Dose escalation based on 18F-FDG PET/CT response in definitive chemoradiotherapy of locally advanced esophageal squamous cell carcinoma: a phase III, open-label, randomized, controlled trial (ESO-Shanghai 12)

Abstract

Introduction Definitive chemoradiotherapy has established the standard non-surgical treatment for locally advanced esophageal cancer. The standard dose of 50–50.4 Gy has been established decades ago and been confirmed in modern trials. The theorical advantage of better local control and technical advances for less toxicity have encouraged clinicians for dose escalation investigation. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) have the potential to tailor therapy for esophageal patients not showing response to CRT and pioneers the PET-based dose escalation. Methods and analysis The ESO-Shanghai 12 trial is a prospective multicenter randomized phase 3 study in which patients are randomized to either 61.2 Gy or 50.4 Gy of radiation dose by PET response. Both groups undergo concurrent chemoradiotherapy with paclitaxel/cisplatin regimen for 2 cycles followed by consolidation chemotherapy for 2 cycles. Patients with histologically confirmed ESCC [T1N1-3M0, T2-4NxM0, TxNxM1 (Supraclavicular lymph node metastasis only), (AJCC Cancer Staging Manual, 8th Edition)] and without any prior treatment of chemotherapy, radiotherapy or surgery against esophageal cancer will be eligible. The primary endpoints included overall survival in PET/CT non-responders (SUVmax > 4.0) and overall survival in total population. Patients will be stratified by standardized uptake volume, gross tumor volume and tumor location. The enrollment could be ended, when the number of PET/CT non-responder reached 132 and the total population reached 646 for randomization. Ethics and dissemination This trial has been approved by the Fudan University Shanghai Cancer Center Institutional Review Board. Trial results will be disseminated via peer reviewed scientific journals and conference presentations. Trial registration The trial was initiated in 2018 and is currently recruiting patients. Trial registration number NCT03790553.

Is Escalated Radiation Dose in Definitive Chemoradiotherapy Better for Inoperable Esophageal Carcinoma? A Meta-Analysis and Systematic Review

“…At the 2022 American Society for Therapeutic Radiology and Oncology (ASTRO), a multicenter phase III randomized clinical trial (NROG-001) [27] reported that the HD arm (59.4 Gy) did not present significantly prolonged OS (HR = 0.93, P = 0.54) but exhibited improved PFS (29.1 months to 20.0 months, HR = 0.77, P = 0.023) when compared with the SD arm (50.4 Gy) for local advanced thoracic ESCC. The ongoing Chinese ESO-Shanghai 12 study [28] and British SCOPE2 study [29] are making an earnest endeavor to compare the effects of standard-dose and high-dose radiation treatments. The final results of these clinical studies are awaited.…”

“…After Careful examination and discreet exclusion, seven prospective trials [18] [19] [20] [22] [23] [24] [25] were included in the meta-analysis ultimately (Table 1; exclusion reasons were shown in Figure 1), which consisted of6 randomized clinical trials and 1 non-randomized study. The sample size in each study included in the meta-analysis ranged from 28…”

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

“…ENI irradiates a bunch of lymph node regions, which may aggravate radiotherapy side effects and deteriorate prognosis for patients, and this may be the reason for invalid beneficial effect from high-dose radiotherapy. Unlike previous prospective studies comparing high-dose to standard dose, the ESO-Shanghai 12 study (35) not only evaluated the prognosis of patients based on PET-CT, but also used involved field irradiation (IFI), which is noteworthy.…”

“…However, enhancing the precision of forecasts requires the optimization of particular methods and factors (95-97). Data from clinical studies on LA-ESCC are gradually increasing, and more and more studies are beginning to apply PET/CT to assess patient treatment efficacy and to guide treatment decisions based on imaging response (35,98,99). There are even new PET imaging techniques that can detect tumor PD-L1, allowing noninvasive, real-time monitoring of changes in a patient's PD-L1 status (100).…”