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

Jiang, Mengjie; Hu, Yujie; Liu, Gang; Chen, Chao; Li, Huafeng

doi:10.3389/fimmu.2023.1177085

Cited by 8 publications

(4 citation statements)

References 158 publications

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“…Radiotherapy has also been shown to lead to an abscopal effect. The direct and indirect antitumor effects of radiotherapy may be further augmented by immunotherapy [17]. Immunotherapy may serve as a primer for improved response to subsequent lines of chemoradiation.…”

Section: The Relationship Between Immunotherapy and Chemoradiationmentioning

confidence: 99%

Advancing Esophageal Cancer Treatment: Immunotherapy in Neoadjuvant and Adjuvant Settings

Park,

Jeon,

Yang

et al. 2024

Cancers

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Locally advanced esophageal cancer (LAEC) poses a significant and persistent challenge in terms of effective treatment. Traditionally, the primary strategy for managing LAEC has involved concurrent neoadjuvant chemoradiation followed by surgery. However, achieving a pathologic complete response (pCR) has proven to be inconsistent, and despite treatment, roughly half of patients experience locoregional recurrence or metastasis. Consequently, there has been a paradigm shift towards exploring the potential of immunotherapy in reshaping the landscape of LAEC management. Recent research has particularly focused on immune checkpoint inhibitors, investigating their application in both neoadjuvant and adjuvant settings. These inhibitors, designed to block specific proteins in immune cells, are meant to enhance the immune system’s ability to target and combat cancer cells. Emerging evidence from these studies suggests the possibility of a mortality benefit, indicating that immunotherapy may contribute to improved overall survival rates for individuals grappling with esophageal cancer. This manuscript aims to meticulously review the existing literature surrounding neoadjuvant and adjuvant immunotherapy in the context of LAEC management. The intention is to thoroughly examine the methodologies and findings of relevant studies, providing a comprehensive synthesis of the current understanding of the impact of immunotherapy on esophageal cancer.

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Section: The Relationship Between Immunotherapy and Chemoradiationmentioning

confidence: 99%

Advancing Esophageal Cancer Treatment: Immunotherapy in Neoadjuvant and Adjuvant Settings

Park,

Jeon,

Yang

et al. 2024

Cancers

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“…The most recognized molecular markers are PD-L1, microsatellite instability and tumor mutational load, but they are still some way from being ideal predictive markers. Various external factors, including sample quality, assay conditions, and cutoff values can influence the predictive accuracy of these markers (82)(83)(84).…”

Section: Patient Selection and Predictive Markersmentioning

confidence: 99%

Current and future on definitive concurrent chemoradiotherapy for inoperable locally advanced esophageal squamous cell carcinoma

Xie,

Cai,

Chen

et al. 2024

Front. Oncol.

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Esophageal squamous cell carcinoma (ESCC) is an aggressive and fatal disease that is usually diagnosed when the chances for surgical intervention has been missed. Definitive concurrent chemoradiotherapy (dCRT) is the first choice of treatment for inoperable locally advanced esophageal squamous cell carcinoma (LA-ESCC). Nevertheless, the local recurrence rate for esophageal cancer patients undergoing dCRT remains high at 40-60%, with a 5-year overall survival rate of solely 10-30%. Immunotherapy in combination with dCRT is a promising treatment for inoperable LA-ESCC, for that improved long-term survival is expected. The present review provides a comprehensive overview of the evolutionary trajectory of dCRT for LA-ESCC, delineates notable relevant clinical studies, addresses unresolved concerns regarding the combination of dCRT with immunotherapy, and highlights promising directions for future research. When dCRT is combined with immunotherapy, the following aspects should be carefully explored in the future studies, including the optimal irradiation dose, segmentation scheme, radiotherapy technique, timing, sequence and duration of radiotherapy, and the selection of chemotherapeutic and immunologic drugs. In addition, further investigations on the mechanisms of how dCRT combined with immunotherapy exerts synergistic anti-tumor effects and molecular biomarkers ensuring precise screening of ESCC patients are needed.

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“…Several case reports and early clinical trials [27,59,60] have described the use of immunoradiotherapy in metastatic SCC. A recently published manuscript [59] suggested that patients with metastatic SCC who received a combination of immune checkpoint inhibitors and radiotherapy resulted in significant tumor regression and prolonged survival. Similarly, early-phase clinical trials have reported objective responses and disease control in patients with metastatic SCC receiving immunoradiotherapy [27,60].…”

Section: Metastatic Diseasementioning

confidence: 99%

“…These reports highlight the potential of immunoradiotherapy to induce tumor regression and achieve durable responses in metastatic disease. Despite the promising results [27,59,60], challenges exist in the successful implementation of immunoradiotherapy in metastatic SCC.…”

Section: Metastatic Diseasementioning

confidence: 99%

Navigating a Complex Intersection: Immunotherapy and Radiotherapy Synergy in Squamous Cell Carcinoma of the Skin—A Comprehensive Literature Review

Georgescu,

Trifanescu,

Serbanescu

et al. 2023

Cosmetics

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Skin squamous cell carcinoma (SCC) represents a major public health concern due to its high incidence and potential for local invasion and metastasis. Compared to local recurrence, metastatic SCC represents an even greater therapeutic challenge. Once distant metastasis occurs, the disease becomes incurable, and treatment focuses on palliation and prolonging survival. The immune microenvironment of SCC is characterized by an infiltration of immune cells, including tumor-infiltrating lymphocytes. In addition to its direct cytotoxic effects, radiotherapy also induces immunomodulatory effects within the tumor microenvironment. Radiation can promote the release of tumor-associated antigens and induce immunogenic cell death, thereby enhancing the recognition of tumor cells by the immune system. Immunotherapy and radiotherapy have emerged as promising therapeutic modalities for metastatic SCC. This literature review aims to evaluate the potential synergy between these treatments and shed light on their combined efficacy. Within the manuscript, we present a compelling case report of a patient with advanced SCC who exhibited resistance to the combined regimen of immunotherapy and radiotherapy, leading to disease progression. Despite the increasing evidence supporting the synergy between these modalities, this case underscores the complex nature of treatment response and the importance of considering individual patient characteristics.

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

Cited by 8 publications

References 158 publications

Advancing Esophageal Cancer Treatment: Immunotherapy in Neoadjuvant and Adjuvant Settings

Advancing Esophageal Cancer Treatment: Immunotherapy in Neoadjuvant and Adjuvant Settings

Current and future on definitive concurrent chemoradiotherapy for inoperable locally advanced esophageal squamous cell carcinoma

Navigating a Complex Intersection: Immunotherapy and Radiotherapy Synergy in Squamous Cell Carcinoma of the Skin—A Comprehensive Literature Review

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