[Validation and modification of AJCC 8th edition staging system for hepatocellular carcinoma--analysis based on SEER database].

Objective: To assess the accuracy of the American Joint Committee on Cancer (AJCC) 8th edition staging system for hepatocellular carcinoma (HCC) and to make an appropriate modification. Methods: Data of patients diagnosed with HCC who underwent surgery were extracted from 2004 to 2015 within the SEER database. Overall survival (OS) and disease-specific survival (DSS) of patients were analyzed. Results: A total of 7 911 patients were included and there were 2 117 females and 5 794 males. The male-to-female ratio was 1.00: 0.36. There were 4 050 patients older than 60 years old. Tumor size ranged from 24 to 65 mm. Tumors with single lobes (80.8%) or single lesions (62.8%) were more common. There were 230 cases and 2 052 cases received radiotherapy and chemotherapy, accounting for 2.9% and 25.9%, respectively. The median follow-up was 42 months. Analysis of the 8th edition of AJCC staging system showed that the survival curves of ⅣA stage and ⅢA stage intersected in both OS and DSS, and the differences were not statistically significant between them (both P>0.05). Analysis of patients in subgroup of ⅣA stage showed that there was no statistically significant difference in the four groups of T1N1M0/T2N0M0, T2N1M0/T3N0M0, T3N1M0/T4N0-1M0 and T3N1M0/T1-4N0-1M1 (all P>0.05). Therefore, the modified 8th edition of the AJCC staging system was proposed after retaining the definition of T/N/M in the old edition: ⅠA and ⅠB stages were retained; ⅣA stage was split: T1N1M0 was included in Ⅱ stage, T2N1M0 in Ⅲ stage, and Ⅳ stage included T3N1M0, T4N0-1M0 and T1-4N0-1M1. Cox proportional risk regression analysis of the modified 8th edition of the AJCC staging showed that significant differences were observed among the four groups, with ⅠB/ⅠA (HR=1.462, 95%CI:1.294-1.651), Ⅱ/ⅠB (HR=1.091, 95%CI:1.003-1.186), Ⅲ/Ⅱ (HR=2.034, 95%CI: 1.793-2.307) and Ⅲ/Ⅳ (HR=1.374, 95%CI: 1.192-1.583) for OS, respectively. The similar findings were seen in DSS, with ⅠB/ⅠA (HR=2.007, 95%CI:1.671-2.411), Ⅱ/ⅠB (HR=1.140, 95%CI:1.023-1.271), Ⅲ/Ⅱ (HR=2.344, 95%CI: 2.018-2.724) and Ⅲ/Ⅳ (HR=1.391, 95%CI:1.180-1.639), respectively. Conclusion: The modified AJCC 8th edition staging system could predict the survival outcome of HCC more accurately.

[Synthesis and antineoplastic activity of N,N'-disubstituted phenyl-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide derivatives].

AIM: To search for antineoplastic drugs with fewer side effects and improved activities, using tetrazine derivatives with different substituted groups in their phenyl rings. METHODS: The title compounds have been synthesized by reacting 3,6-dimethyl-1,6-dihydro-1,2,4,5-tetrazine with substituted phenyl isocyanates in the presence of p-dimethylamino pyridine as catalyst. RESULTS: Eighteen new N,N'-disubstituted phenyl-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamides have been synthesized. Their structures have been confirmed by IR, 1HNMR and elemental analysis. The antineoplastic activities were screened. The structure-activity relationship has also been studied. CONCLUSION: The meta-substituted tetrazine derivatives showed marked antitumor activities against P388 and A-549 when electronic effect constants and hydrophobic constants of their substitutents are in a certain range.