Osteogenic Sarcoma of the Maxilla: Neutron Therapy for Unresectable Disease

Purpose. To present a case study involving the use of fast neutron therapy to treat an extensive unresectable osteogenic sarcoma arising from the left maxilla. Patient. A 14-year-old male presented with a massive tumor producing severe distortion of his facial structures. He had already received six courses of chemotherapy, which had reduced his pain, but had not measurably reduced the tumor. Methods. The patient was treated with 66 MeV fast neutrons to a dose of 20.4 Gy in 13 fractions over 35 days. Results. CT assessments indicate gradually increasing calcification and noticeable reduction of soft-tissue disease in the frontal sinus, orbit and maxillary antrum.There has been some recontouring of the facial structures.The boy conducts an active life, has no pain, and feels well. He was 17 years old at the last follow-up. Discussion. Fast neutrons have a greater biological effectiveness than conventional photon beams. Their use has been associated with improved chance for local control of unresectable disease.This case illustrates their effectiveness in controlling an unusual and aggressive osteogenic sarcoma of the facial bone and sinuses.


Introduction
Osteogenic sarcom a occurring prim arily in the m axilla is an unusual disease, one for which satisfactory treatm ent results are difficult to obtain. 1 M ulti-m odality therapy is recom m ended for the treatm ent of these tum ors, because surger y is lim ited for osteogenic sarcom a arising in the m axilla, paran asal sinuses and m andible. 2,3 In these sites, radiation therapy plays a m ore prom inent role as part of the de® nitive managem ent. 4 N eutron therapy, in particular, is asso ciated with an im proved chance for local control of unresectable tum ors com pared to sim ilar treatment using conventional photon radiation therapy. 5 We report here a case of a locally advanced osteogenic sarcom a that has responded to chemotherapy and neutron beam therapy.

Patient
A 14-year-o ld H aitian m ale orphan was brought to the U nited States to undergo surgery on a large facial tum or.T he surgeons considered the tumor to be unresecta b le an d su rger y w as lim ited to b io p sy. Pathological diagnosis identi® ed the tum or as an osteogenic sarcom a. T he patient received six courses of chemotherapy, w hich included one course of ifosfam ide with M esna and adriamycin, four courses of high-dose m ethotrexate with leucovorin rescue, and one course of cisplatin and adriamycin by continuous in fu sio n . S u b seq u en t to th e co m p letio n o f chem otherapy, the patient was referred for consideration of neutron beam therapy, having experienced reduction of his pain but no m easurable tum or reduction. Physical exam ination demonstrated a large m ass producing severe distortion of the facial structures, w ith o rb ital hyp er telo r ism seco n d ar y to tu m o r replacement, obliteration of the left nasal cavity, near obliteration of the right nasal cavity, and¯attening of the nose over the facial surface w ith extension into the contralateral m axillary sinus. T he left eye showed signi® cant proptosis, with the eye displaced superiorly and laterally (F ig. 1). C T d em on strated tu m o r extending from the bulging left m axillary sinus into the nasop harynx, sphenoid bone, hard palate and nasal passag eways, w ith nasal bone destruction and invasio n in to the left o rbit (F ig. 2). T he tum or m easured 10.5 3 9.0 cm in greatest diam eter as m easured on the CT scan.

M ethods
The patient went through a full course of neutron therapy, receiving a dose of 20.4 G y delivered in 13 fractions over 35 elapsed days. The neutron beam is ch a racter iz ed a s a p (6 6) B e( 49 ) n eu tr o n b eam produced by 66-M eV protons w hich strike a beryllium target to produce a neutron beam with depth dose characteristics sim ilar to an 8-M V photon beam . T he beam is ® xed and the patient is treated isocentrically in the seated position utilizing a specially m ade chair which can be rotated. A com puterized treatm ent plan required contouring in six planes to achieve an optimal dose distribution. Ten separate neutron beam s were utilized to ful® ll the treatment plan, which included fou r anterior beam s, fou r left posterior oblique beam s and two left anterior oblique beam s. Wedges and m ultiple blocks in various beam s were utilized as well. The patient com pleted the course of treatment nearly on schedule, although he required hyperalim entation and a short hospitalization during treatment.

Results
Follow -up exam inations have dem onstrated reduction in the tum or m ass, gradually increasing calci® cation on CT scan, and noticeable reduction of soft tissue disease in the frontal sinus, orbit and m axillary sinus (Fig. 3). W hile there is persistent proptosis, the patient continues to have vision in the treated left eye. A t la st fo llo w -u p (D ecem b er 19 98 ), th e 17-year-old boy conducts an active life, participates in sports, has no pain, and feels well. T here has been

Discussion
Osteogenic sarcom a of the facial bones and sinuses continues to be an unusual and aggressive disease, as 80± 90% of all osteogenic sarcom as occur in the long bones. 6 Tum o rs of the m axilla accoun t for on ly app roxim ately 2± 3% of patients. 1 This represents about one-third to one-half of osteogenic sarcomas classi® ed as arising in the jaws, with m andibular lesio ns ou tn u m berin g m axillar y lesion s in m ost review s. 7,8 For operable tum ors, wide surgical resectio n is u su a lly p erfo r m ed in co n ju n c tio n w ith ch em o th erap y, a n d r ad iatio n th era p y is o ft en employed as well for close or positive m argins, and in operable and recurrent tum ors. Recent clinical results have demonstrated an im proving cure rate in the treatm ent of surgically resectable tum ors when surgical m argin s are ad equ ate. 9,10 H ow ever, the expectation for local eradication in surgically unresectable patients is poor, despite som e historical results that dem onstrate that tumors of the jaw tend to have a better prognosis than osteogenic sarcom a at other sites, with ® rst evidence of failure m ore likely to be local recurrence than distant m etastases. 9,11 For this aggressive tum or, the radiobiological effect of neutron therapy com pared to conventional photon therapy is greater, and may more likely result in local control of the tumor. 12 Historically, local control for unresectable and/or inoperable osteogenic sarcom a has been greater than 40% in patients (all age groups) treated at the Midwest Institute for N eutron Therapy at Fermilab. 13 Fast neutrons may be considered the best radiation quality used in the treatment of osteogenic sarcomas, as well as other sarcomas of soft tissue and bone in which the local control rate is 53%. 12 Worldwide data from earlier neutron therapy reports indicate a local control rate of 40± 60% for sarcomas of bone and soft tissue, which compares favorably with the 21% local control rate reported utilizing photon irradiation. 5 For high-energy fast neutron beam s, the likelihood and severity of soft tissue complications are similar to those of conventional photon therapy. In addition, there is approxim ately 25% less dose absorption in bony cavities due to the low neutron kerm a in bone, thus lessening the risk of late injury to normal bone compared with conventional photon therapy.
14 Some early studies using low-energy fast neutron beams found unacceptable complications. 15 These low-energy beam s are no longer recom m ended for treatm ent purposes, and all such facilities in the United States have been closed. At present, there are only three high-energy fast neutron therapy facilities in the U nited States and a lim ited n u m b er o f in sta llatio n s w o r ld w id e. Consequently, this treatm ent m odality is of lim ited accessibility to patients, but nevertheless should not be overlooked as a possib le way to im prove control in appropriate cases.