A British randomised study of gemcitabine plus cisplatin (GC) combination showed promising results in biliary tract cancer (BTC) patients. In our study, we evaluated the efficacy and safety of this combination compared with gemcitabine alone (G) in Japanese BTC patients. Overall, 84 advanced BTC patients were randomised to either cisplatin 25 mg m⁻² plus gemcitabine 1000 mg m⁻² on days 1, 8 of a 21-day cycle (GC-arm), or single-agent gemcitabine 1000 mg m⁻² on days 1, 8 and 15 of a 28-day cycle (G-arm). Treatments were repeated for at least 12 weeks until disease progression or unacceptable toxicity occurred, up to a maximum of 48 weeks. A total of 83 patients were included in the analysis. For the GC and G-arms, respectively, the 1-year survival rate was 39.0 vs 31.0%, median survival time 11.2 vs 7.7 months, median progression-free survival time 5.8 vs 3.7 months and overall response rate 19.5 vs 11.9%. The most common grade 3 or 4 toxicities (GC-arm/G-arm) were neutropenia (56.1%/38.1%), thrombocytopenia (39.0%/7.1%), leukopenia (29.3%/19.0%), haemoglobin decrease (36.6%/16.7%) and γ-GTP increase (29.3%/35.7%). Gemcitabine plus cisplatin combination therapy was found to be effective and well tolerated, suggesting that it could also be a standard regimen for Japanese patients.

PURPOSE: This phase I/II study evaluated tremelimumab (anticytotoxic T-lymphocyte–associated antigen-4 monoclonal antibody) and durvalumab (antiprogrammed death ligand-1 monoclonal antibody) as monotherapies and in combination for patients with unresectable hepatocellular carcinoma (HCC), including a novel regimen featuring a single, priming dose of tremelimumab (ClinicalTrials.gov identifier: NCT02519348 ). PATIENTS AND METHODS: Patients with HCC who had progressed on, were intolerant to, or refused sorafenib were randomly assigned to receive T300 + D (tremelimumab 300 mg plus durvalumab 1,500 mg [one dose each during the first cycle] followed by durvalumab 1,500 mg once every 4 weeks), durvalumab monotherapy (1,500 mg once every 4 weeks), tremelimumab monotherapy (750 mg once every 4 weeks [seven doses] and then once every 12 weeks), or T75 + D (tremelimumab 75 mg once every 4 weeks plus durvalumab 1,500 mg once every 4 weeks [four doses] followed by durvalumab 1,500 mg once every 4 weeks). Safety was the primary end point. Secondary end points included objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors v1.1 and overall survival; exploratory end points included circulating lymphocyte profiles. RESULTS: A total of 332 patients were enrolled (T300 + D, n = 75; durvalumab, n = 104; tremelimumab, n = 69; and T75 + D, n = 84). Tolerability was acceptable across arms, with grade ≥ 3 treatment-related adverse events occurring in 37.8%, 20.8%, 43.5%, and 24.4%, respectively. Confirmed ORRs (95% CI) were 24.0% (14.9 to 35.3), 10.6% (5.4 to 18.1), 7.2% (2.4 to 16.1), and 9.5% (4.2 to 17.9), respectively. An early expansion of CD8+ lymphocytes was associated with response across arms, with highest proliferating CD8+ lymphocyte levels occurring in the T300 + D arm. The median (95% CI) overall survival was 18.7 (10.8 to 27.3), 13.6 (8.7 to 17.6), 15.1 (11.3 to 20.5), and 11.3 (8.4 to 15.0) months in the T300 + D, durvalumab, tremelimumab, and T75 + D arms, respectively. CONCLUSION: All regimens were found to be tolerable and clinically active; however, the T300 + D regimen demonstrated the most encouraging benefit-risk profile. The unique pharmacodynamic activity and association with ORR of the T300 + D regimen further support its continued evaluation in HCC.

