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Pancreatic cancer remains a highly lethal disease with a 5-year survival proportion of <10%. Chemoradiotherapy is a treatment option for unresectable locally advanced (UR-LA) or borderline resectable (BR) pancreatic cancer, but its efficacy is not sufficient. Induction of the synergistic effect of irradiation and immune checkpoint inhibitors can be an attractive strategy. An open-label randomized phase III trial has been conducted since October 2020 to confirm the superiority of nivolumab plus S-1-based chemoradiotherapy over S-1-based chemoradiotherapy alone in patients with UR-LA or BR pancreatic cancer. A total of 216 patients will be enrolled in 14 institutions within 3.5 years. The primary endpoint of the safety run-in part is dose-limiting toxicity, and that of the phase III part is overall survival. This trial was registered at the Japan Registry of Clinical Trials as jRCT2080225361 (https://jrct.niph.go.jp/latest-detail/jRCT2080225361)., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background/objective: Caveolin-1 (Cav1) expressed in cancer cells (cCav1) or cancer-associated fibroblasts (fCav1) exerts either pro- or anti-tumorigenic effects depending on the cancer type or stage of cancer. We aimed to clarify the impact of cCav1 or fCav1 on survival, recurrence patterns, and efficacy of neoadjuvant chemotherapy (NAC) in resected pancreatic ductal adenocarcinoma (PDAC)., Methods: Tissue microarrays were constructed including 615 patients who underwent curative resection for PDAC. Cav1 expression was evaluated by immunohistochemistry. Patients were divided into two groups based on Cav1 expression in cancer cells (cCav1 high vs. cCav1 low ) or cancer-associated fibroblasts (fCav1 high vs. fCav1 low )., Results: Among all 615 patients, 40.7% were cCav1 high and 72.7% were fCav1 high . cCav1 high was associated with worse overall survival (OS) (p = 0.001) and recurrence-free survival (RFS) (p = 0.001) than cCav1 low , and was an independent prognostic factor in multivariate analysis of OS and RFS (OS: p = 0.001, hazard ratio [HR] 1.361; RFS: p = 0.001, HR 1.348). Among 596 patients with resectable/borderline resectable PDAC, cCav1 high patients with NAC showed better OS than those without, while there was no significant difference between cCav1 low patients with NAC and those without. cCav1 high was associated with early recurrence (< 6 months) and liver metastasis after resection. Multivariate analysis revealed cCav1 high as an independent predictor of liver metastasis., Conclusions: cCav1 high correlated with worse survival, early recurrence, and liver metastasis after resection for PDAC, while NAC improved survival in cCav1 high patients. The Evaluation of cCav1 status could provide additional information contributing to the personalized management of PDAC., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Identification of homologous recombination deficiency (HRD) remains a challenge in advanced pancreatic cancer (APC). We investigated the utility of circulating tumour DNA (ctDNA) profiling in the assessment of BRCA1/2 and ATM mutation status and treatment selection in APC., Methods: We analysed clinical and ctDNA data of 702 patients with APC enroled in GOZILA, a ctDNA profiling study using Guardant360., Results: Inactivating BRCA1/2 and ATM mutations were detected in 4.8% (putative germline, 3.7%) and 4.4% (putative germline, 0.9%) of patients, respectively. Objective response (63.2% vs. 16.2%) and PFS (HR 0.55, 95% CI 0.32-0.93) on platinum-containing chemotherapy were significantly better in patients with putative germline BRCA1/2 (gBRCA) mutation than those without. In contrast, putative gBRCA mutation had no impact on the efficacy of gemcitabine plus nab-paclitaxel. In 2 patients treated with platinum-containing therapy, putative BRCA2 reversion mutations were detected. Three of seven patients with somatic BRCA mutations responded to platinum-containing therapy, while only one of four with putative germline ATM mutations did. One-third of somatic ATM mutations were in genomic loci associated with clonal haematopoiesis., Conclusion: Comprehensive ctDNA profiling provides clinically relevant information regarding HRD status. It can be a practical, convenient option for HRD screening in APC., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Early tumor shrinkage (ETS) is a prognostic predictor for patients treated with chemotherapy in colorectal cancer, although scarce studies evaluated its potential in locally advanced pancreatic cancer (LAPC). In this exploratory analysis of JCOG1407, a randomized phase II study comparing modified 5-fluorouracil, levofolinate, irinotecan, and oxaliplatin (mFOLFIRINOX) and gemcitabine plus nab-paclitaxel (GnP), we evaluated whether ETS can predict prognosis of patients with LAPC., Methods: Of the 126 patients enrolled in JCOG1407, 112 with measurable lesions were included in this study. ETS was defined as a ≥20 % reduction in tumor diameter compared with baseline at the initial imaging assessment 6-10 weeks after initiating chemotherapy. Patients were divided into the ETS (achieved ETS) and non-ETS (failed to achieve ETS) groups based on their ETS status. The impact of ETS on overall survival (OS) was compared using multivariable Cox regression analysis., Results: Fourteen of 55 (25.5 %) and 24 of 57 (42.1 %) patients in the mFOLFIRINOX and GnP arms, respectively, achieved ETS. In the overall population, mFOLFIRINOX arm, and GnP arm, the median OS in the ETS and non-ETS groups was 27.1 and 20.4, 29.8 and 20.6, and 24.1 and 20.4, months, respectively. The adjusted hazard ratios of OS for the ETS group in the overall population, mFOLFIRINOX arm, and GnP arm were 0.451 (95 % confidence interval [CI]: 0.270-0.754), 0.371 (95 % CI: 0.149-0.926), and 0.508 (95 % CI: 0.255-1.004), respectively., Conclusions: ETS may be a prognostic predictor in chemotherapy-naïve patients with LAPC treated with mFOLFIRINOX or GnP., Competing Interests: Declaration of competing interest JF reports grants from the Japan Agency for Medical Research and Development (AMED) and the National Cancer Center Research and Development Fund, during the study, as well as grants from Ono Pharmaceutical, MSD, J-Ph arma, Taiho Pharmaceutical, Takeda Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Eisai, Daiichi Sankyo, Sanofi, Sumitomo Dainippon, Astellas, Delta-Fly-Pharma, and Incyte Biosciences Japan and personal fees from Fujifilm, Delta-Fly-Pharma, Onco Therapy Science, Merck Biopharma, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Chugai Pharmaceutical, Astellas, AstraZeneca, Incyte Biosciences Japan, J-Pharma, Eisai, Daiichi Sankyo, Eli Lilly Japan, Yakult Honsha, Nihon Servier, Novartis Pharma, Takeda Pharmaceutical, Bayer, Teijin Pharma, Terumo, and Incyte Biosciences Japan outside the submitted work. KN reports personal fees from Ono Pharmaceutical, Yakult Honsha, Chugai Pharmaceutical, AstraZeneca, and Taiho Pharmaceutical outside the submitted work. HI reports grants from Ono Pharmaceutical and Nihon Servier and personal fees from Nihon Servier, Yakult Honsha, Boston Scientific, Kaneka Medix, Medico's Hirata, and SB KAWASUMI LABORATORIES outside the submitted work. SS reports grants from AstraZeneca, Incyte Corporation, and Delta-Fly-Pharma outside the submitted work. SK reports personal fees from Yakult Honsha outside the submitted work. CM reports grants from Eisai, Yakult Honsha, Ono Pharmaceutical, Taiho Pharmaceutical, J-Pharma, AstraZeneca, Merck Biopharma, Daiichi Sankyo, HITACHI, and Boehringer Ingelheim and personal fees from Yakult Honsha, MSD, Nihon Servier, Boehringer Ingelheim, Taiho Pharmaceutical, Novartis Pharma, Teijin Pharma, Eisai, and AstraZeneca outside the submitted work. MU reports grants from Japan AMED and the National Cancer Center Research and Development Fund, during the study, as well as grants from Ono Pharmaceutical, Taiho Pharmaceutical, J-Pharma, AstraZeneca, Merck Biopharma, MSD, Astellas, Eisai, Boehringer Ingelheim, Delta-Fly-Pharma, Incyte Biosciences Japan, Chugai Pharmaceutical, and Novartis Pharma and personal fees from Yakult Honsha, MSD, Nihon Servier, Ono Pharmaceutical, Chugai Pharmaceutical, Boehringer Ingelheim, Taiho Pharmaceutical, Novartis Pharma, J-Pharma, Incyte Biosciences Japan, Daiichi Sankyo, and AstraZeneca outside the submitted work. All other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Pancreatic cancer has a high risk of developing osteoporosis. However, the impact of osteoporosis has not been well-studied. This study aimed to evaluate bone loss over time and risk of osteoporosis in patients with advanced pancreatic cancer., Methods: We retrospectively examined consecutive patients with unresectable pancreatic cancer who had evaluable computed tomography before treatment and at 1-year follow-up. Bone mineral density at the first lumbar vertebra was measured on computed tomography, and osteoporosis was defined as bone mineral density < 135 Hounsfield units. The prevalence and risk factors for osteoporosis, changes in bone mineral density over time and incidence of bone fractures were analyzed., Results: Three hundred eighty patients were included. Osteoporosis was associated with older age, female sex, low body mass index and poor performance status at baseline. A consistent decrease in bone mineral density was observed over time regardless of age, sex or disease status, resulting in an increase in the prevalence of osteoporosis over time (47% at baseline, 79% at 1 year, 88% at 2 years, 89% at 3 years, 95% at 4 years and 100% at 5 years). Changes in bone mineral density from baseline were greater in patients with locally-advanced pancreatic cancer, in those who received modified FOLFIRINOX or S-IROX for more than 3 months, and in those who received radiation therapy. Incident fractures developed in 45 patients (12%) during follow-up., Conclusions: Osteoporosis and osteoporotic fractures were highly prevalent in patients with advanced pancreatic cancer. This study highlights the importance of screening for osteoporosis in such patients., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objective: Pancreatic cancer with lung oligometastasis may have favourable overall survival. The aim of this study was to evaluate outcomes of pancreatic cancer with lung oligometastases including both synchronous and metachronous metastases., Methods: Consecutive pancreatic cancer patients with lung metastasis treated at our institution between February 2015 and December 2021 were identified from our prospectively maintained database. Clinical characteristics and outcomes were compared and analysed according to the extent of lung metastases. Predictors for overall survival were analysed using the Cox proportional hazards model., Results: A totoal of 171 patients were included (oligometastasis/polymetastasis/multi-organ metastasis: 34/50/87). Patients with oligometastases were more likely to undergo surgical resection (41% vs. 0% vs. 2%) and showed a longer median overall survival (41.3 vs. 17.6 vs. 13.1 months) compared with those with other types of metastases. Oligometastasis (hazard ratio, 0.43; 95% confidence interval, 0.24-0.76; P = 0.004) was identified as an independent factor predicting favourable overall survival in patients with lung-only metastasis. Disease status (synchronous vs. metachronous) was not associated with survival in patients with oligometastasis (29.4 vs. 41.3 months, P = 0.527) and polymetastasis (17.9 vs. 16.7 months, P = 0.545). Selected patients who underwent surgical resection showed a median overall survival of 52.7 months., Conclusions: Patients with lung oligometastases presented a favourable prognosis. Surgical resection in selected patients was associated with a long median overall survival., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background/aim: FOLFIRINOX (FFX) is a standard treatment for patients with advanced pancreatic cancer. However, it often causes serious hematological adverse events. This study aimed to identify the risk factors for febrile neutropenia (FN) and grade 4 (G4) neutropenia during treatment with FFX in the real world., Patients and Methods: We analyzed data obtained from a nationwide multicenter observational study (JASPAC 06) that included 399 patients with unresectable or recurrent pancreatic cancer who received FFX at 27 institutions in Japan., Results: Nadir neutrophil counts occurred from day 8 to day 22 of cycle 1, and granulocyte colony-stimulating factor was administered to over a quarter of the patients in the first cycle. Of 399 patients, FN and G4 neutropenia occurred in 51 (13%) and 108 (27%) patients, respectively. Most FN (83%) and G4 neutropenia (75%) occurred in the first or second cycles. Multivariate logistic regression analyses showed that total bilirubin (TB) > the upper limit of normal range (ULN) and no dose modification from the original regimen were significantly associated with FN, and that TB > ULN, no dose modification from the original regimen, low platelet count (<15×10 4 /μl), and recurrent disease after pancreatectomy were independent risk factors for G4 neutropenia., Conclusion: No dose modification from the original regimen and TB > ULN were risk factors for FN and G4 neutropenia., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Undifferentiated carcinoma (UC) of the pancreas is a rare subtype of pancreatic cancer displaying no definitive direction of differentiation. UC has been reported as a highly aggressive malignant neoplasm, with a median overall survival of <1 year, except for several surgical series. On the other hand, UC tissue sometimes contains non-neoplastic osteoclast-like giant cells (OGCs), and such cases have been reported to have relatively longer survival. Thus, the World Health Organization (WHO) classification histologically distinguishes UC with OGCs (UCOGCs) from UC, and UCs were subclassified into three subtypes: anaplastic UC, sarcomatoid UC and carcinosarcoma. However, still less is known about UC due to its rarity, and such situations lead to further difficulties in treatment for UC. To date, only surgical resection can offer curative treatment for patients with UC, and no clear evidence for chemotherapy exists for them. However, a retrospective cohort study and case reports showed that relatively promising results paclitaxel-containing regimens for treatment of patients with unresectable UC. Furthermore, high programmed cell death protein 1 expression has been reported in sarcomatoid UCs and UCOGCs, and promising responses to anti-programmed death-ligand 1 therapy have been described in case reports of UCOGCs. Recent advances in chemotherapeutic agents and molecular technologies are opening up the possibilities for expanded treatments., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: The efficacy of neoadjuvant chemotherapy with gemcitabine plus S-1 (NAC-GS) in the prognosis of patients with resectable pancreatic ductal adenocarcinoma (PDAC) has been reported. NAC-GS is now assumed to be a standard regimen for resectable PDAC in Japan. However, the reason for this improvement in prognosis remains unclear., Methods: In 2019, we introduced NAC-GS for resectable PDAC. From 2015 to 2021, 340 patients were diagnosed with resectable PDAC (anatomical and biological [carbohydrate antigen (CA) 19-9 < 500 U/mL]) and were divided according to the treatment period (upfront surgery [UPS] group, 2015-2019, n = 241; NAC-GS group, 2019-2021, n = 80). We used "intention-to-treat" analysis to compare the clinical outcomes of NAC-GS to those of UPS., Results: Of the 80 patients with NAC-GS, 75 (93.8%) completed two cycles of NAC-GS, and the resection rate of the NAC-GS group was comparable to that of the UPS group (92.5 vs. 91.3%, P = 0.73). The R0 resection rate was significantly higher in the NAC-GS group than in the UPS group (91.3 vs. 82.6%, P = 0.04), even though the surgical burden was smaller. Progression-free survival tended to be better (hazard ratio [HR] = 0.70, P = 0.06), and overall survival was significantly better in the NAC-GS group than in the UPS group (HR 0.55, P = 0.02)., Conclusions: NAC-GS provided improvements in microscopic invasion leading to a high R0 rate and smooth administration and completion of adjuvant therapy, which might lead to an improved prognosis in patients with resectable PDAC., (© 2023. Society of Surgical Oncology.)

