Dynamic PET/CT Evaluated the Response of Neoadjuvant Anti-PD1 Combination With Chemotherapy for Ⅱa-Ⅲb NSCLC — DYNAPET  

Non-small Cell Lung Cancer Stage III Clinical Trial

Official title: Dynamic Positron Emission Tomography/Computed Tomography Evaluated the Response of Neoadjuvant Anti-programmed Cell Death Protein 1 Combination With Chemotherapy for Stage Ⅱa-Ⅲb Non-small Cell Lung Cancer

Status Recruiting

Clinical Trial Summary

The neoadjuvant Immune Checkpoint Inhibitor (ICI) or ICI combination with chemotherapy for Non-small cell lung cancer (NSCLC) had induced higher major pathologic response (MPR) and complete pathological response (PCR). However, the RECIST underestimated the therapeutic response of neoadjuvant ICI therapy. In this study, dynamic PET/CT compared with RECEST 1.1 for the prediction of therapeutic response of NSCLC treated with neoadjuvant ICI combination with chemotherapy.

Clinical Trial Description

The prognosis of stage Ⅱa-Ⅲb NSCLC was worse, with 5-year survival rate between 26%-60% after resection. Neoadjuvant ICI or ICI combination with chemotherapy had induced high rate major pathologic response (MPR) and complete pathological response (PCR) for NSCLC. CT image (RECIST) underestimate the response of neoadjuvant therapy. In Checkmate 159 trial, 21 patients with stage Ⅰ-Ⅲa NSCLC received two dose preoperative Nivolumab, only 2 (10%) patients were partial response on CT image assessment. While 9 of 20 (45%) patients were MPR on pathological examination. 2 patients shows tumor progression on CT, but one patient achieved PCR and another patient achieved MPR.Therefore, conventional RECIST criteria cannot accurately assess tumor response to treatment.

The occurrence, development and metastasis of tumor are essentially a series of biochemical processes of abnormal gene expression and metabolism, dysfunction and structural change. 18F-FDG can reflect the metabolic changes of the body at the cellular and molecular level, and the transmission of these metabolic information is earlier than the anatomical changes. By detecting the uptake of 18F-FDG and analyzing tumor metabolism, tissue blood perfusion, receptor, etc., it can provide a theoretical basis for monitoring the therapeutic effect of lung cancer with PET.

As a new imaging technique, 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (18F-FDG) PET/CT is playing an increasingly important role in the diagnosis of tumors. 18F-FDG PET/CT reflects the glucose metabolism process of tumor tissues, and the diagnosis of benign and malignant tumors is based on the difference in glucose metabolism activity between tumor cells and normal tissue cells. 18F-FDG is an isomer of glucose, which is involved in glucose metabolism. Because it is deoxidized and cannot produce hexose bisphosphate, it cannot participate in the next metabolism, and is trapped in cells. In tumor cells, 18F-FDG uptake is increased due to high expression of glucose transport messenger ribonucleic acid (mRNA), elevated glucose transporter Glut-1 and Glut-3 levels, increased hexokinase expression, and down-regulation of glucose-6-phosphatase levels.Molecular imaging using 18F-FDG PET/CT can provide metabolic information to enable better differentiation of benign and malignant tissues and reveal functional abnormalities before structural damage. At the same time, 18F-FDG PET-CT is an effective method for early monitoring of tumor response. It can monitor the metabolic changes of the body before and after tumor treatment, so as to suggest the response of the body to relevant treatment. However, all the PET/CT scans reported in the relevant literature are based on routine static scans, that is, the image data is based on the static images of the tracer obtained at a fixed time point after injection of 18F-FDG. Conventional static PET (60min post-injection scan) can only be used for qualitative visual analysis or semi-quantitative indicator standardized uptake values (SUV) to determine tumor response to treatment. SUV is vulnerable to the influences of uptake time, blood glucose concentration, insulin level, individual weight and injection dose, making it difficult to accurately and quantitatively evaluate tumor response before and after treatment. In order to improve, we plan to adopt dynamic scanning, that is, collecting dynamic data of whole body tissues at all times from the instant of injection of 18F-FDG to one hour. Dynamic scanning can provide information about the temporal metabolism and distribution of the tracer in the tissue, so it can provide more abundant information about the metabolism and distribution of tumor foci and metastasis foci than static scanning, so it can accurately quantify the tumor response before and after treatment. At the same time dynamic PET does not increase the patient's radiation dose compared to static PET.

This study intends to evaluate the efficacy of neoadjuvant anti-programmed cell death protein 1 (anti-PD1) immunotherapy combined with chemotherapy followed by surgery, evaluate the evaluation value of dynamic PET-CT for the efficacy of neoadjuvant therapy, and evaluate the relationship between circulating tumor DNA (ctDNA) changes and efficacy. ;

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer Stage II
• Non-small Cell Lung Cancer Stage III
• PET/CT

• NCT number: NCT04586465
• Study type: Interventional
• Source: Fifth Affiliated Hospital, Sun Yat-Sen University
• Contact: QingDong Cao, MD
• Phone: 0756-2528825
• Email: cqd8866@163.com
• Status: Recruiting
• Phase: Phase 2
• Start date: October 10, 2020
• Completion date: June 30, 2022