¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) for the prognostication and stratification for patients with nasopharyngeal carcinoma and esophageal squamous cell carcinoma : a perspective from precision medicine in clinical practice

Abstract

Nasopharyngeal carcinoma (NPC) and esophageal squamous cell carcinoma (ESCC) are two common cancers in Hong Kong causing significant morbidity and mortality. Standardized treatment results in heterogeneous outcomes, and hence, tailoring treatment according to individual profile is needed. PET/CT scan comprehensively assess metabolic and morphologic information for all lesions within one scan, potentially allowing patients to be risk-stratified for precision medicine. Thus, quantitative parameters of PET/CT were comprehensively explored for prognostication and risk stratification in clinical practice. A prospective cohort of newly diagnosed NPC patients (T1~4N0~3M0) was recruited for pretreatment evaluation using both PET/CT and MRI (n=200). The primary tumor and cervical nodes were segmented, using PET and MRI, and staged with AJCC-TNM classification (7th edition). Maximal SUV (SUVmax), metabolic tumor volume (MTV) and morphologic tumor volume (VOL) of the primary tumor and cervical nodes were computed respectively. Using recurrence-free survival (RFS) as an end-point, 3 risklayers were identified (p<0.001) ;(1), Stage I or Stage II with nodal VOL<18cc [HR=1]; (2), stage III /IV with nodal VOL<18cc [HR=2.93]; (3), nodal VOL≥18cc regardless of disease stage [HR=7.84]. Using overall survival (OS) as the endpoint, 2 risk-layers (nodal VOL<18ccvs nodal VOL≥18cc [HR=4.23], P=0.001) were identified. Therefore, nodal VOL is the predominant risk-factor, placing patients the highest risk level when exceeding 18cc, whereas PET offers no additional value. Furthermore, the 18cc-threshold was verified by an independent cohort (n=105). Based on this threshold, 35 patients (17.5%) would have a higher risk than suggested by the TNM-staging system. Thus, this threshold is highly recommended to be incorporated into the TNM-staging system to replace the “6cm dimension” standard for the N3 disease.

Secondly, consecutive ESCC patients (n=52) were reviewed for response evaluation using PET/CT scan at the baseline (PET0) before neoadjuvant chemoradiotherapy (nCRT), and 4~5 weeks after nCRT (PET1). SUVmax, SUVmean, MTV and total lesion glycolysis [TLG] at both scans and their corresponding decrease (absolute and percentage) from PET0 to PET1 were calculated for the primary tumor and regional nodes respectively. We found SUVmax<2.7 of the primary tumor at PET1 to be the best indicator of pathological complete remission (pCR). For survival analysis, only TLG and SUVmax of regional nodes at PET0 were independently predictive of OS (P=0.002) and RFS (P=0.003), respectively.

These results showed that metabolic and morphologic imaging parameters are of potential use in NPC and ESCC, for patient risk stratification, prognostication, and response evaluation. This may impact on patient selection for the various treatment modalities and the novel chemotherapeutic agents now available and in the pipeline, advancing the understanding of the role of 18F-FDG PET/CT in precision medicine.