Immunotherapy with or without radiotherapy for metastatic or recurrent esophageal squamous cell carcinoma: A real-world study

Wu, Xiaoyue; Li, Yanqi; Zhang, Kunning; Guo, Zhoubo; Li, Yang; Zhao, Fangdong; Zhang, Tian; Chen, Xi; Wei, Hui; Zhang, Wencheng; Wang, Ping; Pang, Qingsong

doi:10.1016/j.ctro.2022.10.011

Cited by 9 publications

(11 citation statements)

References 31 publications

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“…Several large retrospective studies have confirmed that the addition of aggressive primary tumor radiotherapy to the treatment of advanced esophageal cancer has positive implications for patients, but further research is needed on patient selection ( 22 , 123 ). In the real-world study, the addition of radiotherapy to immunochemotherapy in locally recurrent ESCC significantly prolonged OS (median OS 19.5 vs 7.7 months), while no difference in PFS or OS was observed with or without radiotherapy in the entire cohort ( 124 ). This underscores the importance of patient selection.…”

Section: Discussion: Current Progress and Future Directionmentioning

confidence: 91%

“…The subgroup analysis of CheckMate 577 study demonstrated a superior survival benefit for commencing Nivolumab beyond 10 weeks after surgery, as opposed to initiating treatment within 10 weeks, which could be attributed to the extended period of time needed for the immune system to recuperate after neoadjuvant chemoradiotherapy and radical surgery ( 42 ). Real-world study of metastatic/recurrent ESCC found that patients treated with radiation within 90 days before and after immunotherapy exhibited extended median PFS and OS than those treated with radiation beyond 90 days ( 124 ). Clinical trials for metastatic ESCC necessitate an interval of no more than 8 weeks between conventional radiotherapy and ICI ( 79 , 81 ), and one week between SBRT and ICI ( 91 – 93 ).…”

Section: Discussion: Current Progress and Future Directionmentioning

confidence: 99%

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Radiotherapy combined with immune checkpoint inhibitors in locally advanced/metastatic esophageal squamous cell carcinoma: clinical trials, efficacy and future directions

Jiang

Liu

et al. 2023

Front. Immunol.

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Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide and often diagnosed at advanced stages with poor prognosis. Combination of radiotherapy and immunotherapy seems to be a promising approach for treating ESCC. This comprehensive review article summarizes the current state of combination of radiotherapy and immunotherapy in locally advanced/metastatic ESCC, delineates the clinical trials that merit attention, and outlines unresolved issues and future research directions in this field. The clinical trial findings suggest that radio-immunotherapy combination may improve tumor response and overall survival with manageable side effects, highlighting the importance of patient selection and the necessity for further research to optimize treatment strategies. Issues such as irradiation dosage, fractionation regimen, irradiation site and technique of radiotherapy, as well as the timing, sequence and duration of combination therapy will all affect treatment outcomes, justifying further in-depth investigation.

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Section: Discussion: Current Progress and Future Directionmentioning

confidence: 91%

Section: Discussion: Current Progress and Future Directionmentioning

confidence: 99%

Radiotherapy combined with immune checkpoint inhibitors in locally advanced/metastatic esophageal squamous cell carcinoma: clinical trials, efficacy and future directions

Jiang

Liu

et al. 2023

Front. Immunol.

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“…It have been shown in the phase III randomized clinical trials that for advanced esophageal cancer patients, ICIs combined with chemotherapy rather than chemotherapy alone have been regarded as the rst-line treatment. In patients with locally advanced or relapsing/metastatic (LA/RM) ESCC, the addition of radiotherapy to ICIs and chemotherapy has become a new strategy, which may have synergistic effects and better e cacy; however, studies that focused on these triple modalities for LA/RM ESCC are few [14][15][16]. To explore the e cacy of ICI combination modalities in the real world, a retrospective analysis of 198 LA/RM ESCC cases was performed in this study.…”

Section: Discussionmentioning

confidence: 99%

“…Compared with those studies, the OS or PFS rates in our study were slightly lower, which was considered to be related to the inclusion of many stage patients and those treated after the failure of the rst-line treatment. Wu et al [20] retrospectively analyzed the treatment of 127 patients with metastatic or recurrent ESCC, of whom 40 received radiotherapy combined with ICIs, and the median OS and PFS rates of these patients were 11.9 months and 5.45 months, respectively. Radiotherapy-ICI combination therapy could increase the OS rates of patients with local recurrence (P = 0.026).…”

Section: Discussionmentioning

confidence: 99%

Immune checkpoint inhibitors combined with radiotherapy/chemoradiotherapy in treating locally advanced or recurrent/metastatic esophageal squamous cell carcinoma: A real-world study