Objective: JCOG1106, a randomized phase II trial conducted to compare chemoradiotherapy (S-1 concurrent radiotherapy) with (Arm B) or without (Arm A) induction chemotherapy using gemcitabine in patients with locally advanced pancreatic cancer, showed a more favorable long-term survival in Arm A. This study was aimed at exploring whether some subgroups classified by the systemic inflammatory response might derive greater benefit from either treatment., Methods: All subjects eligible for JCOG1106 were included in this analysis (n = 51/49 in Arm A/B). This exploratory subgroup analysis was performed by Cox regression analysis to investigate the impact of the systemic inflammatory response, as assessed based on the serum C-reactive protein, serum albumin (albumin), Glasgow Prognostic Score and derived neutrophil-lymphocyte ratio, at the baseline on overall survival. P values <0.1 for the interaction were regarded as denoting significant association., Results: Glasgow prognostic score showed significant treatment interactions for overall survival. Hazard ratios of Arm B to Arm A were 1.35 (95% confidence interval, 0.82-2.23) in the Glasgow Prognostic Score 0 (C-reactive protein ≤10 mg/L and albumin ≥35 g/L) (n = 44/34 in Arm A/B) and 0.59 (95% confidence interval, 0.24-1.50) in the Glasgow Prognostic Score 1/2 (C-reactive protein >10 mg/L and/or albumin <35 g/L) (n = 7/15) (P-interaction = 0.06). C-reactive protein alone and albumin alone also showed significant treatment interactions for overall survival., Conclusions: Survival benefits of induction chemotherapy in chemoradiotherapy for locally advanced pancreatic cancer were observed in patients with elevated Glasgow Prognostic Score, high C-reactive protein and low albumin. These results suggest that systemic inflammatory response might be considered to apply induction chemotherapy preceding chemoradiotherapy., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objective Anamorelin, a novel selective ghrelin receptor agonist, was approved in Japan for the treatment of cachexia in pancreatic cancer (PC), albeit with limited evidence. This study evaluated the efficacy and safety of anamorelin in PC and examined the impact of the extent of weight loss on the efficacy of anamorelin. Methods We retrospectively investigated consecutive PC patients with cachexia who received anamorelin at our institution between June 2021 and January 2022. Patients were divided into two groups: moderate-weight-loss group (5-10%) and severe-weight-loss group (>10%). The primary outcome was changes in body weight. The secondary outcomes were changes in appetite and laboratory measures as well as treatment-related severe adverse events. Results A total of 24 patients were included (moderate/severe weight loss: 8/16). The moderate-weight-loss group showed significantly more weight gain than the severe-weight-loss group. Improvements in appetite were consistently observed in each weight-loss group. Changes in laboratory markers were not significantly different between groups. Hyperglycemia (four patients) was the most common cause of severe adverse events, followed by abdominal distension, nausea, elevated liver function tests, and bulimia. Conclusion The efficacy of anamorelin was associated with the extent of weight loss. Although anamorelin improved appetite in each weight-loss group, it increased body weight only in the moderate-weight-loss group. Anamorelin was well-tolerated among advanced PC patients, although caution must be practiced when it is used in patients with concomitant diabetes mellitus.

