Radiotherapy and radiosurgery for skull base tumors

SKULL BASE TUMOR SURGERY

00304665/01 $16.00

+ .OO

RADIOTHERAPY AND RADIOSURGERY FOR SKULL BASE TUMORS William M. Mendenhall, MD, Robert J. Amdur, MD, Russell W. Hinerman, MD, Patrick J. Antonelli, MD, Douglas B. Villaret, MD, and Scott P. Stringer, MD

This article reviews the roles of radiotherapy and radiosurgery in the management of skull base tumors. It is beyond the scope of this article to address the roles of radiotherapy and radiosurgery in all skull base neoplasms. Accordingly, the treatment of malignant tumors such as nasopharynx cancer, chordomas, and squamous cell carcinomas that invade the temporal bone or cavernous sinuses are not discussed. The article focuses on the treatment of benign skull base tumors, including chemodectomas, schwannomas, juvenile angiofibromas, pituitary adenomas, and meningiomas. ANALYSIS OF END RESULTS

To evaluate the effectiveness of a particular treatment modality relative to other forms of therapy, it is necessary to analyze end results. Parameters of interest include local control, survival, and complications. Whereas failure after treatment of a squamous cell carcinoma of the head and neck usually occurs within 2 or 3 years, recurrences after treatment of benign lesions may occur many years after radiosurgery or radiotherapy. Patients must have long-term follow-up, and local control and survival must be analyzed with a method that accounts for length of follow-up, such as the product-limit m e t h ~ d .The ~ , ~definition ~ of local control after radiotherapy for benign lesions, such as chemodectomas, has been the subject of considerable debate.21Malignant tumors usually regress completely after a successful course of radiotherapy; residual scarring frequently is observed on subsequent physical examinations and radiographic studies. In contrast, benign tumors often remain stable or partially regress, yet they may not increase in ~~

From the Department of Radiation Oncology (WMM, RJA, RWH), Department of Otolaryngology (PJA, DBV, SPS), University of Florida College of Medicine, Gainesville, Florida ~

~~

OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA

-

VOLUME 34 NUMBER 6 * DECEMBER 2001

1065

1066

MENDENHALL et a1

size despite many years of follow-up. As long as the tumors do not increase in size, they are effectively ”locally controlled.” After a seemingly complete resection, local control means that the tumor does not recur locally. Although subclinical deposits of tumor may remain and regrow in some patients who undergo a seemingly complete excision, some authors believe that a grossly “complete resection” is equivalent to a cure. After surgery, as with radiotherapy, patients must have many years of follow-up to determine whether any residual tumor cells will regrow. Long-term absolute survival rates are of little value in determining the effectiveness of treatment for benign tumors because few patients die of the tumor. Intercurrent disease accounts for most deaths. Cause-specific survival, in which deaths caused by intercurrent disease are censored, is a more appropriate method for evaluating the effect of a particular treatment on survival rates. When analyzing cause-specific survival rates, deaths resulting from treatment complicationsor tumor are coded as cause-specific deaths. Selection of Treatment

Patients who have benign skull base tumors that are amenable to complete resection and who are believed to be medically suitable for surgery are operated on. Patients who are elderly, medically unfit, and have small, asymptomatic tumors may be monitored closely.16The remainder of patients are treated with radiation using radiotherapy or radiosurgery, depending on the extent of the lesion. In general, there is no advantage to performing a subtotal resection and radiotherapy compared with radiotherapy in terms of local control or complications. An exception is a patient with. a pituitary adenoma with compression of the optic chiasm in whom the subtotal resection and decompression of the chiasm may result in some restoration of vision. Although some investigators suggest that subtotal resection and postoperative irradiation of a smaller volume of tissue results in a reduced likelihood of the already very low risk of a radiation-induced malignancy, there are no convincing data to support this hypothesis. Radiotherapy Techniques