Zhao

Gao

Wen

et al. 2023

Preprint

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Objective: This study was designed to investigate the prognostic factors for immune checkpoint inhibitors (ICIs) combined utilization with radiotherapy (RT)/chemoradiotherapy (CRT) and to evaluate their toxicity in locally advanced or recurrent/metastatic esophageal squamous cell carcinoma (LA/RM ESCC). Methods: In this study, 198 LA/RM ESCC patients who received ICIs combined with RT/CRT in the Department of Radiotherapy of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. Univariate and multivariate analyses were performed to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). Subgroup analysis was utilized to explore the prognostic factors, the treatment respond and treatment-related adverse events (trAEs) were analyzed. Results: The median OS and PFS were 30.4 months (95% confidence interval [CI]: 15.1–45.7 months) and 15.3 months (95% CI: 12.8–17.8 months), respectively. The median OS and PFS for patients achieving objective respond (ORR group, including complete response and partial response) were 50.8 months (95% CI: 25.8–75.7 months) and 20.5 months (95% CI: 14.1–27.0), respectively, which were higher than those in non-ORR group (OSnon-ORR:17.5 months, 95% CI: 14.0–21.0; χ2 = 13.881, P < 0.001; PFSnon-ORR: 12.1 months, 95% CI: 10.1–14.1, χ2 = 10.676, P = 0.001). Results from subgroup analysis illustrated combined ICIs with radiotherapy could improve the treatment respond (χ2 = 47.725, P = 0.000). The OS rate (χ2 = 18.836, P < 0.001) and PFS rate (χ2 = 6.881, P = 0.009) were significantly higher in the whole-lesion radiotherapy group than in the partial-lesion radiotherapy group. Multivariate analysis showed that the number of immune cycles, the coverage of radiotherapy target, the modality of ICIs-combination therapy and treatment response were independent prognosis factors for OS (hazard ratio [HR] = 0.512, 2.043, 1.889, and 1.912, respectively; P = 0.001, 0.001, 0.013, and 0.002, respectively). Radiotherapy coverage and treatment response were independent factors for PFS (HR = 1.478 and 1.597, respectively; P = 0.032 and 0.012, respectively). In the entire study population, 83 patients (41.9%) had ≥ grade 2 trAEs. Conclusions: ICIs combined with radiotherapy/chemoradiotherapy are safe and effective in LA/RM ESCC patients. The addition of radiotherapy could improve the treatment respond and whole-lesion radiotherapy improve prognosis compared with partial-lesion radiotherapy group. The number of immunotherapy cycles and treatment response are the main factors affecting prognosis.

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“…Real-world studies have shown that the addition of radiotherapy to immunotherapy can significantly prolong the overall survival (OS) of patients with locally recurrent esophageal cancer. In the overall patient cohort, there was no statistically significant difference in progression-free survival (PFS) and OS between patients who received radiotherapy and those who did not (Wu et al 2023 ), highlighting the importance of patient selection. Advanced esophageal cancer with limited metastasis and regional lymph node recurrence has a better prognosis, and the combination of active local and systemic treatments may provide an opportunity for curative treatment, which should be considered when choosing treatment options for patients.…”

Section: Patient Choice and Biomarkers: Updates And Challengesmentioning

confidence: 99%

Opportunities and challenges in combining immunotherapy and radiotherapy in esophageal cancer

Zhang,

Cai,

Yan

2023

J Cancer Res Clin Oncol

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Background Immunotherapy has shown promise in the treatment of esophageal cancer, but using it alone only benefits a small number of patients. Most patients either do not have a significant response or develop secondary drug resistance. The combination of radiotherapy and immunotherapy appears to be a promising approach to treating esophageal cancer. Purpose We reviewed milestone clinical trials of radiotherapy combined with immunotherapy for esophageal cancer. We then discussed potential biomarkers for radiotherapy combined with immunotherapy, including programmed cell death-ligand 1 (PD-L1) status, tumor mutation burden (TMB), tumor-infiltrating lymphocytes, ct-DNA, imaging biomarkers, and clinical factors. Furthermore, we emphasize the key mechanisms of radiation therapy-induced immune stimulation and immune suppression in order to propose strategies for overcoming immune resistance in radiation therapy (RT). Lastly, we discussed the emerging role of low-dose radiotherapy (LDRT) , which has become a promising approach to overcome the limitations of high-dose radiotherapy. Conclusion Radiotherapy can be considered a triggering factor for systemic anti-tumor immune response and, with the assistance of immunotherapy, can serve as a systemic treatment option and potentially become the standard treatment for cancer patients.

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Immunotherapy with or without radiotherapy for metastatic or recurrent esophageal squamous cell carcinoma: A real-world study

Cited by 9 publications

References 31 publications

Radiotherapy combined with immune checkpoint inhibitors in locally advanced/metastatic esophageal squamous cell carcinoma: clinical trials, efficacy and future directions

Radiotherapy combined with immune checkpoint inhibitors in locally advanced/metastatic esophageal squamous cell carcinoma: clinical trials, efficacy and future directions

Immune checkpoint inhibitors combined with radiotherapy/chemoradiotherapy in treating locally advanced or recurrent/metastatic esophageal squamous cell carcinoma: A real-world study

Opportunities and challenges in combining immunotherapy and radiotherapy in esophageal cancer

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