Yun Zheng

Engineering the tumor microenvironment via 3D multicellular bioprinting for personalized immunotherapy assessment and resistance deciphering

Purpose: To compare the clinical outcomes of different systemic therapies, specifically PD(L)1 inhibitors plus Lenvatinib versus Atezolizumab plus Bevacizumab, when combined with hepatic arterial infusion chemotherapy (HAIC) based on the FOLFOX regimen (oxaliplatin, fluorouracil, and leucovorin) as first line treatment for unresectable hepatocellular carcinoma. Patients and Methods: This real-world retrospective study enrolled 294 patients with unresectable HCC. All patients received HAIC in combination with either PD(L)1 inhibitors plus Lenvatinib (PLEN-HAIC) or Atezolizumab plus Bevacizumab (AT-HAIC). Propensity score matching (PSM) was performed to balance patient characteristics. The overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared. Results: After PSM, 80 and 130 patients received AT-HAIC and PLEN-HAIC, respectively. No significant differences were found in ORR between the AT-HAIC and PLEN-HAIC groups (50.0% vs 40.0% per RECIST, p = 0.202; 60.0% vs 57.7% per mRECIST, p = 0.853). Both groups showed similar disease control rates. Median PFS was 14.3 months for PLEN-HAIC versus 8.8 months for AT-HAIC (p = 0.018). Median OS was significantly better in the PLEN-HAIC group (p = 0.045, both not reached). Subgroup analysis revealed that Lenvatinib showed a better OS compared to Bevacizumab when combined with HAIC and PDL1 inhibitors (p = 0.023). Conclusion: PLEN-HAIC offers significant survival benefits over AT-HAIC in advanced HCC. Given its remarkable efficacy, PLEN-HAIC could be a promising first-line option for unresectable HCC.

Background: The widely accepted view that portal hypertension (PHT) is a contraindication to hepatectomy for patients with hepatocellular carcinoma (HCC) is being increasingly challenged. The long‐term survival outcomes and safety of partial hepatectomy versus interventional treatment using ablation with or without pre‐ablation transarterial chemoembolization (TACE) in patients with HBV‐related HCC within the Milan criteria and with clinically significant PHT were compared in this study. Methods: This open‐label randomized clinical trial was conducted on consecutive patients with clinically PHT and hepatitis B virus (HBV)‐related HCC with tumors which were within the Milan criteria. These patients were randomized 1:1 to receive either partial hepatectomy or interventional treatment between December 2012 and June 2018. The primary endpoint was overall survival (OS); secondary endpoints included recurrence‐free survival (RFS) and therapeutic safety. Results: Each of the 2 groups had 80 patients. The 1‐, 3‐ and 5‐year OS rates in the partial hepatectomy group and the interventional treatment group were 95.0%, 86.2%, 69.5% versus 93.8%, 77.5%, 64.9%, respectively ( P = 0.325). The corresponding RFS rates were 78.8%, 55.0%, 46.2% versus 71.3%, 52.5%, 45.0%, respectively ( P = 0.783). The partial hepatectomy group had a higher complication rate compared to the interventional group (67.5% vs. 20%, P < 0.001). However, the differences were mainly in Clavien‐Dindo Grade I complications ( P < 0.001), while not significant in Grade II/III/IV/V (All P > 0.05). Conclusions: This study shows that partial hepatectomy treatment did not meet prespecified significance for improved OS and RFS compared to interventional treatment for patients with HBV‐related HCC within the Milan criteria and with clinically significant PHT. However, partial hepatectomy is still a safe procedure and should be considered as a treatment option rather than a contraindication.

Background: The optimal subsequent management for patients with initially unresectable hepatocellular carcinoma (uHCC) who have achieved complete response (CR) following conversion therapy remains unclear. This study aims to evaluate the feasibility and outcomes of the watch-and-wait (W-W) strategy versus surgical resection (SR) for these patients. Materials and methods: This retrospective study reviewed patients with initially uHCC who underwent conversion therapy employing transarterial therapies combined with or without systemic therapies. Radiologic CR (rCR), clinical CR (cCR), and pathologic CR (pCR) were evaluated. Overall survival (OS) and progression-free survival (PFS) were compared between the W-W and SR groups. Results: Among 1880 patients with uHCC who underwent conversion therapy, 207 (11.0%) achieved rCR. Finally, we enrolled 149 patients meeting the inclusion criteria, including 74 receiving W-W strategy and 75 undergoing SR. Among the 149 patients with rCR, the W-W group demonstrated comparable 3-year OS rates to the SR group (80.9 vs 83.1%, P=0.77), but demonstrated inferior PFS rates (14.4 vs 46.5%, P=0.002). These results remained consistent after propensity score matching. For the 57 patients who achieved cCR, the W-W group exhibited comparable 3-year OS (88.1 vs 87.9%, P=0.89) and PFS rates (27.8 vs 40.8%, P=0.34) compared to SR group. Among the 75 patients in the SR group, 31 (41.3%) achieved pCR and 44 (58.7%) reached non-pCR. When compared with patients with pCR, those who achieved rCR in the W-W group showed comparable OS but inferior PFS rates. Moreover, patients who achieved rCR in the W-W group displayed both comparable OS and PFS rates to those with non-pCR. Conclusion: The W-W strategy offered comparable survival outcomes to SR in patients with initially uHCC who achieved rCR or cCR after conversion therapy. For these patients, the W-W strategy could be offered as an alternative treatment option.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China, accounting for the majority of primary liver cancer cases. Liver resection is the preferred curative method for early-stage HCC. However, up to 80–85% of patients have already missed the opportunity of radical surgery due to tumor advances at the time of consultation. Conversion therapies are a series of medications and treatments for initially inoperable patients. For early-stage unresectable HCC (uHCC) patients, conversion therapies are designed to meet surgical requirements by increasing the volume of the residual liver. Meanwhile, for advanced cases, conversion therapies strive for tumor shrinkage and down-staging, creating the opportunity for liver resection or liver transplantation. This review summarizes the latest advances in conversion therapies and highlights their potential for improving the survival benefit of patients with uHCC.

