maxillary squamous cell carcinomas staged by computed tomography

Inl. J. Radiation Oncology Bid. Phys.. Vol. 12, pp. I I l-l 16 0360-3016/86 $03.00 + 40 Printed in the U.S.A. All rights reserved Copyright 0 1986 Pqamon Press Ltd.

??Brief Communication

MAXILLARY SQUAMOUS CELL CARCINOMAS STAGED BY COMPUTED TOMOGRAPHY

MAKOTO KONDO, M.D.,* YUTAKA ANDO, M.D.,* YUKIO INUYAMA, M.D.,? HAYAO SHIGA, M.D.+ AND SHOZO HASHIMOTO, M.D.*

Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan

In 72 patients with maxillary squamous cell carcinoma, computed tomography (CT) alone was used for T-staging according to the AJC classification. Five, 31, and 36 tumors were diagnosed as T2, T3, T4, respectively. In NO patients with a minimum follow-up of 2 years, local control rates for T2, T3, and T4 tumors were 33% (l/3), 64% (16/25) and 38% (9/24), respectively. Addition of maxillectomy to treatment seemed to have improved the local prognoses in T3 and T4 tumors. High radiation doses of 60 Gy or more seemed to be beneficial for patients with T3 tumors and without maxillectomy. CT will be of great help in classifying tumors objectively. But more importantly, it will reve.al resectability and dictate treatment of choice by delineating the tumor extent precisely.

Maxillary sinus, $iquamous cell carcinoma, Computed tomography, Maxillectomy, Radiotherapy.

INTRODUCTION

The primary goal of therapy of maxillary squamous cell carcinoma (SCC) should be to achieve local control, because most patients who relapsed had local recurrence during the course of the disease.13 However, treatment policies for the primary tumors vary markedly among institutions: either surgery alone,* radiation therapy alone,3 radiation and surgery,” or combined trimodal therapy (radiation, surgery, and chemotherapy)‘43’6-18 may be used for tumors of the same extent. It is very difficult to compare the reported success rates, because different investigators used different end points and different staging systems. I3 At present, th. ere are several staging systems, including the TNM classification of the American Joint Committee for Cancer Staging and End-Results Reporting (AJC),‘,” but no UICC classification for the maxillary sinus; it is also likely thad each institution uses different staging procedures. Although pretreatment nonsurgical staging is ideal by the definition of the TNM classification, the sinonasal cavities are difficult to assess noninvasively. 2*7,8 These problems make it difficult to draw mean- ingful conclusions about staging and treatment of maxillary SCC.

Computed tomography (CT) can readily show destruction of the fine bone structures of the sinonasal cavities and tumor invasion to the deeper sites such as the orbit,

infratemporal fossa, pterygopalatine fossa, nasopharynx and intracranial fossa.‘*” The ability of CT to diagnose the tumor extent is better than conventional tomography,’ and may be better than surgical procedures short of maxillectomy.13 Because we have treated most patients with irradiation and chemotherapy after exploratory maxillotomy, we have used CT for staging maxillary SCC, and compiled the treatment results according to CT stages. This would be of help to examine the usefulness of the staging system in clinical settings in many institutions that do not use major surgery for patients with maxillary SCC.

METHODS AND MATERIALS

From 1978 through 1984, 115 patients with malignant tumors originating from the sinonasal cavities underwent CT examinations before treatment. Using the AJC classification, which should be applied for SCC only, 79 patients with SCC histology were identified. All CT scans were reviewed without reference to the clinical information. Original sites were estimated based on the CT findings only. If an original site could not be determined with confidence, for example, a tumor involving the maxillary sinus and nasal cavity with destruction of the medial maxillary wall only, the tumor was arbitrarily included

* Dept. of Radiology. t Dept. of Otorhinolaryngology. $ Dept. of Diagnostic Raldiology. Reprint requests to: Makoto Kondo, M.D., Department of

Radiology, Keio University School of Medicine, 35 Shinano- machi, Shinjuku-ku, Tokyo 160, Japan.

Accepted for publication 27 August 1985.

