Ethmoidal cancers: A retrospective study of 22 cases

Inl J Rodrarwn Oncoio+y Biol Phys Vol Printed m the U S.A. All nghts reserved.

25. pp.

I I3-

I 16

0360-3016/93 $6.00 + .OO Copyright 0 1992 Pergamon Press Ltd

??Brief Communication

ETHMOIDAL J. M. DILHUYDY,

CANCERS:

M.D.,’

A RETROSPECTIVE

P. LAGARDE,

P. SOUBEYRAN,

M.D.,’

L. TRAISSAC,

M.D.,’

A. S. ALLAL,

P. RICHAUD, M.D.2

STUDY

M.D.,’

M.D.,’

OF 22 CASES Y. BI~COUARN,

A. FAUCHER,

AND D. STOLL,

M.D.,’

M.D.,’

M.D.3

’Departments of Radiotherapy, Surgery and Medical Oncology, Fondation BergoniC, Comprehensive Cancer Center, 180 rue de Saint-Get&, 33076, Bordeaux Cedex; 2Department of Otorhinolaryngology, Centre des SpCcialitCs, Rue des SabliZres, 33000 Bordeaux; and 3Department of Otorhinolaryngology, Hhpital Pellegrin, Place Am&lie Raba L&on, 33076 Bordeaux Cedex, France From April 1978 to June 1990,22 patients with ethmoidal cancer were treated at Fondation Bergonik by a combination of surgery and radiation therapy. The mean age was 59.6 years (range 34-79 years) and the sex ratio is 2.7 (16 males/6 females). Histologic types were: adenocarcinoma, 13 cases; squamous carcinoma, 4 cases; undifferentiated carcinoma, 3 cases and esthesioneuroblastoma, 2 cases. Exposure to wood dust was encountered in 11 patients, especially in cases of adenocarcinoma: lo/13 (77%). Staging according to the classification of the University of Florida was: Stage I, 10 patients; Stage II, 5 patients and Stage III, 7 patients. Resection was considered as complete in 16 cases and only one orbital exenteration was performed. The postoperative radiation therapy delivered a mean given dose of 55.7 Gy (range 50-70 Gy) expressed to the hot spot using a technique adapted to tumor location and extension. Complete remission was achieved in 20 cases. Median follow-up is 28 months. The 5-year overall and disease-free survival are 44% and 38%, respectively. Analysis of recurrences according to staging gives: 5/10 Stage I, 2/5 Stage II and 5/7 Stage III. Recurrence is pejorative since death occurs in all cases within an average of 6 months following salvage treatment, except for three patients still alive within less than 6 months and in second remission. Prognosis of ethmoidal cancer depends on staging and local control. Ethmoidal

cancer, Combined

treatment,

Staging,

Local control.

INTRODUCTION

19 patients were excluded from analysis for the following reasons: sarcoma, five cases: previous treatment or treated elsewhere, five cases; neoadjuvant chemotherapy, five cases and exclusive radiation therapy, four cases. Thus, 22 patients were included in this retrospective study. The diagnosis was established by biopsy and confirmed by surgery with a histologic distribution as follows: adenocarcinoma, 13 cases: squamous carcinoma, four cases; undifferentiated carcinoma, three cases and esthesioneuroblastoma, two cases. Staging was established after clinical examination, nasofibroscopic, radiographic, tomographic, operative and histopathologic findings. All the patients were then retrospectively classified according to the classification of the University of Florida (Table 1). The retrospective distribution according to this staging is: Stage I, 10 patients; Stage II, five patients and Stage III, seven patients. All patients were NoMo since nodes and/ or metastases were an indication of chemotherapy (exclusion criteria). The main patient characteristics were a mean age of 59.6 years (range 34-79 years) and a sex ratio of 2.7 (16 males/6 females). Exposure to wood dust was encountered in 11 patients with an exposure time range

Cancers of the paranasal sinuses differ from other head and neck cancers in certain characteristics. The central location with frequent large local involvement compared with relatively poor lymphatic and/or metastatic involvement explains late diagnosis and difficulties in determining the site of origin (5, 20). The low incidence, 0.2% of all cancers and 3% of all upper aerodigestive tract cancers ( 13. 14, 18) explains the small size of published series and difficulties in comparing them. Nevertheless, we decided to focus our study on ethmoidal cancer owing to original patterns like frequent exposure to wood dust which is often correlated with adenocarcinoma and is now recognized as a professional disease ( 1, 6, 11). This retrospective study reports the results of local combined treatment by surgery and postoperative radiation therapy. METHODS From April moidal cancer

Reprint

AND

1978 to June were referred

requests

MATERIAL

1990, 41 patients with ethto our Institute. A total of

to: J. M. Dilhuydy.

