In, J Kodrormn Oncology lhol Phys Vol Prtnted I” the U S A All rights reserved
X. pp 1045-1049
0 Brief Communication COMPARISON OF PRE- AND POSTOPERATIVE RADIATION IN THE COMBINED TREATMENT OF CARCINOMA OF MAXILLARY SINUS Hu Yu-HUA,* Tu GUI-YI,~ Qr Yu-QIN,* Xu GUO-SHEN,* Wu XUI-LIN,* CAI WUI-MING,* QIN DE-XIN,* YAN JEI-HUA,* Gu XIAN-ZHI* Cancer Institute
of Medical Sciences,
A series of 50 patients with cancer of the maxillary sinus treated by either preoperative or postoperative radiation from February, 1958 to June, 1974 is presented. In the postoperative group the patients were either free from recurrence, of if there was recurrence, the tumor was less than 0.5 cm in diameter. In the preoperative group, 23 of 36 patients survived for more than five years (64 % ). In the postoperative group, 4 of 14 patients survived for more than five years (26%). There is an obvious superiority in the preoperative radiation group. The surgical complication rate in the preoperative group was 29% as compared to 14% in the postoperative group. Although the incidence of complications in the preoperative group is higher, we believe it is worth attempting in clinical practice because of the more favorable survival rates. Cancer of maxillary
sinus, Pre- vs postoperative radiation,
The patients included in this analysis were those who had biopsy-proven squamous cell carcinoma
Cancer of the maxillary sinus comprises 1.2% of all malignancies and 14% of all malignant ENT tumors in the human being.’ Surgery alone is effective in the very early cases, which are rarely seen in the clinic.’ For most of the patients with advanced and moderately advanced disease, the combined treatment of radiation and surgery is the only effective method for cure.4,5.7 With such treatment, the five-year survival rate has recently been raised to about 5O%.5,“,9However, controversy remains as to whether radiation should be given preoperatively or postoperatively.“.7.n~‘o This analysis is done in an attempt to solve this problem so as to provide basis in the clinical management of cancer of the maxillary sinus. METHODS
mas and total
hospital or elsewhere. Only those patients who had been referred operation
to us for radiation in another
two months after
hospital were studied. Also,
patients who had received irradiation and were referred
to us for operation
included in the analysis. There was no patient who had had surgery in our hospital hospital for irradiation.
The patients rejected from this analysis were those treated by surgery alone, chemotherapy alone, intracavitary radium therapy, intra-arterial chemotherapy, and those patients who had received both pre- and postopera-
From 1958, most of the patients with cancer of the maxillary sinus treated in our hospital have been managed by combined preoperative radiation and surgery. In addition, some patients having received surgery elsewhere, were subsequently referred to us for postoperative radiation on a “prophylactic” basis. These patients received irradiation immediately after the operation, before any recurrence became apparent. To compare the effect of pre- and postoperative radiation, a retrospective and selective analysis was done, using all patients with cancer of the maxillary sinus treated between February 1958 to June 1974. They were followed for more than five years; none were lost to follow-up.
*Dept. Radiation Oncology. THead and Neck Section, Dept. Surgical
Also rejected were patients with biopsy-
and those with postopera-
tive recurrence of more than 0.5 cm in diameter. A total of 50 patients were analyzed. They were divided into two groups: those treated with preoperative
tion (pre-group) and those treated with postoperative irradiation (post-group). The comparison of these two groups was based mainly on the difference between their respective five-year survival rates. There were 35 males and I5 females in this series. Age ranged from 30 to 64 years, with the age peak between 30 and 39 (I 8 patients, 56%). There were 47 patients with squamous cell carcinoma and three patients with cystic adenoid epitheliomas. All three patients with cylindroma
??Biology 0 Physics
had T, lesions. These three patients underwent surgery and radiation in our hospital. Two of these patients were given preoperative radiation followed by total maxillectomy. Two patients are living and well after five years. The third patient with cylindroma was given postoperative irradiation preceded by total maxillectomy, this patient died three years after the operation. Two of the 50 patients, one with T, and one with T, lesions, had metastases in the neck, which were successfully treated by neck dissection. The staging was done according to Sisson’s system (Table 1). Modifications were made because some of the patients with very advanced disease had extensions to sites not covered in Sisson’s classification. Thus, those patients with involvement of the nasal cavity and the posterior wall of the maxillary sinus were staged as T, and those with involvement of the gingiva, soft palate, zygomatic arch and nasopharynx were classified as T,. The patient distribution according to Sisson’s staging method was as follows: Tz, four patients; T,, 31 patients, and T,, 14 patients. The staging was not clear in one patient who had surgery performed elsewhere. Treatment Surgery. For six advanced lesions, extended excision of maxilla was done after incision of the ascending ramus of
1. Sisson’s system of staging of cancer of maxillary sinus (modified)