Objective: This study investigates the use of serum DUPAN-2 in predicting the PC progression in CA19-9 nonsecretors., Background: Although we previously reported that serum CA19-9 >500U/ mL is a poor prognostic factor and an indication for enhanced neoadjuvant treatment, there is not a biomarker surrogate that equivalently predicts prognosis for CA19-9 nonsecretors., Methods: We evaluated consecutive PC patients who underwent pancreatectomy from 2005 to 2019. All patients were categorized as either nonsecretor or secretor (CA19-9 ≤ or >2.0U/mL)., Results: Of the 984 resected PC patients, 94 (9.6%) were nonsecretors and 890 (90.4%) were secretors. The baseline characteristics were not statistically different between the 2 groups except for the level of DUPAN-2 (720 vs. 100U/mL, P < 0.001). Survival curves after resection were similar between the 2 groups (29.4 months vs. 31.3 months, P = 0.900). Survival curves of patients with DUPAN-2 >2000U/mL in the nonsecretors and patients with CA19-9 >500U/mL in the secretors were nearly equivalent as well (hazard ratio 2.08 vs. 1.89). In the multivariate analysis, DUPAN-2 >2000U/mL (hazard ratio 2.53, P = 0.010) was identified as independent prognostic factor after resection., Conclusion: DUPAN-2 >2000U/mL in CA19-9 nonsecretors can be an unfavorable factor that corresponds to CA19-9 >500U/mL in CA19-9 secretors which is an indicator for enhanced neoadjuvant treatment. The current results shed light on the subset of nonsecretors with poor prognosis that were traditionally categorized in a group with a more favorable prognosis group., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The use of duckbill-type anti-reflux metal stents (DMS) in reinterventions after covered metal stent (CMS) dysfunction has been reported in patients with distal malignant biliary obstruction (MBO). However, the superiority of DMS over conventional CMS (c-CMS) has not been established. Therefore, we conducted this retrospective study to evaluate the long-term efficacy and safety of DMS as a second stent in comparison with c-CMS., Methods: We investigated consecutive patients with distal MBO due to unresectable pancreatic cancer who underwent reintervention after dysfunction of initial biliary CMS at our institution. We compared causes of recurrent biliary obstruction (RBO), time to RBO (TRBO), adverse events (AEs), and reintervention rates of DMS and c-CMS in this stenting., Results: A total of 76 patients were included (DMS 41 and c-CMS 35). While overall RBO rates were similar between the two groups (46% vs. 63%, p = 0.172), RBO due to non-occlusion cholangitis tended to be less frequent in the DMS group than in the c-CMS group (2% vs. 14%, p = 0.089). Median TRBO was significantly longer in the DMS group (286 days vs. 112 days, p = 0.029). DMS was identified as the only significant risk factor for TRBO (hazard ratio, 0.52; p = 0.044). Overall AE rates were significantly lower in the DMS group (2% vs. 23%, p = 0.010), with non-occlusion cholangitis being the most common AE in the c-CMS group. Endoscopic reintervention was successfully performed in all patients in both groups, despite failed stent removal in 15% of patients in DMS group., Conclusions: DMS was associated with a significantly longer TRBO and lower rate of AEs compared with c-CMS in reinterventions after initial CMS dysfunction. DMS may be preferable to c-CMS as a second stent after biliary CMS dysfunction., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Osteosarcopenia, defined as the combination of osteoporosis and sarcopenia, has recently gained attention as a novel prognostic factor for survival in patients with cancer. This study aimed to evaluate the prognostic impact of osteosarcopenia in metastatic pancreatic cancer (PC)., Methods: We retrospectively investigated consecutive metastatic PC patients receiving first-line gemcitabine plus nab-paclitaxel (GnP). Skeletal muscle index at the third lumbar vertebra and bone mineral density at the first lumbar vertebra were measured using pretreatment computed tomography. Treatment outcomes of osteosarcopenia and non-osteosarcopenia groups were compared and analyzed. Multivariate analysis was performed to identify variables associated with survival., Results: Among 313 patients, osteosarcopenia was present in 59 patients (19%). The osteosarcopenia group was associated with older age, higher proportion of females, worse performance status, and higher modified Glasgow prognostic scores (mGPS). Response rates to chemotherapy, progression-free survival (3.5 months vs. 6.4 months, p < 0.001), and overall survival (5.6 months vs. 13.0 months, p < 0.001) were significantly better in the non-osteosarcopenia group. Osteosarcopenia, performance status of 1-2, mGPS score of 1-2, carcinoembryonic antigen ≥10 ng/mL, and carbohydrate antigen 19-9 ≥ 1000 IU/mL were identified as independent factors predicting shorter survival. Grade 3 or higher anemia and febrile neutropenia occurred more frequently in the osteosarcopenia group., Conclusions: Osteosarcopenia was associated with poor survival in metastatic PC treated with first-line GnP. Screening for osteosarcopenia may be helpful for better management of metastatic PC., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2023 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objectives: Clinical Practice Guidelines for Pancreatic Cancer was first published in 2006 by the Japan Pancreas Society, and revised in 2009, 2013, 2016, and 2019. In July 2022, Clinical Practice Guidelines for Pancreatic Cancer was newly revised in Japanese., Methods: For this revision, we developed an entirely new guideline according to the Minds Manual for Guideline Development 2020, which includes the concepts of GRADE-Grading Recommendations Assessment, Development, and Evaluation, to enable a better understanding of the current guidelines. Patients and the public were actively involved in both the development and implementation of the guideline., Results: The guideline includes algorithms for diagnosis, treatment, chemotherapy, and precision medicine of pancreatic cancer, and addresses 7 subjects: diagnosis, surgical therapy, adjuvant therapy, radiation therapy, chemotherapy, stent therapy, and supportive & palliative medical care. It includes 73 clinical questions and 112 statements. The statements correspond to the clinical questions, evidence levels, recommendation strengths, and agreement rates., Conclusions: This guideline represents the most standard clinical and practical management guideline available until date in Japan. This is the English synopsis of the Clinical Practice Guidelines for Pancreatic Cancer 2022 in Japanese, and is an attempt to disseminate the Japanese guideline worldwide to introduce the Japanese approach to the clinical management of pancreatic cancer., (© 2023. The Author(s).)

Aim: We compared the efficacy of modified 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) with that of gemcitabine plus nab-paclitaxel (GnP) for locally advanced pancreatic cancer (LAPC)., Methods: Patients with untreated LAPC were randomly assigned (1:1) to receive mFOLFIRINOX or GnP. One-year overall survival (OS) was the primary endpoint. The major secondary end-points included progression-free survival (PFS), response rate (RR), carbohydrate antigen 19-9 (CA19-9) response, and adverse events. The sample size was 124 patients to select a more effective regimen with a minimum probability of 0.85 and to examine the null hypothesis of the 1-year OS <53%., Results: Of the 126 patients enrolled from 29 institutions, 125 were deemed eligible. The 1-year OS was 77.4% (95% CI, 64.9-86.0) and 82.5% (95% CI, 70.7-89.9) in the mFOLFIRINOX and GnP arms, respectively. The median PFS was 11.2 (95% CI, 9.9-15.9) and 9.4 months (95% CI, 7.4-12.8) in the mFOLFIRINOX and GnP arms, respectively. The RR and CA19-9 response rate were 30.9% (95% CI, 19.1-44.8) and 57.1% (95% CI, 41.0-72.3) and 42.1% (95% CI 29.1-55.9) and 85.0% (95% CI, 70.2-94.3) in the mFOLFIRINOX and GnP arms, respectively. Grade 3-4 diarrhoea and anorexia were predominant in the mFOLFIRINOX arm., Conclusion: GnP was considered the candidate for a subsequent phase III trial because of its better RR, CA19-9 response, and mild gastrointestinal toxicities. Both regimens displayed higher efficacy in the 1-year survival than in the historical data of gemcitabine monotherapy., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Liver oligometastatic pancreatic cancer (PC) may have favorable outcomes. This study aims to evaluate outcomes and factors associated with overall survival (OS) of these patients., Methods: We retrospectively investigated consecutive PC patients with liver metastasis treated at our institution between 2013 and 2020. Clinical characteristics and outcomes were compared and analyzed according to the extent of liver metastasis. Cox proportional hazards model was used to identify prognostic factors for OS., Results: A total of 417 patients were included (multi-organ metastasis/polymetastasis/oligometastasis 174/158/85). Oligometastasis showed a longer OS compared to other types of metastases (7.7 vs 8.2 vs 13.1 months). Age <70 years, performance status of 0, modified Glasgow prognostic score of 0, carbohydrate antigen 19-9 <1000 U/mL were identified as significant prognostic factors for OS. A prognostic index consisting of these four factors successfully stratified the prognosis of these patients (prognostic index; high vs low, 19.9 vs 8.3 months). Highly selected patients who underwent surgical resection showed a median OS of 54.6 months., Conclusions: Oligometastasis presented a relatively favorable outcome. Our new prognostic index was useful in stratifying the prognosis of these patients. Multimodal treatment including surgery may have additional survival benefits for highly selected patients., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Neoadjuvant chemotherapy (NAC) is widely used to treat borderline resectable pancreatic cancer. This study aimed to evaluate the serum carbohydrate antigen (CA)19-9 response, in association with survival, after four cycles of NAC-gemcitabine plus nab-paclitaxel., Methods: From 2015 to 2018, patients with borderline resectable pancreatic cancer were treated with NAC. Patients were stratified into two groups after excluding CA19-9 non-secretor: Group L (CA19-9 ≥2 and ≤500 U/mL) and Group H (CA19-9 >500 U/mL). The CA19-9 decrease during NAC was evaluated as a response of NAC and was assessed in association with survival concomitant with other prognosis factors., Results: Eighty-seven patients were evaluated (Group L: n = 43, Group H: n = 44). In intention-to-treat-based analysis, Group L exhibited significantly better progression-free survival (PFS) than Group H (median PFS: 24 vs 14months). In resection cohort, no correlation was detected between the CA19-9 decrease and survival in Group L. In Group H, the CA19-9 decrease ≤80% was associated with unfavorable survival in multivariate analysis [Hazard ratio: 4.738 (P = 0.007)]., Conclusion: In patients with pre-treatment CA19-9 >500 U/mL, the CA19-9 decrease ≤80% was strongly associated with poor survival and new strategy should be reconsidered for these patients., Competing Interests: Conflict of interest All authors have no conflicts of interest related to this article. As a relevant financial activity outside this work, Naoki Sasahira received research funding from Taiho Pharmaceutical., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objective The coronavirus disease (COVID-19) pandemic has altered the delivery of medical care. The present study evaluated the impact of COVID-19 on the outcomes of unresectable pancreatic cancer (PC) patients who received end-of-life care. Methods We retrospectively compared the management of PC patients during the COVID-19 pandemic (from April 2020 to March 2021) to the preceding year, which was unaffected by the pandemic (from April 2019 to March 2020), based on a prospectively maintained institutional database. Results A total of 178 patients were included in the COVID-19-exposed group and 201 patients were included in the COVID-19-unexposed group. The median overall survival was similar between the groups (exposed vs. unexposed: 12.6 vs. 11.9 months, p=0.174). Treatment regimens and relative dose intensities and the progression-free survival of GnP (gemcitabine in combination with nab-paclitaxel) and mFOLFIRINOX as first- and second-line chemotherapy did not differ significantly between the two groups. Only 9.0% of patients died at home in the COVID-19-unexposed group, compared to 32.0% in the COVID-19-exposed group (p<0.001). A multivariate analysis revealed that death during the COVID-19 exposed period was independently associated with home death (odds ratio: 4.536, 95% confidence interval: 2.527-8.140, p<0.001). Conclusions While the COVID-19 pandemic did not seem to influence chemotherapeutic treatment for PC patients at our institution, it had a large impact on end-of-life care. These findings may promote discussion about end-of-life care in Japan.

