No abstract

Purpose To evaluate and compare the efficiency and safety of raltitrexed-or floxuridine (FUDR)-based transarterial chemoembolization (TACE) in patients with unresectable colorectal cancer liver metastasis (CRCLM). Methods We conducted a retrospective analysis of 81 patients with unresectable CRCLM who failed systemic chemotherapy and were treated with TACE in our department from Oct 2014 to Oct 2017. Of these, 61 patients received TACE using raltitrexed, oxaliplatin, and pirarubicin (raltitrexed group), and 20 received TACE using FUDR, oxaliplatin, and pirarubicin (FUDR group). The objective response rate (ORR), disease control rate (DCR), overall survival (OS, from the first TACE), progression-free survival (PFS, from the first TACE), and adverse reactions were evaluated and compared between the two groups, and prognostic factors for OS were analyzed. Results The ORRs of the raltitrexed group and FUDR group were 67.2 and 45.0%, respectively (P = 0.076), and the DCRs were 86.9 and 80.0%, respectively (P = 0.452). The median OS (from first TACE) was 14.0 months in the raltitrexed group and 13.0 months in the FUDR group (P = 0.556). The median PFS (from first TACE) was 2.1 months in the raltitrexed group and 2.4 months in the FUDR group (P = 0.878). Univariate and multivariate analyses showed that the primary tumor site, Child-Pugh class, and combination with local ablation (RFA or CRA) were independent significant factors affecting survival. There were no significant differences in adverse reactions between the two groups (P > 0.05), and no treatmentrelated death occurred in either group. Conclusion TACE treatment based on raltitrexed or FUDR is an efficient and safe alternative choice for treating unresectable CRCLM.

No abstract

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is expressed in T cells and plays an important role in the regulation of T cell. CTLA-4 has long been considered to be associated with various kinds of diseases. With the attempt to examine the association between CTLA-4 A49G polymorphism and colorectal cancer risk in a Chinese Han population, we employed TaqMan assay to genotype the CTLA-4 A49G polymorphism in 311 colorectal cancer cases and 389 cancer-free controls. We found evidence of the association between CTLA-4 A49G polymorphism and colorectal cancer risk (GG vs. AA: OR = 2.01, 95% CI = 1.29-3.07, P = 0.002; GA vs. AA: OR = 2.32, 95% CI = 1.53-3.57, P = 0.001; GA + GG vs. AA: OR = 2.16, 95% CI = 1.46-3.21, P = 0.001). Next, we performed a meta-analysis to comprehensively examine the association between CTLA-4 A49G polymorphism and colorectal cancer risk. We found a significant association between CTLA-4 A49G polymorphism and colorectal cancer risk among Asians, which is consistent with our result. However, we found no evidence for the association between CTLA-4 A49G polymorphism and colorectal cancer risk among Caucasians. In conclusion, we demonstrated that the CTLA-4 A49G polymorphism increased the susceptibility of colorectal cancer in Asian population.

To assess the safety and tolerability of neoadjuvant radiotherapy combined with toripalimab for locally advanced, resectable esophageal squamous cell cancer (ESCC). Materials/Methods: A total of 22 patients with newly diagnosed locally advanced, resectable ESCC (clinical stage: T3-4N0M0/T1-4N+M0, according to the 8th AJCC stage system) were enrolled. Patients received neoadjuvant radiotherapy (NRT) with 41.4 Gy in 23 fractions by intensity modulated radiotherapy (IMRT) combined with 4 cycles (240mg, Q3W) of toripalimab. Surgery was performed within 7-8 weeks after completion of NRT. The primary endpoints are treatment-related adverse events (TRAEs). The second endpoints are pathological complete response (pCR) and objective response rate (ORR). ORR was evaluated after NRT according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Results: A total of 22 patients were enrolled between October 2019 to December 2020. 17 patients were male and 5 patients were female. The median age was 60 years (range, 48 to 70 years). 9 patients were in stage II and 13 patients were in stage III. All patients finished NRT as planned, 3 (13.6%) patients discontinued toripalimab treatment, one for progressive disease after 3 cycles of toripalimab, one for treatment-related AEs after 2 cycles and one for patient wishes after 2 cycles. 2 (9.1%) patients achieved complete response, 13 (59.1%) patients achieved partial response of which 1 patient had liver metastasis after 4 cycles of toripalimab, 6 (27.3%) patients remained stable disease, and 1 (4.5%) patient had progression disease. ORR was 68.2% (15/22), and disease control rate (DCR) was 95.5% (21/22). As of Feb. 26, 2021, 14 (63.6%) patients had received radical surgery, among them 7 (50.0%) experienced pCR of primary tumor and lymph nodes, 8 (57.1%) presented primary tumor pCR, and 9 (64.3%) had a major pathological response (MPR), 2 (9.1%) patients did not undergo surgery for progressive disease (1 patient of left supraclavicular lymph node metastasis and 1 patient of liver metastasis), and the remaining 6 patients still awaits radical surgery as scheduled. 15 (68.2%) patients experienced TRAEs. The common TRAEs were mild (grade 1 or 2) including leukopenia (n = 9), radiation esophagitis (n = 8) and aspartate transaminase (AST) elevation (n = 5), pruritus (n = 2), alanine transaminase (ALT) elevation (n = 1) and pneumonitis (n = 1). Only 1 (4.5%) patient developed grade 3 myocarditis, grade 3 AST elevation and grade 3 ALT elevation 2 weeks after NRT, improved after treatment with methylprednisolone, and is currently waiting for radical surgery. Conclusion:The trial showed that NRT plus toripalimab demonstrated a manageable safety profile and encouraging therapeutic effect in patients with locally advanced, resectable ESCC, which warrants additional investigations in larger cohorts. The trial was registered in Chictr.org.cn ((Registration Number: ChiCTR1900022282).