Introduction

The combination of Atezolizumab plus Bevacizumab (atezobeva) has changed the treatment landscape of advanced hepatocellular carcinoma (HCC), but its efficacy and safety in patients with impaired liver function or portal hypertension is still debated.

Aims & Methods

In this multicenter, real-life, study we compared 247 patients with unresectable HCC treated with atezobeva, matched to 494 patients treated with tyrosine kinase inhibitors (TKIs). We evaluated the impact of liver function and decompensation on treatment outcomes.

Results

Patients in the atezobeva group showed longer median overall survival (OS; 18·30 vs 10·20 months, p<0·0001), longer time to progression (TTP; 13·60 vs 10·10 months, p=0·0002) and increased progression-free survival (PFS; 10·50 VS 6·10 months, p<0·0001) compared with the TKIs group. Although survival was better in Child Pugh A patients than in Child Pugh B patients (20·20 vs 9·83 months, p=0·0008), no clear differences in TTP and overall treatment safety were observed· Liver decompensation occurred in 63 (25·51%) patients, specifically 41 (27·89%) Child Pugh A and 22 (51·16%) Child Pugh B and was associated with worse survival (10·50 vs 20·20 months; p=0·006). Among decompensated patients, 26 patients (41·26%) were able to resume atezobeva after decompensation, achieving an OS comparable to those who never decompensated (20·87 vs 20·2 months; p=0·77), and significantly better than those who permanently stopped treatment (8·07 months; p=0·02). Treatment interruption following decompensation was an independent predictor of survival (HR 2·04, 95% CI 1·25-3·33, p=0·004), while ALBI score 2-3 (HR 2·21, 95%CI 1·07-4·55; p=0·03), Child Pugh class B (HR 1·81, 95% CI 1·03-3·18; p=0·04), portal hypertension (HR 2·54, 95%CI 1·37-4·72; p=0·003) and sAEs (HR 1·71, 95%CI 1·04-2·82; p=0·04) emerged as predictors of decompensation. Time to decompensation was similar for patients with ALBI 2, regardless of Child Pugh class, and the probability of recovery from decompensation was similar for Child A and B patients.

Conclusion

In this real-life multicentric study atezobeva was effective in both Child Pugh A and B patients. Child Pugh B patients despite their higher risk of decompensation have an equal chance of recovery. The possibility to resume treatment after an episode of decompensation highlights the necessity of integrated hepato-oncological management, optimizing the therapeutic efficacy of atezobeva.

References

-Finn R.S. et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med 2020.
-Cabibbo G, et al. Optimizing systemic therapy for advanced hepatocellular carcinoma: the key role of liver function. Dig Liver Dis 2022.
-D’Alessio A, et al. Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: A real-world study. Hepatology 2022.
-Pinato DJ et al. Immunotherapy in hepatocellular cancer patients with mild to severe liver dysfunction: adjunctive role of the ALBI grade. Cancers Basel 2020.
-Kudo M, et al. Albumin-Bilirubin Grade Analyses of Atezolizumab plus Bevacizumab versus Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: A Post Hoc Analysis of the Phase III IMbrave150 Study. Liver Cancer 2023.
-Tanaka T, et al. Therapeutic efficacy of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma in patients with Child-Pugh class A or B liver function in real-world clinical practice. Hepatol Res 2022.
-Vitale A, et al. Personalised management of patients with hepatocellular carcinoma: a multiparametric therapeutic hierarchy concept. Lancet Oncol 2023.
-Thabut D, et al Treatment of portal hypertension in patients with HCC in the era of Baveno VII. J Hepatol 2023.

Disclosure

​None

Introduction

Gastric Gastrointestinal Stromal Tumors (GISTs) are among the most common mesenchymal tumors arising in the gastrointestinal tract. Despite many international guidelines, the treatment of GISTs with tumor diameters less than 50 mm remains controversial. Although surgical resection is indicated for histologically diagnosed GISTs, endoscopic resection has recently been reported. However, endoscopic resection, mainly Endoscopic submucosal dissection (ESD), often requires a full-layer resection of the gastric wall, which requires extensive suturing. Therefore, we have developed an ESD technique for endoscopic resection of the gastric wall that uses a threaded clip and a detachable snare to strangulate the muscle layer prior to resection and allows safe and easy complete resection without perforation (EISMR: Endoscopic inversion and strangulation of the muscle layer and resection). We now report seven cases of EISMR for gastric GISTs.

Aims & Methods

We evaluated the safety and efficacy of EISMR for GISTs. Seven gastric GISTs (4 males and 3 females) with tumor diameters of 50 mm or less for which we performed EISMR were included in this study, and the en bloc resection rate, R0 resection rate, procedure time, and complications were investigated. All patients underwent EUS and abdominal CT scan before treatment to confirm that the pathological diagnosis was GIST, that the tumor diameter was less than 50 mm, and that the tumor was intraluminal growth type.
In the EISMR procedure, sodium hyaluronate solution was first injected into the submucosal layer of the lesion to dissect the submucosa as in ESD. After a yellowish GIST continuity with the muscularis propria is observed, the submucosa and muscle layer are dissected to expose as much of the submucosa as possible without damaging the tumor. Next, a threaded clip is attached to the tumor and pulled in order to invert the muscle layer. The muscle layer is then retracted into the gastric lumen to form a polyp-like shape, and the base of the muscle layer is strangulated using an detachable snare (PolyLoop Ligating Device, Olympus). The upper margin of the strangulated area is then incised to complete the resection. After confirming that there is no perforation, the strangulated area is additionally sutured with a clip.

Results

All seven cases could be resected en bloc, with a median time of 90.5 minutes (58-120). Of the seven EISMR cases, five cases were performed by experts and two by non-experts. All patients were discharged on postoperative day 5 or 6 without adverse events. Pathology results showed complete resection in the low-risk GIST group. Upper endoscopy 3-6 months after EISMR showed no tumor recurrence and only scarring.

Conclusion

EISMR for gastric GISTs is potentially safe, easy and useful without excessive invasion.