Stefano Telera

Brain metastases from solid tumors: disease outcome according to type of treatment and therapeutic resources of the treating center

BackgroundTo evaluate the therapeutic strategies commonly employed in the clinic for the management of brain metastases (BMs) and to correlate disease outcome with type of treatment and therapeutic resources available at the treating center.MethodsFour Cancer centres participated to the survey. Data were collected through a questionnaire filled in by one physician for each centre.ResultsClinical data regarding 290 cancer patients with BMs from solid tumors were collected. Median age was 59 and 59% of patients had ≤ 3 brain metastases. A local approach (surgery and stereotactic radiosurgery) was adopted in 31% of patients. The local approach demonstrated to be superior in terms of survival compared to the regional/systemic approach (whole brain radiotherapy and chemotherapy, p = <.0001 for survival at 2 years). In the multivariate analysis local treatment was an independent prognostic factor for survival. When patients were divided into 2 groups whether they were treated in centers where local approaches were available or not (group A vs group B respectively, 58% of patients with ≤ 3 BMs in both cohorts), more patients in group A received local strategies although no difference in time to brain progression at 1 year was observed between the two groups of patients.ConclusionsIn clinical practice, local strategies should be integrated in the management of brain metastases. Proper selection of patients who are candidate to local treatments is of crucial importance.

Treatment and outcome of advanced external auditory canal and middle ear squamous cell carcinoma.

This is a retrospective study to evaluate the outcomes and complications of combined treatment, surgery with or without adjunctive intraoperative radiotherapy, of locally advanced temporal bone squamous cell carcinoma. A series of 17 patients with locally advanced squamous cell carcinoma of the temporal bone were treated between September 2002 and February 2007. Eleven patients had primary tumors, and 6 patients had recurrences. According to the University of Pittsburgh staging system, 5 patients were stage II (T2 N0), 6 patients were stage III (5, T3 N0 and 1, T1 N1), and 6 patients were stage IV (5, T3 N2b and 1, T4 N0). All patients underwent lateral temporal bone resection and pedicle flap reconstruction. Eight patients received intraoperative and postoperative radiotherapies, 4 patients underwent postoperative radiation alone, whereas 5 patients did not receive any adjunctive treatment. Median follow-up was 29.5 months. No major complications were observed. No patients were found to have residual gross tumor. Disease-free survival was 73.3%, and overall survival was 75.6%. Radical external auditory canal and/or middle ear canal resection is of utmost importance to obtain a good surgical outcome. Postoperative radiotherapy is necessary to obtain good local control; no major adverse effects were observed in the intraoperative radiotherapy patients. The incidence of major complication is minimal after pedicle flap reconstruction.

Treatment of recurrent malignant gliomas with fotemustine monotherapy: impact of dose and correlation with MGMT promoter methylation

BackgroundIn recurrent malignant gliomas (MGs), a high rate of haematological toxicity is observed with the use of fotemustine at the conventional schedule (100 mg/m2 weekly for 3 consecutive weeks followed by triweekly administration after a 5-week rest period). Also, the impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status on fotemustine activity has never been explored in the clinical setting.Methods40 patients with recurrent pretreated MG were identified as being treated with fotemustine at doses ranging from 65 mg/m2 to 100 mg/m2. Patients were classified into 3 groups according to the dose of fotemustine received, from the lowest dosage received in group A, to the highest in group C. Analysis of MGMT promoter methylation in tumor tissue was successfully performed in 19 patients.ResultsOverall, 20% of patients responded to treatment, for a disease control rate (DCR, responses plus stabilizations) of 47.5%. Groups A and B experienced a response rate of 40% and 26.5% respectively, while the corresponding value for group C was 10%. Out of 19 patients, MGMT promoter was found methylated in 12 cases among which a DCR of 66.5% was observed. All 7 patients with unmethylated MGMT promoter were progressive to fotemustine.ConclusionLow-dose fotemustine at 65–75 mg/m2 (induction phase) followed by 75–85 mg/m2 (maintenance phase) has an activity comparable to that of the conventional schedule. By determination of the MGMT promoter methylation status patients might be identified who are more likely to benefit from fotemustine chemotherapy.

Unilateral limited laminectomy as the approach of choice for the removal of thoracolumbar neurofibromas

Study Design. The paper reports a minimally invasive approach to the dorsolumbar spine for the removal of neurofibromas. Objectives. Demonstrating that a limited unilateral approach is the one of choice for this kind of tumors. Summary of Background Data. Spinal intradural extramedullary tumors are generally removed by single-level or multilevel laminectomy with midline dural incision. Cases of delayed postoperative kyphosis and spinal instability (6%) may be reduced by unilateral microsurgery, causing minimum damage to ligaments and joints. Methods. Ten patients with dorsolumbar neurofibroma were operated on between June 2000 and June 2002. There were 5 males (all with lumbar) and 5 females (2 with lumbar and 3 with inferior dorsal neurofibromas). One female had 3 lumbar tumors and required two operations. Surgery was performed in the prone position with a unilateral approach, sparing the joint and the ligamentum interspinosum. The dura was opened paramedially and the tumor dissected from the root and removed in one piece when possible. Water-tight dural closure was done with 5–0 or 6–0 stitches. Results. All the patients were mobilized on day 2 and discharged on day 4 or day 5. No complications resulting from the technique were observed. Static and dynamic plain radiograph films showed that none of them had kyphosis and/or instability 6 months postoperatively. Neurologic results were good. Conclusions. Hospital stay may be reduced and stability may be preserved with an appropriate microsurgical technique. The technique reported in the paper should thus become the one of choice and extended to other spinal intradural extramedullary tumors.