Accepted for publication 113

8 July 1992.

114 Table

I. J. Radiation Oncology 1. Staging system developed for ethmoidal

Stage I Stage II Stage III

0 Biology 0 Physics

at the University cancer

1. 1993

Limited to nasal cavity and sinuses with or without skin infiltration Extension to orbit and/or nasopharynx Base of skull or pterygoid destruction; intracranial extension

Stulistical methods All data were collected in March 1992, so the median follow-up is 28 months. All the patients were reviewed in Table 2. Characteristics

of radiation

therapy No. patients

Technique

25. Number

of Florida

from 12 to 52 years. This risk factor was referred in 10 out of 13 adenocarcinomas (77%). All the patients underwent a combined treatment by surgery followed by radiation therapy. The surgery was single curettage in two cases and a total ethmoidectomy in 20 cases: four transfacial approachs/l6 mixed craniofacial approachs. Neither neck dissection nor orbital exenteration (except one) was performed. The quality of the resection was considered as complete in 16 cases. Postoperative radiation therapy was performed 4 weeks after resection. The target volume was planned according to preoperative clinical examination completed by radiographic (CTscan), operative and histopathologic findings. The fields with ocular protection were then delineated in order to encompass only the involved part of the orbit. The entire orbit was irradiated in the only case of exenteration whereas no prophylactic irradiation was performed on the lymphatic areas. The technique depended on the location of the target volume. Anterior tumors were irradiated by a single mixed electron and y-ray beam. Posterior tumors were irradiated rather by 2 lateral y or x-ray beams plus an additional anterior electron beam in cases of anterior involvement. The study of dose distribution in the irradiated volume took into account the balistics, the choice of energy, the weight of each beam and the wedge filter (analysis in Table 2). CTscan was used in the most recently treated patients with the patient’s head in a thermal plastic mask as a basis for dose planning. including tissular heterogeneities. The total dose was given to the hot spot with a mean dose of 55.7 Gy (range 5070 Gy). This dose was delivered at 2 Gy per day and 5 days per week over 5-7 weeks. A boost up to 60-70 Gy was administered in cases of incomplete resection.

Energy

Volume

y or x-ray beams electron + y or x-ray beams 1 anterior portal 1 anterior + 1 lateral portals 1 anterior + 2 lateral portals

follow-up consultation during 1992 and none were lost to follow-up. Overall survival and duration of complete remission were calculated from the date of surgery. The curves of overall and disease-free survival were established according to the Kaplan Meier (product limit) method (IO). The analysis of the main characteristics was made by comparison of disease-free survival curves and prognostic significance was evaluated according to the logrank test (17).

RESULTS Complete remission was obtained for all patients, except for two with progressive disease. Therefore, 20 patients (99%) achieved a complete remission. Figure I shows that 5-year overall and disease-free survival are 44% and 38%, respectively. Of the 22 patients, 12 recurrences occurred: two progressive diseases and 10 recurrences among the 20 patients who achieved a complete remission within an average duration of 18 months complete remission. No lymphatic or metastatic recurrences occurred. Thus, all the recurrences were local in the irradiated area, except two marginal recurrences in cutaneous and intra-parotidal tissues. Table 3 shows the distribution ofthe recurrences according to staging and resection quality. Distribution of recurrences according to histologic type gives: adenocarcinoma 6/ 13 and other types 6/9. The prognostic value according to the log-rank test is not significant (p = 0,39). Of the 22 patients, 11 died: two from intercurrent cause and nine from disease. All the patients with recurrence died of disease within an average of 6 months following salvage treatment, except three patients still alive but within less than 6 months and in second remission. Various complications occurred during follow-up. Most Table 3. Local tumor

10

Complete resection + radiation therapy

12 5

1 (orbital exenteration) 16 (5/16 with wedge filter)

Stage

I

Stage II Stage III

4/S l/4 214

recurrences

by stage and treatment

Incomplete resection + radiation therapy l/2 l/l 313

Total No.

