ratio, 3.15; P<0.001) and >0-<1.0 mm (hazard ratio, 2.64; P<0.001) were independent predictors of poor overall survival. CONCLUSIONS:RMD assessment with dual cutoffs of 0 and 1.0 mm was simple and clinically relevant and effectively stratified postoperative recurrence risk and survival in pCCA patients.

Abstract Topic Esophageal Cancer: Other Background Systemic inflammation and immune status play a critical role in the development and progression of cancers. We evaluated the clinical significance of the preoperative systemic immune-inflammation index (SII) for predicting the long-term outcomes of patients who received neoadjuvant therapy for esophageal squamous cell carcinoma (ESCC). Methods The subjects of this study were 277 patients who underwent curative resection of ESCC after neoadjuvant therapy. The SII was calculated as follows: SII = neutrophil × platelet/lymphocyte counts. Patients were stratified into high and low preoperative SII groups according to the cut-off value calculated by a receiver operating characteristic curve analysis. The Kaplan–Meier method and Cox proportional regression analysis were used to evaluate the correlation of SII to prognosis. Results The optimal cutoff of the preoperative SII was set at 700. Patients were categorized into preoperative SII-low (n = 203) and SII-high (n = 74) groups. The preoperative SII was significantly associated with tumor size. The relapse-free survival of patients in the SII-high group was significantly shorter (P = 0.0087) and preoperative SII-high was identified as an independent prognostic factor (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.06–2.28, P = 0.0229). The prevalence of hematogenous recurrence was significantly higher in the SII-high group. When we stratified patients into three groups with an additional cutoff value of 1200, we observed an incremental decrease in relapse-free survival rates. Conclusion High preoperative SII was associated with shorter relapse-free survival times for ESCC patients who underwent curative resection after neoadjuvant therapy

ABSTRACT Background Retroperitoneal tumors (RPTs) are rare and anatomically complex neoplasms, for which surgery remains the mainstay of treatment. However, real‐world data on their surgical management in Japan have been limited. Objective To describe the clinical characteristics and short‐term outcomes of patients undergoing resection for RPTs in Japan, based on data from gastroenterological surgical practice. Methods This study analyzed data from the Japanese National Clinical Database (NCD) for gastroenterological surgery. A total of 4948 patients with RPT who underwent surgery between 2019 and 2021 were included. Results There were 2360 men (47.7%) and 2588 women (52.3%), with a median age of 66 years. RPTs were histologically classified as malignant in 75.3% and benign in 24.7% of cases. The median operative time was 205 min, and the median blood loss was 150 mL. Postoperative complications occurred in 23.9% of patients, with 7.5% experiencing severe complications (Clavien–Dindo grade III or higher). The 30 day postoperative mortality rate was 0.5%, and the perioperative mortality rate was 1.0%. Conclusion This analysis demonstrates that a substantial number (approximately 1650 per year) of RPTs surgeries are performed annually by gastrointestinal surgeons in Japan, and that the short‐term surgical outcomes are acceptable. These data provide an important reference to exhibit the current surgical practice in Japan and to develop future strategies for RPTs.

To evaluate short- and long-term surgical outcomes in non-benchmark (non-BM) patients with perihilar cholangiocarcinoma (pCCA) using a multicenter cohort from Japan. Benchmark (BM) criteria have been proposed to standardize surgical outcomes in complex hepatopancreatobiliary procedures. However, BM studies typically exclude patients with significant medical comorbidities or those requiring technically demanding procedures. As a result, the majority of real-world pCCA cases, classified as non-BM, remain underrepresented in the literature, and their outcomes are insufficiently characterized. Between 2014 and 2018, a total of 648 patients underwent curative intent resection for pCCA at six high volume centers in Japan. Among them, 412 patients (64%) were categorized as non-BM and 236 patients (36%) as BM according to established surgical and medical exclusion criteria. Perioperative and oncologic outcomes were analyzed and compared with benchmark thresholds previously reported in the literature. Non-BM cases were further stratified into surgical, medical, and dual subgroups for subgroup analysis. The median operative time (644 minutes), intraoperative blood loss (1185 mL), and postoperative hospital stay (31 d) exceeded BM thresholds. Nevertheless, most postoperative outcomes, including Grade B/C post-hepatectomy liver failure (16.7%), bile leakage (22.8%), and in-hospital mortality (2.9%), remained within benchmark reference values. The median overall survival was 46.0 months, with 1-, 3-, and 5-year survival rates of 85.8%, 55.0%, and 37.1%, respectively. Subgroup analysis revealed decreasing survival with increasing complexity: 5-year survival rates were 50.5% in medical, 34.1% in surgical, and 15.4% in dual non-BM patients. Notably, left trisectionectomy was associated with the highest mortality (9.5%) among all procedures. Despite increased surgical complexity and patient-related risk factors, non-BM pCCA patients can achieve acceptable perioperative and long-term outcomes when treated at experienced, high-volume centers. Stratification by non-BM subgroup provides meaningful prognostic insight and may help guide surgical decision-making in complex pCCA cases.

