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      Fractionated stereotactic radiotherapy in the treatment of pituitary macroadenomas

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          Abstract

          Background

          The use of fractionated stereotactic radiotherapy ( fsrt) has evolved with technical advances in noninvasive immobilization, radiation delivery, and image guidance. The application of fsrt to pituitary tumours is aimed at reducing toxicity through improved dose conformality and reduced treatment margins. The aim of the present paper is to report our own experience and to review the published data on fsrt for pituitary macroadenomas.

          Methods

          Between September 2000 and October 2005, 13 patients with pituitary macroadenoma underwent fsrt at our institution. In 12 patients, radiotherapy treatment followed surgical resection (transsphenoidal resection in 8, frontal craniotomy in 3, and multiple transsphenoidal resections followed by craniotomy in 1). In 4 patients, the tumours were functional (2 adrenocorticotropic hormone–secreting, 1 prolactinoma, and 1 growth hormone–secreting); the tumours in the remaining patients were clinically non-secretory. Before radiation, 3 patients had panhypopituitarism, and 6 patients had visual field defects. All patients were treated with fsrt using non-coplanar micro–multileaf collimation portals. A median dose of 50.4 Gy (range: 45–60 Gy) was prescribed to the 76.9%–95.2% isodose surface and delivered in 1.8-Gy fractions. The median planning target volume (gross tumour plus 3 mm) was 33.5 cm 3 (range: 3.2–75 cm 3).

          Results

          After a median follow-up of 24 months (range: 6–60 months), local control was 100%. One patient achieved clinical complete response. Treatment was well tolerated acutely for all patients. Neither radiation-induced optic neuropathy nor any radiation-related endocrine dysfunction was observed in our patients.

          Conclusions

          In accordance with published series, we found fsrt to be safe and effective in the management of large pituitary macroadenomas.

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          Most cited references32

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          Observation alone after transsphenoidal surgery for nonfunctioning pituitary macroadenoma.

          Transsphenoidal surgery is the treatment of choice for nonfunctioning pituitary macroadenomas (NFMA). In this study we evaluated the long-term effects of a treatment strategy in which postoperative radiotherapy was not routinely applied to patients with NFMA. This was a retrospective follow-up study. We included 109 consecutive patients (age 56 +/- 13 yr) operated for NFMA between 1992 and 2004. Radiological imaging revealed a macroadenoma in all patients, with suprasellar extension in 96% and parasellar/infrasellar extension in 36% of cases. Visual field defects were present in 87% of the patients and improved in 84% of these patients after surgery. Only six patients received postoperative radiotherapy. Ten patients died during the follow-up period. Ninety-seven patients could be assessed for tumor regrowth or tumor recurrence after a mean follow-up period of 6.0 +/- 3.7 yr. In nine patients there was evidence for tumor regrowth, and in one patient tumor recurrence was observed. The mean time to tumor growth/recurrence after initial therapy was 6.9 (range 3-12) yr. Follow-up duration was found to be an independent predictor for tumor regrowth. Transsphenoidal surgery without postoperative radiotherapy is an effective and safe treatment strategy for NFMA, without evidence for tumor regrowth in 90% of all patients, at least for the duration of follow-up presented in this study. Additional studies are required to exclude higher regrowth and recurrence rates during prolongation of the duration of follow-up.
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            The long-term efficacy of conservative surgery and radiotherapy in the control of pituitary adenomas.

            We assessed the long-term efficacy and toxicity of conservative surgery and radiotherapy in the control of pituitary adenomas. Retrospective study of patients treated at the Royal Marsden Hospital. Four hundred and eleven patients with pituitary adenomas treated with conventional external beam radiotherapy at the Royal Marsden Hospital between 1962 and 1986. Two hundred and fifty-two patients had clinically non-functioning pituitary adenomas, 131 had hormone secreting tumours and in 28 patients the secretory status was not known. Three hundred and thirty-eight patients had surgical intervention of whom only 11 had complete tumour excision. All patients received conventional fractionated external beam radiotherapy to a dose of 45-50Gy in 25-30 fractions. Actuarial progression free survival and overall survival and assessment of toxicity, particularly in terms of vision, requirement for hormone replacement therapy and incidence of second tumours. The actuarial progression free survival was 94% at 10 years and 88% at 20 years for all patients and 97% at 10 years and 92% at 20 years for patients with clinically non-functioning adenomas. Only secretory status was an independent prognostic factor for disease control. The 10 and 20-year survivals for all patients were 77 and 58% respectively. When compared with the normal population the relative risk of death was 1.76 (P < 0.001) and no prognostic factors for survival were identified. The morbidity of radiotherapy was low. Visual deterioration, assumed to be radiation induced, occurred in 1.5% of patients and the risk of second brain tumour was 1.9% at 20 years. Fifty per cent of patients received hormone replacement therapy by 19 years. Conventional external beam radiotherapy as described here combined with conservative surgery is safe and effective in the control of pituitary adenomas. These results should form a baseline for comparison with new treatment strategies.
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              The clinical and endocrine outcome to trans-sphenoidal microsurgery of nonsecreting pituitary adenomas.

              From 1962 to 1987, 126 patients underwent trans-sphenoidal surgery for primary treatment of pituitary adenomas unassociated with clinical or biochemical evidence of hormonal overproduction. There were 73 male and 53 female patients (mean age, 50 +/- 12 years). Before surgery, 56% of the patients (70 of 124) had headaches, 74% (94 of 126) had deterioration of vision, and 12% (15 of 126) had ophthalmoplegia. Endocrine evaluation revealed the presence of hypogonadism in 75% (87 of 115), adrenal insufficiency in 36% (46 of 126), and hypothyroidism in 18% (21 of 122). Plasma prolactin was increased in 65% (56 of 86) with a mean level of 39 +/- 14 micrograms/l (normal, 3 to 20 micrograms/l). Radiologic enlargement of the sella turcica was documented in all cases: 67% (84 of 126) had enclosed and 33% (42 of 126) had invasive adenomas. After surgery, vision was normalized or improved in 75% (71 of 94) of the patients. Thyroid, adrenal, and gonadal functions were improved in 14% (three of 22), 41% (19 of 46), 11% (ten of 87), were unchanged in 82% (100 of 122), 77% (97 of 126), 89% (102 of 115), and worsened in 15% (19 of 22), 8% (ten of 126), 3% (102 of 115), respectively. Permanent diabetes insipidus occurred in 5% (seven of 126). Two patients died during the immediate postoperative period. The recurrence rate in patients with a mean follow-up of 6.4 +/- 4.2 years was 21% (15 of 71). These data indicate that trans-sphenoidal microsurgery is an effective and safe initial treatment for patients with nonsecreting pituitary adenoma and may reverse hypopituitarism.
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                Author and article information

                Journal
                Curr Oncol
                CO
                Current Oncology
                Multimed Inc. (66 Martin St. Milton, ON, Canada L9T 2R2 )
                1198-0052
                1718-7729
                December 2008
                : 15
                : 6
                : 286-292
                Affiliations
                [* ]Department of Radiation Oncology, McGill University Health Center, Montreal, QC
                []Department of Medical Physics, McGill University Health Center, Montreal, QC
                Author notes
                Correspondence to: Thierry Muanza, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4. E-mail: thierry.muanza@ 123456mcgill.ca
                Article
                co15-6-286
                2601024
                19079630
                d081ef63-4012-4ec7-95f5-447f84887d49
                2008 Multimed Inc.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Radiation Oncology

                Oncology & Radiotherapy
                fractionated stereotactic radiotherapy,pituitary adenoma,radiotherapy,macroadenoma

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