Background: To compare the treatment outcomes of nanoliposomal-irinotecan (nal-IRI) plus fluorouracil and leucovorin (5-FU/LV) and modified FOLFIRINOX (mFFX) as second-line treatment after gemcitabine with nab-paclitaxel (GnP) for metastatic and recurrent pancreatic cancer., Methods: We retrospectively analyzed consecutive patients with metastatic or recurrent pancreatic cancer treated with nal-IRI plus 5-FU/LV or mFFX after first-line GnP treatment between March 2014 and October 2021 in our hospital. Patient characteristics, treatment outcomes and adverse events were extracted for comparison., Results: Two hundred sixteen patients were included (nal-IRI plus 5-FU/LV/mFFX: 50/166). Patients in the nal-IRI plus 5-FU/LV group were older, had poorer ECOG PS, and a higher rate of peritoneal metastasis than those in the mFFX group. Median overall survival was 9.5 and 9.8 months (P = 0.97), respectively, and the median progression-free survival was 4.5 vs 4.8 months (P = 0.61), respectively. Anorexia, fatigue and peripheral neuropathy were more common in the mFFX group, but there was no difference in grade 3/4 adverse events between the two groups., Conclusions: There was no significant difference in efficacy between nal-IRI plus 5-FU/LV and mFFX after GnP. Nal-IRI plus 5-FU/LV appears to be a viable alternative to mFFX as second-line treatment after GnP., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background/objectives: Pancreatic adenosquamous carcinoma (PASC) is a rare variant of pancreatic ductal adenocarcinoma (PDAC). The usual treatment for metastatic or recurrent PASC is systemic chemotherapy in accordance with the PDAC treatment strategy. This study aimed to investigate the efficacy of chemotherapy, especially the benefit of recent combination therapies, in patients with metastatic or recurrent PASC., Methods: We conducted a multicenter retrospective analysis of 116 patients with metastatic or recurrent PASC treated with first-line chemotherapy between April 2001 and December 2017 at 24 Japanese institutions., Results: Combination chemotherapies included gemcitabine + nab-paclitaxel (GnP, n = 28), fluorouracil/leucovorin + irinotecan + oxaliplatin (FFX, n = 10), gemcitabine + S-1 (GS, n = 10), and others (n = 9). Monotherapies included gemcitabine (n = 51) and S-1 (n = 8). The median overall survival (OS) was 6.5, 7.3, and 4.3 months for the whole cohort, the combination therapy group, and the monotherapy group, respectively. Multivariate analysis indicated that combination therapy showed a better trend in OS than monotherapy (hazard ratio = 0.68; 95% confidence interval, 0.38-1.20). GnP or FFX were selected in 58.7% of patients after FFX was approved in Japan, and revealed a median OS, median progression-free survival, and objective response rate of 7.3 months, 2.8 months, and 26.9% in GnP and 7.2 months, 2.3 months, and 20.0% in FFX respectively., Conclusions: This study suggests that combination therapy may be more effective than monotherapy. GnP and FFX showed similar and clinically meaningful efficacy for patients with metastatic or recurrent PASC., (Copyright © 2022 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background/aim: Carbohydrate antigen 19-9 (CA19-9) levels may aid in the determination of subsequent treatment in patients with unresectable locally-advanced pancreatic cancer (LAPC) treated with chemotherapy. However, the relationship between the timing and magnitude of CA19-9 changes and clinical outcomes remains unclear. This study was conducted to identify the timing and magnitude of CA19-9 changes, which are most strongly associated with outcomes in LAPC patients., Patients and Methods: We retrospectively analyzed consecutive LAPC patients treated with gemcitabine plus nab-paclitaxel (GnP) or modified FOLFIRINOX (mFFX) as the first-line chemotherapy between March 2014 and December 2018 in our hospital. Multivariate analyses were performed to identify prognostic factors of chemotherapy in LAPC., Results: Ninety-four patients were included (GnP/mFFX: 72/22). The median overall survival was 20.3 months, and the median progression-free survival was 8.8 months. CA19-9 values before treatment did not affect prognosis. However, CA19-9 <100 U/ml or more than a 70% reduction in CA19-9 four months after commencing treatment was associated with a good prognosis (hazard ratio=0.17; 95% confidence interval=0.09-0.33; p<0.01)., Conclusion: CA19-9 values 4 months after commencing treatment are a significant prognostic factor in LAPC patients undergoing chemotherapy., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Gemcitabine plus nab-paclitaxel (GnP) has been a standard treatment for unresectable pancreatic cancer (uPC); however, the current treatment status and usefulness in older adults with uPC remain unclear. Therefore, we aimed to investigate the patient background and compare the efficacy and safety of GnP versus other treatments in older adults with uPC., Patients and Methods: In this prospective observational study, we enrolled 233 eligible patients aged ≥76 years with pathologically proven, clinically uPC, and no history of chemotherapy from 55 Japanese centers during September 2018-September 2019. The main endpoints were overall survival (OS), progression-free survival (PFS), and safety. Geriatric assessments were performed upon registration and after 3 months. To adjust for confounders, we conducted propensity score-matched analyses., Results: GnP, gemcitabine alone (Gem), best supportive care, and other therapies were administered to 116, 72, 16, and 29 patients, respectively. In the propensity score-matched analysis, 42 patients each were selected from the GnP and Gem groups. The median OS was longer in the GnP group than in the Gem group (12.2 vs. 9.4 months; hazard ratio [HR], 0.65; 95% CI, 0.37-1.13). The median PFS was significantly longer in the GnP group than in the Gem group (9.2 vs. 3.7 months; HR, 0.38; 95% CI, 0.23-0.64). The incidence of severe adverse events was higher with GnP than with Gem; however, the difference was not significant., Conclusion: GnP is more efficacious than Gem in patients aged ≥76 years with uPC despite demonstrating a higher incidence of severe adverse events., (© The Author(s) 2022. Published by Oxford University Press.)

Background: This phase 1b trial evaluated the toxicity and efficacy of S-1, irinotecan, and oxaliplatin combination therapy (S-IROX) as first-line chemotherapy in patients with advanced pancreatic cancer (APC)., Methods: Patients aged 20-75 years with APC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible to receive escalating doses of S-1 (60 or 80 mg m 2 ·day) on days 1-7, fixed doses of oxaliplatin (85 mg/m 2 ) biweekly, and escalating doses of irinotecan (150, 165, or 180 mg/m 2 ) once every 2 weeks. In the dose-escalation cohort, a 3 + 3 design was used to determine the maximum-tolerated dose (MTD) and explore the recommended dose (RD). A dose-expansion cohort was added to further evaluate the safety and efficacy of the combination. This trial was registered at UMIN-CTR (UMIN000012054)., Results: Approximately 47 patients were enrolled, of whom 45 were eligible for the analysis. The MTD was not determined, but the RD was determined to be dose level 1 based on a review of data from each level. Among the 45 patients, the ORR was 51.1% [95% confidence interval (CI), 35.8-66.3%]. The median progression-free survival and median overall survival was 6.9 months (95% CI, 5.1-8.8 months) and 15.8 months (95% CI, 9.8-20.8 months), respectively. Common adverse events included neutropenia, elevated liver enzyme levels, diarrhoea, and nausea., Conclusions: The S-IROX regimen showed promising efficacy with manageable toxicities in Japanese patients with APC. A randomised phase 2/3 trial comparing S-IROX, mFOLFIRINOX, and gemcitabine plus nab-paclitaxel is currently ongoing (jRCTs031190009)., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. A.O. has received honoraria from Yakult and Taiho. N.O. has received honorarium from Taiho. F.M. has received research funding from Yakult, Taiho, and Daiichi Sankyo, honoraria from Yakult, Taiho, and Daiichi Sankyo. M.S. has received honorarium from Yakult. H.I. has received honorarium from Yakult. C.M. has received research funding from Yakult, Taiho, and Daiichi Sankyo, honoraria from Yakult and Taiho. M.O. has received honorarium from Yakult. M.I. has received research funding from Yakult, honoraria from Yakult and Taiho. J.F. has received research funding from Yakult, Taiho, and Daiichi Sankyo, honoraria from Yakult, Taiho, and Daiichi Sankyo. T.O. has received honoraria from Yakult, Taiho, and Daiichi Sankyo. All remaining authors have declared no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A 67-year-old woman underwent distal pancreatectomy for pancreatic cancer. Recurrence in the form of lung metastasis was discovered eight months after surgery, and chemotherapy was initiated. Two years after the surgery, she was admitted for the evaluation of melena. Esophagogastroduodenoscopy revealed multiple subepithelial lesions with ulceration from the gastric body to the fornix. The histopathology of biopsy specimens was consistent with ductal adenocarcinoma, which appeared similar to the resected pancreatic cancer. The patient was diagnosed with multiple gastric metastases of pancreatic cancer. We herein report a case of pancreatic cancer with multiple gastric metastases that occurred after surgery for pancreatic tail cancer.

