760 Background: The modified Glasgow Prognostic Score (mGPS), which combines serum levels of C-reactive protein and albumin, has been reported as a prognostic predictor in several malignancies. In this exploratory analysis of JCOG1611, a randomized phase II/III trial comparing gemcitabine plus nab-paclitaxel (GnP), modified 5-fluorouracil, levofolinate, irinotecan, and oxaliplatin (mFFX), and S-1, irinotecan, and oxaliplatin (S-IROX), we evaluated whether mGPS can predict prognosis of patients with metastatic pancreatic cancer. Methods: All patients eligible for JCOG1611 (n = 527) were included in this analysis. Patients were categorized into two groups according to their mGPS score: mGPS 0 and mGPS 1-2. The association between mGPS and overall survival (OS) was evaluated using multivariable Cox regression analysis. Results: The numbers of patients with mGPS 0 and mGPS 1-2 were 128 and 48 in the GnP arm, 129 and 46 in the mFFX arm, and 130 and 46 in the S-IROX arm, respectively. The median OS for mGPS 0 vs. 1-2 was 16.9 vs. 11.2, 14.3 vs. 9.5, and 14.7 vs. 10.6 months in the GnP, mFFX, and S-IROX arms, respectively. The adjusted hazard ratios (HRs) of OS were 1.359 (95% confidence interval [CI]:0.920–2.009) in the GnP arm, 1.289 (95% CI: 0.878–1.892) in the mFFX arm, and 1.612 (95% CI: 1.094–2.374) in the S-IROX arm, respectively. The median progression-free survival (PFS) for mGPS 0 vs. 1-2 was 7.0 vs. 5.6, 6.9 vs. 4.4, and 6.8 vs. 4.5 months in the GnP, mFFX, and S-IROX arms, respectively. The adjusted HRs of PFS were 1.160 (95% CI:0.812–1.657) in the GnP arm, 1.246 (95% CI: 0.866–1.793) in the mFFX arm, and 1.500 (95% CI: 1.033–2.177) in the S-IROX arm, respectively. Conclusions: mGPS showed a trend toward prognostic significance in patients with metastatic pancreatic cancer treated with GnP or mFFX, and suggested potential prognostic relevance in those treated with S-IROX.

Background/Objectives: To investigate early treatment outcomes, including tumor response, predictors of response, and safety of nivolumab plus ipilimumab (Nivo/Ipi) therapy for unresectable hepatocellular carcinoma (uHCC) in a multicenter setting. Methods: We conducted a retrospective analysis of 64 Japanese patients with uHCC who received Nivo/Ipi therapy at participating centers between July 2025 and April 2026. Treatment efficacy was assessed according to RECIST version 1.1, and adverse events (AEs) were evaluated using CTCAE version 5.0. Results: Among the 64 patients, 28 received first-line therapy, and 36 received later-line therapy. The median observation period was 5.4 months. The overall response rate (ORR) was significantly higher in the first-line group (60.7%) than in the later-line group (30.6%) (p = 0.016). ORRs according to CRAFITY score were 25.0% for score 0, 55.6% for score 1, and 53.8% for score 2. The ORR in patients with CRAFITY scores ≥ 1 was significantly higher than in patients with a CRAFITY score of 0 (55.0% vs. 25.0%; p = 0.022). Multivariable analysis of pretreatment variables predicting response revealed first-line treatment (OR 3.83, 95% CI 1.270-11.558; p = 0.017) and a CRAFITY score ≥ 1 (OR 4.02, 95% CI 1.232-13.106; p = 0.021) as significant independent factors. Immune-mediated AEs occurred in 70.3% of patients overall and were grade ≥ 3 in 35.9%. Conclusions: Nivo/Ipi yielded a favorable response when used as first-line therapy. The baseline CRAFITY score may be a useful predictor of response to Nivo/Ipi therapy.