Fractionated external-beam Fadiotherapy and stereotactic radiosurgery are external-beam radiotherapy techniques. Benign and malignant tumors can be controlled locally with a single fraction of radiotherapy given by conventional external-beam techniques or stereotactic radiosurgery. The likelihood of late complications is related to dose, dose per fraction, volume, and the amount and type of normal tissue included in the treatment volume. Stereotactic radiosurgery is not surgev, but rather a single large dose of external-beam radiation delivered to a relatively small, well-defined target with minimal normal tissue included in the treatment volume. The treatment fields are localized very precisely using stereotactic techniques, and the radiation is delivered with a gamma knife or linacbased system with equivalent results. As the target volume increases (either because the tumor is larger or because its poor definition requires irradiation of a margin of seemingly normal tissue), the risk of late complications secondary to a single large dose of radiation increases, and it becomes advantageous to fractionate the radiotherapy to allow the normal tissues to recover from sublethal damage between fraction^.'^ Fractionated external-beam radiotherapy can be given with a variety of techniques to decrease the amount of normal tissue included in the fields, including three-dimensional conformal treatment planning and intensity-modulated

RADIOTHERAPY A N D RADIOSURGERY FOR SKULL BASE TUMORS

1067

radi~therapy.'~ Stereotactic radiotherapy implies that the external-beam fields are precisely aligned daily using stereotactictechniques.' In general, patients who have small, well-defined lesions that have a high likelihood of local control and a low risk of complications after radiosurgery are treated with this technique. The advantage of radiosurgery compared with fractionated radiotherapy is that it requires only one treatment and there are few, if any, acute effects. Patients who are not suitable for radiosurgery because the tumor is large or ill defined are treated with radiotherapy. The treatments are given once daily at 1.8 Gy per fraction, 5 days a week, in the following doses: 35 Gy, juvenile angiofibromas; 45 Gy, chemodectomas and pituitary adenomas; and 50 to 55 Gy, acoustic schwannomas and meningiomas.2,12,17,18,24 Pretreatment Workup

CT scanning and MR imaging are used to define the location and extent of the tumor. Synchronous tumors must be identified in patients with lesions that may be associated with multiple tumors, such as chemodectomas, meningiomas, and schwannomas associated with neurofibromatosis. The presence of multiple lesions likely influences the treatment plan. CT scans of the neck and chest radiographs are indicated in patients in whom malignancy is suspected to rule out the possibility of metastases to the regional nodes and lungs. Because endocrine activity has been reported in a small subset (1%-3%) of head and neck chemodectomas,evaluation for production of catecholaminesby the tumor occassionally is indicated. Staging

There is no American Joint Committee on Cancer (AJCC) or International Union Against Cancer (UICC) staging system for any of the tumors addressed in this article. The likelihood of local control after radiotherapy seems to be unrelated to tumor size and extent. The value of a staging system from the radiation oncologist's point of view is to define an operation appropriate if the treatment is surgery. TREATMENT RESULTS Chemodectomas

At the University of Florida, 40 patients with 42 temporal bone chemodectomas were treated with radiotherapy alone (37 tumors) or with subtotal excision and radiotherapy (five tumors) between 1968 and 1992.18Thirty-four tumors originated in the glomus jugulare, and six tumors originated in the glomus tympanicum. The precise site of origin could not be determined for two lesions. Thirtythree lesions hadn't been treated, and nine lesions had received previous therapy (surgery, six lesions; radiotherapy, one lesion; surgery and radiotherapy, two lesions) and were treated for locally persistent or recurrent disease. All three patients who had received previous radiotherapy had been treated at other institutions. Patients had minimum follow-up times as follows: 2 years, 40 patients (100%);5 years, 31 patients (78%);10 years, 21 patients (53%); 15 years, 16 patients (40%);20 years, nine patients (23%);and 25 years, two patients (5%).Two patients who had no evidence of disease progression were lost to follow-up at