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112 I. J. Radiation Oncology 0 Biology 0 Physics January 1986, Volume 12, Number I

as maxillary sinus origin. With this policy, a relatively large number of tumors were selected as maxillary sinus origin: 72, 4, 1 and 2 tumors were classified as maxillary sinus, ethmoid sinus, frontal sinus and nasal cavity origin, respectively. Twenty-five patients were also included in the previous reports. 13,14 Twenty-nine patients were examined with third generation CT scanners, and the rest were examined with earlier machines. All examinations were performed with the patient positioned to produce standard transverse axial views, with the gantry directed parallel to the orbitomeatal line. Coronal sections were obtained in only 33 patients because of heavy case load and difficulties in maintaining the position in elderly patients. Contrast injection was done when intracranial extension was suspected. These 72 tumors of maxillary SCC were classified according to the AJC system (Table 1) based on the CT findings only.

Criteria for interpretation of CTjindings If there was doubt concerning the correct T stage, the

lower (i.e., less advanced) category was chosen. Only distinct destruction or deviation of the bone was interpreted as positive. Similarly, clouded sinuses without distinct destruction of the sinus wall(s) was not considered as positive. Clouded sinuses were often a result of obstructive sinusitis without invasion. ‘.I2 In a few instances when the pterygoid plate was not apparently destroyed or displaced, but surrounded by the tumor, it was assumed that the pterygoid plate was involved (Fig. 1).

Treatment methods For the analysis of the treatment results, 7 patients were

excluded, 4 patients with cervical or distant metastases at first presentation and 3 patients under treatment as of this writing, thus leaving 65 patients. The treatment of choice during that period was combined trimodal therapy for most patients. All patients received exploratory maxillotomy with or without mass reduction. Afterwards, radiation therapy was performed in all but one patient, in whom a total maxillectomy was performed. Either 6-MeV linac X rays or cobalt-60 gamma rays were used with a

Table 1. The AJC classification for maxillary SCC

Tl Tumor confined to the antral mucosa of the infrastructure* with no bone erosion or destruction

T2 Tumor confined to the suprastructure mucosa without bone destruction, or to the infrastructure with destruction of medial or inferior bony walls only

T3 More extensive tumor invading skin of cheek, orbit, anterior ethmoid sinuses, or pterygoid muscle

T4 Massive tumor with invasion of cribriform plate, posterior ethmoids, sphenoid, nasopharynx, pterygoid plates, or base of skull

* Ohngren’s line, a theoretic plane joining the medial canthus of the eye with the angle of the mandible, may be used to divide the maxillary antrum into the anteroinferior portion (the infrastructure) and the superoposterior portion (the suprastructure).

Fig. I. A tumor destroys the medial and posterior maxillary walls and invades to the infratemporal fossa and nasal cavity. The pterygoid plate seems to be preserved. However, the tumor surrounds the pterygoid plate medially (arrow) and anteriorly. Therefore, it would be justified to assume the pterygoid plate is involved. CT stage is T4.

box-field technique using a wedge pair. All had a conventional fractionation schedule of 2 Gy per day, 5 times per week. Total radiation doses ranged from 16 to 72 Gy (median: 50 Gy). Three patients received less than 40 Gy; the irradiation was prematurely terminated because of chemotherapy-enhanced mucositis. Maxillectomy was performed when regression of the tumor was poor, or when patient’s consent was obtained: 15 patients underwent total maxillectomy, and 8 patients had partial maxillectomy. Fifty-eight patients received chemotherapy either before or during irradiation. There was no concrete guideline for chemotherapy during that period. Fifty-one patients had intraarterial infusion via a catheter in the superficial tem- poral artery, and the others received chemotherapy intra- venously. Bleomycin (BLM), peplomycin (PEP), 5-fluo- rouracil (5-FU) and cisplatinum (CDDP) were used. Thirty-seven patients had single agent chemotherapy, and 21 had combination chemotherapy. 5-FU was given for 33 patients with total doses of 1 to 10 g (median: 3 g), PEP for 22 patients with total doses of 25 to 200 mg (median: 50 mg), CDDP for 19 patients with total doses of 50 to 240 mg (median: 160 mg), and BLM for 10 patients with total doses of 20 to 180 mg (median: 45 mg).