Not clear Total
Involvement Anterior wall with skin intact; inferior naso-antral wall involved; anterior medial plate involved Inferior wall involved but muscle intact; superior wall involved but orbit not involved Pterygoid muscle involved; anterior ethmoid cells involved but cribiform plate intact; orbit involved; anterior wall with skin involved (posterior wall involved)* Cribiform plate involved; pterygomaxillary fossa involved; extension to nasal fossa or other antrum; extension to ethmo-sphenoid recess or sphenoid sinus; invasion of posterior ethmoid cells; invasion of pterygoid plate; (invasion of soft palate, zygomatic arch, buccal mucosa, nasopharynx)*
June 1982, Volume 8, Number 6
the mandible. Exenteration of the orbital contents was performed if the orbit was invaded. Forty-two patients were treated by Barbosa’s total maxillectomy after the method described in the literature.’ Two patients were treated by partial maxillectomy. Radiation. External radiation was given according to the technique reported previously. Thirty-seven patients received telecobalt therapy, four patients received high energy electron beam therapy of 25 to 35 MeV, six received conventional deep X ray (HVI = 3 mmCu), and three patients were treated with mixed cobalt and deep X ray therapy. RESULTS In the pre-group. 23 of 36 patients (64%) survived for more than five years. Twenty-five of these 23 patients were free from evidence of cancer-a five-year cure rate of 6 I %. In the post-group, four of I4 patients (29%) were alive after five years. Three of these four patients were free from any evidence of cancer (21%) (Tables 2 & 3). Comparison of pre- and post-groups were also assessed by stage (Table 4); The present series comprises mainly T, patients 31/50 (62%). The T, patients showed far better results in the pre-group (77%) than that in the post-group (40%) although there were only 5 patients in the latter. The number of T, patients was so small that it is difficult to say whether the pre-group (I of 6 patients survived for more than five years) or the post-group (2 of 8 patients survived for more than five years) is better. As a whole, there is an obvious superiority in the pre-group (P < 0.05). tnjuence of different institutions on surgery In the present series, 42 patients underwent surgery in our hospital; eight patients had surgery performed elsewhere. Table 5 shows the influence of the different institutions where the operation was performed. In the 36 pre-group patients, 22 of 35 patients who were operated upon in our hospital survived for more than five years (63%). Only one patient underwent surgery elsewhere; this patient survived for more than five years also. In the post-group, the five year survival was 29%, no matter where the operation was performed. These results show that the most important prognostic factor is not the place where the surgery is performed, but the sequence of the treatment, ie., whether the radiation is given before or after the operation. Table 2. Five year survival rates of pre- and postoperative radiation
Note: items in parentheses added according to extent of lesions in the present series. N, = Lymph node not involved; N, = Clinically palpable lymph node(s) that are fixed, metastasis suspected; N, = Clinically palpable lymph node(s) that are fixed; M, = No distant metastasis; M, = Clinical and/or radiographic evidence of metastasis except to the cervical lymph node regions.
Five year survival No. treated
P < 0.05
Table 3. Five year cure rates of pre- and postoperative radiation
Table 4. Treatment
results assessed by
Sisson’s staging Post-group
Pre-group Five year cure Treatment
T* T, T, Not staged
P < 0.05 14
on radiation series of 50 patients, 45 patients
In the present were irradiated in our hospital and five patients were irradiated
elsewhere. In the pre-group, 20 of 31 patients who received irradiation treatment in our hospital survived for more than five years (65%). Three out of five patients irradiated elsewhere survived for more than five years. In the post-group, all 14 patients were irradiated in our hospital, of whom four survived five years (29%). None of the patients who underwent surgery in our hospital were referred to another hospital for radiation. Thus, whether the radiation was given in our hospital or not, preoperative radiation yielded. better results than postoperative radiation (Table 5). Optimum sinus
dose at the posterior
wall of the maxillary
In cancer of the maxillary sinus, involvement of the anterior, medial, lateral and the inferior wall is amenable to surgical removal. Even the involvement of the superior wall can be managed with exenteration of the orbital contents. Yet the involvement of the posterior wall may mean the invasion of the pterygo-palatine fossa or even the infratemporal fossa, where thorough removal of the cancerous tissue is difficult. Therefore, the whole of the maxillary sinus should be given an even dose of 4000 rad in preoperative irradiation. This can be accomplished either by two-field wedge filter technique, or the three field uneven dosage technique.4 Also, the dose at the posterior wall should receive a boost to 6000 rad. To accomplish this, a booster dose should be given through an ipsilateral small vertical field, usually 3 x 6 cm. In the present series, the pre-group patients who had Table 5. Influence of different
No. survived/ No. treated
No. survived/ No. treated
214 20126 ‘16
215 2/g o/t
) denotes too few patients.