1068

MENDENHALL et a1

8 years and 1.5 years, respectively. For calculation of cause-specific survival and local control curves, they were censored at the date of last follow-up. One patient discontinued radiotherapy against medical advice because of radiation mucositis after receiving 21.8 Gy in 13fractions. The doses ranged from 37.7 to 50 Gy (mean, 42.9 Gy) in the remaining 39 patients. All patients were treated with once-daily fractionation at 1.5 to 1.96 Gy per fraction (mean, 1.77 Gy). Twenty patients received 45 Gy in 25 fractions over 5 weeks. Local recurrence developed in three patients at 2.3,2.5, and 8.3 years, respectively. Local control was achieved in 31 of 33 (94%)previously untreated tumors compared with eight of nine (89%)previously treated chemodectomas (Table l).] The probability of local control, calculated by the product-limit method, is depicted for 42 lesions and for the subset of 39 tumors not previously irradiated (Fig. 1).l8A local recurrence developed in the patient who discontinued treatment at 21.8 Gy against medical advice; otherwise, no obvious relationship existed between local control and the radiation dose over the narrow range of doses used in this study. One patient who underwent salvage surgery was disease-free for 2.5 years after the operation. The cause-specific survival curves for the entire group of 40 patients and for the subset of 37 previously unirradiated patients are shown in Figure 2.18 Two patients died with progressing tumors, one patient in the previously irradiated group and another patient who discontinued radiotherapy at 21.8 Gy. Powell et al' reported a series of 64 patients with temporal bone chemodectomas who were treated at the Royal Marsden Hospital (London, England) between 1949 and 1985 with surgery alone (four patients), surgery and radiotherapy (13 patients), radiotherapy alone (46 patients), and no treatment (one patient). The actuarial rate of local control after radiotherapy alone was 90% at 10 years and 73% at 25 years. The tumor remained locally controlled from 1 to 22 years in all 13 patients treated with surgery and radiotherapy (mean, 9 years). Local recurrence developed in all four patients who were treated with surgery alone. Between 1958 and 1978, 45 patients at the Princess Margaret Hospital (Toronto, Canada) were treated for temporal bone chemodectomas using the following treatment plans: subtotal excision and radiotherapy (nine patients), radiotherapy alone for a local recurrence after previous surgery (two patients), and radiotherapy alone (34 patient^).^ Most patients received 35 Gy in 14 to 16 fractions

Table 1. LOCAL CONTROL" VERSUS STAGE AND PREVIOUS TREATMENT? PreviousTreatment (number controlledlnumbertreated) McCabe-Fletcher" Tumor Stage

I (tympanic) I1 (tympanomastoid) 111 (petrosal/extrapetrosal)

Total

None

Surgery

RT

Surgery and RT

7/7

1/1

Q/Q

9/9 15/17§ 31/33 (94%)

3/3 2/2

o/o

o/o o/o

1/1

1/2

6/6

1/1

1/2

Total 8/8 12/12 19/22 39/42

*Calculated by the direct method?' t Forty-two chemodectomas in 40 patients.

5 Treatment was discontinued in one patient in whom local recurrence developed after 21.8 Gy in 13 fractions. From Mendenhall WM, Parsons JT, Stringer Sc et a1 Radiotherapy in the management of temporal bone chemodectoma. Skull Base Surgery 5:83-91,1995; with permission.

Text continued on page 1071

RADIOTHERAPY AND RADIOSURGERY FOR SKULL BASE TUMORS

1069

t

n

c

c

20 Successfully treated

0 -

I

I

I

I

I

I

I

I

I

I

I

I

I~

looI

8ot

20 Successfully treated

0

I

I

I

I

I

I

I

I

I

I

I

I

I

Figure 1. Local control after treatment of chemodectomas at the University of Florida calculated by the product-limit method. A, Overall group of 42 lesions in 40 patients. The probability of local control was 95% at 2.5 years, dropped to 89% at 8 years, and remained stable thereafter. B, Thirty-nine lesions in 37 patients who had not been previously irradiated. The likelihood of local control was 97% at 2.5 years, dropped to 91% at 8 years, and remained stable thereafter. (From Mendenhall WM, Parsons JT, Stringer SP, et al: Radiotherapy in the management of temporal bone chemodectoma. Skull Base Surgery 5:83-91,1995.)

1070

%

MENDENHALL et a1

80

W

-a 2

5

60

v1 0

!4u

k

9

40

P B

0 20 successfully treated

0

I

I

I

I

I

I

I

I

I

I

r

I

I

A

Successfully treated

0

6

I

I

I

I

I

I

I

I

I

2

4

6

8

10

12

14

16

18

I

I

I

I

20

22

24

I1

26

Time (y)

Figure 2. Cause-specific survival curves after treatment of chemodectomas at the University of Florida calculated by the product-limit method. A, Overall group of 40 patients. The probability of survival was 94% at 2.5 years and remained stable thereafter. B, Subset of 37 previously unirradiated patients. The likelihood of survival was 97% at 2.5 years and remained stable thereafter. (From Mendenhall WM, Parsons JT, Stringer SP, et al: Radiotherapy in the management of temporal bone chemodectoma. Skull Base Surgery 5:83-91, 1995.)