Analysis of treatment results Because local recurrence is a major cause of death in

this disease,13 only local-recurrence-free survival or local control rates were considered in this study. Local recurrence that had developed subsequent to cervical or distant relapse was included, because reseeding from the meta- static sites to the primary site seems unlikely to occur. One patient included in the local control group was alive as well at this writing, 5 years following salvage maxillectomy.

Local-recurrence-free survival curves were calculated according to Kaplan and Meier.” Gehan’s modification

Maxillary squamous cell carcinomas 0 M. KONW et al. II3

of the generalized Wilcoxon test was employed to evaluate differences in survival c:urves.6 For calculation, patients with local control who died of cervical or distant metastases, or other causes, were included as alive and free of local recurrence at the latest follow-up. No patients were lost to follow-up.

R:ESULTS

Staging results using CT alone Five tumors were diagnosed as T2, 31 as T3, and 36

as T4 according to the A.JC classification. All 5 T2 tumors involved the nasal cavity with destruction of the medial maxillary wall only (Fig. 2). Reasons to classify the tumors as T4 are listed in Table 2. Involvement of the posterior ethmoids were most commonly seen either as a sole critical site (9 of the 36 T4 tumors or 25%) or combined with other criteria (15/36 or 42%) (Fig. 3). Pterygoid plate involvement was also common either as a sole T4 criterion (8/36 or 22%) or coupled with involvement of other critical sites ( 13/36 or 36%). On the other hand, nasopharynx involvement was seen in combination with other T4 criteria ( 13/36 or 36%), that is, invasion of either the posterior ethmoids or pterygoid plate. Invasion of the sphenoid, base of skull and cribriform plate was less frequently en- countered (four, six, and one occasions, respectively), and was never seen as a sole T4 criterion. All tumors extending to the sphenoid, base of skull or cribriform plate had invasion of the posterior ethmoids.

In the 29 patients examined by the third generation CT scanners, T2, T3, and T4 tumors were diagnosed in 1, 10, and 18 patients, respectively; the corresponding figures for patients examined by earlier generation machines were 4, 2 1, and 1:s patients. The difference of dis- tribution, however, was not statistically significant by Chi square test. In the 33 patients with coronal sections, 4,

Fig. 2. This slice shows that a tumor destroys the medial maxillary wall only, and extends to the nasal cavity (arrow). The contra- lateral maxillary sinus was also investigated by maxillotomy, which revealed chronic sinusitis. CT diagnosis is T2 considering general rules of TNM classifications (see discussion).

Table 2. Critical sites of involvement in the 36 T4 tumors

Site of involvement No. of tumors

PE PP

PE + Na PE + SP PE + PP PE + BS

PP + Na PE + PP + Na PE + PP + SP PE + PP + BS PE + PP + Na + BS PE + PP + Na + CP PE + PP + Na + Sp + BS Total

4 1

3

36

BS: base of skull; CP: cribriform plate; Na: nasopharynx; PE: posterior ethmoids; PP: pterygoid plate; Sp: sphenoid.

15, and 14 patients were diagnosed to have T2, T3, and T4 tumors, respectively; the corresponding figures for the patients without coronal sections were 1, 16, and 22.

Treatment results according to CT stage Expected 5-year local-recurrence-free survivals for pa-

tients with T2, T3, and T4 tumors, and all patients were 30, 58, 31 and 44%, respectively (Fig. 4). Because there was no local recurrence 2 years after diagnosis in our previous experience, ’ 3 and only one patient in this series developed local recurrence after that period, local control rates were calculated in 52 patients with a minimum follow-up of 2 years. Local control rates of T2, T3, T4 and all tumors were 33% (l/3), 64% (16/25), 38% (9/24), and 50% (26/52), respectively. Local control rates in the T4 tumors did not differ depending on whether the tumors had involvement of one critical site or more sites (34 vs. 28%).

Fig. 3. The anterior and posterior ethmoids are involved with destruction of the medial orbital wall. The tumor extends into the orbit. This tumor is T4.