Objectives: Serial pancreatic-juice aspiration cytologic examination (SPACE) is useful for diagnosis of pancreatic ductal stenosis. This study investigates the utility of adding brush cytology to SPACE during the same procedure., Methods: We retrospectively analyzed consecutive patients who underwent SPACE with brush cytology for pancreatic ductal stenosis between February 2014 and July 2020 in our hospital., Results: Thirty-four patients were included. Eleven had lesions in the pancreatic head lesions, and 23 had lesions in the pancreatic body or tail. Malignancies were found in 22 patients. Endoscopic ultrasound, computed tomography, and magnetic resonance imaging showed distal pancreatic duct dilation in 81.8% to 90.6% of cases, with a sensitivity of 63.0% to 65.5%. The sensitivity and diagnostic accuracy of SPACE, brush cytology, and SPACE with brush cytology were 63.6%, 50.0%, and 77.3% (P = 0.19) and 73.5%, 67.6%, and 82.4% (P = 0.42), respectively. No significant differences in diagnostic yield were observed for either pancreatic head lesions or pancreatic body/tail lesions. Post-endoscopic retrograde cholangiopancreatography pancreatitis was observed in 4 cases (11.8%)., Conclusions: The utility of adding brush cytology to SPACE was limited., Competing Interests: N.S. received research funding from Taiho Pharmaceutical. M.O. received honoraria from Taiho Pharmaceutical, Yakult, Bayer, Pfizer, Ono Pharmaceutical, and Bristol-Myers Squibb. The other authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The prognosis of initially unresectable pancreatic cancer (UR-PC) has improved since the introduction of FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GNP) treatment. Nonetheless, the indications and optimal timing for conversion to resection remain unclear for UR-PC. The aim of this study is to evaluate the characteristics of cases with initially UR-PC who received modified FFX or GNP treatment., Methods: This retrospective study reviewed 454 consecutive Japanese UR-PC cases who received modified FFX/GNP treatment. Cases were categorized according to resection status, and overall survival (OS) was evaluated using a multivariable prognostic scoring model (0-4 points, higher score indicating more favorable prognostic factors)., Results: The overall resection rate was 16% for locally advanced UR-PC (UR-LA) and 5% for metastatic UR-PC (UR-M). The resection group had better OS than the nonresection group (median OS time: not reached versus 13.0 months, P < 0.001). The independent prognostic factors were normalized CA19-9 concentration, modified Glasgow prognostic score of 0, tumor shrinkage after chemotherapy, chemotherapy duration ≥ 8 months, and resection. Cases were grouped according to their prognostic score, and the results suggested that candidates for resection might have prognostic scores of 4 points in UR-M cases or 2-4 points in UR-LA cases., Conclusions: Stratification according to prognostic score was useful in predicting the outcomes of UR-PC cases and may aid in identifying cases who might benefit from surgical treatment after responding to chemotherapy., (© 2022. Society of Surgical Oncology.)

Background: Early-onset pancreatic cancer (≤50 years, EOPC) is uncommon. This study aims to characterize the clinical and survival characteristics of EOPC in comparison to late-onset pancreatic cancer (>50 years, LOPC)., Methods: We retrospectively investigated consecutive PC patients treated at our institution between 2010 and 2019. We analyzed and compared clinicopathological characteristics, treatments, and outcomes of EOPC and LOPC., Results: Of 1646 PC patients identified (768 resectable/borderline resectable; 248 locally advanced; 630 metastatic), 127 (8%) had EOPC. Current smoking and heavy drinking were associated with EOPC. EOPC presented at a more advanced stage and had higher neutrophil-to-lymphocyte ratios than LOPC. Survival outcomes were similar between the two groups, both in the entire cohort and in each resectability group. In patients undergoing resection, EOPC tended to have a higher N stage (p = 0.099) and had a higher pathological stage (stage IV, 20% vs. 7%, p = 0.005) and a lower rate of macroscopically curative resection (80% vs. 93%, p = 0.006). Liver recurrence was more commonly observed in EOPC (42% vs. 23%, p = 0.015). In the metastatic cohort, combination chemotherapy regimens were more frequently administered in EOPC as first-line treatment (79% vs. 64%, p = 0.028). Both median PFS (4.4 vs. 5.3 months, p = 0.647) and OS (11.5 vs. 9.5 months, p = 0.183) were not significantly different between the two groups., Conclusions: EOPC presented with a more aggressive tumor biology. Survival outcomes were similar to LOPC due to more intensive treatment., (Copyright © 2022 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background/aim: This study evaluated the efficacy of adjuvant chemotherapy (AC) for intraductal papillary mucinous carcinoma (IPMC)., Patients and Methods: We retrospectively analyzed patients who underwent pancreatectomy for invasive IPMC from January 2007 to June 2020. We evaluated outcomes of AC in the entire cohort and in patients with known prognostic factors., Results: A total of 51 patients with invasive IPMC underwent surgery, of which 35 received AC. In the entire cohort, there was no significant difference in median overall survival (OS) between the AC and surgery alone (SA) group [hazard ratio (HR)=0.54; p=0.232]. For patients with poorly differentiated adenocarcinoma, median OS was significantly longer in the AC group (HR=0.27; p=0.022). For patients with lymph node metastasis, median OS was significantly higher in the AC group (HR=0.07; p<0.001)., Conclusion: AC may be effective for selected invasive IPMC patients., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Hereditary pancreatic cancers are caused by several inherited genes. Familial pancreatic cancer is defined as pancreatic cancer arising in a patient with at least two first-degree relatives with pancreatic cancer in the absence of an identified genetic cause. Hereditary pancreatic cancer syndromes and familial pancreatic cancers account for about 10% of pancreatic cancer cases. Germline mutations in BRCA1, BRCA2, ATM, PALB2, CDKN2A, STK11, and TP53 and mismatch repair genes ( MLH1, MSH2, MSH6, PMS2, and EPCAM ) are among the well-known inherited susceptibility genes. Currently available targeted medications include poly (ADP-ribose) polymerase inhibitors (PARP) for cases with mutant BRCA and immune checkpoint inhibitors for cases with mismatch repair deficiency. Loss of heterozygosity of hereditary pancreatic cancer susceptibility genes such as BRCA1/2 plays a key role in carcinogenesis and sensitivity to PARP inhibitors. Signature 3 identified by whole genome sequencing is also associated with homologous recombination deficiency and sensitivity to targeted therapies. In this review, we summarize molecular features and treatments of hereditary pancreatic cancer syndromes and surveillance procedures for unaffected high-risk cases. We also review transgenic murine models to gain a better understanding of carcinogenesis in hereditary pancreatic cancer.

Primary pancreatic lymphomas are extremely rare, accounting for 0.1-0.5% of malignant lymphomas and about 0.2% of primary pancreatic tumors. They occur most commonly in the pancreatic head of elderly males, with diffuse large B-cell lymphoma being the most common subtype. Primary pancreatic follicular lymphoma is the most commonly reported primary pancreatic indolent lymphoma, accounting for 9-14% of primary pancreatic lymphomas. We report two cases of primary pancreatic follicular lymphoma treated with obinutuzumab, a second-generation humanized anti-CD20 monoclonal antibody, and bendamustine. One was diagnosed by endoscopic ultrasound-guided fine-needle aspiration, while the other required laparoscopic lymph node sampling to reach a diagnosis. Both achieved complete response with induction therapy and opted for maintenance therapy with obinutuzumab. We also conducted a literature review of primary pancreatic follicular lymphoma cases reported over the last 30 years., (© 2021. Japanese Society of Gastroenterology.)

Pancreatic cancer is the fourth leading cause of cancer-related death in Japan. Pancreatic cancer is categorized as resectable, borderline resectable, or unresectable based on the degree of adjacent vascular invasion and the presence of distant metastases. Neoadjuvant chemotherapy with gemcitabine and S-1 (NAC-GS) has recently become a standard option for resectable pancreatic cancer in Japanese patients. According to previous reports, GS is considered to be relatively safe and feasible treatment for Japanese patients, including the elderly. However, NAC-GS is occasionally associated with severe adverse events which may ultimately render the patient unfit for surgery. A 60-year-old man with resectable pancreatic cancer suffered from severe necrotic enteritis during NAC-GS, which required surgical resection. Considering the time course and histological findings of the resected bowel, S-1 was believed to be the causative agent. The low urinary dihydrouracil to uracil ratio also suggested possible dihydropyrimidine dehydrogenase deficiency, which may have hindered the metabolism of S-1 and contributed to the development of necrotic enteritis. Life-threatening enteritis occurs in approximately 0.3% of all patients who receive S-1. As initial symptoms are non-specific, patients should be instructed to lower the hurdle for contacting the hospital during NAC-GS., (© 2021. Japanese Society of Gastroenterology.)

