Peer-review started: October 4, 2023
First decision: November 30, 2023
Revised: December 13, 2023
Accepted: January 8, 2024
Article in press: January 8, 2024
Published online: January 28, 2024
Processing time: 110 Days and 12.9 Hours
The incidence of adenocarcinoma of esophagogastric junction (AEG) has increased worldwide, and the survival rate is unsatisfactory. Generally, most patients are diagnosed in the advanced stage. Multimodal treatment has become the standard of care for locally advanced AEG. The NAC regimen for AEG patients differ regionally. Some research has indicated superiority of a docetaxel-based regimen over the established regimens, including S-1 and oxaliplatin, and cisplatin and fluorouracil. The Eastern Asia countries mostly used docetaxel, oxaliplatin and S-1 (DOS) as first-line NAC. However, research has demonstrated that patients who do not respond to DOS have a significantly worse prognosis. For docetaxel-based regimens, the key is to select AEG patients who optimally benefit from DOS and who do not respond to DOS in clinical practice.
The optimal treatment choice for AEG relies on the TNM staging and anatomical location. To evaluate the TNM stage and location, endoscopic ultrasound and computed tomography (CT) are the most common choices at present. Compared with endoscopic ultrasound, CT can clearly show the morphological characteristics of the tumor, in addition to cT stage, cN stage and location of the lesion, and can measure tumor diameter and volume to assess the response to NAC. To our knowledge, there is no report on the development of a model based on CT characteristics to predict the response to DOS for advanced AEG patients.
Our study aimed to establish and validate a novel nomogram based on CT characteristics to predict response to DOS, which could be helpful to choose optimal treatment and avoid the toxicity of DOS.
One hundred and twenty-eight consecutive patients with confirmed Siewert type II/III AEG underwent CT before and after three cycles of NAC with DOS, and were randomly and consecutively assigned to the training cohort (TC) (n = 94) and the validation cohort (VC) (n = 34). Therapeutic effect was assessed by disease-control rate and progressive disease according to the Response Evaluation Criteria in Solid Tumors (version 1.1) criteria. Possible prognostic factors associated with responses after DOS treatment including Siewert classification, gross tumor volume (GTV), and cT and cN stages were evaluated using pretherapeutic CT data in addition to sex and age. Univariate and multivariate analyses of CT and clinical features in the TC were performed to determine independent factors associated with response to DOS. A nomogram was established based on independent factors to predict the response. The predictive performance of the nomogram was evaluated by Concordance index (C-index), calibration and receiver operating characteristics curve in the TC and VC.
Univariate analysis showed that Siewert type (52/55 vs 29/39, P = 0.005), pretherapeutic cT stage (57/62 vs 24/32, P = 0.028), GTV (47.3 ± 27.4 vs 73.2 ± 54.3, P = 0.040) were significantly associated with response to DOS in the TC. Multivariate analysis of the TC also showed that the pretherapeutic cT stage, GTV and Siewert type were independent predictive factors related to response to DOS (odds ratio = 4.631, 1.027 and 7.639, respectively; all P < 0.05). The nomogram developed with these independent factors showed an excellent performance to predict response to DOS in the TC and VC (C-index: 0.838 and 0.824), with area under the receiver operating characteristic curve of 0.838 and 0.824, respectively. The calibration curves showed that the practical and predicted response to DOS effectively coincided.
This study illustrated that pretherapeutic cT stage, GTV and Siewert type could be independent prognostic factors for response to DOS. Based on the three independent prognostic factors, a novel nomogram was established to predict the response to DOS.
We have developed a novel nomogram based on the independent prognostic factors including pretherapeutic cT stage, GTV and Siewert type of AEG as depicted on CT to predict response to DOS. We hope that our nomogram will help clinicians select suitable patients with Siewert types II and III AEG to undergo DOS, and identify non-responders to adjust the treatment strategies and to avoid toxicity associated with DOS.