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I. J. Radiation Oncology 0 Biology 0 Physics January 1986, Volume 12, Number 1

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1 2 3 4 5 6 7Y Fig. 4a. Local-recurrence-free survival curves of all patients, and patients with T2 tumors. Fig. 4b. Local-recurrence-free survival curves of patients with T3 and T4 tumors.

Patients undergoing total or partial maxillectomy showed better local prognoses than those with maxillotomy only. In the patients with and without maxillectomy, expected 5-year local-recurrence-free survivals were 60 and 34%, respectively. The difference was more marked in T3 patients than T4 patients. T3 patients with and without maxillectomy showed 5-year local-recurrence-free

survival of75 and 4 l%, respectively (Fig. 5); corresponding figures for T4 patients were 47 and 24%. However, these differences were not statistically significant. There was no significant difference in local prognoses of T3 tumors be- tween partial maxillectomy and total maxillectomy: expected 5-year local-recurrence-free survival of 9 patients with total maxillectomy and 5 patients with partial maxillectomy were 73 and 80%, respectively. There were too few a patients with T2 or T4 tumors to compare the surgical procedures.

In the T3 category, patients with total radiation doses of 60 Gy or more did not show a higher local-recurrence- free survival than patients with total doses of less than 60 Gy (60 vs. 56%); corresponding figures for the T4 patients were 28 and 32%. However, total radiation doses may be important in patients with maxillotomy alone. In patients with T3 tumors and maxillotomy, the local-recurrence- free survival was 53% when 60 Gy or more was given, and 29% when less than 60 Gy was irradiated, although the difference was not statistically significant (Fig. 6).

Because local prognoses of maxillary SCC would be influenced by several factors, multivariate regression analyses were done in the 52 patients with a minimum follow-up of 2 years according to the method of Walker and Duncan.” Tested variables were age, sex, type of surgery, total radiation doses, total doses of BLM, PEP, 5- FU and CDDP. In the T2 + T3 patients, an analysis could not be completed because of divergence in the calculation, probably because of the small number of patients. In the T4 patients, no factors were significant in improving local control probability.

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Fig. 5. Local-recurrence-free survival curves of patients with T3 tumors who received maxillectomy (total or partial) and maxillotomy.

Maxillary squamous cell carcinomas 0 M. KONW et al. 115

Fig. 6. Local-recurrence-free survival curves according to total radiation doses in patients with T3 tumors who had maxillotomy.

DISKUSSION

This study showed that most tumors of maxillary SCC were classified as T3 or T4 by CT findings only, and a small number of patients had T2 tumors. In the AJC classification, T2 tumors should be confined to the infrastructure if the medial or inferior bony walls are destroyed. However, by CT it is difficult to differentiate such tumors from those extending to the suprastructure (Fig. 2). Therefore, these tumors should be classified to the lower stage, considering the general rules of the TNM classification. This policy would have classified some actual T3 tumors as T2, and might be a reason for the low local control rate of the T2 tumors.

Many tumors were cla.ssified as T4 because of involvement of the posterior ethmoids or pterygoid plate alone. If invasion of these sites was excluded from the T4 criteria, as done by the Japanese Joint Committee (JJC) classification, a rather large number of tumors would be classified as T3 instead of T4.“,18 If the JJC classification was ap plied to the present series, based on the CT findings alone, 5 tumors were staged as T2,48 as T3, and 19 as T4.

The patterns of involvement of the T4 tumors can easily be understood if one considers the anatomy of the sinonasal cavities. For example, it is difficult for maxillary tumors to reach the sphenoid without invasion of the posterior ethmoids. Similarly, extension to the base of skull would accompany involvement of the ethmoids, sphenoid or orbit, or may be secondary to involvement of the tem- poral fossa.

The cribriform plate was involved in only one occasion, although many tumors invaded the ethmoids. One reason might be that only a sma.11 portion of the patients under-

went coronal sections. Transaxial sections are almost im- possible for detecting destruction of the cribriform plate; this difficulty was also present for examining the base of skull without coroneal sections. However, because tumors with invasion of the cribriform plate or base of skull should have other T4 criteria, the overall incidence of T4 tumors diagnosed by CT would not be changed by the addition of coronal sections. In this study, no tumors were upstaged based on the findings of the coronal sections. On the other hand, the use of the third generation CT scanners would increase the number of tumors in higher stages, because the quality of the images is better than the former machines, so that destruction of the finer bone structures is more readily depicted. We felt that destruction of the ethmoid cells was especially hard to see on the old machines.