Background/Objectives: The uniform application of total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC) risks overtreatment and surgical complications. We evaluated a novel tailor-made therapy that personalizes radiotherapy and chemotherapy to balance oncological safety with organ preservation. Methods: We retrospectively analyzed 38 patients with cStage II-III LARC treated between 2023 and 2025. Patients were stratified by sphincter preservation feasibility and high systemic risk (cN2, extramural vascular invasion, lateral lymph node enlargement). Group A (sphincter-preserving, n = 20) received induction chemotherapy; long-course chemoradiotherapy (LCCRT) was omitted in favorable responders but added if MRF-positive or to aim for non-operative management (NOM) in exceptional responders. Group B (non-sphincter-preserving, low systemic risk, n = 8) received LCCRT plus consolidation chemotherapy. Group C (non-sphincter-preserving, high systemic risk, n = 10) received short-course radiotherapy plus consolidation chemotherapy. Results: Over a median observation period of 20 months (range, 6-37), NOM was initiated in 7 patients (18% overall; Group A: 10%, Group B: 50%, Group C: 10%), with one local regrowth observed to date, resulting in 6 of 7 patients (85.7%) successfully maintaining NOM. Preoperative radiotherapy was safely omitted in 32% of the total cohort, and notably in 60% of patients in Group A. Surgery was performed in 28 patients (74%), achieving an R0 resection rate of 100% across all groups. Distant metastasis recurrence during preoperative treatment occurred in 5 patients (13%). Risk-stratified, tailor-made therapy for LARC facilitates the highly customized application or omission of radiotherapy. Conclusions: Risk-stratified, tailor-made therapy facilitates the safe omission or targeted application of radiotherapy in LARC. This personalized approach prevents overtreatment, maintains complete surgical curability, and achieves successful organ preservation in appropriately selected patients.

Objective: To evaluate the prognostic impact of radial margin distance (RMD) in patients with perihilar cholangiocarcinoma (pCCA) and establish clinically relevant cutoff values. Background: A positive radial margin is conventionally defined by cancer cell exposure at the transection plane. However, a standardized classification for pCCA has yet to be established. Methods: pCCA patients who underwent tumor resection between 2005 and 2020 were retrospectively analyzed. The relationships between histologically measured RMDs and long-term outcomes were examined. Results: Among the 658 study patients, the median RMD was 0.4 mm (interquartile range, 0.1–1.1 mm). The hazard for overall survival peaked at an RMD of 0 mm (conventional cutoff), decreased with increasing RMD, and plateaued at approximately 1.0 mm, which was identified as the optimal threshold in rank statistics (|z|, 11.09; P <0.001). On the basis of these findings, patients were categorized into three groups according to their RMDs (0 mm (n=101, 15.3%), >0–<1.0 mm (n=356, 54.1%), and ≥1.0 mm (n=201, 30.5%)); the 5-year cumulative recurrence rates were 83.5%, 68.8%, and 23.9%, respectively ( P <0.001), with local recurrence rates of 63.0%, 37.0%, and 11.1%, respectively ( P <0.001), and the 5-year overall survival rates were 21.8%, 36.0%, and 78.5%, respectively ( P <0.001). Multivariable analysis confirmed that RMDs of 0 mm (hazard ratio, 3.15; P <0.001) and >0–<1.0 mm (hazard ratio, 2.64; P <0.001) were independent predictors of poor overall survival. Conclusions: RMD assessment with dual cutoffs of 0 and 1.0 mm was simple and clinically relevant and effectively stratified postoperative recurrence risk and survival in pCCA patients.

OBJECTIVE:To evaluate short- and long-term surgical outcomes in non-benchmark (non-BM) patients with perihilar cholangiocarcinoma (pCCA) using a multicenter cohort from Japan. BACKGROUND:Benchmark (BM) criteria have been proposed to standardize surgical outcomes in complex hepatopancreatobiliary procedures. However, BM studies typically exclude patients with significant medical comorbidities or those requiring technically demanding procedures. As a result, the majority of real-world pCCA cases, classified as non-BM, remain underrepresented in the literature, and their outcomes are insufficiently characterized. METHODS:Between 2014 and 2018, a total of 648 patients underwent curative intent resection for pCCA at six high volume centers in Japan. Among them, 412 patients (64%) were categorized as non-BM and 236 patients (36%) as BM according to established surgical and medical exclusion criteria. Perioperative and oncologic outcomes were analyzed and compared with benchmark thresholds previously reported in the literature. Non-BM cases were further stratified into surgical, medical, and dual subgroups for subgroup analysis. RESULTS:The median operative time (644 minutes), intraoperative blood loss (1185 mL), and postoperative hospital stay (31 d) exceeded BM thresholds. Nevertheless, most postoperative outcomes, including Grade B/C post-hepatectomy liver failure (16.7%), bile leakage (22.8%), and in-hospital mortality (2.9%), remained within benchmark reference values. The median overall survival was 46.0 months, with 1-, 3-, and 5-year survival rates of 85.8%, 55.0%, and 37.1%, respectively. Subgroup analysis revealed decreasing survival with increasing complexity: 5-year survival rates were 50.5% in medical, 34.1% in surgical, and 15.4% in dual non-BM patients. Notably, left trisectionectomy was associated with the highest mortality (9.5%) among all procedures. CONCLUSIONS:Despite increased surgical complexity and patient-related risk factors, non-BM pCCA patients can achieve acceptable perioperative and long-term outcomes when treated at experienced, high-volume centers. Stratification by non-BM subgroup provides meaningful prognostic insight and may help guide surgical decision-making in complex pCCA cases.

