Increased FDG uptake on late-treatment PET in non-tumour-affected oesophagus is prognostic for pathological complete response and disease recurrence in patients undergoing neoadjuvant radiochemotherapy.

PURPOSE: Early side effects including oesophagitis are potential prognostic factors in patients undergoing radiochemotherapy (RCT) for locally advanced oesophageal cancer (LAEC). We assessed the prognostic value of 18F-fluorodeoxyglucose (FDG) uptake within irradiated non-tumour-affected oesophagus (NTO) during restaging positron emission tomography (PET) as a surrogate for inflammation/oesophagitis. METHODS: This retrospective evaluation included 64 patients with LAEC who had completed neoadjuvant RCT and had successful oncological resection. All patients underwent FDG PET/CT before and after RCT. In the restaging PET scan maximum and mean standardized uptake values (SUVmax, SUVmean) were determined in the tumour and NTO. Univariate Cox regression with respect to overall survival, local control, distant metastases and treatment failure was performed. Independence of clinically relevant parameters was tested in a multivariate Cox regression analysis. RESULTS: Increased FDG uptake, measured in terms of SUVmean in NTO during restaging was significantly associated with complete pathological remission (p = 0.002) and did not show a high correlation with FDG response of the tumour (rho < 0.3). In the univariate analysis, increased SUVmax and SUVmean in NTO was associated with improved overall survival (p = 0.011, p = 0.004), better local control (p = 0.051, p = 0.044), a lower rate of treatment failure (p < 0.001 for both) and development of distant metastases (p = 0.012, p = 0.001). In the multivariate analysis, SUVmax and SUVmean in NTO remained a significant prognostic factor for treatment failure (p < 0.001, p = 0.004) and distant metastases (p = 0.040, p = 0.011). CONCLUSIONS: FDG uptake in irradiated normal tissues measured on restaging PET has significant prognostic value in patients undergoing neoadjuvant RCT for LAEC. This effect may potentially be of use in treatment personalization.

Prognostic value of SUR in patients with trimodality treatment of locally advanced esophageal carcinoma.

The prognosis of patients with esophageal carcinoma remains dismal despite ongoing efforts to improve treatment options. For locally advanced tumors, several randomized trials have shown the benefit of neoadjuvant chemoradiation followed by surgery compared to surgery alone. The aim of this exploratory study was to evaluate the prognostic value of different baseline positron emission tomography (PET) parameters and their potentially additional prognostic impact at the end of neoadjuvant radiochemotherapy. Furthermore, the standard uptake ratio (SUR) as a new parameter for quantification of tumor metabolism was compared to the conventional PET parameters metabolic active volume (MTV), total lesion glycolysis (TLG), and standardized uptake value (SUV) taking into account known basic parameters. Methods:18F-FDG-PET/CT was performed in 76 consecutive patients ((60±10) years, 71 males) with newly diagnosed esophageal cancer before and during the last week of neoadjuvant radiochemotherapy. MTV of the primary tumor was delineated with an adaptive threshold method. The blood SUV was determined by manually delineating the aorta in the low dose CT. SUR values were computed as scan time corrected ratio of tumor SUVmax and mean blood SUV. Univariate Cox regression and Kaplan-Meier analysis with respect to locoregional control (LRC), freedom from distant metastases (FFDM), and overall survival (OS) was performed. Additionally, independence of PET parameters from standard clinical factors was analyzed with multivariate Cox regression. Results: In multivariate analysis two parameters showed a significant correlation with all endpoints: restaging MTV and restaging SUR. Furthermore, restaging TLG was prognostic for LCR and FFDM. For all endpoints the largest effect size was found for restaging SUR. The only basic factors remaining significant in multivariate analyses were histology for OS and FFDM and age for LRC. Conclusion: PET provides independent prognostic information for OS, LRC, and FFDM in addition to standard clinical parameters in this patient cohort. Our results suggest that the prognostic value of tracer uptake can be improved when characterized by SUR rather than by SUV. Overall, our investigation revealed a higher prognostic value of restaging parameters compared to baseline PET; therapy-adjustments would still be possible at this point of time. Further investigations are required to confirm these hypothesis-generating results.

Prognostic Value of Pretherapeutic Tumor-to-Blood Standardized Uptake Ratio in Patients with Esophageal Carcinoma.

UNLABELLED: Despite ongoing efforts to develop new treatment options, the prognosis for patients with inoperable esophageal carcinoma is still poor and the reliability of individual therapy outcome prediction based on clinical parameters is not convincing. The aim of this work was to investigate whether PET can provide independent prognostic information in such a patient group and whether the tumor-to-blood standardized uptake ratio (SUR) can improve the prognostic value of tracer uptake values. METHODS: (18)F-FDG PET/CT was performed in 130 consecutive patients (mean age ± SD, 63 ± 11 y; 113 men, 17 women) with newly diagnosed esophageal cancer before definitive radiochemotherapy. In the PET images, the metabolically active tumor volume (MTV) of the primary tumor was delineated with an adaptive threshold method. The blood standardized uptake value (SUV) was determined by manually delineating the aorta in the low-dose CT. SUR values were computed as the ratio of tumor SUV and blood SUV. Uptake values were scan-time-corrected to 60 min after injection. Univariate Cox regression and Kaplan-Meier analysis with respect to overall survival (OS), distant metastases-free survival (DM), and locoregional tumor control (LRC) was performed. Additionally, a multivariate Cox regression including clinically relevant parameters was performed. RESULTS: In multivariate Cox regression with respect to OS, including T stage, N stage, and smoking state, MTV- and SUR-based parameters were significant prognostic factors for OS with similar effect size. Multivariate analysis with respect to DM revealed smoking state, MTV, and all SUR-based parameters as significant prognostic factors. The highest hazard ratios (HRs) were found for scan-time-corrected maximum SUR (HR = 3.9) and mean SUR (HR = 4.4). None of the PET parameters was associated with LRC. Univariate Cox regression with respect to LRC revealed a significant effect only for N stage greater than 0 (P = 0.048). CONCLUSION: PET provides independent prognostic information for OS and DM but not for LRC in patients with locally advanced esophageal carcinoma treated with definitive radiochemotherapy in addition to clinical parameters. Among the investigated uptake-based parameters, only SUR was an independent prognostic factor for OS and DM. These results suggest that the prognostic value of tracer uptake can be improved when characterized by SUR instead of SUV. Further investigations are required to confirm these preliminary results.