received a dose of 4000-8000 rad (mostly 6000 rad), yielded the highest survival rate (9/10 patients) (Table 6). We believe that whatever the sequence of radiation, the
posterior wall should receive a higher dose. In those patients who received a dose less than 4000 rad, a five year survival rate of only 45% was obtained. At 40008000 rad, the five year survival was 78% and 5000-7000 rad gave a survival rate of 77% (IO/l3 patients). In this group, the pre-group yielded a survival rate as high as 86% (8/9 patients). Therefore, the dose at the posterior wall should always be high, preferably 6000 rad, whether the radiation is given pre- or postoperatively. DISCUSSION Cancerous growth consists of a main body tumor mass and peripheral micro-extensions (referred to as peripheral micro-foci) around it (Fig. 1). Cure of a cancerous growth calls for the elimination or removal of both. Unfortunately, cancer surgery in the head and neck region is notoriously limited by the presence of vital organs near the main body of the tumor. Cancer of the maxillary sinus, being one of the outstanding examples, is most commonly cured by the combined use of operation and irradiation. Busche and Galate’ in 1959, tried radical preoperative X ray irradiation in primarily inoperable advanced cancers in the head and neck with encouraging immediate results. These authors speculated that the combined use of irradiation and surgery might open a great possibility in the treatment of head and neck cancers. Hoye and Smith6 experimented preoperative radiation on transplanted tumors in mice. They gave 7 15
where treatment was given Five year survival
No. survived/No. Pre-group
) denotes too few patients.
Post-group Pre-group Post-group
Our hospital Other hospital Our hospital Other hospital
22135 t/t 217 217
Our hospital Other hospital Our hospital Other hospital
20131 315 4114 O/O
(29) (29) (Z$ 29
Table 6. Adequate
Biology 0 Physics
dose at posterior
June 1982. Volume
Table 7. Complications
of pre- and post-group
Five year survival Pre-group
Pre-group (36); Total Complication
< 4,000 4,000-8,000 rad > 8,000 rad Not stated
O/l l/2 64
Sloughing of skin graft Poor wound healing Hemorrhage more than IO00 ml Late rupture of wound Osteonecrosis Trismus Hospital Death *Number
r, a dose unable to sterilize cancer, to five different types of malignant tumors before operation. The results of surgical treatment showed there was a 90% reduction in the incidence of hematogenous and lymphatic spread. Fig. I shows a schematic rationale of cancer cure. The radiosensitive peripheral micro-foci are sterilized first by a medium size preoperative radiation dose but the centrally located main body tumor mass would survive this treatment. A subsequent operation removes the main body of the tumor and a cure is theoretically achieved. Yet In clinical practice, there has always been active debate as to whether radiation be given before or after the operation. The disadvantages of preoperative radiation are said to be hemorrhage, too many adhesions, which are detrimental to surgical manipulations, poor wound healing and high incidence of late necrosis of the maxilla (Table 7). Furthermore, there would be a considerable delay of the operation if radiation is to be given first. This delay is usually accepted by the surgeons only with great reluctance. The advantages of preoperative radiation are believed to be that the peripheral micro-foci around the main body of the tumor mass, being radiosensitive them-
No. 2 5 I I I 0 0
5% 6 I4 3 3 3
No. 0 0 0 0 I I 0
selves, could be eliminated by one half to two thirds of a curative dose, ie., 4000-5000 rad. After these peripheral micro-foci are eradicated, the main body of the tumor mass is removed by the operation. Thus, cure is likely to be achieved as indicated in Fig. I. Those who favor the postoperative irradiation, do so because there is lower incidence of operative complications. The operation can be done without delay and the patient can be referred directly to the radiotherapist after the operation. The argument against postoperative is that the blood supply of the tumor is reduced by the operation. Hence, the peripheral micro-foci are rendered radioresistant by the fibrosis resulting from the operation. Although the main body of the tumor is removed by the operation, local