Dr. Cordero will discuss hypopituitarism after gamma knife radiosurgery for pituitary adenomas, a multi-center international study. Thank you. Can I pass this here? Just click here? Okay. Thank you very much. My name is Joe Cordero. I'm from Brazil, doing a research fellow at UVA. I don't have any disclosure. This is from other authors. Just a brief introduction. Pituitary adenomas are common primary intracranial tumors. They correspond to 10 to 20% of all brain tumors, and they can be classified as non-functional pituitary adenomas or function pituitary adenomas based on clinical and biochemical endocrine secretory activity. Surgery is first-line treatment, with exception of prolactinomas. After resection, we have a recurrence of progression, 10 to 50%, depending on the series. Radiation therapy has been used to treat this recurrence of progression, but in the last two or three decades, stereotactic radiosurgery has been applied. Hypopituitarism is the most frequent adverse effect of stereotactic radiosurgery, with an incidence of 20% to 100% in previous series. In this study, it's from the International Gamma and Alpha Research Foundation, 17 centers, from 1988 to 2016. Patients that were treated with previous radiation therapy, they were excluded from the analysis, which led us to a total of 1,023 patients. The patient character is 40% of these 1,023 patients were non-function pituitary adenomas, 26% they were Cushing disease, and 34% they were acromegaly patients. Only 72 patients has upfront gamma knife, all the other patients, they had previous surgeries, ranging from one to seven previous surgeries. The median age was 47, ranging from 12 years old to 92 years old, 92 years. The evaluation was done in all of these patients, 24 hours, urine-free cortisol, serum cortisol, ACTA, IGF-1, growth hormone, all this panel, and of course, also evaluation for diabetes insipidus. This is the summary of gamma knife radiosurgery characteristics. The median margin dose was 20 gray, maximum dose 40 gray, seven ISO centers were the median, and the treatment volume was 2.47. The median ISO dose line prescribed was 50%, ranging from 20 to 90%. Gamma knife technique, since the disease I studied, I'd spent several decades. This changed a little, but in general, it was the MRI protocol with thin slices, pre and post contrast, combined with fat suppression. We used different gamma knife models. You'll see perfection in ICOM. The indications for gamma knife radiosurgery treatment were recurrence, progression, postoperative remains, and hypersecretory states. Follow-up was done every six months in the first one to two years, then annually, with this endocrine evaluation of all this hormonal panel. Radiological response, we consider tumor growth more than 10% of the previous treated volume, and shrinkage regression less than more than 10% shrinkage, and stable between this 10%. The radiological response, the follow-up median was 51 months. Tumor control was achieved in 96.3% of the patients, and adenoma progression in only 38 patients, 3.7%. Hypopituitarism developed in 248 patients, 24.2% of the total of the patients. They developed new hypopituitarism at the last follow-up. We can see that 39% of these patients, they were acromegaly patients. Adenoma progression, pituitary adenomas, 35%, and Cushing's disease, 26%. The time to new onset of hypopituitarism, the median time was 39 months, range 3 to 107 months, single hormonal deficiency in 150 patients, multiple hormonal deficiency in 98 patients, and panhypopituitarism in only 7 patients. The actual hypopituitarism rate at one year was 7.8%, 5 years, 22.4%, and 10 years, 31.3%. Here is a Kaplan-Meier curve. We can see the prevalence of hypopituitarism. Almost all the case, they occur within the first five years, although we have some case that develop after 10 years, even close to 15 years. After gamma knife radial surgery. Here we can see the most common hormonal deficiencies. In total, we can see the most common was thyrotropin deficiency. Then we had gonadotropin deficiency, cortisol, GH, and diabetes insipidus in only 11 patients. This is by tumor type. It more or less repeats the pattern here, although we can see, like, acromegaly, only one patient has a GH deficiency. In univariate and multivariate analysis, we got these results. In univariate analysis, whole cellar treatment, an iso-dose line prescription of less than 50%, and function pituitary adenomas, they were at more risk of developing new endocrine deficits. In multivariate analysis, the only variable that remained significant was iso-dose line less than 50% as a risk factor for new endocrine deficiencies, with a P value of 001, hazard ratio 1.38. Here we have some frequency by the iso-dose line. We can see most of the patients, they were treated with an iso-dose line of 50%. The volume was similar in all of these cases, despite the median margin dose in iso-dose line less than 50% was 15 gray, less than the other two ones. We still have this iso-dose line less than 50% as a risk factor. The time to new hypopituitarism, we can see here, iso-dose line less than 50%, 13 months, 50% 18 months, and iso-dose line more than 50%, 46.5 months in the median, with this range that we can see. Radiologic control was similar in all the groups. Iso-dose line was not a significant factor for radiologic control, only for time to new hypopituitarism. In this Kaplan-Meier, we can see here, the circle here, we can see iso-dose line more than 50%. They have a less incidence of hypopituitarism, comparing to iso-dose line less than 50%, and this one here, 50%, a P value of 005. This study has several limitations. A retrospective study, that is, we can have selection, treatment bias, and follow-up variations. Some patients, they have follow-up with local physicians, and we have to gather this information from local clinicians. Treatment span is several decades, so gamma knife technology, neuroimaging protocols, the changes during these years, irregularities in endocrine testing could have impacted the time to new onset of hypopituitarism, and the normal range of assays that have changes during the years, and this can underestimate the rates of hypopituitarism. In conclusion, hypopituitarism remains the most frequent adverse effect of gamma knife radial surgery for pituitary adenomas. Treating the target with an iso-dose line of 50% or greater, and avoid wholesale radial surgery unless it is necessary, can mitigate the risk of post-gamma knife radial surgery hypopituitarism. Longitudinal follow-up for this patient is required, since we can see these patients can develop new hypopituitarism even 10 years after gamma knife radial surgery. We think this iso-dose line prescription less than 50% can convey, does not as steep a follow-up dose as we have in iso-dose line more than 50% or equal 50%, and this can lead to radiation to normal structures like pituitary stalk and hypothalamus. Acknowledgements, these are all the people that were involved in this study. Thank you very much. Thank you.

hypopituitarism

gamma knife radiosurgery

pituitary adenomas

endocrine deficiencies

iso-dose line