Clinical investigation
Primary tumor volume of nasopharyngeal carcinoma: prognostic significance for local control

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Abstract

Purpose

To study the prognostic significance of primary tumor volume on local control of nasopharyngeal carcinoma.

Methods and materials

Between 1998 and 2001, 308 consecutive patients with nasopharyngeal carcinoma treated with radical intent were staged with MRI. On the basis of the extent of tumor infiltration outlined by a diagnostic radiologist, the gross tumor volume of the primary and involved retropharyngeal nodes (GTV-P) was delineated by a radiation oncologist for three-dimensional conformal radiotherapy to the nasopharyngeal region using the Helax-TMS Planning System. All patients were treated with 2 Gy daily to a total dose of 70 Gy in 6–7 weeks. Additionally, chemotherapy was given to 128 patients (42%).

Results

The median GTV-P for the whole series was 22 cm3 (range, 1.4–218 cm3). Although the GTV-P varied substantially within each T stage, the overall correlation between these two parameters was strongly significant (p <0.01), with the median GTV-P 2.7 cm3 for T1, 13.2 cm3 for T2, 28.1 cm3 for T3, and 65.5 cm3 for T4. With a median follow-up of 1.9 years (range, 0.1–3.9 years), the 3-year local failure-free rate was 87%. The 3-year local failure-free rate was 97% for patients with a GTV-P <15 cm3 compared with 82% for those with a GTV-P ≥15 cm3 (p <0.01). On multivariate analysis (with T stage as a covariate), GTV-P remained an independent prognostic factor for the local failure-free rate (hazard ratio, 1.01; 95% confidence interval, 1.00–1.02; p <0.01).

Conclusion

Our data suggested that GTV-P is a strongly significant factor for predicting local control of nasopharyngeal carcinoma. The risk of local failure was estimated to increase by 1% for every 1 cm3 increase in primary tumor volume.

Introduction

The accurate prediction of prognosis and failure is crucial for optimizing treatment strategies for cancer patients. Tremendous efforts have been made in improving the TNM staging systems to provide basic guidance for treatment decisions and uniform categorization for sharing data. However, it is well recognized that the current TNM staging approach has limitations. The incorporation of additional prognostic factors might be useful for further refinement of prognostic accuracy.

One of the most promising factors is tumor volume, because larger tumor is related to adverse radiobiologic factors, including increased clonogen number 1, 2, hypoxia 3, 4, and radioresistance 5, 6. Studies using CT have shown that the primary tumor volume (gross tumor volume of the primary and involved retropharyngeal nodes [GTV-P] in our study) was a significant prognostic factor for carcinoma of the larynx 7, 8, 9, hypopharynx, and nasopharynx 10, 11. Furthermore, the study by Chua et al.(10), on nasopharyngeal carcinoma (NPC), suggested that the GTV-P was even more sensitive than the T stage by Ho's system (12) for predicting local control.

Despite the strong radiobiologic basis, volume has not been widely advocated as a prognostic factor in clinical practice. One major obstacle is the difficulty involved in measuring the tumor volume accurately. In the available CT-based reports, tumor volume was calculated by summation of the areas using redigitalized CT films.

Little controversy exists that MRI could substantially improve accuracy in the delineation of the gross tumor extent 13, 14, 15, 16, 17, 18. With the advent of computerized planning systems and routine mapping of the gross tumor target for three-dimensional planning, accurate data on the GTV-P can now be readily available for all patients treated with radical radiotherapy (RT). It is, thus, important that the prognostic significance of the volume be assessed, particularly for NPC, because the therapeutic margin is notoriously narrow, and treatment should be maximally refined for individual need.

Section snippets

Patient characteristics

We performed a retrospective study of 308 consecutive patients with NPC treated with radical intent at the Pamela Youde Nethersole Eastern Hospital (Hong Kong) between November 1998 and June 2001. All but 1 patient had nonkeratinizing or undifferentiated carcinoma (World Health Organization Grade 2-3). Their median age was 48 years (range, 17–83 years), and 71% of patients were men.

All patients underwent noncontrast and contrast-enhanced MRI of the nasopharyngeal and cervical region for

Results

With a median follow-up of 1.9 years (range, 0.1–3.9 years), 56 patients had relapse: 22 local, 7 nodal, and 34 distant. Thirty-four patients had died. The 3-year LFFR was 87%, the PFS rate was 73%, and the OS rate was 84%.

The median GTV-P of the whole series was 22 cm3 (range, 1.4–218 cm3) Table 1 shows the T stage distribution and GTV-P for each T stage. Although the variation within the same T stage was wide, the median GTV-P increased orderly with advancing T stage: T1, 2.7 cm3; T2, 13.2 cm

Discussion

In all the staging systems developed for NPC, the anatomic extent has been the only parameter for classifying the T stage. This is hardly surprising because the measurement of the tumor size is by no means easy for this highly infiltrative cancer located in an inaccessible site.

Although all available studies have shown that the current TNM system is superior to past systems 23, 24, 25, 26, 27, 28, 29, ambiguity and controversies regarding some of the demarcating criteria remain. The

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