Objective: With the introduction of modified FOLFIRINOX and gemcitabine plus nab-paclitaxel therapy for unresectable pancreatic cancer, erlotinib plus gemcitabine therapy is now occasionally used as late-line therapy. This study investigates outcomes of treatment with erlotinib plus gemcitabine for unresectable pancreatic cancer., Methods: We retrospectively analysed consecutive patients with unresectable pancreatic cancer treated with erlotinib plus gemcitabine as the third or later-line chemotherapy between March 2014 and December 2020 in our hospital., Results: A total of 56 patients were included (third line/fourth or later line = 42/14). All patients were previously treated with gemcitabine plus nab-paclitaxel and 45 patients were previously treated with modified FOLFIRINOX. The median progression-free survival (PFS) and overall survival (OS) were 1.6 and 4.6 months, respectively. The disease control rate was 21.4%. Performance status, modified Glasgow prognostic score and carcinoembryonic antigen level were independently associated with survival. Our prognostic model using these parameters could classify patients into good (n = 32) and poor (n = 24) prognostic groups. The median PFS and OS were longer in good than in poor prognostic group, but the difference in PFS was very small (PFS: 2.1 vs. 1.4 months, P = 0.01. OS: 6.8 vs. 2.4 months, P < 0.01). Interstitial pneumonia occurred in one patient (1.8%)., Conclusions: Benefits of erlotinib plus gemcitabine as late-line chemotherapy were limited, particularly with respect to PFS. Development of more effective third-line treatment options is desirable in the future., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Peritoneal metastasis is one of the most important poor prognostic factors in advanced pancreatic cancer (PC). Whether the prognosis of PC with peritoneal metastasis has improved with the advent of gemcitabine plus nab-paclitaxel (GnP) and modified FOLFIRINOX (mFFX) is uncertain. The aim of this study was to evaluate the improvements in treatment outcomes of PC with peritoneal metastasis., Methods: We retrospectively investigated consecutive PC patients with peritoneal metastasis treated with chemotherapy at our institution between 2010 and 2019. We compared the clinical characteristics and survival outcomes according to the period of diagnosis (group A, 2010-2014; group B, 2015-2019) and chemotherapy regimen. We also examined the prognostic factors for overall survival (OS)., Results: Among 180 patients included (GnP 88; mFFX 14; other regimens 78), distant metastasis was confined to the peritoneum in 89 patients. Although group B had a worse performance status compared to group A, median OS was significantly longer in group B. GnP and mFFX showed a significantly higher objective response rate and disease control rate in addition to longer progression free survival and OS compared to other regimens. The administration of GnP or mFFX, performance status, and neutrophil to lymphocyte ratio ≥5 were identified as independent prognostic factors for OS. Furthermore, the amount of ascites and extent of peritoneal metastasis were significantly associated with OS in patients with distant metastasis confined to the peritoneum., Conclusions: The prognosis of PC with peritoneal metastasis has significantly improved over time with the advent of GnP and mFFX., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2021 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background . A higher Ki-67 labeling index is associated with a poorer prognosis in gastroenteropancreatic neuroendocrine neoplasms. It has also been proposed that the Ki-67 labeling index may increase during disease progression from the primary site to metastatic sites. Although biopsy specimens are used to measure the Ki-67 labeling index, heterogeneity in lesions is thought to affect the assessment of the Ki-67 labeling index. To overcome tumor heterogeneity, we evaluated the variability in the Ki-67 labeling index between primary lesions and hepatic metastases by analyzing only surgically resected specimens. Methods. We conducted a single-center retrospective study to analyze the variability in the Ki-67 labeling index and the change in tumor grade between the primary site and metastatic hepatic sites in 19 patients diagnosed with gastroenteropancreatic neuroendocrine neoplasms at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from 1998 to 2018. Both the primary site and metastatic hepatic sites were surgically resected. Results. Among the 19 patients with gastroenteropancreatic neuroendocrine neoplasms, 12 patients (63%) showed higher levels of the Ki-67 labeling index at metastatic hepatic sites than at the primary site. The median Ki-67 labeling index levels for the primary lesion and metastatic hepatic lesions were 5% and 10%, respectively. The Ki-67 labeling index levels were significantly elevated in the metastatic hepatic lesions compared to the primary lesion ( P  = .002). Conclusions. This study addressed the heterogeneity of the Ki-67 labeling index by analyzing only surgically resected specimens. We observed a statistically significant increase in the Ki-67 labeling index in hepatic metastases compared to the primary lesion.

Aim: Combination therapy with gemcitabine and nanoparticle albumin-bound paclitaxel (nab-paclitaxel), known as GnP therapy, significantly prolongs the survival of pancreatic cancer patients compared with gemcitabine monotherapy. However, it may cause severe neutropenia, requiring discontinuation of treatment. This study aimed to clarify the risk factors for Grade 3/4 neutropenia during GnP therapy., Methods: Clinical data of pancreatic cancer patients who underwent GnP therapy at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from December 2014 to December 2016 were retrospectively collected. The relationship of Grade 3/4 neutropenia onset to laboratory values and patient background factors was investigated by multivariate logistic regression analysis., Results: Clinical data of 222 patients were analyzed. Grade 3/4 neutropenia occurred in 118 patients (53.2%) in the first cycle of GnP therapy. Multivariate analysis identified low absolute neutrophil count (ANC), high total bilirubin (T-Bil), and low C-reactive protein (CRP) as risk factors for Grade 3/4 neutropenia. Age was not a risk factor. The incidence of neutropenia was 85.7% in patients with all three risk factors, but only 27.7% in patients with none of them., Conclusion: Low ANC, high T-Bil, and low CRP may be risk factors for Grade 3/4 neutropenia in patients receiving GnP therapy, even if these laboratory values are within normal reference ranges. Patients with these risk factors should be carefully monitored for adverse events., Competing Interests: The authors have declared that no competing interests exist.

Background: Elderly pancreatic cancer (PC) patients are often considered vulnerable to treatment and standard treatment strategy for this subpopulation is uncertain. Cachexia and sarcopenia are reported to be associated with reduced physical performance, reduced anti-tumor response, increased chemotherapy toxicity, and poor prognosis in several malignancies. The aim of this study was to evaluate the impact of cachexia and sarcopenia on the clinical course of elderly PC patients receiving chemotherapy., Methods: We retrospectively investigated consecutive elderly metastatic PC patients (≥ 75 years) treated with chemotherapy at our institution between January 2015 and April 2020. Skeletal muscle index was calculated at the third lumbar vertebra using pretreatment computed tomography. We evaluated time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), early treatment discontinuation, relative dose intensity (RDI), and severe adverse events (AEs)., Results: Among 80 patients included (gemcitabine plus nab-paclitaxel [GnP] 52; gemcitabine 21; S1 6; modified FOLFIRINOX 1), cachexia and sarcopenia were present in 48 (60%) and 61 (76%) patients, respectively. Cachexia was associated with older age, worse performance status, higher level of neutrophil to lymphocyte ratio, worse nutritional status, and shorter TTF and PFS. Furthermore, it was also associated with early treatment discontinuation, reduced RDI of nab-paclitaxel, and increased incidence of grade 4 neutropenia in patients receiving GnP. On the other hand, sarcopenia had less impact on the clinical course of elderly PC patients., Conclusions: In our experience, cachexia was considered an effective tool in the management of elderly PC patients receiving palliative chemotherapy.

Intraductal papillary mucinous neoplasm (IPMN) sometimes forms fistulas with other organs due to high pressure of pancreatic duct filled with huge amount of mucus. Pancreatobiliary fistula may cause obstructive jaundice due to the mucus and it is hard to manage the jaundice by endoscopic biliary stenting because of high viscosity of the bile. We report a case of IPMN with pancreatobiliary fistula managed by endoscopic ultrasound (EUS)-guided hepaticogastrostomy (HGS). The patient was 87 years old and presented with obstructive jaundice. As a transpapillary biliary stent was considered to have a risk of migration due to the absence of bile duct stenosis, a nasobiliary catheter was placed as an initial drainage. However, the catheter was frequently obstructed by mucus. The patient was intolerable for surgery because of his age. Considering the intrahepatic bile was serous, EUS-HGS was performed and jaundice improved successfully. This case study revealed that EUS-HGS might be a therapeutic option for obstructive jaundice caused by an IPMN-associated pancreatobiliary fistula.

