Tumor Remission and Tumor-Infiltrating Lymphocytes During Chemoradiation Therapy: Predictive and Prognostic Markers in Locally Advanced Esophageal Squamous Cell Carcinoma

Dong, Qian; Wang, Yuwen; Zhao, Gang; Cao, Fuliang; Er, Puchun; Chen, Xi; Cheng, Jingjing; Zhang, Wencheng; Li, Xiaoxia; Zhang, Baozhong; Guan, Yihui; Zhou, Dejun; Wang, Jun; Jiang, Hongjing; Yu, Zhentao; Wang, Ping; Pang, Qingsong

doi:10.1016/j.ijrobp.2019.06.079

Cited by 24 publications

(29 citation statements)

References 45 publications

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“…Although no study has identified tumor immune categories in EC, it has been reported that a high density of CD8 cells was significantly correlated with more favorable OS and RFS in patients who received post-CRT (18). Similarly, we found that high levels of TILs induced by CCRT were associated with improved clinical response and survival (19). Furthermore, the effect of intratumoral location of TILs on the survival of ESCC patients varies.…”

Section: Icis Required For Escc Treatmentsupporting

confidence: 50%

Immune checkpoint inhibitors for esophageal squamous cell carcinoma: a narrative review

2020

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Esophageal cancer (EC) has the seventh highest incidence and the sixth highest mortality rate of any type of cancer worldwide. In China, esophageal squamous cell carcinoma (ESCC) accounts for more than 95% of EC patients. The main treatment for EC patients is surgery and/or chemoradiotherapy (CRT). A large proportion of EC patients are already at an advanced stage of the disease by the time they are diagnosed. In these cases, CRT is left as the only treatment choice, and the treatment outcome is poor. Immune checkpoint inhibitors (ICIs) can improve clinical response and patient survival of patient with many types of tumors through reactivating antitumor immune response. The study of ICIs in ESCC is relative delayed compared with that in other solid tumors. Recent results from clinical trials have demonstrated the safety and efficacy of ICIs either alone or combined with chemotherapy or chemoradiotherapy in ESCC patients. Accumulated evidences also have shown the improved treatment outcome was associated with PD-L1 expression, tumor DNA instability-induced tumor mutational burden (TMB), and drawing lymphocytes into the tumor. Based on these findings, ICIs combined with CRT or radiotherapy (RT) are the focus of ongoing studies. This review will summarize the recent progress in this field, especially the mechanism of ICIs used in ESCC, their clinical efficacy and toxicities, and potential biomarkers.

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Section: Icis Required For Escc Treatmentsupporting

confidence: 50%

Immune checkpoint inhibitors for esophageal squamous cell carcinoma: a narrative review

2020

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“…Outcome measures included objective response rate, overall survival (OS), and progression-free survival (PFS). A major pathological response was defined as <10% viable residual tumor cells 22 on a deep biopsy collected from the tumor primary site where residual tumor cells were most likely located guided by the endoscopic ultrasound image after 40 Gy radiation.…”

Section: Study End Pointsmentioning

confidence: 99%

Addition of camrelizumab to docetaxel, cisplatin, and radiation therapy in patients with locally advanced esophageal squamous cell carcinoma: a phase 1b study

et al. 2021

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Patients with locally advanced esophageal squamous cell carcinoma (ESCC) show poor survival after concurrent chemoradiotherapy. This study investigated the safety and feasibility of combining concurrent chemoradiotherapy with the anti-PD-1 antibody camrelizumab as first-line treatment for these patients. In this phase 1b study (ClinicalTrials.gov NCT03671265), patients received concurrent chemotherapy (cisplatin [25 mg/m 2 ] plus docetaxel [25 mg/m 2 ] for 4 weeks) and radiotherapy (2.0 Gy/fraction, total 60 Gy) with camrelizumab (200 mg every 2 weeks for 32 weeks). Primary endpoints were safety and tolerability, and health-related quality of life. Secondary endpoints were radiological and pathological response rates, overall survival (OS), and progression-free survival (PFS). Candidate biomarkers in tumor and peripheral blood were monitored at baseline and after 40 Gy radiation. Twenty patients were enrolled. The most common treatment-related grade 3 adverse events included radiation esophagitis (20%) and esophageal fistula (10%). Serious treatment-related adverse events occurred in eight (40%) patients. No treatment-related deaths were reported. Health-related quality of life did not deteriorate. Thirteen (65%) patients had an objective response after 40 Gy radiation. At a median follow-up of 23.7 months (95% CI 21.9–24.5), OS and PFS time ranged from 8.2–28.5 and 4.0–28.5 months, respectively. The 12-month and 24-month OS rate was 85.0% and 69.6%; PFS rate was 80.0% and 65.0%. Tumor PD-L1 expression and CD11c + dendritic cells and peripheral-blood IL-27, IL-15, Eotaxin-3, and IL-22 were associated with OS. First-line concurrent chemoradiotherapy plus camrelizumab had a manageable safety profile and promising antitumour efficacy for ESCC, and deserves further study.

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“…Dynamic efficacy predictors during cancer treatment were important areas of exploration. Some studies confirmed that high levels of tumor-infiltrating lymphocytes were associated with better survival in patients with ESCC (31,32). Furthermore, several reports indicated that the efficacy of PD-1 inhibitors might be related to peripheral blood lymphocytes.…”

Section: Discussionmentioning

confidence: 91%

Anti-PD-1 Immunotherapy Combined With Stereotactic Body Radiation Therapy and GM-CSF as Salvage Therapy in a PD-L1-Negative Patient With Refractory Metastatic Esophageal Squamous Cell Carcinoma: A Case Report and Literature Review

2020

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Esophageal squamous cell carcinoma (ESCC) is a malignancy with poor prognosis, which is often diagnosed at a late stage. Effective treatment options are limited when patients fail standard systemic therapy. The application of PD-1 inhibitors have led to a paradigm shift in the treatment of ESCC, but its efficacy as monotherapy is limited. Previous studies have shown that the antitumor effects may be reinforced when a PD-1 inhibitor is combined with radiotherapy or GM-CSF. This study aimed to report a case of a patient about advanced unresectable ESCC negative expression of PD-L1, who experienced tumor progression after chemoradiotherapy and targeted therapy.A significant systemic effect was seen after PD-1 inhibitor combined with GM-CSF and stereotactic body radiotherapy (SBRT) for metastatic lesions, however, severe pneumonia occurred after the triple-combination therapy. This study also reviewed several reports about the efficacy and safety of combination therapy.

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Tumor Remission and Tumor-Infiltrating Lymphocytes During Chemoradiation Therapy: Predictive and Prognostic Markers in Locally Advanced Esophageal Squamous Cell Carcinoma

Cited by 24 publications

References 45 publications

Immune checkpoint inhibitors for esophageal squamous cell carcinoma: a narrative review

Immune checkpoint inhibitors for esophageal squamous cell carcinoma: a narrative review

Addition of camrelizumab to docetaxel, cisplatin, and radiation therapy in patients with locally advanced esophageal squamous cell carcinoma: a phase 1b study

Anti-PD-1 Immunotherapy Combined With Stereotactic Body Radiation Therapy and GM-CSF as Salvage Therapy in a PD-L1-Negative Patient With Refractory Metastatic Esophageal Squamous Cell Carcinoma: A Case Report and Literature Review

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