The current standard first-line treatment for patients with advanced biliary tract cancer (BTC) is a combination chemotherapy regimen. However, whether the efficacy of combination therapy is superior to that of monotherapy in older patients with BTC remains unclear. Therefore, in this study, we aimed to compare the efficacy and safety of monotherapy with those of combination therapy in such patients. We retrospectively enrolled 157 patients with unresectable or recurrent BTC aged ≥ 75 years who received systemic chemotherapy between August 2011 and November 2020. We compared the efficacy and safety of combination therapy (gemcitabine [GEM] + cisplatin and GEM + S-1) with those of monotherapy (GEM or S-1 alone). We assessed patients’ characteristics, survival, adverse events, and dose intensity. Statistical significance was set at p < 0.05. Patients who received monotherapy were older and had worse performance status (PS), lower albumin levels, and higher carcinoembryonic antigen (CEA) levels than those who received combination therapy. The median overall survival (OS) was 16.4 and 12.8 months in the combination therapy and monotherapy groups, respectively (Hazard ratio [HR], 0.69; 95

BACKGROUND:Liposomal irinotecan (nal-IRI) plus fluorouracil/folinic acid (5-FU/LV) improves survival in gemcitabine-refractory metastatic pancreatic cancer (PC) but requires a central venous port. S-1, an oral fluoropyrimidine with proven efficacy in PC, may replace 5-FU/LV in nal-IRI plus 5-FU/LV, potentially enhancing both convenience and antitumor effect. METHODS:This single-arm, open-label, phase 1/2 study included patients with histologically or cytologically confirmed adenocarcinoma, aged 20-80 years, an Eastern Cooperative Oncology Group performance status of 0-1, with metastatic disease, and refractory to gemcitabine-based treatment. The primary endpoint in phase 1 part was the frequency of dose-limiting toxicity (DLT) to nal-IRI plus S-1. The primary endpoint in phase 2 part was overall survival. This trial was registered in the Japan Registry of Clinical Trials database (jRCTs031210040). RESULTS:In phase 1 part, one patient with DLT was observed at nal-IRI 70 mg/m2 (day 1) with S-1 80 mg/m2/day (day 1-7) in a 2-week cycle, establishing this as the recommended phase 2 dose (RP2D). Forty-nine patients from phase 1 (n = 6) and phase 2 part (n = 43) were treated with the RP2D, and their results were pooled. Median overall survival was 10.3 months (95 % confidence interval, 8.1-12.0 months). A confirmed partial response was achieved in 10 patients (20.4 %). The most frequent treatment-emergent adverse events were hypoalbuminemia (98.0 %), anemia (98.0 %), and anorexia (81.6 %). There were no treatment-related deaths. CONCLUSIONS:This study demonstrated that nal-IRI plus S-1 exhibited promising efficacy and an acceptable safety profile in patients with metastatic PC refractory to gemcitabine-based treatment.

737 Background: There were some reports that nal-IRI + 5FU/LV (NAPOLI) therapy was effective for patients with unresectable pancreatic cancer who had a history of treatment containing conventional irinotecan (IRI) though the others did not. We aimed to investigate the factors that contribute to the effectiveness of NAPOLI therapy for patients who have already received IRI-containing treatment. Methods: We retrospectively enrolled the consecutive patients who had previously treated with IRI-containing treatment and started NAPOLI therapy at our hospital between June 2020 and December 2022. We compared the patient backgrounds of patients who achieved CR, PR, or SD according to RECISTv1.1 (effective group) and those who did not (ineffective group). Continuous variables were divided into two groups by the median of the entire population, and factors contributing to the effectiveness of NAPOLI therapy were determined by logistic regression analysis. Results: The subjective were 52 patients. The reason for discontinuation of IRI-containing treatment was refractory and intolerant in 45 and 7 patients, respectively. The median age was 65 years. Twenty-three patients (44%) had ECOG PS of 0, and 41 patients (79%) had metastatic disease. The median albumin, CRP, CEA and CA 19-9 was 3.8 g/dL, 0.3 mg/dL, 8.5 ng/mL and 2082 U/mL, respectively. Twenty-one patients (40%) showed SD and they were allocated in the effective group whereas 31 patients were in the ineffective group. Of the 21 patients in the Effective Group, 16 patients(76%) were refractory, while of the 31 patients in the Ineffective Group, 29 patients (94%) were refractory. The factors contributing to disease control were PS of 0 (odds ratio, 5.79; 95% confidence interval, 1.34–25.0), CA 19-9 <1000 U/mL (odds ratio, 5.53; 95% confidence interval, 1.26–24.3), and Alb >3.8 g/dL (odds ratio, 5.19; 95% confidence interval, 1.14–23.7). Age, sex, disease stage, serum level of CRP, and CEA did not affect the effectiveness of NAPOLI therapy. Conclusions: Even in patients who have already received IRI treatment, the NAPOLI regimen is expected to be effective in patients with PS of 0, Alb >3.8 g/dL, and CA 19-9 <1000 U/mL.

