Effects of neoadjuvant radio-chemotherapy on 18F-FDG-PET in esophageal carcinoma

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Abstract

Aim. To investigate whether results of [F-18]-fluorodeoxy-d-glucose (FDG) positron emission tomography (PET) of esophageal cancer (EC) before and after neoadjuvant radio-chemotherapy correlate with histopathology after esophageal resection.

Methods. Twenty consecutive patients with EC without distant metastases were examined twice with 18F-FDG-PET during primary staging and after neoadjuvant radio-chemotherapy. FDG standardised uptake values (SUV) were correlated with the histopathological findings (percentage of viable tumour cells, tumour regression grade 1–5).

Results. Regression analysis revealed a slight (not significant) positive correlation between SUVpre (R=0.41, p=0.08) and SUVpost (R=0.37, p=0.11) and the percentage of viable tumour cells in the resectate. Although all patients showed a significant decrease in SUV after radio-chemotherapy (p<0.01), the percentual decrease of the SUV after therapy (ΔSUV%) did not significantly differ between the TRG-groups. In 12 of 20 patients (60%), therapy-induced esophagitis was detected in post-therapeutic PET images.

Conclusion. In EC, a higher pre-therapeutic SUV might be correlated with a higher fraction of vital tumour cells remaining after radio-chemotherapy. Applying the neoadjuvant therapy protocol and the study design used in this examination, there is no correlation between decrease in SUV and histopathology.

Introduction

The therapy of choice in non-metastatic esophageal carcinoma (EC) is surgical resection of the primary tumour. Preoperative radio-chemotherapy is not generally established but is increasingly applied for local downstaging and systemic disease control.1., 2., 3. A pathologic complete response to neoadjuvant therapy is the strongest predictor of long-term survival.4 However, more than half of patients with solid carcinomas have poor response to this neoadjuvant therapy.2., 3., 5., 6. There are presently no reliable procedures available to identify prior to therapy those patients who will respond.

Computed tomography (CT) and endosonography play important roles in the staging of EC.7 However, although CT has become wide-spread in the control of therapy, no correlation was found between the morphological findings and the response to therapy.8 The predictive value of endoscopic ultrasound is also a matter of controversy.9., 10.

Metabolic imaging of EC with [F-18]-fluorodeoxy-d-glucose (18F-FDG) positron emission tomography (PET) has been widely investigated in recent years. It is known that both squamous epithelial carcinoma and adenocarcinoma of the esophagus show marked FDG-accumulation.6., 11., 12., 13. The impact of PET-examinations for identifying therapy responders in esophageal carcinoma is still controversially discussed. Pilot studies have brought evidence of a possible benefit of follow-up FDG-PET examinations, which makes it possible to distinguish therapy responders from non-responders.14., 15., 16., 17., 18. However, one study could not determine any correlation between the results of FDG-PET and histopathology.19 The studies cited differ considerably with respect to the therapy modalities applied, the examination protocols and the target parameters for therapy response.

Our study investigated the correlation between histopathological findings and FDG-uptake before and after radio-chemotherapy in EC with respect to the neoadjuvant protocol applied in our clinic.

Section snippets

Patient characteristics

Between 1999 and 2002, following approval by the local Ethics Commission, 20 consecutive patients (17 males, 3 females), ages 53.7±9.5 years with histologically-confirmed EC (5×pT2, 15×pT 3, M0) were examined with 18F-FDG-PET during primary staging and at intervals of 2.7±0.6 weeks after neoadjuvant radio-chemotherapy. All patients had granted informed consent. Tumour histology showed adenocarcinoma in 13 cases and squamous cell carcinoma in seven cases. All patients were assessed clinically

Results

The patient characteristics, pre-therapeutic and post-therapeutic SUVs and the results of the histopathological examinations are summarised in Table 1.

In Table 2, patients were classified according to the tumour regression grades (TRG).29 Accordingly, five patients were assigned to TRG 1, eight patients to TRG 2, six patients to TRG 3 and one patient to TRG 4.

Means of tumour length and wall-thickness, measured by CT before therapy, did not vary considerably within the TRG-groups. It was not

Discussion

Response evaluation with 18F-FDG-PET is currently under discussion in many tumour entities.5 Above all, the method is based on the hypothesis that the glucose metabolism of a tumour is directly related to the number of viable tumour cells.23., 24. Typically, a decrease in tumour FDG uptake is seen early during effective treatment whereas no significant decrease or even increase is noted in ineffective therapy.5

The present study evaluated the effects of neoadjuvant radio-chemotherapy on glucose

Conclusions

The study data suggest that a higher pre-therapeutic SUV might be correlated with a higher fraction of remaining viable tumour cells after radio-chemotherapy. Applying the neoadjuvant therapy protocol and the study design used in this examination, there is no correlation between the amount of decrease in SUV (ΔSUV%) and histopathology. Evaluation of therapy response with FDG-PET appears critical when radio-chemotherapy causes extensive esophagitis.

Acknowledgements

The authors thank Ursula Sahm, Ph.D., Kenneth Stålmo, and Bernd Morasch for producing the radioisotope and radiopharmaceutical; and we are indebted to Claudia Santini-Böttcher and Harald Dietsche for their technical assistance.

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