Abstract
Objective: To investigate the variability in primary tumour volume in nasopharyngeal carcinoma and compare it with the tumour staging of the 1997 American Joint Committee on Cancer.
Design: Prospective study.
Setting: Tertiary care centre.
Method: A series of 33 newly diagnosed patients who were treated with high-dose radiotherapy participated in the study.
Main Outcome Measures: Using computed tomographic scans, primary tumour volumes were measured using the summation-- of-areas technique, and the variability in tumour volume was determined. The Mann-Whitney test was used for statistical analysis.
Results: A large variation in primary tumour volume was observed, especially in advanced-stage cases.
Conclusions: Nasopharyngeal carcinoma shows considerable variability in primary tumour volume. Incorporation of primary tumour volume may lead to further refinement of the 1997 tumour staging system.
Sommaire
Objectifs: Le but de cette etude est d'investiguer la variabilite du volume tumoral dans les carcinomes nasopharynges et de le comparer avec la classification de 1997 de l'American Joint Committee on Cancer.
Devis: Etude prospective.
Localisation: Centre de soins tertiaires.
Methode: Nous avons evalue une serie de 33 patients nouvellement diagnostiques et traites avec radiotherapie externe a hautes doses.
Mesures: Nous avons evalue les volumes tumoraux en utilisant une technique d'addition des aires sur des epreuves tomodensitometriques et determine la variabilite du volume tumoral. Nous avons utilise le test Mann-Whitney pour faire l'analyse statistique.
Resultats: Nous avons note une grande variation dans le volume tumoral en particulier chez les cas de pathologies avancees.
Conclusion: Les carcinomes nasopharynges presentent une variabilite importante dans le volume de tumeur primaire. L'addition de ce facteur a la classification tumorale pourrait raffiner le systeme developpe en 1997.
Key words: American Joint Committee on Cancer tumour-stage classification, nasopharyngeal carcinoma, primary tumour volume
Tumour bulk is an important prognostic factor in patients with malignancy treated with primary radiation therapy as that increasing tumour bulk means increasing numbers of tumour clonogen need to be sterilized.1-3 The main purpose of any staging system is to segregate patients into subgroups with different prognoses, so that an appropriate treatment modality can be employed. A variety of staging systems have been formulated for nasopharyngeal carcinoma (NPC). The most widely used systems are those of the American Joint Committee on Cancer (AJCC),4 the International Union Against Cancer (UICC),5 and Ho.6 With respect to tumour-stage classification, all of the staging systems are based on anatomic location and cranial nerve involvement. However, after much debate, no system was selected to be used internationally, and each of these systems has its limitations. In 1997, the AJCC system modified tumour-stage classification, and the adequacy of the new, modified classification will require further clinical confirmation.
The current study aimed at delineating the relationship between primary tumour volume and the tumour staging of the 1997 AJCC system in NPC.
Patients and Methods
From July 1998 to June 1999, 33 patients with newly diagnosed NPC were included in a prospective study in our centre. Only patients satisfying the following conditions were included: (1) newly diagnosed patients with histologic confirmation of NPC; (2) treated with high-dose irradiation (>= 70 Gy); (3) complete baseline computed tomography (CT) information in our centre; and (4) displayed distinct tumour boundaries and were free of motion and/or dental artifact.
The exclusion criteria were (1) the presence of distant metastasis on presentation and (2) did not complete radiotherapy. Patients were staged according to the AJCC stage classification system modified in 1997.4 Pretreatment work-up included a complete physical examination, hematologic and biochemical profile, chest radiography, endoscopic tumour mapping and biopsy of the nasopharynx, CT of the primary site and whole neck, liver echocardiography, and whole-body bone scan. Gadolinium-enhanced magnetic resonance imaging (MRI), pure-tone audiometry, a thyroid function test, and an olfactory test were obtained when necessary. The patients' characteristics, histology, AJCC stage, and treatment are listed in Table 1.
The CT scans were performed on a GE HiSpeed CT/I and proSpeed plus scanner (GE Medical Systems, Milwaukee, WI). All studies performed as axial scan plane parallel to the infraorbital-meatal line were obtained extending from the skull base to the top of the manubrium with contiguous 5-mm scan and a 25-cm field of view; direct coronal scans were obtained when possible. A total of 100 mL of contrast medium (Iopamiro 300, Bracco s.p.a., Milano, Italy) were administered, using a medrad CT injector with an injecting rate between 1 and 2.5 mL/sec after 5 mL of an initial testing dose.
For the actual volume analysis, we used the summation-of-areas technique. All scans were assessed by clinicians for tumour extent. The contour of the tumour was outlined manually by radiation oncologists on each CT image using the commercial planning system ADAC (ADAC Laboratories, Milpitas, CA), with the assistance of otorhinolaryngologists and diagnostic radiologists.
