Hypothalamic/pituitary function following high-dose conformal radiotherapyto the base of skull: Demonstration of a dose-effect relationship using dose-volume histogram analysis

Purpose: To evaluate the incidence and pattern of hypopituitarism from hypo thalamic (HT) and pituitary gland (PG) damage following high-dose conformal fractionated proton-photon beam radiotherapy (PPRT) to the base of skull ( BOS) region in adults, The relationship between dose, volume, and PG functi on is explored. Methods and Materials: Between May 1982 to October 1997, 107 adults with no n-PG and non-MT neoplasms (predominantly chordoma and chondrosarcomas) of t he BOS were treated with PPRT after subtotal resection(s). The median age w as 41.2 years (range, 17-75) with 58 males and 49 females. Median prescribe d target dose was 68.4 cobalt gray equivalent (CGE) (range, 55.8-79 CGE) at 1.80-1.92 CGE per fraction per day (where CGE = proton Gy x 1.1), The MT a nd PG were outlined on planning CT scans to allow dose-volume histograms (D VH) analysis. All patients had baseline and follow-up clinical testing of a nterior and posterior pituitary function including biochemical assessment o f thyroid, adrenal, and gonadal function, and prolactin secretion, Results: The 10-year actuarial overall survival rate was 87%, with median e ndocrine follow-up time of 5.5 years, thus the majority of patients were av ailable for long-term follow-up. Five-year actuarial rates of endocrinopath y were as follows: 72% for hyperprolactinemia, 30% for hypothyroidism, 29% for hypogonadism, and 19% for hypoadrenalism, The respective 10-year endocr inopathy rates were 84%, 63%, 36%, and 28%. No patient developed diabetes i nsipidus (vasopressin deficiency). Growth hormone deficiency was not routin ely followed in this study. Minimum target dose (Dmin) to the PG was found to be predictive of endocrinopathy: patients receiving 50 CGE or greater at Dmin to the PG experiencing a higher incidence and severity (defined as th e number of endocrinopathies occurring per patient) of endocrine dysfunctio n. Dmax of 70 CGE or greater to the PG and Dmax of 50 CGE or greater to the HT were also predictive of higher rates of endocrine dysfunction, Conclusion: Radiation-induced damage to the HT & PG occurs frequently after high-dose PPRT to the BOS and is manifested by anterior pituitary gland dy sfunction, Hyperprolactinemia was detected in the majority of patients. Pos terior pituitary dysfunction, represented by vasopressin activity with diab etes insipidus, was not observed in this dose range. Limiting the dose to t he MT and PG when feasible should reduce the risk of developing clinical hy popituitarism, (C) 2001 Elsevier Science Inc.