The purpose of this study is to evaluate the outcomes and identify predictors of neoadjuvant anti-PD-1 plus chemotherapy in locally advanced resectable esophageal squamous cell carcinoma (ESCC). In this single-center cohort study, we are aiming to (1) evaluate the therapeutic efficacy and survival benefits on patients with locally advanced resectable ESCC (cT3-4aN0-1M0); (2) evaluate the value of genomic indicators including MMR alternation status in predicting therapeutic responses and prognosis; (3) evaluate the value of transcriptomic indicators including B cell lineage features in predicting therapeutic responses and prognosis; (4) evaluate the value of microbial and metabolite indicators in predicting therapeutic responses and prognosis. Whole exome sequencing, RNA sequencing, 16S rRNA sequencing and Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) of samples of patients to neoadjuvant chemoimmunotherapy before and after treatment are performed to explore the mechanisms of drug resistance and identification of predictive and prognosis biomarkers.
Multiple clinical trials investigated the safety and feasibility of neoadjuvant anti-PD-1 plus chemotherapy in esophageal squamous cell carcinoma (ESCC). However, the efficacy of neoadjuvant chemoimmunotherapy was undetermined and existing biomarkers failed to provide stable prediction of therapeutic responses. This study seek to further evaluate the clinical outcomes and identify biological predictors of neoadjuvant anti-PD-1 plus chemotherapy in locally advanced resectable esophageal squamous cell carcinoma (ESCC). In this single-center cohort study, our aims include: 1. evaluate the therapeutic efficacy and survival benefits on patients with locally advanced resectable ESCC (cT3-4aN0-1M0); 2. evaluate the value of genomic indicators in predicting therapeutic responses and prognosis; 3. evaluate the value of transcriptomic indicators in predicting therapeutic responses and prognosis; 4. evaluate the value of microbial and metabolite indicators in predicting therapeutic responses and prognosis. Whole exome sequencing, RNA sequencing, 16S rRNA sequencing and Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) of samples of responders and non-responders to neoadjuvant chemoimmunotherapy before and after treatment are performed to explore the mechanisms of drug resistance and identification of predictive and prognosis biomarkers, providing guidance to clinical decisions.
Study Type
OBSERVATIONAL
Enrollment
40
Patients will be given preoperative treatment as below once recruited: 1. Chemotherapy is delivered and composed of two cycles of Nab-paclitaxel 135mg per square meter of body-surface area and cisplatin 75mg per square meter of body-surface area every 3 weeks; 2. PD-1 antibody is delivered 200 mg (iv, in 30 minutes) every 3 weeks; 3. After neoadjuvant therapy of 3-4 cycles, esophagectomy is performed. We advise starting 4 cycles of identical chemoimmunotherapy in 6w after surgery.
Zhongshan Hospital, Fudan University
Shanghai, Shanghai Municipality, China
RECRUITINGMajor pathological regression (MPR) rate
The resected specimen following neo-adjuvant treatment are assessed by using standardised work up of the resection specimen in the pathology department and standardised histological criteria for tumour regression grading. MPR was defined as ≤10% residual viable tumor.
Time frame: Up to the date of pathological reports obtained since the date of enrollment, up to 6 months
Pathological response rate(pCR)
The resected specimen following neo-adjuvant treatment are assessed by using standardised work up of the resection specimen in the pathology department and standardised histological criteria for tumour regression grading. PCR was defined as no evidence of vital residual tumor cells.
Time frame: Up to the date of pathological reports obtained since the date of enrollment, up to 6 months
objective response rate (ORR)
ORR is evaluated by chest, abdominal \& pelvic CT/MRI based on RESIST 1.1. Evaluation will be conducted every 6 weeks during neoadjuvant therapy and every 6 months after surgery.
Time frame: 36 months after the last subject participating in
overall survival (OS)
OS is defined as time interval from recruitment to all-caused death or censoring.
Time frame: 36 months after the last subject participating in
Progression-free survival(PFS)
Disease recurrence is defined as locoregional (esophageal bed or anastomotic or regional lymph nodes) or metastatic (supraclavicular lymph nodes or distant organs).
Time frame: 36 months after the last subject participating in
The correlation between detection of genomic, immune, microbial and metabolite features and the rate of therapeutic responses.
The detection of genomic, immune, microbial and metabolite features from biological samples before and after neoadjuvant chemoimmunotherapy is performed to analyze the correlation to treatment vulnerability.
Time frame: 36 months after the last subject participating in
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.