RADIOTHERAPY AND RADIOSURGERY FOR SKULL BASE TUMORS

1071

over 3 weeks. Follow-up ranged from 3 to approximately 25 years with a mean follow-up of 10 years. Local control was achieved in 42 patients (93%).All three patients who developed local recurrences were salvaged successfully by an operation (one patient) or a second course of radiotherapy (two patients). Two of three local recurrences were believed to be results of inadequate radiation treatment volume (i.e., geographic miss). Late complications after moderate-dose radiotherapy for temporal bone chemodectomas are unlikely. The following late complications were observed in the University of Florida series: transient seventh cranial nerve palsy (one patient), moderate trismus (one patient who was irradiated after two previous surgical procedures), cholesteatoma (one patient who was treated with a subtotal excision and radiotherapy), and partial optic neuropathy (one patient who underwent two operations and radiotherapy).18There were no fatal complications, permanent cranial nerve injuries, or radiation-induced malignancies. Powell et alZ3noted that 2 of 46 patients (4%) at the Royal Marsden Hospital who were treated with radiotherapy alone developed a seventh cranial nerve palsy. These patients received doses of 64 and 66 Gy, respectively, which are substantially higher than the currently recommended doses. The authors noted no radiation-induced malignancies or fatal complications.Cummings et a13 reported complicationsin two of 45 patients (4%)treated with radiotherapy at the Princess Margaret Hospital. One patient required debridement of a bone necrosis after 58 Gy in 20 fractions, and another patient died of a brain necrosis after 70 Gy in 16 fractions. The latter patient accidentally was given twice the intended dose. Additional complications included chronic otitis externa (four patients), stenosis of the external auditory canal (one patient), and chronic otitis media that necessitated drainage (one patient). There are limited data with relatively short follow-up pertaining to radiosurgery for chemodectomas. Foote et a15 reported nine patients at the Mayo Clinic were treated with gamma-knife radiosurgery between 1990 and 1995 with 7 to 65 months (median, 20 months) of follow-up. The tumors remained locally controlled in all patients, and no patient experienced a significant complication. Jordan et a16reported eight patients at the University of Texas Southwestern Medical Center were treated with radiosurgery for glomus jugulare tumors between 1990 and 1998 and had follow-ups for 7 to 102 months (mean, 27 months). One patient required hospitalization for intractable vertigo. No patient experienced tumor progression.

Schwannomas Skull base schwannomas include acoustic schwannomas and the less common schwannomas that arise from the remaining cranial nerves.I5, Although the presentation varies depending on the site of the tumor, the response of the tumor to radiotherapy or radiosurgery is essentially the same. Because acoustic schwannomas are much more common than schwannomas arising in other sites, most of the available data pertain to the former but can be extrapolated to the latter. Wallner et aIz9r3Oreported the results of surgery, alone or with radiotherapy, in a series of 124 patients with acoustic schwannomas treated at the University of California, San Francisco, between 1945 and 1983. Thirty-one patients received radiotherapy as part of their initial treatment (postoperative, 25 patients; preoperative, six patients), and seven patients were irradiated for recurrence after previous surgery. Surgical procedures were classified as total resection, near-total resection, subtotal resection, and biopsy. Patients had follow-ups for 2.6 to 40.7 years after therapy. The local control rates after surgery alone compared with surgery