Background: The prognostic impact of tumour location (pancreatic head vs. pancreatic body/tail) and first-line chemotherapy regimen (gemcitabine plus nab-paclitaxel vs. modified FOLFIRINOX) has not been fully elucidated in locally advanced pancreatic cancer. Therefore, we conducted this study to examine the prognostic impact of tumour location and first-line chemotherapy regimen., Methods: We retrospectively investigated locally advanced pancreatic cancer patients who initiated first-line chemotherapy (gemcitabine plus nab-paclitaxel or modified FOLFIRINOX) between March 2014 and December 2019. We compared clinical characteristics and survival outcomes according to chemotherapy regimen and tumour location. Furthermore, we examined the prognostic factors associated with overall survival using cox proportional hazards model. Distant metastasis pattern was also compared according to tumour location., Results: A total of 128 patients were included (GnP 95, mFFX 33; Ph 66, Pbt 62). Distribution of chemotherapy regimen was balanced between pancreatic head and pancreatic body/tail cancers. Eight patients underwent conversion surgery and 81 patients (63%) developed distant metastasis. Although patients receiving modified FOLFIRINOX were significantly younger and tended to have better performance status compared to patients receiving gemcitabine plus nab-paclitaxel, radiological tumour response, progression-free survival, overall survival and chemotherapy-related adverse events were similar between the two groups except for grades 3-4 anorexia (9% vs. 1%, P = 0.05). Furthermore, overall survival was similar between pancreatic head and pancreatic body/tail cancers. Conversion surgery and radiation therapy were identified as independent prognostic factors for overall survival. The most common site of distant metastasis was liver metastasis in both groups and pattern of distant metastasis was not different between the two groups., Conclusions: In our experience, tumour location and first-line chemotherapy regimen were not a prognostic factor for overall survival in locally advanced pancreatic cancer., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Although the efficacy of neoadjuvant chemotherapy with gemcitabine plus S-1 (NAC GS) has recently been reported in resectable pancreatic cancer, severe adverse events were frequently observed. Sarcopenia has been reported to be associated with reduced antitumor response and chemotherapy toxicity in several malignancies. The aim of this study is to evaluate the impact of body composition on short-term outcomes of NAC GS in resectable pancreatic cancer patients., Methods: Clinicopathological data of consecutive patients treated with NAC GS at our institution from February 2019 to April 2020 were retrospectively reviewed. Anthropometric variables were calculated at the third lumbar vertebra using pretreatment computed tomography images. We investigated the association between body composition variables, and antitumor response and chemotherapy toxicity., Results: Among 62 patients included in this study, 25 patients (40%) were sarcopenic at diagnosis. Sixty-one patients received surgery at our institution and 57 patients received pancreatic resection (R0/R1 resection 56/1). Fifty-six patients completed two cycles of NAC GS and severe adverse events (≥grade 3) occurred in 42 patients (hematologic toxicity 41 patients [66%]; non-hematologic toxicity 3 patients). Body mass index and total adipose tissue index were significantly lower in sarcopenic patients compared to non-sarcopenic patients. Completion rate of NAC, rate of treatment delay/interruption, relative dose intensity of gemcitabine and S-1, radiological and pathological tumor response after NAC were not different between sarcopenic and non-sarcopenic patients. Furthermore, there was no significant association between body composition, and severe adverse events and intolerance., Conclusions: In our experience, NAC GS was similarly tolerable and effective in resectable pancreatic cancer patients regardless of the presence of sarcopenia., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objectives: To compare the treatment outcomes of gemcitabine with nab-paclitaxel (GnP) and modified FOLFIRINOX (mFFX; a combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin) for metastatic pancreatic cancer., Methods: We retrospectively analyzed consecutive patients with metastatic or recurrent pancreatic cancer treated with GnP or mFFX as the first-line chemotherapy between March 2014 and December 2019 in our hospital. Treatment outcomes were compared using propensity score matching to adjust for age, sex, performance status, carcinoembryonic antigen levels, carbohydrate antigen 19-9 levels, and disease status (metastatic or recurrent)., Results: Five hundred sixty-eight patients were included (GnP/mFFX, 456/112). After propensity score matching, 218 patients were extracted. The median age was around 61 years, and the proportion of performance status 0 was approximately 90%. The median overall survival values were 14.6 and 15.5 months (P = 0.45), and the median progression-free survival was 7.4 months (P = 0.53) for GnP and mFFX, respectively. The disease control rates were higher in the GnP group (82.6% vs 67.9%, P = 0.02). In nonhematologic adverse events, grade 3/4 anorexia and diarrhea occurred significantly more frequently in the mFFX group., Conclusions: Gemcitabine with nab-paclitaxel had a higher disease control rate and lower rates of severe anorexia and diarrhea in our propensity-matched population., Competing Interests: The authors declare no conflict of interests. Conflicts of interests outside this work are as follows: N.S. received research funding from Zeria, Eisai, Kyowa Hakko Kirin, Baxalta, and Taiho Pharmaceutical. M.O. received honoraria from Taiho Pharmaceutical, Yakult, Bayer, Pfizer, Novartis, Takeda Pharmaceutical Company Limited, Eisai, EA Pharma, and Mitsubishi Tanabe Pharma Corporation and research funding from Merck & Co, Inc, Incyte, ASLAN Pharmaceuticals, Taiho Pharmaceutical, and Yakult. T.S. received honoraria from Taiho Pharmaceutical and Eisai., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Drug-induced interstitial lung disease (ILD) is one of the most serious adverse events with a high mortality rate and represents a serious clinical problem. However, gemcitabine plus nab-paclitaxel (GnP)-induced ILD in pancreatic cancer (PC) patients has not been thoroughly investigated. Therefore, we conducted this study to examine the clinical characteristics of GnP-induced ILD and identify risk factors for developing ILD., Methods: We retrospectively investigated consecutive patients with PC who received GnP between January 2015 and April 2020. We compared the clinical characteristics and overall survival (OS) according to ILD occurrence and explored risk factors including ABO blood type for developing ILD., Results: Of the 910 patients included in this study, ILD occurred in 20 patients (2.2%). PC patients who developed ILD had a significantly higher frequency of blood type B compared to those without ILD (42% vs. 22%, p ˂ 0.05). Other baseline characteristics including smoking history and current/previous lung disease were not different between the two groups. Median time from initiation of GnP to onset of ILD was 80 days. All patients recovered from ILD and OS was not significantly different according to ILD occurrence. Multivariate analysis revealed that blood type B was an independent risk factor for developing ILD., Conclusions: We demonstrated that GnP-induced ILD occurred in 2.2% of PC patients with no mortality and OS did not differ according to ILD occurrence. Furthermore, we clarified that ABO blood type B was an independent risk factor for developing ILD in PC patients receiving GnP.