Aims:Carbon-ion radiation therapy (CIRT) is a promising technological innovation for treating hepatocellular carcinoma (HCC). This study aimed to evaluate the effectiveness and safety of CIRT for primary, solitary, potentially resectable HCC in comparison to liver resection (LR). Methods and Results:We retrospectively compared treatment effectiveness and safety between patients treated with CIRT and those who underwent LR for potentially resectable HCC at our institution. The clinical data for the CIRT group were obtained from a prospective observational study carried out at our institution, and additional information was obtained from clinical records. Their data were compared with those of patients who underwent LR during the same period. Twenty-three patients were included in the CIRT group and 41 in the LR group. In the overall cohort, the respective 3-and 5-year overall survival (OS) rates were 86.5% and 65.9% for the CIRT group and 90.2% and 79.7% for the LR group. The OS rates did not significantly differ between the two groups in the propensity score-matched cohort. The 3- and 5-year local control rates after CIRT were 77.0% and 77.0%, respectively. CIRT was associated with elevated albumin-bilirubin (ALBI) scores 3 and 6 months after treatment. Conclusion:CIRT for primary, solitary, potentially resectable HCC was associated with favorable clinical outcomes and satisfactory safety, with an acceptable elevation of the ALBI score. CIRT might achieve a favorable OS comparable to LR for potentially resectable HCC; however, further large-scale, prospective studies are needed for confirmation.

This study aimed to compare outcomes between carbon ion radiotherapy (C-ion RT) and transarterial chemoembolization (TACE) in patients with unresectable solitary hepatocellular carcinoma (HCC) >3 cm. Fifty-eight patients who had been treated with C-ion RT (C-ion RT group) and 34 treated with TACE (TACE group) were retrospectively enrolled between January 2016 and December 2021. Propensity score matching was conducted to account for differences between the two groups. The median follow-up duration was 42.1 months for all patients. Propensity score matching successfully balanced the two groups with 29 patients matched to each group. The 3-year overall survival (OS), progression-free survival (PFS) and local control (LC) rates in the C-ion RT vs TACE groups were 75.9% vs 45.4%, 44.8% vs 16.1% and 85.2% vs 23.2%, respectively. The C-ion RT group showed better OS (hazard ratio [HR], 0.578 [95% confidence interval (CI): 0.295-1.132]; P = 0.106), PFS (HR, 0.460 [95% CI: 0.254-0.835]; P = 0.009) and LC (HR, 0.155 [95% CI: 0.062-0.390]; P < 0.001) than the TACE group. Multivariate analysis indicated that C-ion RT was significantly associated with increased PFS (HR, 0.562 [95% CI: 0.341-0.926]; P = 0.024) and LC (HR, 0.282 [95% CI: 0.150-0.528]; P < 0.001). C-ion RT provided better OS, PFS and LC than TACE in patients with solitary HCC >3 cm. This study indicated that C-ion RT is a possible alternative to TACE, which is the standard of care for patients with medium-to-large-sized HCCs.