1072

MENDENHALL et a1

and planned postoperative radiotherapy were as follows: total resection, 60 of 62 (97%)versus no data; near total resection, 14 of 15 (93%)versus 2 of 2 (100%); subtotal resection, 7 of 13 (54%)versus 17 of 20 (85%);and biopsy, no data versus 3 of 3 (100%).Three patients, all of whom underwent a subtotal resection, received less than 45 Gy, and the tumor was controlled locally in only one of three patients. In contrast, local control was observed in 16 of 17 remaining patients (94%)who underwent a subtotal resection followed by postoperative radiotherapy of more than 45 Gy. The 15-year relapse-free survival rates after subtotal resection were 41% after surgery alone compared with 94% after surgery and more than 45 Gy of postoperative radiotherapy (P = .01).Six patients received preoperative radiotherapy after an initial incomplete resection, which was the result of excessive tumor vascularity in five patients and adherence of the tumor to the brainstem in one patient. All six patients had definitive resections 2 to 7 months after radiotherapy. A total resection eventually was performed in two patients, whereas four patients underwent subtotal excisions. The tumor was controlled locally in four of six patients and recurred locally in the remaining two patients. Seven patients were treated with radiotherapy for local recurrence after surgery. Tumors were controlled locally in three of seven patients at 5, 15, and 20 years after radiotherapy. Maire et all0 reported 24 patients at Hopital Sainte-Andre (Bordeaux, France) were treated with external-beam radiotherapy for acoustic schwannomas between 1986 and 1992. Because one patient had bilateral tumors, 25 schwannomas were irradiated. Patients received a median total dose of 51 Gy at 1.8 Gy per fraction. Follow-ups ranged from 7 to 84 months (median, 60 months). Two patients were lost to follow-up with the tumor controlled at 14 and 24 months, respectively, after radiotherapy. Of the 25 tumors treated, nine (36%)regressed, 13 (52%) remained stable, and three (12%)progressed. Two patients died secondary to progressing tumors, and one patient with a local recurrence was salvaged successful1 by surgery. Varlotto et a1 reported 12 patients at Harvard Medical School (Boston, MA) treated with stereotactic radiotherapy between 1992 and 1994 with follow-up for 16 to 44 months. Patients received 54 Gy in 27 to 30 fractions over 6 weeks. Local control was obtained in all patients. One patient experienced worsening of a pre-existing fifth cranial nerve palsy, and one patient experienced decreased hearing. All nine patients with serviceable hearing before treatment maintained useful hearing after radiotherapy. Data pertaining to the efficacy of external beam radiotherapy for noneighth nerve schwannomas are limited. Wallner et alZ9reported 19 patients at the University of California, San Francisco, treated with surgery alone or surgery combined with radiotherapy between 1945 and 1983. One patient who died postoperatively was excluded, leaving 18 patients available for analysis. The nerves of origin included the fourth cranial nerve? fifth cranial nerve: ninth/tenth/ eleventh. cranial nerve complex,8 and the twelfth cranial nerve.' Local control rates according to surgical procedure alone or combined with radiotherapy were as follows: total excision, five of five versus one of one; near total excision, one of two versus two of three; subtotal excision, one of two versus one of three; and biopsy, zero of zero versus one of two. The only patient who underwent radiotherapy and a total excision was irradiated preoperatively to reduce tumor vascularity. Long-term local control results after stereotactic radiosurgery are available from Sweden. Stereotactic radiosurgery has only been used in the United States since 1987. Noren et all9 reported 110 patients with 115 acoustic schwannomas were treated with stereotactic radiosurgery using a gamma knife at the Karolinska Hospital (Stockholm,Sweden) between 1969 and 1984. Sixteen additional patients

L

RADIOTHERAPY AND RADIOSURGERY FOR SKULL BASE TUMORS

1073

were not included in the series because of insufficient data. Patients had followups for 0.5 to 12.8 years (mean, 4.0 years). Overall, the tumor either decreased in size or remained stable in 86% of cases. Ninety-one percent of 91 unilateral tumors were locally controlled compared with 67% of 24 tumors associated with neurofibromatosis. Flickinger et a14 reported the results of gamma-knife radiosurgery in a series of 273 patients with unilateral acoustic schwannomas treated between 1987 and 1994 at the University of Pittsburgh. The 7-year clinical and radiologic control rates were 96%and 91%, respectively. Fifty-six patients with acoustic schwannomas were treated with stereotactic radiosurgery at the University of Florida between July 1988 and November 1994.16 Follow-up was at least 1 year, and no patient was lost to follow-up. The likelihood of local control at 5 years was 95%. Pollock et a122reported the results of stereotactic radiosurgery in six patients with trigeminal schwannomas and five patients with jugular foramen schwannomas treated at the University of Pittsburgh. Local control was achieved in all six patients with trigeminal tumors (mean follow-up, 21 months; range, 7 to 35 months) and in four of five patients with jugular foramen schwannomas (mean follow-up, 10 months; range, 7 to 19 months). No patient developed a new cranial nerve or brainstem deficit after radiosurgery. Mabanta et a19 reported 18 patients with nonacoustic schwannomas treated with radiosurgery at the University of Florida between 1989 and 1997. Local control was obtained in all patients. Three patients experienced complications including worsening of a pre-existing seventh cranial nerve palsy (one patient), new onset of hearing loss (two patients), and ataxia (one patient). No surgical intervention or prolonged steroid use was necessary for any patients with complications. The acute and late effects of external-beam fractionated radiotherapy for acoustic schwannomas are similar to those observed after radiotherapy for temporal bone chemodectomas.The risk of complications is higher because the dose is a little higher than that used to treat chemodectomas. Wallner et alZ9r3Oreported no significant radiotherapy complicationsin their series. After radiosurgery, Noren et all9 noted facial nerve weakness in 15%of their patients and trigeminal nerve weakness in 18%.Mild and transient nerve weakness usually was noted 6 to 9 months after treatment. Flickinger et a14 observed rates of temporary or permanent fifth and seventh cranial nerve palsies of 23% and 17%,respectively, at 3 years after radiosurgery. The likelihood of cranial neuropathy was related to transverse tumor diameter and minimum tumor dose. Complications developed in 13 of 56 patients (23%)treated with radiosurgery at the University of Florida between 1988 and 1994. The likelihood of complications was related to dose and tumor volume.16 Juvenile Angiofibromas Fifteen patients with juvenile nasopharyngeal angiofibromas were treated with radiotherapy between 1975 and 1996 at the University of Florida. All these patients had follow-ups for at least 2.5 years, and no patient was lost to followupF4 Six patients received radiotherapy as initial treatment, and nine patients had radiotherapy for recurrence after previous surgery. Local control was obtained in 13 patients (85%).Two patients who experienced a local recurrence were salvaged successfully, so the ultimate local control rate was 100%.Cummings et a13 reported 55 patients treated with megavoltage radiation at the Princess Margaret Hospital. The local control and ultimate local control (including patients successfully salvaged) rates were 80%and loo%, respectively.

