Clinical Features and Outcomes of Conversion Therapy in Patients with Unresectable Hepatocellular Carcinoma

Abstract

This retrospective multicenter study analyzed 244 patients with unresectable hepatocellular carcinoma treated with lenvatinib (LEN) and atezolizumab + bevacizumab (Atezo + Bev) to examine the characteristics, treatment courses, and prognoses. The cases of patients who could achieve HCC downstaging from Barcelona Clinic Liver Cancer (BCLC) stage B or C to A or zero indicated the need for conversion therapy. The patients’ prognoses with and without conversion therapy were compared. Of the 244 patients, 12 (4.9%) underwent conversion therapy, six out of 131 (4.6%) were treated with LEN, and six out of 113 (5.3%) were treated with Atezo + Bev. Eleven patients (91.7%) with a modified albumin bilirubin (mALBI) grade 1 or 2a and BCLC-B stage showed significantly higher rates of transition during conversion therapy (p < 0.05). The patients undergoing conversion therapy had a significantly longer median overall survival rate than those receiving chemotherapy alone (1208 [1064–NA] vs. 569 [466–704] days, p < 0.01). A comparison of the patients who achieved a partial response with and without conversion was evaluated using propensity score matching to reduce the confounding factors, showing a significant survival benefit in the conversion group (1208 [1064–NA] vs. 665 days, p < 0.01). Among the patients with u-HCC who were treated with LEN and Atezo + Bev, those with mALBI 1 + 2a and BCLC-B were likely to achieve conversion therapy with downstaging.

Cure can be Achieved by Conversion to Microwave Ablation following Atezolizumab-Bevacizumab Therapy in Unresectable Hepatocellular Carcinoma

“…Achieving curative conversion has indeed been found to result in better overall survival not only in the overall population of patients given systemic treatment, but also among those with partial radiologic response. [14] Our study also shows a similar bene t in survival, (Fig. 4a) and contributes to the increasing evidence that upfront systemic treatment in patients who are initially deemed to be poor candidates for TACE and/or resection can still receive potentially curative treatments later on.…”

“…4a) and contributes to the increasing evidence that upfront systemic treatment in patients who are initially deemed to be poor candidates for TACE and/or resection can still receive potentially curative treatments later on. [8, [10][11][12]14] The combination of thermal ablation with ICI is of particular interest because of evidences that RFA and MWA have been found to induce and enhance tumor-speci c immune responses [19,20] and may work in synergism with ICI's. Although there have been reports of thermal ablation as a modality for curative conversion, they have either limited ablation to tumors that were 3 cm.…”

“…Although there have been reports of thermal ablation as a modality for curative conversion, they have either limited ablation to tumors that were 3 cm. and smaller, [14] or have not de ned their criteria for ablation.…”

“…The need for further systemic therapy after curative conversion is, however, still subject to debate. Although a retrospective analysis did not show a difference in recurrence-free survival between patients who continued and discontinued systemic treatment following curative conversion with ablation or resection, [14] the recently published IMbrave050 trial suggests otherwise, in that continued immunologic surveillance in treatment-naïve patients after resection or ablation showed a bene t of longer recurrence-free survival for patients given adjuvant Atezolizumab-Bevacizumab. [21] A longer period of follow-up of patients with or without systemic treatment following curative conversion is required to clarify this question.…”

“…conversion is in fact not only limited to Atezolizumab-Bevacizumab but can also be achieved using other 12,13] Most reports on curative conversion employ surgical modalities to effect cure, with only a minority mentioning thermal ablative therapies like radiofrequency ablation (RFA) and microwave ablation (MWA). [8,10,14] This is understandable since thermal ablation is usually limited to smaller tumor sizes, and patients who undergo systemic therapy usually have large tumor sizes at the start of treatment. However, with the improvement in ablation techniques and technology, HCC as large as 7-8 cm.…”