Piero Picozzi

The role of stereotactic radiotherapy in patients with growth hormone-secreting pituitary adenoma

CONTEXT Single-session stereotactic radiotherapy (SR) may be a potential adjuvant treatment in acromegaly. OBJECTIVE We analyzed the safety and efficacy of SR in patients who had previously received maximal surgical debulking at our center. DESIGN The study was a retrospective analysis of hormonal, radiological, and ophthalmologic data collected in a predefined protocol from 1994 through 2006. SETTING The study was performed at a university hospital. PATIENTS Eighty-three acromegalic patients, 52 women and 31 men, with a mean age of 42.6 +/- 1.2 yr, participated in the study. The median follow-up was 69 months (interquartile range 44-107 months). INTERVENTION The patients were treated with SR for residual or recurrent GH-secreting adenoma. MAIN OUTCOME MEASURE Normalization of age- and sex-adjusted IGF-I levels together with a basal GH level below 2.5 microg/liter without concomitant GH-suppressive drugs was the goal of therapy. RESULTS Fifty patients (60.2%) reached the main outcome of the study. The rate of remission was 52.6% at 5 yr [95% confidence interval (CI) 40.6-64.6%]. Another 13 patients (15.7%), who were resistant to somatostatin analogs, were in remission after SR. Multivariate analysis showed that low basal GH and IGF-I levels were associated with a favorable outcome. No serious side effects occurred after SR. The 5-yr cumulative risk of new onset hypogonadism, hypothyroidism, or hypoadrenalism was 3.6% (95% CI 0-8.6%), 3.3% (95% CI 0-7.7%), and 4.9% (95% CI 0-10.4%), respectively. CONCLUSION In a highly selected group of acromegalic patients, SR treatment had good efficacy and safety. This may lead to reconsider the role of SR in the therapeutic algorithm of acromegaly.

Gamma knife radiosurgery for uveal melanoma: 12 years of experience

Aim: To present our treatment protocol and evaluate the results of Gamma knife radiosurgery (GKR) in treating patients with uveal melanoma. Methods: Seventy-eight consecutive patients with uveal melanoma underwent stereotactic radiosurgery (radiation dose 30–50 Gy) with a Leksell Gamma-Knife at the San Raffaele University Hospital, Milan, Italy between 1994 and 2006. The main outcome measures evaluated were: survival rate, local tumour control, eye retention rate, visual acuity and treatment-related complications. Results: Survival rate was 88.8% at 3 years and 81.9% at 5 years. Local tumour control was achieved in 91.0% of patients. The median tumour thickness reduction after treatment was 1.96 mm (p<0.0001) (−32.1%). The eye retention rate was 89.7%. A significant relative reduction of visual acuity was observed during follow-up. The most frequent treatment-related complications were: exudative retinopathy (33.3%), neovascular glaucoma (18.7%), radiogenic retinopathy (13.5%) and vitreous haemorrhages (10.4%). Conclusion: GKR can be considered an alternative to enucleation for the treatment of choroidal melanomas.

C-11 choline versus F-18 fluorodeoxyglucose for imaging meningiomas: an initial experience.

Purpose: Positron emission tomography/computed tomography (PET/CT) with C-11 choline has been used for staging, restaging, and follow-up of various tumors, whereas its role for imaging meningiomas has only been preliminarily explored. The aim of this study was to compare C-11 choline and F-18 fluorodeoxyglucose (F-18 FDG) uptake in meningiomas and relate these findings to the histopathological analysis. Methods: Two sequential three-dimensional PET/CT scans with 370 MBq (10 mCi) of C-11 choline and 370 MBq (10 mCi) of F-18 FDG were performed 2 hours apart in 7 patients with histologically confirmed meningiomas. Five patients had WHO grade I and 2 had WHO grade II meningioma. For each scan, two-dimensional regions of interest were drawn on tumor boundaries and on the contralateral side on CT images and copied to the corresponding PET images. SUVmax and tumor-to-background ratio were calculated. Results: Relative to the contralateral side, C-11 choline uptake was increased in all meningiomas, whereas F-18 FDG uptake was decreased in 6 patients and increased in 1 of the 2 patients with grade II meningiomas. In the whole group, SUVmax of C-11 choline and F-18 FDG were 3.6 ± 1.3 and 5.7 ± 1.3, respectively. The tumor-to-background ratio for C-11 choline was much higher than that for F-18 FDG (5.3 ± 0.8 vs. 0.9 ± 0.2, respectively) (P < 0.001). The uptake of C-11 choline was higher in patients with grade II than in grade I meningiomas. Conclusions: These preliminary results suggest that C-11 choline may better image meningiomas in comparison with F-18 FDG. Clinical applications of C-11 choline PET/CT for grading and follow-up of meningiomas need to be assessed in further studies.