1074

MENDENHALL et a1

Three patients who received radiotherapy at the University of Florida experienced complications that included cataracts (three patients), delayed transient CNS syndrome (one patient), and basal cell carcinoma of the skin (one patient)F4 Cummings et a13 observed two patients with possible radiation-induced malignancies. One patient experienced thyroid carcinoma 14 years after radiotherapy, and the other patient had basal cell carcinoma at 13 years. Pituitary Adenomas

One-hundred forty-one patients received radiotherapy at the University of Florida between 1965 and 1993 and had follow-ups for at least 2 years (median, 9.2 years)?2 One-hundred twenty-one patients received radiotherapy for previously untreated tumors. This treatment included surgery plus radiotherapy (98 patients) and radiotherapy alone (23 patients). Twenty patients were treated for recurrent tumors with surgery plus radiotherapy (ten patients) or radiotherapy alone (ten patients). The overall tumor control rates were 94%,93%,and 93% at 5, 10, and 15 years, respectively. The 10-year rates of local control after treatment were 95% after surgery and radiotherapy and 90% after radiotherapy alone ( P = .58). Multivariate analysis of local control revealed that only young age ( P = .035) significantly influenced these end points. Secretory adenomas may have slightly worse local control rates compared with nonsecretory adenomas. Patients whose tumors are controlled by radiotherapy require approximately 2 years for hormone levels to slowly decrease. Absolute survival rates were 86%, 72%, and 63% at 5, 10, and 15 years, respectively. Two patients treated with radiotherapy alone and one patient treated with surgery plus radiotherapy experienced transient CNS syndrome. Unilateral blindness developed in one patient after surgery, and optic neuropathy developed in two patients. Kjellberg and Kliman8reported a large series of patients treated with protonbeam radiosurgery for pituitary adenomas. A total of 678 patients were treated. The disease remained controlled locally in all but five patients (1%).The major risk associated with radiosurgery for patients with pituitary adenomas is optic neuropathy if the tumor extends close to the optic nerve. Because the risk of optic neuropathy is related to total radiotherapy dose and dose per fraction, these patients are better treated with radiotherapy.’O Meningiomas

Two-hundred sixty-two patients with benign meningiomas were treated at the University of Florida between 1964 and 1992 for previously untreated benign meningiomas and had follow-ups for a minimum of 2 years (median, 8.2 years).’ Treatmeht consisted of total excision (174 patients), subtotal excision (55 patients), and surgery plus radiotherapy (21 patients). Twelve additional patients received radiotherapy alone, and five patients were treated with radiosurgery. At 15 years, local control rates were as follows: total excision, 76%; subtotal excision plus radiotherapy, 87%;and subtotal excision, 30% (Fig. 3).’ Both total excision and subtotal excision plus radiotherapy resulted in significantly better local control rates compared with subtotal excision alone ( P = .0001). Cause-specific survival rates at 15 years were significantly lower after subtotal excision alone (51%) compared with total excision (88%) or subtotal excision plus radiotherapy (86%) ( P = .0003) (see Fig. 3). Severe complications that necessitated surgical