The reported incidence of each T-stage according to the AJC classification and the end results are shown in Table 3. There were marked differences in the distribu- tions of T-stages and the success rates. When compared with our previous study, I3314 there was a higher proportion of T4 tumors in the present series. Although the previous patients were staged surgically, most of them had maxillotomy only as surgical procedures; and although maxillectomy was as good as CT in staging tumors, maxillotomy was insufficient for staging tumors invading the deeper sites.13 The quality of staging procedures may be responsible for the different incidence of T-stages.

Referral patterns may also influence the incidence of T-stages. Patients who come to the dentist because of teeth pain or other symptoms related to the oral cavity may have a higher chance to have tumors confined to the infrastructure because of earlier discovery and diagnosis. In this series, however, only three patients were referred from the Department of Oral Surgery. Most patients were seen because of cheek swelling or pain, nasal obstruction or discharge, eye pain, headache, etc. Tumors in such patients were likely to be at least T3. Another possible reason for the differences in the incidence of T-stages and the success rates is that most series included carcinomas other

Table 3. Reported incidence of AJC T-stage and local control

No. of success/No. of patients

Tl T2 T3 T4

Bush and Bagshaw3 - l/l 7114 2/12* Cheng and Wang4t l/2 5/11 8124 012 Kondo et al.“$ - 213 28155 7127 Lee and Ogura” 517 14117 13127 1 s/45* Weymuller et aL2’ - - 14/23* 8/24* Present series5 - l/3 16125 9124

* Includes N+ patients, or no information about N status. t 3-year relapse-free survival as end points. Otherwise, local

control. $ Staged based on surgical findings without CT information.

Squamous cell carcinoma only. $ Staged based on CT findings only. Selected patients with a

minimum follow-up of 2 years. Squamous cell carcinoma only.

116 I. J. Radiation Oncology 0 Biology 0 Physics January 1986, Volume 12, Number 1

than SCC histology. 3-5,‘5,‘7.’ 8,20 Because the results were reported in combined fashion with SCC and other carcinomas, the success rates were difficult to compare.

Total maxillectomy seemed to improve the local prognoses compared with maxillotomy. Unlike the previous study,14 partial maxillectomy was equally effective as total maxillectomy in the T3 tumors. This may be a result of better understanding of the tumor extent with the help of CT scans and appropriate choice of surgical procedures. On the other hand, importance of total radiation doses was less impressive than the previous experience.14 Only the T3 tumors with maxillotomy seemed to benefit from high radiation doses of 60 Gy or more. In our previous study, however, there were many patients who received insufficient doses of less than 40 Gy because of chemotherapy-enhanced mucositis. In this study, only three patients had less than 40 Gy, probably because of the modification of treatment schedules with better understanding of interaction of chemotherapy and irradiation. This de- crease of patients with lower doses would have lessened the significance of total radiation doses.

currence, then, information provided by CT is of primary importance to select tumors suitable for maxillectomy. For example, T3 tumors with a little destruction of the inferior orbital wall and minimal invasion of the orbit are easier to resect than those extending into the apex of the orbit. This study, however, was retrospective, and the numbers of patients in subgroups were too small to draw definite conclusions. In addition, treatment chosen for the each patient was seriously biased, because maxillectomy was usually mutilating with removal of the eye sometimes being dictated, so that many patients refused such surgery. Further study of the effectiveness of surgery, radiation therapy and possibly chemotherapy is war- ranted.

If maxillectomy is truly helpful in decreasing local re-

In conclusion, CT provides an opportunity to classify the primary tumors of maxillary SCC objectively and noninvasively. First, has it become possible to compare the results among the different institutions equally if they all use CT for staging. However, more importantly, CT is of value, because it shows resectability of the tumors and dictates treatment of choice by delineating the tumor extent precisely.