Background:Nanoliposomal irinotecan combined with fluorouracil plus leucovorin (nal-IRI + 5-FU/LV) is a standard second-line treatment for patients with advanced pancreatic cancer. Despite its efficacy, the prognostic factors for treatment efficacy remain unclear in clinical practice. Objectives:To investigate prognostic factors for survival with nal-IRI + 5-FU/LV. Design:Single-centre retrospective cohort. Methods:We included 204 patients who were treated with nal-IRI + 5-FU/LV at our institution between July 2020 and March 2022. These patients had unresectable or recurrent pancreatic adenocarcinoma refractory to a gemcitabine-containing regimen. A Cox regression hazard model was used to explore prognostic factors for overall survival (OS). Results:Of the 204 eligible patients, 127 (64%) had received only one prior treatment. Most patients (90%) had metastatic disease, with 93, 61 and 55 patients having metastases to the liver, lungs and peritoneum, respectively. Among them, 18 patients had peritoneal metastasis without ascites. The median OS and progression-free survival (PFS) were 8.7 (95% confidence interval (CI), 7.5-9.8) and 3.6 (95% CI, 3.0-4.2) months, respectively. An Eastern Cooperative Oncology Group performance status (PS) of 0, serum albumin (Alb) level ⩾3.5 g/dL, C-reactive protein (CRP) level <0.5 mg/dL, carbohydrate antigen 19-9 (CA 19-9) level <1000 U/mL and peritoneum metastasis without ascites were independent prognostic factors for OS. The hazard ratios for these factors were 2.08, 1.96, 2.34, 2.22 and 1.92 with p-values of ⩽0.001, 0.001, <0.001, <0.001 and 0.043, respectively. Peritoneal metastasis, with or without ascites, was associated with 2-year OS rates compared to those without: 14.5% versus 6.0%, and 27.8% versus 6.5% (p-value = 0.053 and 0.010, respectively). Conclusion:A PS of 0, Alb >3.5 g/dL, CRP <0.5 mg/dL, CA 19-9 <1000 U/mL and the presence of peritoneal metastasis, especially without ascites, were favourable prognostic factors for survival in patients with advanced pancreatic cancer treated with nal-IRI + 5-FU/LV.

AIM:This study aims to evaluate the efficacy and safety of lenvatinib radiofrequency ablation (RFA) sequential therapy for certain hepatocellular carcinoma (HCC) patients. METHODS:One hundred and nineteen patients with unresectable HCC in the intermediate stage with Child-Pugh A were retrospectively recruited in a multicenter setting. Those in the lenvatinib RFA sequential therapy group received lenvatinib initially, followed by RFA and the retreatment with lenvatinib. The study compared overall survival (OS), progression-free survival (PFS), tumor response, and adverse events (AEs) between patients undergoing sequential therapy and lenvatinib monotherapy. RESULTS:After propensity score matching, 25 patients on sequential therapy and 50 on monotherapy were evaluated. Independent factors influencing OS were identified as sequential therapy, modified albumin-bilirubin (mALBI) grade, and relative dose intensity (%) with hazard ratios (HRs) of 0.381 (95% confidence interval [CI], 0.186-0.782), 2.220 (95% CI, 1.410-3.493), and 0.982 (95% CI, 0.966-0.999), respectively. Stratified analysis based on mALBI grades confirmed the independent influence of treatment strategy across all mALBI grades for OS (HR, 0.376; 95% CI, 0.176-0.804). Furthermore, sequential therapy was identified as an independent factor of PFS (HR, 0.382; 95% CI, 0.215-0.678). Sequential therapy significantly outperformed monotherapy on survival benefits (OS: 38.27 vs. 18.96 months for sequential therapy and monotherapy, respectively, p = 0.004; PFS: 13.80 vs. 5.32 months for sequential therapy and monotherapy, respectively, p < 0.001). Sequential therapy was significantly associated with complete response by modified Response Evaluation Criteria in Solid Tumors (odds ratio, 63.089). Ten of 119 patients experienced grade 3 AEs, with no AE beyond grade 3 observed. CONCLUSION:Lenvatinib RFA sequential therapy might offer favorable tolerability and potential prognostic improvement compared to lenvatinib monotherapy.

