Laura Tomazzoli

Analysis of long-term outcomes and prognostic factors in patients with non—small cell lung cancer brain metastases treated by gamma knife radiosurgery

OBJECT The authors conducted a study to evaluate the long-term outcomes and prognostic factors for survival in a large series of patients treated by gamma knife surgery (GKS) for non-small cell lung cancer (NSCLC) brain metastases. METHODS The study is based on the retrospective analysis of clinical and radiological records obtained during a 10-year period (1993-2003), concerning 836 lesions in 504 patients. The lesions were primary in 86% and recurrent 14% of the cases; they were solitary in 31%, single in 29%, and multiple in 40%. The mean follow-up period was 16 months (range 4-113 months). The most common histological types were adenocarcinoma (51%) and squamous cell carcinoma (27%). Dose planning parameters were as follows: mean target volume 6.2 cm3 (range 0.06-22.5 cm3); mean prescription dose 21.4 Gy (range 15.5-28 Gy); and mean number of isocenters 6.7 (range one-18). Progression-free and actuarial survival curves were calculated using the Kaplan-Meier method. The main factors affecting survival were determined by unimultivariate analysis (log-rank test and Cox proportional hazard models). Analysis of long-term outcomes seemed to confirm that GKS is a primary therapeutic option in these patients. The 1-year local tumor control rate was 94%. The overall median survival was 14.5 months, with extremely rewarding quality of life indices. The recursive partitioning analysis classification was the dominant prognostic factor. CONCLUSIONS Gamma knife surgery is a useful treatment for brain metastases from NSCLC.

Stereotactic Radiosurgery of Uveal Melanomas: Preliminary Results with Gamma Knife Treatment

Twelve cases of uveal melanoma (T3N0M0:11 patients, T4N0M0:1 patient) treated with Gamma Knife stereotactic radiosurgery are reported. Our protocol includes preoperative ocular and systemic assessments with complete ocular examination, ophthalmoscopy, fundus photography, fluorangiography, standardized echography, CT and MRI, chest X-rays, liver echography and blood tests. The follow-up program is mainly based on echographic evaluation of tumor thickness and size. The procedures include fixation of the eye, application of the stereotactic Leksell frame G, CT/MRI localization of the melanoma, dose planning and treatment with the Gamma Knife (B type). A mean surface dose of 55 +/- 10 Gy was administered at the 60-90% isodose curve using 4- to 14-mm collimators and a number of shots ranging from 1 to 6. A significant reduction (10-41%) in echographic thickness of the tumor was shown in 6 cases with a follow-up of 3-12 months. In 4 patients, the tumor size was still unchanged after 1-10 months. The single high-dose radiation delivered to the target and the high spatial accuracy are the main advantages of stereotactic radiosurgery for the treatment of posterior uveal melanomas. A longer followup is needed to further validate this new application of Gamma Knife radiosurgery.

Multiple brain metastases from “lymphoepithelioma-like” thymic carcinoma: a combined stereotactic-radiosurgical approach

Thymic carcinoma (TC) is a rare malignancy (approximately 150 reported cases) [1] which differs from thymoma in that it displays cytologically malignant features, extensive local invasion, and a substantial potential for metastasis, mainly to the liver and kidneys [3,4,6,7]. Most patients with TC present with an anterior mediastinal mass, while myasthenia gravis or other thymoma-associated syndromes are unusual findings. Clinico-pathological classifications based upon oncotype grading currently play a major predictive role: low grade tumors, including squamous cell, basaloid, and mucoepidermoid types, are characterized by a less aggressive course, whereas high grade tumors—small cell, sarcomatoid, clear cell, and “lymphoepithelioma-like” (LEL-TC)—mostly carry a distinctly grim prognosis, with a median survival barely exceeding one year [3,7]. The appearance of brain metastases seems to be crucial in this regard, being associated with an average life expectancy of only a few months [4,8]. This report describes long-term survival in a patient suffering from LEL-TC with multiple intracranial lesions, who was successfully treated by combined stereotactic neurosurgery and Gamma Knife (GK) radiosurgery. Case Report

Gamma Knife Stereotactic Radiosurgery of Ocular Metastases: A Case Report

A case of a choroidal metastasis treated with Gamma Knife stereotactic radiosurgery is reported. A 48-year-old Caucasian man afflicted with lung cancer (adenocarcinoma) was referred to the University Hospital of Verona, Italy, for loss of vision in his left eye due to a choroidal mass with exudative retinal detachment. Clinical investigation was conclusive of a well-defined, bilobed choroidal metastasis located in the temporal and inferior portion of the posterior pole of the eye. The lesion was characterized by a maximum thickness of 5.2 mm and a maximum lateral extension of 14 mm. The staging was negative for other metastatic localizations. Using the Gamma Knife technique, a surface dose of 25 Gy was administered at the 50% isodose line using the 8-mm collimator (5 shots) with equally weighted fields. After a 3-month follow-up period, a marked reduction in the lesion size as well as in the exudative retinal detachment was observed. This improvement was unchanged 6 months after the treatment, and the lesion appeared completely controlled. To the best of our knowledge, this is the first case report of an ocular metastasis treated with stereotactic Gamma Knife radiosurgery.