(%)

5110 215 517

(50) (40) (71)

Ethmoidal cancers 0 J. M.

patients free of disease developed synechial and rhinitis requiring a nasal washing, while one patient had a definitive anosmia. Some patients developed xerophtalmia and keratoconjonctivitis, but no loss of vision was encountered. The major complication was fistula due to necrosis: one in the medial corner of the eye (necrosis of the maxillary bone flap) and three intracranial fistula (necrosis of the dermal and frontal bone flaps) of which two required reconstructive surgery. DISCUSSION The patient characteristics in this retrospective series confirm the data of the literature ( 1, 12, 15) with a mean age of 59.6 years and a sex ratio of 2.7. Likewise, an exposure to wood dust is often encountered in adenocarcinema (77%) and means that ethmoidal adenocarcinoma is a professional disease (1, 6, 11). Some tumor characteristics are also consistent with those already reported (12, 20) with a prevalence of adenocarcinoma (59%) and a low incidence of nodal presentation (five patients exclude owing to chemotherapy). Staging of ethmoidal cancer is difficult because of the lack of a standard classification (14,20). As there is no staging in the international nomenclature (TNM), we use the classification of the University of Florida (Table 1) which has demonstrated a significant prognostic value in local control (7, 16). All our patients underwent a combined treatment by surgery and radiation therapy. The surgical approach depends on the local involvement assessed by CTscan and now Magnetic Resonance Imaging (MRI) which differentiates reactionnal inflammation from specific involvement (13). Resection quality is decisive. According to certain authors (2) patients with adenocarcinoma limited to the ethmoid and without any extension to the cribriform plate require surgery followed by radiation therapy only when the resection is incomplete. This explains why four patients were excluded from this study owing to previous treatment by ethmoidectomy alone. Radiosurgical treatment as first line or salvage therapy gives the same prognosis since 3 of the 4 patients with recurrence at the presentation are still alive 2, 5 and 6 years and in second remission. However, most authors recommend radiosurgical procedure as a first line (4, 5, 8, 12, 14, 18, 20). The dose delivered by pre ( 14, 20) or postoperative (4, 5. 8, 12, 14, 18, 20) radiation therapy is usually 60 or 66 Gy in the target volume. According to most authors, a part or the entire orbit is irradiated in cases of orbital involvement (4, 7, 19) and the lymphatic areas are never irradiated as a prophylaxis (5). Analysis of radiosurgical results reveals small series of five patients (5, 14, 18) with two or three long-term survivors at 3 years and larger series of 12 (20) 17 (3) and 19 patients (12) with a 5-year survival of 68, 65, and 50%, respectively. In our series, the 5-year survival of the 22 patients is 44%.

DILHUYDY

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Analysis of the recurrences according to tumor characteristics gives non significance to histologic type (p = 0.39) and a poor prognosis for patients with Stage III (Table 3). The analysis of treatment modalities provides also a poor prognosis for the six patients with incomplete resection, since four have died from disease, one is treated for a marginal intra-parotidal recurrence and the last is alive and disease-free. This raised the question of the value of radiation therapy and the required dose in cases of incomplete resection. Analysis of exclusive radiation therapy depends both on indication and dose. In curative intent up to 70 or 75 Gy, the results are close to the radiosurgical procedure with a 5-year survival as follows: 35% in a series of 23 patients for Brugere (3) 40% in a series of 10 patients for Frazell (9) 46% in a series of 17 patients for Ellingwood (7) and 50% in a series of 10 patients for Parsons (16). In palliative intent with lower doses (advanced tumor and/ or metastasis), the results are bad with two survivors at 3 years in a series of 12 patients for Shidnia ( 18). Likewise, I of the 4 inoperable patients excluded from our study owing to exclusive radiation therapy up to 60-70 Gy is still alive at 3 years. Although no definitive conclusion can be drawn, this points to a useful role for radiation therapy. Analysis of the causes of death shows that all the recurrences led to death, except for three patients within a short follow-up of less than 6 months and in second remission. Thus, prognosis depends on staging and local control. Most disease-free patients developed mild to moderate synechial and chronic rhinitis requiring washing of the nasal cavity. The most important complication of postoperative radiation therapy is necrosis with fistula from the ethmoid sinus to the skin of the medial canthus or to the intracranial structures in the case of the craniofacial approach. Since 1984, Stoll (21) has used the Galea flap technique and homologous cryopreserved bone to avoid fistula and meningitis. The other important complication is ocular with dose-effect (3, 20) and dose-volume (7) relationships. Vision is lost with more than 65 Gy in the entire orbit, while vision is conserved with less than 60 Gy in less than half of the orbit (7, 11). In our series, the entire orbit was irradiated for one patient following an exenteration. No blindness was found in any of the other patients who were spared irradiation in the entire orbit.

CONCLUSION Prognosis of ethmoidal cancer depends on staging and local control. As exposure to wood dust is a risk factor in adenocarcinoma, early detection must be set up for exposed professions. First-line treatment combines complete resection and postoperative radiation therapy, although certain authors still debate the indication in cases of limited adenocarcinoma.

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