Experience of external beam radiotherapy given adjuvantly or at relapse following surgery for craniopharyngioma.

BACKGROUND AND PURPOSE: Evaluation of effect of timing of external beam radiation therapy (EBRT) following surgery for craniopharyngioma. MATERIALS AND METHODS: Between 1976 and 2002, 87 patients (28 children) received EBRT in a regional referral centre. Forty-four patients received EBRT adjuvantly and 43 on relapse. The median total dose was 42.5Gy (range 34.7-52.5Gy) in 2.25-2.83Gy fractions over a median of 20 days (range 17-32). Effect of EBRT timing, type of original surgery, age on survival, progression-free survival (PFS) and quality of life (QOL) was studied. RESULTS: Survival from diagnosis was 86 and 76% and PFS was 78 and 66% at 10 and 20 years, respectively, with no significant difference seen between those treated adjuvantly or at relapse or according to age. QOL deteriorated significantly from diagnosis to last follow-up. Excluding patients who relapsed following EBRT, QOL did not deteriorate significantly overall (P=0.35). Children had worse QOL and greater morbidity at all timepoints compared to adults. CONCLUSIONS: EBRT is effective both adjuvantly and at relapse. QOL deteriorates over time-relapse following EBRT was the only significant factor. Children have greater morbidity compared to adults, but no evidence for greater EBRT-induced toxicity was seen.

The usefulness of the combined growth hormone (GH)-releasing hormone and arginine stimulation test in the diagnosis of radiation-induced GH deficiency is dependent on the post-irradiation time interval.

The diagnostic usefulness of the insulin tolerance test (ITT) in patients with radiation-induced GH deficiency (GHD) is well established, whereas that of the combined GHRH plus arginine stimulation test (AST) is unproven. Both tests were undertaken in 49 adult survivors (aged 16-53.7 yr), who were previously irradiated for non-pituitary brain tumors or leukemia, and 33 age-, gender-, and BMI-matched controls. The aims of the study were to examine the impact of the time interval after irradiation on the pattern of GH responsiveness to the two provocative tests and to establish the role of the GHRH + AST in the diagnosis of radiation-induced GHD. The median (range) peak GH responses to either test were significantly lower (P < 0.0001) in the patients [GHRH + AST, 19.9 (range, 2.7-103.5) microg/liter; ITT, 5 (0.2-34.8) microg/liter] than in normals [GHRH + AST, 55 (5.7-173.5) microg/liter; ITT, 23.8 (4.2-80) microg/liter]. In patients and normal controls, the median peak GH response to the GHRH + AST was significantly greater (P < 0.0001) than the response to the ITT. However, the ratio of the peak GH response to the GHRH + AST over that achieved with the ITT (discordancy ratio) was significantly higher (P = 0.007) in the patients (median, 3.45; range, 0.8-53.5) compared with normals (median, 2; range, 0.34-18.6), consistent with dominant hypothalamic damage and relatively preserved somatotroph responsiveness. The peak GH response to the ITT fell significantly within 5 yr of irradiation with little further change over the subsequent 10 yr. In contrast, the peak GH response to the GHRH + AST barely changed within 5 yr of irradiation but subsequently declined significantly over the next 10 yr. Thus, the evolution of change in GH responsiveness to the two different stimuli over time was markedly different, resulting in a significantly raised discordancy ratio of 6 within the first 5 postirradiation years, which then normalized over the next 10 yr. The peak GH responses to the GHRH + AST and the discordancy ratio were negatively correlated with the time interval after irradiation (r = -0.40, P = 0.0037; and r = -0.4, P = 0.0046, respectively). On a practical clinical level, the discordancy between the GH test results was important; 50% of those classified as severely GHD patients by the ITT were judged normal or only GH insufficient by the GHRH + AST. In conclusion, these findings suggest that hypothalamic dysfunction occurs early and somatotroph dysfunction occurs late, following radiation damage to the hypothalamic-pituitary axis. This time dependency of somatotroph dysfunction may reflect either secondary somatotroph atrophy due to hypothalamic GHRH deficiency or delayed direct radiation-induced damage to the pituitary gland. The high false negative diagnosis rate for severe GHD makes the GHRH + AST an unreliable test in clinical practice when GH status is explored in the early years after cranial irradiation with the intention to treat.

Second primary tumors in neurofibromatosis 1 patients treated for optic glioma: substantial risks after radiotherapy.

PURPOSE: Optic pathway gliomas (OPGs) are the most common CNS tumor in neurofibromatosis 1 (NF1) patients. We evaluated the long-term risk of second tumors in NF1-related OPGs after radiotherapy. PATIENTS AND METHODS: We reviewed 80 NF1 OPG patients from two NF1 clinics to evaluate the long-term risk of developing subsequent nervous system tumors, with or without radiotherapy. RESULTS: Fifty-eight patients were assessable for second tumors. Nine (50%) of 18 patients who received radiotherapy after their OPGs developed 12 second tumors in 308 person-years of follow-up after radiotherapy. Eight (20%) of 40 patients who were not treated with radiotherapy developed nine tumors in 721 person-years of follow-up after diagnosis of their OPGs. The relative risk of second nervous system tumor after radiotherapy was 3.04 (95% CI, 1.29 to 7.15). CONCLUSION: There is a significantly increased risk of second nervous system tumors in those NF1 patients who received radiotherapy for their OPGs, especially when treated in childhood. Thus radiotherapy should only be used if absolutely essential in children with NF1.