539 Background: Although the combination of atezolizumab and bevacizumab (ATZ + BEV) is a standard treatment for advanced hepatocellular carcinoma (HCC), strategies for addressing treatment failure and prognostic factors of post-progression survival remain unestablished. Methods: We conducted a multicenter retrospective study to evaluate post-progression survival following ATZ + BEV treatment in patients with advanced HCC. We classified the patients into four groups: BCLC stage B with or without new intrahepatic lesions (BCLCp-B1 and BCLCp-B2, respectively) and BCLC stage C without or with new extrahepatic lesions (BCLCp-C1 and BCLCp-C2, respectively) at the time of progression. Results: Of the 204 patients who started ATZ + BEV treatment between October 2020 and September 2022, 110 showed disease progression, with 25, 8, 55, and 22 showing the BCLCp-B1, BCLCp-B2, BCLCp-C1, and BCLCp-C2 stages of the disease, respectively. Specifically, patients with the BCLCp-B1 stage of the disease showed better overall survival than those with the BCLCp-B2, BCLCp-C1, and BCLCp-C2 stages (hazard ratios: 2.19 (95% confidence interval [CI], 0.61–7.86), 2.16 (95% CI, 1.13–4.11), and 2.97 (95% CI, 1.42–6.23) for HCC stages BCLCp-B2, BCLCp-C1, and BCLCp-C2, respectively). Via multivariable analysis, we identified the BCLCp-C1 and BCLCp-C2 stages, as well as performance status, Child-Pugh class, and alpha-fetoprotein as poor prognostic factors for post-progression survival. Conclusions: BCLCp-B1 stage was identified as a better prognostic factor for post-progression survival following ATZ + BEV treatment compared with BCLCp-B2 stage as well as BCLCp-C1 and BCLCp-C2 stages. This may help in making decisions regarding subsequent treatment after ATZ + BEV.

Cabozantinib is a multi-kinase inhibitor targeting multiple tyrosine kinases. It improves overall survival and progression-free survival in patients previously treated with sorafenib for advanced hepatocellular carcinoma (HCC) compared to the placebo in the phase 3 CELESTIAL trial. A 71-year-old man presented to our hospital for treatment of HCC with chronic hepatitis C. He was refractory to sorafenib, lenvatinib, regorafenib, and ramucirumab and started atezolizumab and bevacizumab therapy in November 2020. After administering the second cycle on December 10, 2020, the patient was diagnosed with progressive disease in January 2021. Therefore, cabozantinib (60 mg/day) was initiated on January 14, 2021. As the grade 3 aspartate aminotransferase and alanine aminotransferase levels increased, grade 3 anorexia and a decline in performance status were observed in the first week, and cabozantinib was terminated. His performance status and anorexia gradually improved, and contrast-enhanced computed tomography (CT) in June 2021 showed complete remission (CR) according to the modified Response Evaluation Criteria in Solid Tumors. The patient did not show disease progression for 11 months without receiving any treatment for HCC. To the best of our knowledge, this is the first report of CR with cabozantinib in advanced HCC.

