ABSTRACT
Background & Aims: Radiation therapy has been refined with increasing evidence of the benefits of stereotactic body radiation therapy (SBRT) in treating hepatocellular carcinoma (HCC). In this study, we aimed to evaluate whether SBRT could serve as an alternative to radiofrequency ablation (RFA) for small HCC with a single lesion ≤5.0 cm. Methods: Patients with a single HCC lesion ≤5.0 cm who received RFA or SBRT were included. Cumulative local/distant recurrence rate, progression-free survival, overall survival, adverse events and subsequent treatments after recurrence were analyzed. Results: A total of 288 patients receiving RFA (n = 166) or SBRT (n = 122) were enrolled. The baseline characteristics between the two groups were comparable. The cumulative local recurrence rate in the SBRT group was significantly lower than that in the RFA group (hazard ratio [HR] 0.30, 95% CI 0.16-0.57, p <0.001), especially for patients with tumours >2.0 cm (HR 0.20, 95% CI 0.08-0.50, p <0.001) or adjacent to major vessels (HR 0.29, 95% CI 0.13-0.66, p <0.001). Cumulative distant recurrence rate, progression-free survival and overall survival were not significantly different between the two groups (all p >0.050). Adverse events were mild and easily reversible. However, more patients in the SBRT group suffered from Child-Pugh score and total bilirubin increases. More treatment options after recurrence or progression might be available for patients in the RFA group compared to those in the SBRT group (p <0.001). Conclusions: Both RFA and SBRT were effective and safe for HCC with a single lesion ≤5.0 cm. SBRT could be an alternative treatment to RFA, especially for tumours >2.0 cm or adjacent to major vessels. Impact and implications: Stereotactic body radiation therapy (SBRT) may be used as an alternative treatment to thermal ablation for patients with BCLC stage A hepatocellular carcinoma (HCC) who are not candidates for surgical resection, including those with tumours >3 cm and those with 1 to 3 tumours. This study focused on HCC patients with a specific tumour burden, namely a single lesion ≤5.0 cm, demonstrating that SBRT could be an effective and safe alternative to radiofrequency ablation (RFA), especially for those with tumours >2.0 cm or adjacent to major vessels. The findings of this study provided robust empirical evidence supporting the utilization of SBRT in treating small HCC, while also establishing a solid foundation for future prospective clinical investigations.
ABSTRACT
Background: Although the clinical application of osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been a new step forward in the first-line treatment of non-small cell lung cancer (NSCLC), an increasing number of patients with progression on osimertinib represents a great challenge clinically. The patterns of resistance mechanisms and subsequent treatment strategies after first-line osimertinib resistance are not well established. Methods: Between January 1, 2016 and October 31, 2020, a consecutive of 56 EGFR-mutant lung cancer patients treated with osimertinib as first-line therapy at Daping Hospital (Chongqing, China) were retrospective screened. The samples of pre-osimertinib and osimertinib-resistance were all detected by next-generation sequencing (NGS) panels. Statistical analyses were carried out using SPSS 23.0 software. Survival analyses were performed using the Kaplan-Meier method and compared using a log-rank test between groups. Results: Among 47 patients with osimertinib effectiveness analysis, the median progression free survival (mPFS) was 15.4 months (95% confidence interval [CI]: 12.2-24.9 months), and median overall survival (mOS) was 35.5 months (95% CI: 23.9 months -NA). A total of 21 patients underwent repeated NGS tests upon osimertinib resistance. MET amplification was the most common resistance mechanism (6/21, 28.6%), followed by C797S mutation (5/21, 23.8%). A total of 15 patients received subsequent treatments, with mPFS of 7.3 months (95% CI 5.0 months -NA). Among them, 7 patients with EGFR C797 S or/and MET amplification received subsequent second-line targeted therapy, achieving mPFS of 7.3 months (95% CI 4.5 months -NA). Of note, 3 patients received immunotherapy as second- or third-line treatment after osimertinib resistance, achieving median clinical benefit of 37.3 months. Conclusions: MET amplification and C797S mutation are main resistance mechanisms, which could be targeted by crizotinib and gefitinib, respectively. More than 50% patients could receive subsequent anticancer targetable therapies after first-line osimertinib resistance. Immunotherapy may also be an acceptable choice after osimertinib resistance.
ABSTRACT
Aim: The subsequent treatments for patients with hepatocellular carcinoma (HCC) resistant to immunotherapy remain unclear. This study aimed to identify optimal treatments for HCC patients with progression after anti-PD-1 therapy. Methods: The authors retrospectively analyzed 197 HCC patients with progressive disease after anti-PD-1 treatment. These patients were classified into initial resistant and secondary resistant groups. Results: In the initial resistant group, subsequent treatment with PD-1 antibody plus locoregional therapy prolonged post-progression survival and overall survival (p = 0.025 and 0.029, respectively). In the secondary resistant group, subsequent treatment did not improve the prognosis of patients. Conclusion: Subsequent PD-1 antibody plus locoregional therapy could achieve survival benefits in HCC patients initially resistant to anti-PD-1 immunotherapy.
Lay abstract This study explored the optimal subsequent treatments for patients with hepatocellular carcinoma resistant to anti-PD-1 therapy. Patients were classified into initial resistant and secondary resistant groups according to whether they had responses to previous anti-PD-1 immunotherapy. By evaluating the prognosis of different treatment modalities in the initial and secondary resistant groups, the authors found that subsequent PD-1 antibody plus locoregional therapy provided survival benefits for patients with hepatocellular carcinoma initially resistant to anti-PD-1 immunotherapy. As for patients with secondary resistance, the optimal subsequent treatments need to be further explored.