Clinical Epidemiology and Evidence-Based Medicine Research Center/IDEAL China Center collaborated with the Liver Surgery team in the British Journal of Surgery.

Recently, the team of Professor Sun Xin of the Clinical Epidemiology and Evidence-based Medicine Research Center of our hospital/IDEAL China Center and the team of Professor Wen Tianfu of the Department of Liver Surgery jointly published a paper entitled "Programmed cell death protein 1 and tyrosine kinase inhibition" in the top international surgical journal British Journal of Surgery (IF: 11.
782) based on the IDEAL methodological framework Plus Transcatheter Arterial Chemoembolization of Advanced Hepatocellular Carcinoma"
.
By analyzing the diagnosis and treatment of liver cancer patients, this study tested the preliminary safety and efficacy
of lenvatinib combined with hepatic arterial chemoembolization and PD-1 (LEN-TAP), the world's first triple transformation regimen (Huaxi protocol).

IDEAL (Idea, Development, Exploration, Assessment, Long-term follow up) is an internationally recognized methodological framework for surgical clinical research and a guiding framework
for clinical research throughout the life cycle of surgery.
This research was completed using the IDEAL framework with the support of MDT for liver cancer in our hospital, which is another landmark achievement
of IDEAL China Center since its establishment in 2016 with the support of the hospital.

Liver cancer is one of the most common malignant tumors in the world, with an annual incidence of about 800,000 patients, about half of which occur in China, however, more than half of liver cancer patients are at an advanced stage at the time of initial diagnosis, have lost the opportunity for surgery, limited treatment methods, and extremely poor
prognosis.
Conversion therapy is to convert unresectable liver cancer into resectable liver cancer and then remove the tumor, which has not been widely used in clinical practice
due to low conversion efficiency and lack of high-level evidence-based medical evidence.

Under the guidance of IDEAL framework, this study tested the preliminary safety and efficacy of lenvatinib combined with hepatic arterial chemoembolization and PD-1 (LEN-TAP), the world's first triple transformation regimen (Huaxi protocol), described in detail the conceptual formation, patient selection and study design and implementation details of LEN-TAP protocol, and analyzed the diagnosis and treatment of 7 patients enrolled in the first phase of
IDEAL.

The results of the study showed that 6 of the 7 patients were staged as Barcelona Liver Cancer Clinical Stage (BCLC) stage C and 1 as stage B (Table 1), and after LEN-TAP transformational therapy, 2 patients achieved complete tumor remission, 4 patients achieved partial remission, and only 1 patient had tumor progression (Figure 1).

In the end, 4 patients successfully underwent transformation resection surgery (Fig.
2), and no tumor recurrence was seen so far, 2 patients were successfully transformed but did not undergo surgery due to hepatic insufficiency/portal cavernous defiantasia, survived with tumors, and 1 patient died of tumor progression (Fig.
3).

In terms of adverse reactions, although all patients had different degrees of adverse reactions, no grade 4/5 adverse reactions occurred, and the safety was generally controllable
.
Of the four patients who underwent conversion resection, only one patient had a prolonged hospital stay due to grade 2 biliary leakage, and the others did not develop major postoperative complications
.

Table 1.
Baseline characteristics of patients receiving LEN-TAP conversion therapy

Figure 1.
Waterfall plot of mRECIST-based target lesion shrinkage

Figure 2.
Imaging changes and surgical excision of specimens in patients undergoing LEN-TAP conversion therapy

Figure 3.
Survival benefit in patients receiving LEN-TAP conversion therapy

In the new era of comprehensive treatment of liver cancer, the transformation treatment and research of advanced liver cancer are being widely carried out at home and abroad, but the specific plan, conversion treatment course, conversion resection timing and many other details of liver cancer conversion therapy are still inconclusive
.
The IDEAL framework provides theoretical support for the safe introduction of salvage hepatectomy after LEN-TAP conversion therapy, and the results of this study suggest that the LEN-TAP conversion therapy strategy is feasible, the adverse reactions are controllable, the conversion success rate is high, the survival benefit of patients is great, and the salvage hepatic resection after successful transformation is also safe and effective
.

Original link: https://doi.
org/10.
1093/bjs/znac334