PURPOSE: To assess the efficacy and safety of radiofrequency ablation (RFA) versus stereotactic body radiotherapy (SBRT) in treating recurrent small hepatocellular carcinoma (HCC). METHODS: In this trial, patients with recurrent small HCC (single lesion ≤5 cm) were randomly assigned to receive either SBRT or RFA. The primary end point was local progression-free survival (LPFS), and secondary end points were progression-free survival (PFS), overall survival (OS), local control rate, and safety. RESULTS: Between August 2019 and April 2022, 166 patients were assigned to SBRT (n = 83) and RFA (n = 83) groups. After a median follow-up time of 42.8 and 42.9 months in the SBRT and RFA groups, respectively, SBRT demonstrated a significantly better LPFS than that of RFA (hazard ratio [HR], 0.45 [95% CI, 0.24 to 0.87]; P = .014). The 2-year LPFS rates were 92.7% (95% CI, 87.3 to 98.5) with SBRT and 75.8% (95% CI, 67.2 to 85.7) with RFA. The median PFS time of the SBRT and RFA groups was 37.6 (95% CI, 26.0 to 49.2) and 27.6 (95% CI, 20.3 to 34.8) months, respectively (HR, 0.76 [95% CI, 0.50 to 1.15]; P = .190). Nine patients in the SBRT group and 10 in the RFA group died during the follow-up. The 2-year OS rates were 97.6% (95% CI, 94.3 to 100.0) in the SBRT group and 93.9% (95% CI, 88.9 to 99.2) in the RFA group (HR, 0.91 [95% CI, 0.37 to 2.22]; P = .830). The incidences of both acute and late adverse events were comparable between the groups ( P = .436 and P = .715, respectively). CONCLUSION: SBRT achieved better LPFS than that of RFA in patients with single recurrent HCC ≤5 cm, especially in HCC ≤2 cm, whereas PFS, OS, and safety were comparable between the two treatments.

To evaluate the efficacy and safety of toripalimab combined with neoadjuvant chemoradiotherapy (NCRT) for locally advanced esophageal squamous cell carcinoma (ESCC). In this single arm, phase II trial, 44 ESCC patients were enrolled from December 2019 to July 2021 at Sun Yat-sen University Cancer Center (Guangzhou, China). All patients received concurrent radiotherapy (44 Gy in 20 fractions), chemotherapy (paclitaxel 50 mg/m² and cisplatin 25 mg/m² on days 1, 8, 15, and 22), and toripalimab (240 mg on days 1 and 22). Within 6–8 weeks of neoadjuvant treatment, patients underwent surgery. The results of the study patients were compared with those of 86 matched patients between July 2015 and March 2022. The primary endpoint was pathological complete response (pCR) rate, and the secondary endpoints were treatment-related adverse events and R0 rates. This trail was registered with ClinicalTrails.gov, NCT04006041. All patients received neoadjuvant treatment, and 42 completed esophagectomy. Of the 42 patients, 21 (50%; 95% CI 35–65) achieved pCR and 2 (5%) patients were ypT0N+. The R0 resection rate was 98% (41/42). Nine (20%) of 44 patients had grade 3/4 adverse events. Among the perioperative complications (n = 42), anastomotic leakage occurred in five cases (12%), tracheal fistula in three cases (7%), and postoperative death in one case (2%) due to tracheal fistula. Compared with the control cohort, the pCR rate of the study group was higher but without significant difference (50% vs. 36%, P = 0.19). Toripalimab combined with NCRT failed to show significantly better pCR rate than historical data. Nevertheless, considering the signs of efficacy and acceptable safety of this regimen, further evaluation in phase III randomized trials might be warranted. 10.13039/501100001809 National Natural Science Foundation of China .

Esophageal cancer has a high mortality rate and a poor prognosis, with more than one-third of patients receiving a diagnosis of locally advanced cancer. Esophageal squamous cell carcinoma (ESCC) is the dominant histological subtype of esophageal cancer in Asia and Eastern Europe. Although neoadjuvant or definitive chemoradiotherapy (CRT) has been the standard treatment for locally advanced ESCC, patient outcomes remain unsatisfactory, with recurrence rates as high as 30–50%. The combination of immune checkpoint inhibitors (ICIs) and CRT has emerged as a novel strategy to treat esophageal cancer, and it may have a synergistic action and provide greater efficacy. In the phase III CheckMate-577 trial, one year of adjuvant nivolumab after neoadjuvant CRT improved disease-free survival in patients with residual disease on pathology. Moreover, several phase I and II studies have shown that ICIs combined with concurrent CRT may increase the rate of pathologic complete response for resectable ESCC, but they lack long-term follow-up results. In unresectable cases, the combination of camrelizumab and definitive CRT showed promising results against ESCC in a phase Ib trial. Phase III randomized trials are currently ongoing to investigate the survival benefits of ICIs combined with neoadjuvant or definitive CRT, and they will clarify the role of immunotherapy in locally advanced ESCC. Additionally, valid biomarkers to predict tumor response and survival outcomes need to be further explored.

This randomized phase II trial aims to compare the efficacy and safety of induction chemotherapy followed by definitive chemoradiotherapy (CRT) versus CRT alone in patients with esophageal squamous cell carcinoma (ESCC) unsuitable for surgery (N = 110). The primary outcome was overall response rate (ORR), whereas the secondary outcome was overall survival. This trial did not meet pre-specified endpoints. The ORR was 74.5% in the induction chemotherapy group versus 61.8% in the CRT alone group (P = 0.152). The 3-year overall survival rate was 41.8% in the induction chemotherapy group and 38.1% in the CRT alone group (P = 0.584; hazard ratio, 0.88; 95% CI, 0.54–1.41). Grade 3–5 adverse events were similar. Patients who responded to induction chemotherapy had improved survival in the post-hoc analysis. These results demonstrate no improvement in response rate or survival with the addition of induction chemotherapy to CRT in unselected patients with ESCC. Trial number: NCT02403531.