Immune checkpoint inhibitors have revolutionized cancer treatment by targeting the cytotoxic T lymphocyte antigen-4 and programmed death-1/ligand-1. Although immune checkpoint inhibitors show promising therapeutic efficacy, they often cause immune-related adverse events. Immune-related adverse events differ from the side effects of conventional chemotherapy and require vigilant monitoring. These events predominantly affect organs, such as the colon, liver, lungs, pituitary gland, thyroid and skin, with rare cases affecting the heart, nervous system and other tissues. As immune-related adverse events result from immune activation, indicating the reinvigoration of exhausted immune cells that attack both tumors and normal tissues, it is theoretically possible that immune-related adverse events may signal a better response to immune checkpoint inhibitor therapy. Recent retrospective studies have explored the link between immune-related adverse event development and clinical efficacy; however, the predictive value of immune-related adverse events in the immune checkpoint inhibitor response remains unclear. Additionally, studies have focused on immune-related adverse events, timing of onset and immunosuppressive treatments. This review focuses on pivotal studies of the association between immune-related adverse events and outcomes in patients treated with immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) are effective for advanced hepatocellular carcinoma (HCC). However, there are few reports on the correlation between the clinical efficacy of ICIs and the development of immune-related adverse events (irAEs) in patients with HCC. The aim of this study was to investigate the association between irAE development and survival in patients with HCC treated with atezolizumab plus bevacizumab. Patients and Methods: We enrolled 150 patients with advanced HCC treated with atezolizumab plus bevacizumab between October 2020 and October 2021 at 5 territorial institutions. We compared the efficacy of atezolizumab plus bevacizumab between patients who experienced irAEs (irAE group) and those who did not (non-irAE group). Results: Thirty-two patients (21.3%) developed irAEs of any grade. Grade 3/4 irAEs were observed in 9 patients (6.0%). The median progression-free survivals (PFS) in the irAE and non-irAE groups were 273 and 189 days, respectively (P =.055). The median overall survivals (OS) in the irAE and non-irAE groups were not reached and 458 days, respectively (P =.036). Grade 1/2 irAEs significantly prolonged PFS (P =.014) and OS (P =.003). Grade 1/2 irAEs were significantly associated with PFS (hazard ratio [HR], 0.339; 95% confidence interval [CI], 0.166-0.691; P =.003) and OS (HR, 0.086; 95% CI, 0.012-0.641; P =.017) on multivariate analysis. Conclusion: The development of irAEs was associated with increased survival in a real-world population of patients with advanced HCC treated with atezolizumab plus bevacizumab. Grade 1/2 irAEs were strongly correlated with PFS and OS.

The global phase 3 NAPOLI -1 trial of patients with pancreatic ductal adenocarcinoma (PDAC) demonstrated an overall survival (OS) benefit from using liposomal irinotecan and 5-fluorouracil/leucovorin (nal-IRI + 5-FU/LV) after treatment with gemcitabine (GEM) compared to 5-FU/LV alone. However, the efficacy and safety of this regimen in older patients are not well studied. We conducted a single-center retrospective study to compare the therapeutic efficacy of nal-IRI + 5-FU/LV between older and younger patients with cutoff ages of 70 and 75 years, respectively. We included patients with a prior history of one or more GEM-based regimens for locally advanced or metastatic PDAC and were treated with nal-IRI + 5-FU/LV. Of the 115 patients, 54 (47.0

Background Fluorouracil, leucovorin (5FU/LV), and nanoliposomal-irinotecan (nal-IRI) combination therapy has been established as the second-line treatment for advanced pancreatic ductal adenocarcinoma. Oxaliplatin with 5FU/LV (FOLFOX) is often used as a subsequent treatment, although its efficacy and safety are yet to be fully elucidated. We aimed to evaluate the efficacy and safety of FOLFOX as a third- or later-line treatment for patients with advanced pancreatic ductal adenocarcinoma. Methods We conducted a single-centre, retrospective study that enrolled 43 patients who received FOLFOX after failure of gemcitabine-based regimen followed by 5FU/LV + nal-IRI therapy between October 2020 and January 2022. FOLFOX therapy consisted of oxaliplatin (85 mg/m 2 ), levo-leucovorin calcium (200 mg/m 2 ) and 5-FU (2400 mg/m 2 ) every 2 weeks per cycle. Overall survival, progression-free survival, objective response, and adverse events were evaluated. Results At the median follow-up time of 3.9 months in all patients, the median overall survival and progression-free survival were 3.9 months (95% confidence interval [CI], 3.1–4.8) and 1.3 months (95% CI, 1.0–1.5), respectively. Response and disease control rates were 0 and 25.6%, respectively. The most common adverse event was anaemia in all grades followed by anorexia; the incidence of anorexia and grades 3 and 4 was 21 and 4.7%, respectively. Notably, grades 3–4 peripheral sensory neuropathy was not observed. Multivariable analysis revealed that a C-reactive protein (CRP) level of > 1.0 mg/dL was a poor prognostic factor for both progression-free survival and overall survival: hazard ratios were 2.037 (95% CI, 1.010–4.107; p = 0.047) and 2.471 (95% CI, 1.063–5.745; p = 0.036), respectively. Conclusion FOLFOX as a subsequent treatment after failure of second-line treatment with 5FU/LV + nal-IRI is tolerable, although its efficacy is limited, particularly in patients with high CRP levels.

