Treatment response to neoadjuvant therapy in squamous esophageal cancer- Correlation between metabolic response and histopathology

Abstract

Abstract Purpose: Squamous cell carcinoma esophagus has an increasingly growing incidence in India in the current era. Positron emission tomography (PET) in combination with contrast enhanced computed tomography (CECT) is utilized as the standard staging modality. Multimodality treatment has been able to achieve evaluable tumor responses including pathological complete response (pCR), It is, therefore necessary to understand whether the impact of neoadjuvant therapy can be evaluated on imaging i.e. standardised uptake value (SUV) on PET scan done for response assessment and if this can be correlated with histopathological response and survival. study evaluates the former part of the same research question. Methods: This is a single institution, retrospective study. It includes patients of Sqaumous cell Carcinoma esophagus who were operated from 2009 to 2019. 1369 patients were evaluated. Out of these 44 received NACTRT whereas 1325 received NACT followed by curative surgery. The standardized uptake value (SUV) of 18-fluorodeoxyglucose was recorded during post-neoadjuvant treatment (NAT) using positron emission tomography (PET). The histopathology of the final resection specimen was evaluated with subjective response viz. no residual tumor (NRT), scanty residual tumor (SRT) and residual tumor and objective response viz. Tumor regression grade (TRG) 0-5 by Mandard group. We attempted to find a cut off value of the post neaodjuavnt SUV of the primary tumor site which correlated with achievement of better histopathological response. Results: Out of 1325 patients of SCC esophagus who underwent surgery, 943 patients had available data of TRG and it was categorised into the 0-2 category which had 325 patients (34.5%) and 3-5 category, 618 patients (65.5%). The SUV was taken from the PET scan done in the institution and this was available for 186 patients, 151 from the NACT group and 35 from the NACTRT group. ROC method was used to find the cutoff for SUV (5.05) in the NACT cohort, which depicted significant difference in the outcome. Out of these, 93 patients who underwent NACT had SUV >5.05 and 58 had SUV>5.05. It was found that the subjective and objective histopathological scores correlated at a p-value of <0.0001. Specifically, the majority of cases with SRT tended to be in the 3-5 category of TRG whereas cases with NRT are predominantly in the 0-2 category. In the >=5.05 category of SUV there were 76 cases with SRT. In the NACT cohort, the <5.05 category of SUV, there are 26 cases with SRT and 32 cases with NRT. Among cases with SRT, 74.5% had SUV >=5.05, while 25.5% had SUV <5.05. Among cases with NRT, 34.7% had SUV >=5.05, while 65.3% havd SUV <5.05.(p value- 0.007). No significant association was found in the radiopathological correlation in the NACTRT group. Conclusion: Our study confirms the correlation of post neoadjuvant chemotherapy PET SUV with histopathological response, the cutoff of SUV being 5.05 in our cohort. This confirms the predictive value as demonstrated in other studies. Furthermore, its prognostic value with respect to survival has been verified in multiple other studies. With larger scale randomized studies, we may be able to identify the group of patients who have borderline operability anatomically as well as physiologically, where alterantive treatment regimens may be indicated to improve outcomes