87%

80 76%

..I-,

Y

c

3

I

“1

_ _ _ _I I

30% I_ ____

-TE Alone (n = 175)

P = ,0001

.-SE+RT(n=17) --SE Alone (n = 55)

0 0

2

4

6

8

10

A

12

14

18

16

20

Years

. .-SE + RT (n = 17)

P

- .SE Alone (n = 55) 0 1 0

B

=

,0003

I

I

II

I

I

I

I

I

I

I

2

4

6

8

10

12

14

16

18

20

Years

Figure 3.Results according to treatment group. A, Local control. 13,Cause-specific survival. Not shown are 12 patients who had radiotherapy alone and 4 patients who had total excision plus radiotherapy. TE = total excision; SE + RT = subtotal excision followed by radiotherapy; SE = subtotal excision alone. (From Condra KS, Buatti JM, Mendenhall WM, et al: Benign meningiomas: Primary treatment selection affects survival. Int J Radiat Oncol Biol Phys 39:427-436, 1997.)

1075

1076

MENDENHALL et a1

intervention or were fatal developed in 11%of patients who underwent surgery alone and 10% of patients who received surgery and radiotherapy. No patient treated with radiotherapy alone had a severe complication. Shafron et alz6reported 70 patients with 76 meningiomas treated with radiosurgery at the University of Florida between 1989 and 1997. Radiographic follow-up was available to 44 of 50 patients (48 tumors) who had follow-ups for at least 1 year. No patient experienced tumor progression after radiosurgery. Subach et a127 reported 62 patients treated with radiosurgery at the University of Pittsburgh for petroclival meningiomas had follow-ups for a median of 37 months. The local control rate after treatment was 92%. Shafron et alZ6observed two patients who experienced transient cranial neuropathies after radiosurgery at the University of Florida. Subach et alZ7reported that 5 of 62 patients (8%)experienced new cranial nerve deficits within 2 years of radiosurgery without evidence of tumor progression. Two patients experienced complete resolution of the new cranial nerve deficits. The deficits in the remaining three patients did not resolve. SUMMARY

When tumors that involve the skull base are incompletely resectable or when surgery is believed to be associated with significant morbidity rates, patients have a high likelihood of long-term local control after radiotherapy with a relatively moderate risk of complications. ACKNOWLEDGMENT The authors thank the research support staff of the Department of Radiation Oncology for their help with statistics, editing, and article preparation.

References 1. Bova FJ, Buatti JM, Friedman WA, et a1 The University of Florida frameless highprecision stereotactic radiotherapy system. Int J Radiat Oncol Biol Phys 38:875-882, 1997 2. Condra KS, Buatti JM, Mendenhall WM, et al: Benign meningiomas: Primary treatment selection affects survival. Int J Radiat Oncol Biol Phys 39:427436,1997 3. Cummings BJ, Beale FA, Garrett PG, et a1 The treatment of glomus tumors in the temporal bone by megavoltage radiation. Cancer 53:2635-2640,1984 4. Flickinger JC, Kondziolka D, Lundsford L D Dose and diameter relationships for facial, trigeminal, and acoustic neuropathies following acoustic neuroma radiosurgery. Radiother Oncol41:215-219,1996 5. Foote RL, Coffey RJ, Gorman DA, et a1 Stereotactic radiosurgery for glomus jugulare tumors: A preliminary report. Int J Radiat Oncol Biol Phys 38:491495,1997 6. Jordan JA, Roland PS,McManus C, et al: Stereotactic radiosurgery for glomus jugulare tumors. Laryngoscope 11035-38,2000 7. Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am StatisticalAssoc 53:457481, 1958 8. Kjellberg RN, Kliman B Lifetime effectiveness-A system of therapy for pituitary adenomas, emphasizing Bragg peak proton hypophysectomy. In Linfoot JA (ed): Recent Advances in the Diagnosis and Treatment of Pituitary Tumors. New York, Raven Press, 1979, pp 269-288 9. Mabanta SR, Buatti JM, Friedman WA, et al: Linear accelerator radiosurgery for nonacoustic schwannomas. Int J Radiat Oncol Biol Phys 43:545-548,1999