Microwave ablation in solitary hepatocellular carcinoma within 3–5 cm requiring consideration

Background: The long-term survival of patients with hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT) is poor. Systemic therapy, transcatheter arterial chemoembolization (TACE), and hepatic artery infusion chemotherapy are widely used in HCC patients with PVTT. This study aims to explore the efficacy of combining systemic therapy with transarterial-based therapy in HCC patients with PVTT. Materials and methods: The authors retrospectively reviewed data of HCC patients with PVTT treated with combination therapy (TACE-hepatic artery infusion chemotherapy with tyrosine kinase inhibitors and PD-1 inhibitors) or TACE alone in SYSUCC from 2011 to 2020. The overall survival (OS), progression-free survival, and overall response rate were compared. Propensity score matching was used to minimize confounding bias. Results: A total of 743 HCC patients with PVTT received combination therapy (n=139) or TACE alone (n=604). After propensity score matching, the overall response rate was significantly higher in the combination group than in the TACE group [42.1% vs. 5.0%, P < 0.001 (response evaluation criteria in solid tumours); 53.7% vs. 7.8%, P < 0.001 (modified response evaluation criteria in solid tumours)]. The combination group showed significantly better OS than the TACE group (median OS not reached vs. 10.4 months, P < 0.001). The median progression-free survival of the combination and TACE groups was 14.8 and 2.3 months (P < 0.001), respectively. Tumour downstaging followed by salvage liver resection was significantly more common for the combination therapy group than for TACE group (46.3% vs. 4.5%, P < 0.001). After salvage liver resection, 31.6% (30/95) and 1.7% (3/179) of the patients achieved a pathological complete response in the combination and TACE groups, respectively (P < 0.001). The grade 3/4 adverse events rates were similar between the two groups (28.1% vs. 35.9%, P=0.092). Conclusion: Compared with TACE alone, combination therapy was safe enough and resulted in survival benefits. This is a promising treatment option for HCC patients with PVTT.

Original Article Long-term effects of total vs. partial pancreatectomy among patients with pancreatic cancer: a population-based study Zhiwen Yang, Qiang Tao, Salamu Mijiti, Dandong Luo, Xiang Tang, Jia Liu, Lingmin Jiang, Zonghao Liu, Chen Liang, Xinyue Tu, Peng Zhao, Andreas Minh Luu, Francesco Serra, Roberta Gelmini, Yong Wang, Yun Zheng

Background. Whether more tumor numbers detected in surgery compared to preoperative image affecting survival of colorectal liver metastases (CRLM) patients after hepatectomy combined with microwave ablation (MWA) remains unclear. Methods. From 2013 to 2018, 85 CRLM patients who underwent hepatectomy combined with MWA were retrospectively assessed. Compared to the tumor numbers in preoperative image, patients with equal intraoperative tumor numbers were defined as the equal number group ( ); patients detected more tumor numbers in surgery were defined as the more number group ( ). Clinicopathological factors and prognosis were compared between two groups. Results. Compared to the equal number group, the more number group was characterized by more lymphatic metastasis, synchronous metastasis of liver lesion, and tumor numbers over 5 (all ). Median survival time was 46.7 months and 26.8 months in the equal and more number group. Significantly worse overall survival (OS) was found in more number group to the equal number group ( ). In Cox analysis, more tumor number than image and high level of carbohydrate antigen 19-9 (CA19-9) were poor prognostic factors for OS. Conclusion. In patients receiving hepatectomy combined with MWA, detecting more liver metastases in surgery than preoperative image indicates poor long-term survival. These patients were characterized by more lymphatic metastasis, synchronous metastasis of liver lesion, and tumor numbers over 5. Intensive follow-up to detect early recurrence and potent postoperative therapy to improve survival may be justified in patients detected more tumor numbers in surgery with a high CA19-9 level.