recurrence is likely to arise from the peripheral micro-foci. Thus postoperative radiation may lead to more failures. If this dose was given preoperatively, the peripheral micro-foci may be eliminated, which would substantially facilitate the cure after surgical removal of the main tumor mass. The main body of the tumor in the center, being radioresistant by the coexisting edema, infection, hypoxia and necrosis, would be removed by the operation. Moreover, the partial “devitalization” of the tumor cells dislodged either into the wound or the blood stream would be difficult to establish as cancerous foci. These speculations all have factual basis.2,h The results of the present series speaks strongly for the preoperative irradiation which gives more than twice the chance of being cured. The most important factor for cure is the proper sequence of combining radiation and surgery and is not the institution where the treatment was given. Table 8. 30 causes of failure in 25 cases Incidence Cause of failure
Fig. I. Schematic illustration of treatment of cancer by combined radiation and surgery. a. The central main body of tumor and the peripheral micro-foci infiltrating in-to the surrounding tissues; b. The convergent cross-fire of pre-operative irradiation annihilates the peripheral micro-foci but the radio-resistant main body of tumor remains; c. Theoperation removes the main body of tumor and, consequently; d. The operative field heals. Local recurrence is less likely.
Not related to cancer Not recorded Distant metastasis Neck metastasis Local recurrence
20 6 3 I 65
Table 9. Site and distribution
HL PI al.
of 19 local failures Site
Incidence Posterior Wall
The results of our analysis indicate that cancer of the maxillary sinus should be treated by the combined approach whenever possible. Preoperative irradiation is preferred to postoperative irradiation, inspite of higher incidence of minor surgical complications. Cause
Table 8 shows the cause of failure. Among the 30 causes of failure in 25 patients, there were 19 local recurrences, an incidence of 65%, which shows the most
common cause of patients’ death, in our series, was local recurrence. Table 9 shows the site of local faliure. In the post group, IO of the I I patients (91%) who we did not cure failed locally. In the 9 patients, 5 (55%~) had recurrence in the posterior wall. From our series, the posterior wall was the predilection site of local failure both in the pre- and post-groups, although it seemed to be more common in the post-group. To reduce the chance of recurrence at the posterior wall. the dose at that site is preferably to about 6000 rad.
Busche, F.. Galante, M.: Radical preoperative roentgen therapy in primarily inoperable advanced cancers of the
head and neck. Radiology 73: 845-848, 1959. 2. Dept. ENT, Peking Union Medical College Hospital, Analysis of I565 tumors in the ENT region. Chin. J. Ofolar~~gol. 6: 370-373, 1959. First Teaching Hospital, Xian Medical 3. Dept. Oncology, College. Advanced cancer of the maxillary sinus-analysis of 107 cases. Prevention Treat. Cancers 4: 304-308, 1977. Oncology, Ritan Hospital. Results and 4. Dept. Radiation Innovation of Radiotherapy for Cancer of the Maxillary sinus-analysis of I48 cases. Prevention Treat. Cancers 4: 31 l-316, 1976. Ritan Hospital. 5. Head and Neck Section, Dept. Surgery, The combined treatment of the Cancer of the Maxillary sinus. Academic Supplement, Ritan Hospital 20th Year Anniversary. 1978, pp. 490-496.
6. Hoye, R.C.. Smith, R.R.: Electiveness preoperative irradiation in preventing cell dessemination at surgery. (hncer
of small amounts of the growth of tumor 14: 284-295. I96 I.
7. Jesse. R.H.: Pre-operative versus postoperative radiation in the treatment of squamous carcinoma of the paranasal sinuses. Am. J. Surg. 110: 552-556, 1965. 8. Sato, Y., Morita, M.. Nomura, Y., linuma. T., Hiraide, F., Miyakawa. K., Inoue. N.. Kodera, K.. Kaga, K., Ishii. T., Takahashe. H.: Treatment of malignant tumor in the head and neck.-Interdisciplinary collaboration of surgery and radiotherapy. Jap. J. Clin. Oncol. 12: 63-75. 1973. 9. Sisson, G.A.: and summary). IO. Tianjin cancer 1974.
I I I Symposium-paranasal Laryngoscope
sinuses (Discussion 80: 945-953. 1970.
People’s Hospital. The combined treatment of of the maxillary sinus. Tianjin Med. 2: 395-399.