Pituitary Radiotherapy for Cushing’s Disease

Background: The treatment of choice for Cushing’s disease is pituitary surgery. Second-line treatments include repeat pituitary surgery, radiation therapy, medical therapy, and bilateral adrenalectomy. The most used modalities to irradiate patients with Cushing’s disease include fractionated radiotherapy and single-dose Gamma Knife. We aim to review the efficacy and safety of radiotherapy in patients with persistent or recurring Cushing’s disease. Results: Remission of Cushing’s disease after radiotherapy ranges from 42 to 83%. There seems to be no clear difference according to the technique of radiation used. Most patients experience remission of disease within 3 years from treatment, with only few cases reaching normal cortisol secretion after a longer follow-up. Control of tumor growth varies from 93 to 100%. Severe side effects of radiotherapy, such as optic neuropathy and radionecrosis, are uncommon. New-onset hypopituitarism is the most frequent side effect of radiation, occurring in 30–50% of patients treated by fractionated radiotherapy while it has been reported in 11–22% of patients after Gamma Knife. Conclusion: Radiotherapy is an effective second-line treatment in patients with Cushing’s disease not cured by surgery. Consideration of the advantages and disadvantages of radiotherapy in comparison with other therapeutic options should always be carried out in the single patient before deciding the second-line therapeutic strategy for persisting or recurring Cushing’s disease.

A simplified method to integrate metabolic images in stereotactic procedures using a PET/CT scanner

We have developed a method that needs only the computed tomography (CT) indicator box to coregister positron emission tomography (PET) images and integrates this information with magnetic resonance imaging. The study was performed using a PET/CT scanner. A standard CT bed adapter was attached to the scanner couch. Then, the patient, with the Leksell G frame fixed, was positioned into the scanner with the CT indicator box. PET images were acquired using either [18F]fluorodeoxyglucose or [11C]choline as radioisotopes. After acquisition, CT and PET images were exported in DICOM 3 standard and transferred to a dedicated workstation via data link. Homemade software was implemented for multimodal image fusion. PET images were overwritten to their corresponding CT point values using a threshold algorithm, maintaining the stereotactic CT markers. The use of a CT indicator simplifies the procedure, because there is no need for a radioactive solution filling the indicator box. This method was tested first using a phantom and then in patients. The localization accuracy of the PET images is limited only by the slice thickness.

Predictors of radio-induced visual impairment after radiosurgery for uveal melanoma

Aims The aim of the present work is to assess the main predictors of the most clinically relevant radio-induced effects after Gamma Knife stereotactic radiosurgery (GKRS) for uveal melanoma (UM). Materials and methods Medical records and three-dimensional dosimetry data of critical structures of 66 patients were retrospectively reviewed. Cox’s proportional hazard model was used to identify clinical and dosimetric variables as independent risk factor for GKRS-related complications. Results The fraction of the posterior segment receiving more than 20Gy (V20), Bruch’s membrane rupture and tumour thickness were significant prognostic factors for neovascular glaucoma. A clear relationship with the dose received by 1% of the optic nerve (D1%) was found for radiation retinopathy and papillopathy. Multivariables models resulted for visual acuity (VA) reduction >20% of the basal value and for complete VA loss, both including largest tumour diameter and D1% to the optic nerve. The predictive model for complete VA loss includes also Bruch’s membrane rupture. An alternative model for complete visual acuity loss, including the optic nerve-prescription isodose minimum distance, was also suggested. Conclusions We found clinical and dosimetric variables to clearly predict the risk of the main side effects after GKRS for UM. These results may provide dose constraints to critical structures, potentially able to reduce side effects. Constraining D1% to the optic nerve below 12-13Gy may result in a dramatic reduction of blindness risk, while reducing V20 of the posterior segment of the bulb could limit the neovascular glaucoma onset.

Preliminary results of contrast-enhanced sonography in the evaluation of the response of uveal melanoma to gamma-knife radiosurgery

Our aim was to prospectively analyze the use of contrast‐enhanced ultrasound (CEUS) in the quantitative assessment of the response of uveal melanoma (UM) to gamma‐knife radiosurgery (GKR), investigating whether changes in tumor vascularization precede thickness reduction, which on average occurs at 12 months after GKR.