Background: Chemoradiotherapy is a treatment option for locally advanced pancreatic cancer. However, the efficacy of induction chemotherapy prior to chemoradiotherapy is uncertain. The aim of this randomized, multicentre phase II study is to evaluate the efficacy and safety of chemoradiotherapy with and without induction chemotherapy to determine the significance of induction chemotherapy., Methods: Patients with locally advanced pancreatic cancer were randomly assigned to the chemoradiotherapy arm (Arm A) or induction chemotherapy followed by the chemoradiotherapy arm (Arm B). Patients in Arm A underwent radiotherapy with concurrent S-1. Patients in Arm B received induction gemcitabine for 12 weeks, and thereafter, only patients with controlled disease underwent the same chemoradiotherapy as Arm A. After chemoradiotherapy, gemcitabine was continued until disease progression or unacceptable toxicity in both arms. The primary endpoint was overall survival., Results: Amongst 102 patients enrolled, 100 were eligible for efficacy assessment. The probability of survival was greater in Arm B in the first 12 months, but the trend was reversed in the following periods (1-year survival 66.7 vs. 69.3%, 2-year survival 36.9 vs. 18.9%). The hazard ratio was 1.255 (95% confidence interval 0.816-1.930) in favour of Arm A. Gastrointestinal toxicity was slightly more frequent and three treatment-related deaths occurred in Arm A., Conclusions: This study suggested that the chemoradiotherapy using S-1 alone had more promising efficacy with longer-term survival, compared with induction gemcitabine followed by chemoradiotherapy for locally advanced pancreatic cancer., Clinical Trial Registration: The study was registered at the UMIN Clinical Trials Registry as UMIN000006811., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background/purpose: We evaluated efficacy of neoadjuvant therapy with gemcitabine and nab-paclitaxel (GNP-NAT) in borderline resectable pancreatic cancer (BR-PC) patients compared to conventional upfront surgery (UPS)., Methods: This single-center retrospective study assessed 151 consecutive patients: 96 diagnosed in 2008-2014 underwent UPS (UPS group) and 55 diagnosed in 2015-2017 underwent GNP-NAT (GN group). Patient background, surgical, pathological, and survival outcomes were compared between groups., Results: Age, sex, and pretreatment carbohydrate antigen 19-9 were similar between groups. After four courses of NAT-GNP, 46 GN patients (84%) underwent surgery while all UPS patients underwent surgery. Only three GN patients (5%) underwent non-therapeutic procedures, compared to 23 (24%) in the UPS group (P = .004). In the whole cohort, R0-resection was achieved in 40 GN patients (73%) vs 46 UPS patients (48%; P = .004) and the 3-year overall survival was significantly higher in the GN group (median survival time, 31.9 vs 18.1 months, P = .014). In the resection cohort, the R0-resection rate was 93% (GN) vs 63% (UPS; P = .0007). There was no 90-day mortalities in either group., Conclusions: Intention-to-treat-based analysis indicated considerable benefits of GNP-NAT in BR-PCs for long-term survival, contributing to improved tumor suppression and patient selection., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Objectives: The aim of this multicenter retrospective study was to identify the optimal chemotherapeutic regimen for advanced pancreatic acinar cell carcinoma (PACC)., Methods: Fifty-eight patients with histopathologically confirmed advanced PACC who had received chemotherapy between 1996 and 2013 were enrolled. The clinical characteristics of the patients and the treatment efficacy data were collected from the medical records at 16 Japanese institutions, using standardized data collection instrument., Results: The most commonly selected treatment regimens were gemcitabine-, fluoropyrimidine-, platinum-, and irinotecan-containing regimens. The overall response rate in the patients who received first-line chemotherapy were 7% and 38%, respectively, and the median overall survival was 13.2 months. When the data for all the treatment lines were aggregated, the response rates to gemcitabine-, fluoropyrimidine-, platinum-, and irinotecan-containing regimens were 7%, 18%, 40%, and 29%, respectively. The overall survival tended to be better in patients who had received a platinum-containing regimen (hazard ratio, 0.50; 95% confidence interval, 0.23-1.11; P = 0.08) or irinotecan-containing regimen (hazard ratio, 0.42; 95% confidence interval, 0.15-1.19; P = 0.09) at least once in the treatment course as compared with those who had not., Conclusions: Our findings suggested that platinum- and irinotecan-containing regimens exhibited some potential efficacy in patients with advanced PACC., Competing Interests: M.I. has a board membership of Nihon Servier, Novartis, Bayer, Eisai, Eli Lilly, Chugai, AstraZeneca, Shire, Nano Carrier, and ASLAN, grants from Yakult, Ono, Bristol-Myers Squibb, Nano Carrier, Novartis, Bayer, Eisai, Eli Lilly, MSD, Chugai, AstraZeneca, J-Pharma, Pfizer, ASLAN, Merck Serono, and Takeda, payment for lectures from Taiho, Yakult, Nihon Servier, Novartis, Bayer, Eisai, Eli Lilly, Dainippon Sumitomo, MSD, Mylan, Chugai, Astellas, EA pharma, Gilead, Otsuka, and Teijin. Y.K. has a payment for lectures from Taiho, Chugai, Sanofi, Bristol-Myers Squibb, and Eli Lilly. Expert Testimony from AstraZeneca, grants from Ono, Nano Carrier, BeiGene, Taiho, and Takeda. S.K. has a payment for lectures from Bayer, Boston Scientific, Daiichi Sankyo, Eisai, Kyowa Hakko Kirin, Taiho, and Teijin. M.O. has grants from Astellas, Ono, Taiho, MSD, Incyte and Yakult, payment for lectures from Taiho, Yakult, and Novartis. A.K. has a Consulting fee from Taiho. M.U. has a grants from Astellas, Taiho, Daiichi Sankyo, Eisai, AstraZeneca, Ono, MSD, Merck Serono, Dainippon Sumitomo, Incyte, ASLAN and Yakult, payment for lectures from Taiho, Yakult, AstraZeneca, Teijin, Merck Serono, Nipro, MSD, and Daiichi Sankyo. C.M. has a grants from Yakult, Eisai, Taiho, Merck biopharma, AstraZeneca and J-Phama, payment for lectures from MSD, Yakult, Novartis, Teijin, Taiho and AbbVie. J.F. has a Consultancy of Fujifilm, Ono, Yakult, MSD, Merck Bio, J-Pharma, MSD, Chugai, Taiho, Nihon Servier, AstraZeneca, AbbVie, and Astellas, grants from Ono, MSD, Sumitomo Dainippon, J-Pharma, Yakult, AstraZeneca, Daiichi Sankyo, Eisai, Bayer, Pfizer, Nano Carrier, Kyowa Hakko Kirin, Taiho, Chugai, Sanofi, Takeda, Mochida, Astellas, and Eli Lilly Japan, payment for lectures from Eisai, Bayer, Taiho, Ono, Novartis, Yakult, Teijin, Shionogi, EA pharma, Eli Lilly Japan, Takeda, Chugai, Mochida, Nihon Servier, Sanofi, Fujifilm Toyama, Nobel pharma, Pfizer, Sawai, Daiichi Sankyo, Sumitomo Dainippon, Merck Serono, Nippon Kayaku, MSD, Shire, and Kyowa Hakko Kirin. The other authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: In the NAPOLI-1 phase 3 trial, liposomal irinotecan (nal-IRI) +5-fluorouracil/leucovorin (5-FU/LV) significantly increased mPFS versus 5-FU/LV (3.1 vs. 1.5 months [unstratified HR = 0.56, p = 0.0001]) in patients with mPAC that progressed on prior gemcitabine-based therapy. This randomized phase 2 trial evaluated nal-IRI+5-FU/LV tolerability (Part 1), safety, and efficacy (Part 2; outcomes reported here) in Japanese patients with mPAC that progressed on gemcitabine-based therapy., Methods: Patients were randomized 1:1 and stratified by KPS (70 and 80 vs. ≥90) and baseline albumin (≥4.0 g/dl vs. <4.0 g/dl). Primary endpoint was PFS; secondary endpoints were ORR, DCR, OS, TTF, CA19-9 response, and QoL. The ITT population comprised all randomized patients., Results: Patient characteristics differed between nal-IRI+5-FU/LV (n = 40) and 5-FU/LV (n = 39) arms, including baseline hepatic lesions (63% vs. 51%), stage IV disease at diagnosis (78% vs. 51%), and post-study anticancer therapy (55% vs. 72%). Investigator-assessed mPFS increase with nal-IRI+5-FU/LV was clinically meaningful and statistically significant versus 5-FU/LV (2.7 vs. 1.5 months, HR = 0.60). Independently assessed mPFS showed similar trends (1.7 vs. 1.6 months, HR = 0.79). mOS was 6.3 months with nal-IRI+5-FU/LV and not reached with 5-FU/LV. ORR increased significantly with nal-IRI+5-FU/LV versus 5-FU/LV (18% vs. 0, rate difference 17.5). Commonly reported grade ≥3 treatment-emergent AEs were decreased neutrophil count (37% vs. 3%), decreased white blood cell count (20% vs. 0), and diarrhea (17% vs. 3%)., Conclusions: In conclusion, clinically meaningful and statistically significant gains in investigator-assessed PFS and ORR were observed with nal-IRI+5-FU/LV versus 5-FU/LV in Japanese patients, with no new or unexpected safety signals. (Clinicaltrials.gov ID: NCT02697058)., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Data on FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer are limited. In the JASPAC06 study-a nationwide, multicenter, observational study-FOLFIRINOX for patients with unresectable or recurrent pancreatic cancer as any line of treatment showed favorable efficacy and safety in Japanese clinical practice., Methods: We performed exploratory analyses of patients with unresectable or recurrent pancreatic cancer who received FOLFIRINOX as the second-line chemotherapy in Japanese clinical settings., Results: Of the 399 evaluable patients, 44 were eligible for inclusion in the analysis. The patients' characteristics were as follows: median age, 62 years; men, 26 (59%); Eastern Cooperative Oncology Group-Performance status 0/1, 30 (68%)/14 (32%); disease status, recurrent/local/metastatic: 4 (9%)/8 (18%)/32 (73%). The initial dose was reduced in 28 (64%) patients. The median time to treatment failure and number of cycles were 4.5 (range, 0.2-19.1) months and 6 cycles (range, 1-13 or more), respectively. The major grade 3/4 adverse events were neutropenia in 29 (66%), leucopenia in 17 (39%), anorexia in 7 (16%), febrile neutropenia in 5 (11%), and anemia in 5 (11%) patients. The median overall survival, progression-free survival, and 1-year survival rates were 10.3 (95% confidence interval [CI], 7.2-13.3), 4.1 (95% CI, 2.6-5.5) months, and 30%, respectively., Conclusion: Our findings suggest that FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer was effective in patients with a good performance status. It displayed toxicity similar to that observed with its use as a first-line treatment., (Copyright © 2020. Published by Elsevier B.V.)

Background: Undifferentiated carcinoma (UC) of the pancreas is a rare subtype of pancreatic cancer. Although UC has been considered a highly aggressive malignancy, no clinical studies have addressed the efficacy of chemotherapy for unresectable UC. Therefore, we conducted multicenter retrospective study to investigate the efficacy of chemotherapy in patients with UC of the pancreas., Methods: This multicenter retrospective cohort study was conducted at 17 institutions in Japan between January 2007 and December 2017. A total of 50 patients treated with chemotherapy were analyzed., Results: The median overall survival (OS) in UC patients treated with chemotherapy was 4.08 months. The details of first-line chemotherapy were as follows: gemcitabine (n = 24), S-1 (n = 12), gemcitabine plus nab-paclitaxel (n = 6), and other treatment (n = 8). The median progression-free survival (PFS) was 1.61 months in the gemcitabine group, 2.96 months in the S-1 group, and 4.60 months in the gemcitabine plus nab-paclitaxel group. Gemcitabine plus nab-paclitaxel significantly improved PFS compared with gemcitabine (p = 0.014). The objective response rate (ORR) was 4.2% in the gemcitabine group, 0.0% in the S-1 group, and 33.3% in the gemcitabine plus nab-paclitaxel group. Gemcitabine plus nab-paclitaxel also showed a significantly higher ORR compared with both gemcitabine and S-1 (gemcitabine plus nab-paclitaxel vs. gemcitabine: p = 0.033; gemcitabine plus nab-paclitaxel vs. S-1: p = 0.034). A paclitaxel-containing first-line regimen significantly improved OS compared with a non-paclitaxel-containing regimen (6.94 months vs. 3.75 months, respectively; p = 0.041). After adjustment, use of a paclitaxel-containing regimen in any line was still an independent predictor of OS (hazard ratio for OS, 0.221; 95% confidence interval, 0.076-0.647; p = 0.006) in multiple imputation by chained equation., Conclusions: The results of the present study indicate that a paclitaxel-containing regimen would offer relatively longer survival, and it is considered a reasonable option for treating patients with unresectable UC.