Mucinous cystadenocarcinoma (MCAC) with malignant ascites is rare. We report a case of a 28-year-old woman who presented with epigastric pain. The ascites in the Douglas fossa was identified at a nearby gynecology clinic. Computed tomography showed a multiloculated cystic lesion (9.5 × 6.4 cm) in the tail of the pancreas, which was diagnosed as mucinous cystic neoplasm on imaging. Staging laparoscopy was performed, and rapid cytology of ascites revealed adenocarcinoma, leading to a diagnosis of unresectable MCAC. Subsequently, combination chemotherapy with gemcitabine plus S-1 was initiated. Although there were no remarkable changes in the imaging findings, the peritoneal dissemination node was not consistently recognized in any of the imaging findings, and distal pancreatectomy was performed. A peritoneal dissemination node was not observed in the laparotomy findings, but the peritoneal lavage cytology was positive. The postoperative pathological result was non-invasive MCAC, and the ascites was suspected to be caused by cyst rupture. The patient has been recurrence-free, including the reappearance of ascites, for > 8 years after adjuvant therapy with S-1. Although careful follow-up will be required in the future, the very good prognosis in this case suggests that MCAC with malignant ascites without obvious peritoneal dissemination should be considered for surgical resection.

Abstract Aims There is a paucity of comparative data on the use of sorafenib and lenvatinib for unresectable hepatocellular carcinoma. We assessed the real‐world treatment outcomes between using sorafenib and lenvatinib for unresectable hepatocellular carcinoma in the multiple molecular‐targeted therapy era. Methods and Results We enrolled 386 patients treated with sorafenib or lenvatinib as the first‐line therapy for unresectable hepatocellular carcinoma at multiple centers. Propensity score matching was performed to adjust for differences in baseline and tumor characteristics between the two groups. Propensity score matching identified 110 patients in each treatment group. The median overall survival was similar between lenvatinib and sorafenib (14.8 and 13.0 months, respectively; P = 0.352). The median progression‐free survival was longer with lenvatinib than with sorafenib (7.6 and 3.9 months, respectively; P < 0.001). The overall response rate (P < 0.001) and disease control rate (P = 0.015), as defined by the modified Response Evaluation Criteria in Solid Tumors, were significantly better with lenvatinib than with sorafenib. The median overall survival was longer in patients who received subsequent treatment than in those who did not in the sorafenib group (23.1 and 5.7 months, respectively; P < 0.001), whereas the median overall survival with or without subsequent treatment did not differ significantly in the lenvatinib group (17.8 and 14.7 months, respectively; P = 0.439). Conclusion Overall survival with sorafenib and lenvatinib was not significantly different. However, patients who received subsequent treatments had longer overall survival than those who received only first‐line treatment with sorafenib, whereas lenvatinib did not show this effect.

OBJECTIVEThe aim of the study was to clarify the association of skeletal muscle mass and the prognosis of unresectable pancreatic ductal adenocarcinoma (PDAC) treated with gemcitabine plus nab-paclitaxel (GnP).METHODSWe included 124 unresectable PDAC patients who received GnP chemotherapy. Skeletal muscle mass of the third lumbar vertebrae (L3) level was measured by computed tomography immediately before GnP initiation, and the skeletal muscle index (L3-SMI) was calculated. Sarcopenia was defined as L3-SMI less than 42 cm2/m2 in male patients and less than 38 cm2/m2 in female patients.RESULTSSarcopenia was found in 63 patients (50.8%). There was no significant difference in overall survival (OS) between sarcopenia and nonsarcopenia patients; however, in elderly patients (>70 years), the OS of sarcopenia patients was significantly poorer than that of nonsarcopenia patients (390 vs 631 days, respectively; hazard ratio, 2.64; 95% confidence interval, 1.33-5.23). Multivariate analyses in elderly patients revealed that sarcopenia and tumor stage were independent poor prognostic factors. Despite the short OS of elderly sarcopenia patients, there were no significant differences in progression-free survival or response rate.CONCLUSIONSSarcopenia diagnosed by L3-SMI is a prognostic factor in elderly patients who receive GnP for unresectable PDAC. However, GnP exhibits a certain efficacy in sarcopenia and nonsarcopenia patients.

