| Summary: | 博士 === 國立臺灣大學 === 流行病學研究所 === 93 === Objective: Nasopharyngeal carcinoma (NPC) is a head and neck malignancy prevalent in Taiwan. For NPC patients with locoregionally advanced disease, induction chemotherapy (IC) followed by concurrent chemoradiotherapy has been the preferred therapeutic approach for improving locoregional control and eradicating micrometastases. It is of great advantage if we are capable of identifying the non-responders during or immediately after induction therapy such that alternative treatment strategies may be formulated as early as possible. Besides, the loco-regional recurrences and distant metastases are crucial prognostic factors for NPC patients after their treatments. Nonetheless, conventional MRI and CT have relatively low sensitivity and moderate specificity in distinguishing residual/recurrent lesions from post-therapy changes because a variety of changes in the nasopharyngeal tissue caused by radiotherapy may obscure the detection of tumor recurrence by these anatomical imaging studies.
It has been reported that positron emission tomography (PET) using 18-fluoro-2-deoxyglucose (18F-FDG), based on the property that 18F-FDG is prone to accumulate in the malignancy, is a promising tool for evaluating therapeutic responses of several malignancies and for distinguishing recurrent tumors from post-treatment changes in the nasopharynx. To the best of my knowledge, the usages of 18F-FDG PET for NPC patients in these two categories have not been fully evaluated yet. This study of mine is to evaluate the usefulness of 18F-FDG PET for the therapeutic responses during and after induction therapy and the usefulness of 18F-FDG PET for the early detection of recurrence/metastases in the follow-up of NPC patients, and to perform a cost-effectiveness analysis to determine the optimized usage for the follow-up of NPC patients by 18F-FDG PET which is known to be prohibitively expensive.
Study Design: This study includes 3 parts: The first part studies therapeutic responses of NPC patients by PET. 50 patients (19 female and 31 male with age 17-72 years; mean, 45.9 ± 11.9) who had histologically proven locoregionally advanced NPC without distant metastasis and had received IC were recruited in this part of study. Whole-body 18F-FDG PET was performed for each patient after completion of one (33 patients) or two (17 patients) courses of IC. Each patient was restaged by 18F-FDG PET results. Patients who were downstaged to stage I or II were classified as major-responders. The rest were classified as non-major-responders. The PET restaging results were correlated with follow-up results of these patients.
The second part studies 64 Taiwanese NPC patients, 14 female and 50 male (age range, 16-75 years; mean age, 45.8±13.0 years) who received 18F-FDG PET studies at 4-70 months (mean: 14.1± 13.5 months) after radiotherapy or induction chemotherapy followed by concurrent chemoradiotherapy. The second part of study evaluates the effectiveness and prognostic significance of whole-body 18F-FDG PET in the diagnosis of recurrent/metastatic NPC and in the follow-up examination of these NPC patients.
For the third part, an analysis for cost-effectiveness is performed based on the decision-tree model for three different strategies: (1) MRI-only, (2) PET-only, and (3) MRI-PET (performing PET scan if MRI result is uncertain) to analyze the cost-effectiveness of 18F-FDG PET for detecting loco-regional recurrences for NPC patients after RT or CCRT therapy.
Results: (Part 1) Only 1 of the 23 major-responders developed local recurrence afterwards. They were all alive at the time of data analysis. On the other hand, 15 of the 27 non-major-responders had locoregional recurrence or distant metastasis. Among these non-major-responders, 7 died of NPC and 2 died of therapeutic complications at the time of data analysis. Kaplan-Meier survival analysis showed significantly longer recurrence-free survival and overall survival in major-responders (56.4 ±9.2 and 58.1±2.2 months) as compared to non-major-responders (33.7 ±23.2 and 44.7±20.0 months) with p < 0.0001 and p = 0.0024, respectively. (Part 2) The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of 18F-FDG PET images in the diagnosis of NPC recurrence/ metastases and secondary primary cancers were 92%, 90%, 92%, 90% and 91%, respectively. Furthermore, the presence of 18F-FDG hypermetabolism was found to be highly correlated with the survival time of NPC patients. (Part 3) Plugging the data for utilities and life expectancies in the decision tree model, the quality adjusted life expectancies are found to be 16.16 QALYs for strategy 1, 16.70 QALYs for strategy 2 and 17.35 QALYs for strategy 3. The additional cost per additional QALYs for strategy 3 relative to strategy 1 is calculated to be US$62 (US$550/1.19). Strategy 3 dominates over strategy 2 because strategy 3 costs less and yields more QALYs than strategy 2.
Conclusion: The results suggest that (Part 1) early restaging by whole-body 18F-FDG PET performed after the 1st or the 2nd course of IC is useful for predicting therapeutic response and outcome for locoregionally advanced NPC patients; (Part 2) whole-body 18F-FDG PET is a sensitive follow-up diagnostic tool for the evaluation of NPC recurrences and metastases. It is also an effective prognostic indicator for NPC patients. Finally, (Part 3) the decision tree analysis shows that MRI-PET strategy is the most cost-effective for now. In the near future, as the cost of PET scan decreases in a faster rate than the cost of MRI does, it is likely the PET-only strategy will become the most cost-effective strategy for recurrent NPC patients.
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