Abstract Background: Bile tract cancer (BTC) is a malignant tumor with poor prognosis. The genetic background and molecular profiles of BTC remain poorly understood. Objective: To clarify the genetic diversity of BTC using whole-genome analysis and identify gene mutations as targets for novel diagnostic and therapeutic approaches. Methods: Whole-genome sequencing was performed using paired tumor and normal tissue samples from 7 patients with BTC who underwent surgery at our institution. Somatic mutations were detected and annotated using snpEff. Oncoplot analysis visualized mutation accumulation patterns, and associations with clinical factors including lymph node metastasis, vascular invasion, neural invasion, portal vein invasion, and IPNB. Results: On classification of detected somatic mutations, annotation revealed that intergenic region mutations (mean: 31,085, range: 26,588-39,135) were most frequent. Frameshift variants (mean: 16.7, range: 11-25), splice donor/acceptor variants (mean: 34.3, range: 17-45), and stop gained mutations (mean: 7.4, range: 2-10) were identified as important functional mutations. In addition, missense variants (mean: 529.4, range: 363-647) were also identified. Regarding nonsynonymous mutations, missense mutations were most common in variant classification, and SNPs (single nucleotide polymorphisms) were most frequent in variant type. Among SNV classes, T to G and C to T transitions were highly identified. Thirty genes, including MUC16 and MUC6, were identified with mutations in 3 or more of the 7 cases. Oncoplot analysis of these genes suggested that mutations accumulated more extensively and were associated with tumor mutation burden (TMB) in samples without vascular invasion. In contrast, no accumulation patterns of mutations were observed concerning lymph node metastasis, neural invasion, portal vein invasion, or IPNB. Among the genes (331 mutations, 321 genes) registered in The Cancer Genome Atlas (TCGA) bile duct cancer database, our study identified MUC16, OBSCN, and TP53. However, no overlap in their mutations was observed. It suggests extremely high genetic heterogeneity in BTC. Conclusion: BTC is characterized by a high mutational burden and genetic diversity. An association between vascular invasion status and mutation accumulation was suggested. Gene profiling is considered important for personalized medicine, and the identified gene mutations may serve as potential targets for novel diagnostic and therapeutic approaches. Citation Format: Toshio Kokuryo, Masaki Sunagawa, Junpei Yamaguchi, Taisuke Baba, Takashi Mizuno, Shunsuke Onoe, Nobuyuki Watanabe, Mihoko Yamada, Shoji Kawakatsu, Tomoki Ebata. Gene profiling using whole genome analysis of bile tract cancer and its association with clinical factors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3254.

BACKGROUND:Initial results of NUPAT-01 suggest the feasibility of multidrug neoadjuvant chemotherapy for borderline-resectable pancreatic cancer and favorable survival of patients, and we report on the long-term results of this study. METHODS:In this multicenter, phase II trial (NUPAT-01), patients with borderline-resectable pancreatic cancer were randomly assigned to receive neoadjuvant chemotherapy with either FOLFIRINOX (original regimen) or gemcitabine with nab-paclitaxel (GEM/nab-PTX) and underwent subsequent surgery if feasible. The primary endpoint was the R0 resection rate. RESULTS:Fifty-one eligible patients were randomly assigned to FOLFIRINOX (n = 26) or GEM/nab-PTX (n = 25). Forty-three patients underwent surgery, and R0 resection was achieved in 33 patients. An Intention-to-treat (ITT) analysis revealed a 3-year overall survival of 51.0% and a 5-year overall survival of 35.3% with a median survival time of 36.5 months. No significant difference between the FOLFIRINOX group and the GEM/nab-PTX group was found in the ITT analysis or in patient survival after surgery. However, patients with a favorable response to chemotherapy had significantly better disease-free survival. CONCLUSION:These results suggest no significant difference between the benefit of FOLFIRINOX and GEM/nab-PTX as neoadjuvant chemotherapy for borderline-resectable pancreatic cancer, and the survival of patients depends not on the regimen but on the response to chemotherapy.