Background Transarterial chemoembolization (TACE) is the standard treatment for intermediate stage hepatocellular carcinoma (HCC) (Barcelona Clinic Liver Cancer [BCLC] B). However, it often leads to a poor prognosis and decreased hepatic function especially in patients with BCLC substage B2. Lenvatinib (LEN) was demonstrated to be efficacious in these patients in the REFLECT phase 3 trial. We therefore aimed to evaluate the efficacy and safety of LEN as a first-line treatment for the patients with HCC at BCLC substage B2. Methods This prospective observational study used LEN in TACE-naïve patients with HCC at BCLC substage B2 and preserved hepatic function. The primary endpoint was overall survival. A one-year survival rate threshold of 60% and an expected survival rate of 78%, based on previous reports of TACE, was assumed for setting the sample size. With a one-sided α-type error of 5% and 70% detection power, 25 patients were required over a 2-year enrollment period and 10-month follow-up period. Results Thirty-one patients were enrolled in this study from June 2018 to June 2020. The 1-year survival rate was 71.0% (90% confidence interval, 68.4–73.6%). Median overall and progression-free survival periods were 17.0 and 10.4 months, and the objective response rates according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 and modified RECIST criteria were 22.6% and 70.0%, respectively. Common adverse events (AEs) were fatigue (68%), hypertension (65%), anorexia (61%), palmar-plantar erythrodysesthesia (39%), and thrombocytopenia (32%) of any grade; aspartate aminotransferase increased (23%), alanine aminotransferase increased (16%), and grade ≥ 3 proteinuria (13%). Treatment interruption and dose reduction were required in 61% and 81% of patients, respectively. LEN was discontinued in 29 patients due to disease progression ( n = 17), AEs ( n = 9), conversion to curative treatments ( n = 2), and sudden death ( n = 1), whereas post-LEN treatments were administered in 18 patients, including systemic chemotherapy ( n = 11), TACE ( n = 6), transarterial infusion ( n = 1) and clinical trial ( n = 1). Conclusions The results suggest that LEN provides treatment benefits as an initial therapeutic in patients with BCLC substage B2 HCC with a safety profile comparable to that previously reported.

Sarcopenia often affects patients with various types of cancer, and has been reported to affect patient prognosis and therapeutic effects. However, to the best of our knowledge, there are no reports on the relationship between gemcitabine plus nab-paclitaxel combination therapy (GnP) and sarcopenia in patients with unresectable pancreatic cancer. The present study analyzed the relationship between overall survival (OS), progression-free survival (PFS), response rate, disease control rate, adverse events (AEs) and sarcopenia in patients with pancreatic cancer treated with GnP. A total of 121 consecutive patients with advanced pancreatic cancer who received GnP as first-line chemotherapy between January 2015 and December 2017 were retrospectively analyzed. GnP consisted of 1,000 mg/m(2) gemcitabine and 125 mg/m(2) nab-paclitaxel, which were administered on days 1, 8 and 15 every 4 weeks. The skeletal muscle index (SMI) was calculated using bioimpedance analysis (BIA) as an index of sarcopenia prior to GnP. The patients were divided into sarcopenia (n=41) and non-sarcopenia (n=80) groups using cutoff values of 8.87 and 6.42 kg/m(2) for male and female patients, respectively. The sarcopenia and non-sarcopenia groups had a median OS of 8.1 and 13.9 months, respectively [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.53-1.20], and a median PFS of 4.3 and 6.3 months, respectively (HR 0.63; 95% CI 0.42-0.95). The response and disease controls rate were not statistically different between the groups (20 vs. 32%, P=0.20; 81 vs. 80%, P=1.0). In addition, comparison of common grade 3 and 4 AEs between the two groups revealed no statistically significant differences. In conclusion, the results of the present study indicated that SMI obtained by BIA may be a predictor of treatment response and prognosis in patients with advanced pancreatic cancer who undergo GnP.