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I. American Joint Committee for Cancer Staging and End- Results Reporting: Manualfir Staging of Cancer. Chicago, IL, American Joint Committee. 1978, pp. 45-48.

2. Beale, F.A., Molony, T.J.: The role ofradiotherapy in benign and malignant disease of the maxillary antrum. Otolaryngol. Clin. N. Am. 9: 269-289, 1976.

3. Bush, SE., Bagshaw, M.A.: Carcinoma of the paranasal sinuses. Cancer 50: 154-158, 1982.

4. Cheng, V.S.T., Wang, C.C.: Carcinoma of the paranasal sinuses: A study of sixty-six cases. Cancer 40: 3038-304 1, 1977.

5. Frazell, E.L., Lewis, J.S.: Cancer of the nasal cavity and accessory sinuses: A report of the management of 4 16 patients. Cancer 16: 1293-1301, 1963.

6. Gehan, E.A.: A generalized Wilcoxon test for comparing arbitrarily singly-censored samples. Biometrica 52: 203-223, 1965.

7. Harrison, D.F.N.: Critical look at the classification of maxillary sinus carcinomata. Ann. Otol. 87: 3-9, 1978.

8. Ireland, P.E., Bryce, D.P.: Carcinoma ofthe accessory nasal sinuses. Ann. Otol. 75: 698-7 13, 1966.

9. Jeans, W.D., Gilani, S., Bullimore, J.: The effect of CT scanning on staging of tumors of the paranasal sinuses. Clin. Radiol. 33: 173-179, 1982.

10. Jesse, R.H.: Preoperative versus postoperative radiation in the treatment of squamous carcinoma of the paranasal sinuses. Am. J. Surg. 110: 552-556, 1965.

11. Kaplan, E.L., Meier, P.: Nonparametric estimation from incomplete observations. J. Am. Stat. Assoc. 53: 457-481, 1958.

12. Kondo, M., Horiuchi, M., Shiga, H., Inuyama, Y., Dokiya,

T., Takata, Y., Yamashita, S., Ido, K., Ando, Y., Iwata, Y., Hashimoto, S.: Computed tomography of malignant tumors of the nasal cavity and paranasal sinuses. Cancer 50: 226- 231, 1982.

13. Kondo, M., Inuyama, Y., Ando, Y., Tsutsui, T., Yamashita, Y., Hashimoto, T., Kunieda, E., Uematsu, M., Hashimoto, S.: Patterns of relapse of squamous cell carcinoma of the maxillary sinus. Cancer 53: 2206-2210, 1984.

14. Kondo, M., Ogawa, K., Inuyama, Y., Yamashita, S., Tom- inaga, S., Shigematsu, N., Nishiguchi, I., Hashimoto, S.: Prognostic factors influencing relapse of squamous cell carcinoma of the maxillary sinus. Cancer 55: 190- 196, 1985.

15. Lee, F., Ogura, J.H.: Maxillary sinus carcinoma. Laryngo- scope91: 133-139, 1981.

16. Moseley, H.S., Thomas, L.R., Ever& E.C., Stevens, K.R., Ireland, K.M.: Advanced squamous cell carcinoma of the maxillary sinus: Results of combined regional infusion chemotherapy, radiation therapy and surgery. Am. J. Surg. 141: 522-525, 1981.

17. Sakai, S., Hohki, A., Fuchihata, H., Tanaka, Y.: Multidis- ciplinary treatment of maxillary sinus carcinoma. Cancer 52: 1360-1364, 1983.

18. Shibuya, H., Horiuchi, J., Suzuki, S., Shioda, S., Enomoto, S.: Maxillary sinus carcinoma: Result of radiation therapy. Znt. J. Radiat. Oncol. Biol. Phys. 10: 1021-1026, 1984.

19. Walker, S.H., Duncan, D.B.: Estimation of the probability of an event as a function of several independent variables. Biometrica 54: 167- 179, 1967.

20. Weymuller, E.A. Jr., Reardon, E.J., Nash, D.: A comparison of treatment modalities in carcinoma of the maxillary antrum. Arch. Otolaryngol. 106: 625-629, 1980.

maxillary squamous cell carcinomas staged by computed tomography

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