In the 2010 version of the Japan Society of Hepatology (JSH) consensus-based treatment algorithm for the management of hepatocellular carcinoma (HCC), transarterial chemoembolization (TACE) failure/refractoriness was defined assuming the use of superselective lipiodol TACE, which has been widely used worldwide and particularly in Japan, and areas with lipiodol deposition were considered to be necrotic. However, this concept is not well accepted internationally. Furthermore, following the approval of microspheres, an embolic material that does not use lipiodol, in February 2014 in Japan, the phrase ‘lipiodol deposition' needed to be changed to ‘necrotic lesion or viable lesion'. Accordingly, the respective section in the JSH guidelines was revised to define TACE failure as an insufficient response after ≥2 consecutive TACE procedures that is evident on response evaluation computed tomography or magnetic resonance imaging after 1-3 months, even after chemotherapeutic agents have been changed and/or the feeding artery has been reanalyzed. In addition, the appearance of a higher number of lesions in the liver than that recorded at the previous TACE procedure (other than the nodule being treated) was added to the definition of TACE failure/refractoriness. Following the discussion of other issues concerning the continuous elevation of tumor markers, vascular invasion, and extrahepatic spread, descriptions similar to those in the previous version were approved. The revision of these TACE failure definitions was approved by over 85% of HCC experts. © 2014 S. Karger AG, Basel

BACKGROUND: It is not rare to find satellite lesions in patients with small hepatocellular carcinoma (HCC). The purpose of this study was to elucidate the factors associated with satellite lesions in these patients.METHODS: We investigated the prevalence of satellite lesions, the relationship of clinicopathologic factors to satellite lesions, and the distance from the main tumor to the satellite lesion in 149 patients. Patients, who had a solitary HCC of 3.0 cm or less in diameter but no satellite lesions on preoperative imaging procedures, underwent potentially curative resection. The main tumors were macroscopically classified into four groups: early HCC, a vaguely nodular type showing preservation of the preexisting liver structure; single nodular type; single nodular type with extranodular growth; and confluent multinodular type.RESULTS: Of 149 resected specimens, 28 (19%) showed satellite lesions. Of the clinicopathologic factors investigated, the macroscopic type and tumor differentiation were significantly associated with the prevalence of satellite lesions. Both the single nodular type with extranodular growth and the confluent multinodular type showed satellite lesions more frequently than the early HCC and the single nodular type. A significantly higher prevalence of satellite lesions was observed in poorly differentiated HCC than in well and moderately differentiated HCC. The satellite lesions were located 0.5 cm or less from the main tumor in 8 (33%) specimens, 0.6–1.0 cm in 12 (50%), and 1.1–2.0 cm in 4 (17%). No identifiable factors were significantly related to the distance from the main tumor to the satellite lesion. However, all satellite lesions located more than 1.0 cm from the main tumor coexisted with poorly differentiated HCC, which were the single nodular type with extranodular growth or the confluent multinodular type.CONCLUSION: In the single nodular type with extranodular growth, confluent multinodular type, and poorly differentiated HCC, extensive treatment achieving a large safety margin and/or frequent posttreatment follow‐up examinations may be needed because of the high prevalence of satellite lesions. Cancer 2002;95:1931–7. © 2002 American Cancer Society.DOI 10.1002/cncr.10892

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.

The FOLFIRINOX combination of chemotherapy drugs had not been fully evaluated for Japanese pancreatic cancer patients. Therefore, we carried out a phase II study to examine the efficacy and safety of FOLFIRINOX in chemotherapy‐naïve Japanese patients with metastatic pancreatic cancer. FOLFIRINOX (i.v. infusion of 85 mg/m² oxaliplatin, 180 mg/m² irinotecan, and 200 mg/m² l‐leucovorin, followed by a bolus of 400 mg/m² fluorouracil and a 46‐h continuous infusion of 2400 mg/m² fluorouracil) was given every 2 weeks. The primary endpoint was the response rate. The 36 enrolled patients received a median of eight (range, 1–25) treatment cycles. The response rate was 38.9% (95% confidence interval [CI], 23.1–56.5); median overall survival, 10.7 months (95% CI, 6.9–13.2); and median progression‐free survival, 5.6 months (95% CI, 3.0–7.8). Major grade 3 or 4 toxicities included neutropenia (77.8%), febrile neutropenia (22.2%), thrombocytopenia (11.1%), anemia (11.1%), anorexia (11.1%), diarrhea (8.3%), nausea (8.3%), elevated alanine aminotransferase levels (8.3%), and peripheral sensory neuropathy (5.6%). Febrile neutropenia occurred only during the first cycle. There were no treatment‐related deaths. FOLFIRINOX can be a standard regimen showing favorable efficacy and acceptable toxicity profile in chemotherapy‐naïve Japanese patients with metastatic pancreatic cancer.