Results
A large variation in primary tumour volume was observed, especially in advanced-stage cases. The primary tumour volume in early stage (T1 and T2) and advanced stage (T3 and T4) is listed in Table 2. To compare the tumour volume in the two groups, the Mann-Whitney test was used for statistical analysis, and the results revealed that the difference was significant (p < .01). Although, in general, large primary tumour volume was more commonly observed in higher-stage disease, there was a substantial variation in all stages and much overlapping among different stages (Fig. 1).
Discussion
In this study, we used the summation-of-areas technique to calculate primary tumour volume from the pretreatment CT scans of patients with NPC. Various studies showed that the mean percentage errors of volume calculations using this technique were within a range of 5 to 10% when compared with volumes determined by water displacement, and the reproducibility of volume measurements was ever better than 5%,7,8 indicating that this technique can be used for reliable tumour volume measurements.
Although many authors have demonstrated a positive correlation between tumour volume and local tumour control and survival rates,9-12 detailed CT volumetric studies of NPC are few, especially compared with the 1997 AJCC tumour staging. The concept used for tumour staging in different systems was similar, but each system has its limitations, including the newest 1997 AJCC system. In the AJCC system, the designation of T1 or T2, based on the extent of involvement within the nasopharynx, is not meaningful and carries no prognostic significance.13,14 Cranial nerve involvement has been shown to carry a worse prognosis than skull-base involvement,15,16 and both were included in the T4 category in the previous AJCC system. Although in the 1997 AJCC tumour-staging system, the bony destruction of the skull base is assigned to the T3 category, the area and severity of skull-base involvement are very different, which may lead to a different prognosis. Thus, the adequacy of tumour classification of the new, modified 1997 AJCC will require further clinical confirmation. However, the tumour staging of NPC depends mainly on the location in different anatomic regions and subsites of the primary tumour. According to the criteria based on anatomic location, a low-volume tumour present in more than one subsite automatically receives a higher tumour stage than does a voluminous tumour limited to one subsite. In the same manner, low- and high-volume tumour masses could be classified in the same tumour stage if their locations are identical.
Our results revealed that there was a substantial variation in all stages and much overlapping among different stages (see Fig. 1), especially with a large standard deviation in the advanced stage (see Table 2). A similar variability in tumour volume in advanced-stage head and neck cancer was also reported in other studies.2,3,7,9 This reflects the limitation of using the current tumour staging system to segregate advanced cases into large and small tumour bulk. One of the most important goals of the staging is to categorize patients with similar severity, treatment modality, and prognosis into the same group. Ideally, it should include patients with the same prognosis, resulting in maximal discriminative value of the survival curve. In our study, we criticized the tumour, node, metastasis classification of NPC because the tumour staging remains dependent on subjective and unidimensional criteria that fail to define the true dimensional bulk. Although there was a statistical significance between tumour volume and different tumour stages, the variation in tumour volume was very large. Chua et al.2 reported that the primary tumour volume was the only significant factor in predicting local failure.
Computed tomography-based volumetric measurement is the most accurate way to assess NPC, which is not easily accessible clinically and tends to be infiltrated with an irregular contour. One limitation of our study was that it could not reliably measure small tumours confined in the nasopharynx, especially involving the roof of the nasopharynx, as well as early disease with no more than mild mucosal irregularity. Thus, magnetic resonance tumour volumetry may be a more accurate tool in the measurement of small-volume tumours.
Another limitation of our study was that some clinicians thought that the actual volume analysis was time consuming. In our experience, outlining the tumour and data processing required about 20 minutes for the scanner. The volume data may help to identify prognostic differences, especially within the same stage; the cost efficiency should be evaluated further. In addition, with the advances in imaging techniques and increases in technological sophistication and refinement with time, the cost of tumour volumetry will be reduced with more benefit.
Conclusions
Detailed knowledge of turnout volume has clinical relevance because many authors have demonstrated a positive correlation between tumour volume and primary tumour control and survival rates. In this study, we have found considerable variability in tumour volume in different stages of NPC and much overlapping among the stages. This confirmed that the 1997 AJCC tumour classification is unable to group tumours with the same size into the same tumour-stage group in NPC. We suggest that volumetric analysis of primary tumour volume in NPC would lead to a further refinement of the current tumour-staging system and assist physicians in selecting patients with a poor prognosis in whom the treatment modality may be different.
Received 08/02/00. Received revised 31/10/00. Accepted for publication 13/12/00.
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Cheng-Chuan Chang, Mu-Kuan Chen, and Yung-Sung Wen: Department of Otorhinolaryngology, Head and Neck Surgery, Mu-Kuan Chen: Research Center of Nasopharyngeal Carcinoma, Mu-Tai Liu, Tong-Hao Chang, Le-Jung Wu, Sung-Yan Lin, and Jao-Perng Lin: Department of Radiation Oncology, Hwa-Koon Wu: Department of Diagnostic Radiology, Changhua Christian Hospital, Changhua, Taiwan.
Address reprint requests to: Dr. Cheng-Chuan Chang, Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, 135 Nanhsiau Street Changhua, 500, Taiwan.
Copyright Decker Periodicals, Inc. Aug 2001