Anterior Optic Gliomas with Precocious or Pseudoprecocious Puberty

5 patients with gliomas of the anterior optic pathways, histologically assessed or with strong diagnostic evidence, who developed precocious or pseudoprecocious puberty (2 cases) before the operation or after radiation treatment, are presented. Only 2 patients presented familial and/or personal evidence of neurofibromatosis. The production mechanism of these sexual changes is discussed.

Gliomas of the Optic Nerve and Chiasm

A series of 24 children with anterior optic gliomas, observed and for the most part operated upon in a neurosurgical service, is reviewed. A low incidence of unilateral nerve tumors and of associated neurofibromatosis, and a rather high frequency of precocious or pseudoprecocious puberty were noted in comparison with other series. Most tumors were low-grade growths. The results of surgical treatment reflect a good prognosis for unilateral tumors and an increasing prognostic ominousness for the posterior neoplastic development. Cerebrospinal fluid shunts and radiation treatment do have a role as adjuncts to surgical exploration and biopsy, which are generally indicated since no preoperative test seems to grant an absolute diagnosis. The opinion that chiasmal tumors should not be treated at all is not shared. When the treatment of an illness falls as far short of the ultimate, as does the therapy of neoplastic disease, then it is necessary to reconsider frequently the principles upon which it is based and the results it achieves. These results are two-fold, curative and palliative and, while our efforts are directed toward the former, we realize only too frequently that the best results will sometimes lie in palliation. The disappointment in accepting this lesser goal must not allow us to underestimate its importance or neglect the help it may give.

Opto-chiasmatic arachnoiditis: A review of traditional neuroradiological diagnosis (82 cases, 1951–1976)

SummaryA retrospective appraisal of traditional neuroradiological techniques (such as direct röntgenograms, cerebral angiography RISA-cisternography, and pneumo-cisterno-encephalography, as opposed to the “new” technique of computer-assisted tomography) was carried out in a series of 82 cases of opto-chiasmatic arachnoiditis, all surgically verified. It is concluded that none of these examinations can provide a reliable diagnosis of opto-chiasmatic arachnoiditis, which preoperatively can only be a tentative diagnosis that becomes final only when confirmed by surgical findings. In the presence of certain progressive neuro-ophthalmological symptoms and signs, a negative neuro-radiological investigation should not deter the neurosurgeon from exploring the chiasmatic region. Computer-assisted tomography, of which the authors have no personal experience in these cases, may hold the future answer to the diagnostic problem.

Tuberculosis and the anterior optic pathways

Sixteen patients (one with tuberculoma of the anterior optic pathways, the other 15 with opto-chiasmatic arachnoiditis) are presented. They are divided into three categories (definite, likely, possible) from the point of view of the pathogenetic link of their optic pathology with a primary tuberculous infection. Neurosurgical treatment had a positive effect upon the visual symptoms in five patients (31.25%), no effect in three cases (18.75%); in the other eight patients (50%) it could not prevent progression of visual impairment.

Opto-Chiasmatic Arachnoiditis in the Young

14 young patients, operated upon for opto-chiasmatic arachnoiditis by craniotomy are presented. 2 main etiopathogenetic forms (and their respective clinical equivalents) of the disease could be recognized. Only 1 postoperative death occurred, in a patient with a dominant clinical picture of intracranial hypertension. Results of surgery (craniotomy and lysis of adhesions) could be distinguished as positive (functional improvement) in 5 cases, indifferent or negative in the others, with a follow-up duration of up to 23 years. The role of the diagnostic value of the pneumoencephalogram as a basis for surgical indication is discussed: it is felt that this examination, when reported as negative, is not of sufficient value to rule out the diagnosis, which must essentially rely upon clinical data.

Exophthalmos from vascular orbital and retro-orbital lesions:Neurosurgical experience of 84 cases, 1951-1976

A series of 84 patients with exophthalmos caused by vascular lesions, or neoplastic lesions with a predominant vascular component, is discussed. All patients, observed in the period before CT scan, were investigated by traditional neuroradio-logical techniques, notably angiographic ones (carotid arteriogram and orbital phlebogram). In several cases, cerebral vascular lesions such as saccular aneurysms and arterio-venous malformations, cerebral angiomas and uncommon arterio-venous shunts, were the cause of the exophthalmos. The case is argued for the continuing importance of both types of angiographic examination, especially cerebral angiography, in the investigation of exophthalmos after ‘non-invasive’ techniques (CT scan, ultrasonography) have allowed a preliminary screening and established a firmer indication for ‘invasive’ examinations.