RADIOTHERAPY AND RADIOSURGERY FOR SKULL BASE TUMORS

1077

10. Maire JP, Caudry M, Darrouzet V, et al: Fractionated radiation therapy in the treatment of stage 111 and IV cerebello-pontine angle neurinomas: Long-term results in 24 cases. Int J Radiat Oncol Biol Phys 32:1137-1143,1995 11. McCabe BF, Fletcher M: Selection of therapy of glomus jugulare tumors. Arch Otolaryngo1 89:182-185,1969 12. McCord MW, Buatti JM, Fennel1 EM, et al: Radiotherapy for pituitary adenoma: Longterm outcome and sequelae. Int J Radiat Oncol Biol Phys 39:437444,1997 13. Meeks SL, Buatti JM, Bova FJ, et al: Potential clinical efficacy of intensity-modulated conformal therapy. Int J Radiat Oncol Biol Phys 40:483495,1998 14. Mendenhall WM, Amdur RJ, Siemann DW, et a1 Altered fractionation in definitive irradiation of squamous cell carcinoma of the head and neck. Curr Opin Oncol12:207-214, 2000 15. Mendenhall WM, Friedman WA, Bova FJ: Linear accelerator-based stereotactic radiosurgery for acoustic schwannomas. Int J Radiat Oncol Biol Phys 28:803-810,1994 16. Mendenhall WM, Friedman WA, Buatti JM, et al: Preliminary results of linear accelerator radiosurgery for acoustic schwannomas. J Neurosurg 85:1013-1019,1996 17. Mendenhall WM, Friedman WA, Parsons JT, et al: Radiation therapy and stereotactic radiosurgery for temporal bone tumors. Oper Techniques Otolaryngol Head Neck Surg 7208-218,1996 18. Mendenhall WM, Parsons JT, Stringer SP, et a1 Radiotherapy in the management of temporal bone chemodectoma. Skull Base Surgery 5:83-91,1995 19. Noren G, Arndt J, Hindmarsh T, Hirsch A: Stereotactic radiosurgical treatment of acoustic neurinomas. In Lundsford LD (ed): Modern Stereotactic Neurosurgery. Boston, Martinus Nijhoff, 1988, p 481489 20. Parsons JT, Bova FJ,Fitzgerald CR, et al: Radiation optic neuropathy after megavoltage external-beam irradiation: Analysis of time-dose factors. Int J Radiat Oncol Biol Phys 30~755-763,1994 21. Parsons JT, McCarty PJ, Rao PV, et al: On the definition of local control [editorial]. Int J Radiat Oncol Biol Phys 18:705-706,1990 22. Pollock BE, Lunsford LD, Kondziolka D, et al: Outcome analysis of acoustic neuroma management: A comparison of microsurgery and stereotactic radiosurgery. Neurosurgery 36:215-229,1995 23. Powell S, Peters N, Harmer C: Chemodectoma of the head and neck: Results of treatment in 84 patients. Int J Radiat Oncol Biol Phys 22:919-924,1992 24. Reddy KA, Mendenhall WM, Amdur RJ, et a1 Long-term results of radiation therapy for juvenile nasopharyngeal angiofibroma. Am J Otolaryngol2000, in press 25. SAS Institute: SAS Technical Report P-179, Additional SAS/STAT Procedures. Release 6.03. Cary, NC, SAS Institute, 1988, pp 49-89 26. Shafron DH, Friedman WA, Buatti JM, et al: Linac radiosurgery for benign meningiomas. Int J Radiat Oncol Biol Phys 43:321-327,1999 27. Subach BR, Lunsford LD, Kondziolka D, et a 1 Management of petroclival meningiomas by stereotactic radiosurgery. Neurosurgery 42437445,1998 28. Varlotto JM, Shrieve DC, Alexander E3, et a1 Fractionated stereotactic radiotherapy for the treatment of acoustic neuromas: Preliminary results. Int J Radiat Oncol Biol Phys 36:141-145,1996 29. Wallner KE, Pitts LH, Davis RL, et al: Radiation therapy for the treatment of non-eighth nerve intracranial neurilemmoma. Int J Radiat Oncol Biol Phys 14287-290,1988 30. Wallner KE, Sheline GE, Pitts LH, et al: Efficacy of irradiation for incompletely excised acoustic neurilemomas. J Neurosurg 67:858-863,1987

Address reprint requests to William M. Mendenhall, MD Department of Radiation Oncology University of Florida Health Science Center 2000 Archer Road Gainesville, FL 32610-0385 e-mail: mendewil8shands.ufl.edu