Epigenetic silencing of miR-145-5p contributes to brain metastasis.

Brain metastasis is a major cause of morbidity and mortality of lung cancer patients. We assessed whether aberrant expression of specific microRNAs could contribute to brain metastasis. Comparison of primary lung tumors and their matched metastatic brain disseminations identified shared patterns of several microRNAs, including common down-regulation of miR-145-5p. Down-regulation was attributed to methylation of miR-145s promoter and affiliated elevation of several protein targets, such as EGFR, OCT-4, MUC-1, c-MYC and, interestingly, tumor protein D52 (TPD52). In line with these observations, restored expression of miR-145-5p and selective depletion of individual targets markedly reduced in vitro and in vivo cancer cell migration. In aggregate, our results attribute to miR-145-5p and its direct targets pivotal roles in malignancy progression and in metastasis.

Surgery of malignant gliomas: advances and perspectives

Purpose of review One of the most controversial issues in the combined treatment of malignant gliomas is the role of surgical resection, even though the relevance of surgery in obtaining tissue diagnosis and alleviating clinical symptoms is well defined; more debated is the importance of radical surgery in improving the patient final outcome. This review aims to present an overview of the recommendations for surgical treatment of malignant gliomas, and to describe the potential role of locoregional treatments. Recent findings An increasing series of data are being collected in favour of radical surgical removal, with the support of intraoperative imaging and fluorescence guide. More controversial, but theoretically relevant, are the experiences of locoregional treatments, mainly in the contest of present combined modality treatments; different interesting approaches are being studied, without any significant therapeutical advantage in phase III studies, and only biodegradable carmustine wafers entered in the clinical practice. Summary The gold standard of surgical treatment of malignant gliomas has to include well tolerated and radical tumour removal, taking advantage of the introduction of new technological tools. The future role of neurosurgical treatment of malignant glioma is linked to intratumoural administration of antiblastic agents and the development of more efficient delivery systems; localized therapies have to be considered in a well defined multistep therapeutic strategy.

Spontaneous cerebrospinal fluid rhinorrhea as the presenting symptom of sellar pathologies: three demonstrative cases

Spontaneous rhinorrhea due to sellar pathologies is a rare and insidious disease that may represent a diagnostic challenge. Since the precipitating cause is not apparent in most patients, delayed diagnosis and/or improper treatments are not uncommon and may be detrimental for the patients. The precise mechanisms of such rhinorrhea are still incompletely understood. Proposed etiological factors include constant cerebrospinal fluid pulsations against the anterior skull base trasmitted by primitive or acquired arachnoid invaginations in combination with either elevated ICP or congenital/pathologic erosions of sellar and parasellar bone structures. Advances in the diagnosis and surgical techniques have recently modified the decision-making approach to this pathology. The present paper reports three unusual cases of sellar pathologies revealed by rhinorrhea as the first symptom discussing controversial issues on pathogenesis, complications and current management of this kind of fistula.

Unilateral Laminectomy Approach for the Removal of Spinal Meningiomas and Schwannomas: Impact on Pain, Spinal Stability, and Neurologic Results

BACKGROUND Spinal intradural tumors are usually removed with laminectomy/laminotomy with a midline dural incision. Pain, discomfort, postoperative kyphosis, and instability may be minimized with unilateral microsurgery. METHODS Seventy patients with schwannoma (73 tumors) and 27 patients with meningioma (29 tumors) were operated on with unilateral hemilaminectomy (June 2000 to March 2014). Surgery was generally kept to 1 or 2 levels, removing all the craniocaudal ligamentum flavum. Careful radioscopic identification is mandatory; in thoracolumbar schwannomas, the tumor may be mobile; in the prone position, it may move cranially than appears on magnetic resonance imaging. The dura was opened paramedially, and the tumor was dissected and removed either en bloc or piecemeal after ultrasonic debulking. Neurophysiologic monitoring was performed. The tumor was approached tangentially with no cord rotation or minimal manipulation. Average duration of surgery was 160 minutes (100-320 minutes). Removal was total in 72 of 73 schwannomas; Simpson grade was 1 in 10 meningiomas and 2 in 19. RESULTS Patients with no complications were discharged on day 5-7. Ten patients had orthostatic headaches; 2 had pseudomeningocele that required reoperation. Pain improvement (Dennis Scale) was significant either at discharge or at follow-up (P < 0.0001 schwannomas, P < 0.001 meningiomas). Neurologic results (McCormick Scale, Karnofsky Performance Score) were excellent/good: of 39 patients with preoperative neurologic impairment, 19 recovered completely, 17 had minor spasticity, and 3 had moderate spasticity but autonomous ambulation. Sphincters recovered in 5 of 10 patients At follow-up, average Karnofsky Performance Score improved from 60 to 90 (P < 0.0001) and the McCormick score decreased from 121 to 55 (P < 0.0001). No spinal instability was observed. CONCLUSIONS Neurologic and oncologic results were good and postoperative pain and discomfort were reduced. Stability was preserved with a unilateral technique. No bracing was necessary, permitting early rehabilitation.

Symptomatic Spinal Cord Necrosis After Irradiation for Vertebral Metastatic Breast Cancer

Cerebral radionecrosis is a well known but infrequent complication that may occur after undergoing whole-brain radiotherapy (RT) and/or radiosurgery. Although quite rare, spinal cord radionecrosis is a feared complication after irradiation of the spine for metastatic disease. Current understanding of factors affecting the spinal cord’s tolerance to radiation is still not completely known. There may be mechanisms combining either radiotoxic potential or glucocorticoid/ alkylating agents that induce vasculitis. Those factors include radiation dose per fraction, total radiation dose, and interfraction interval. In addition, recent technological advances in radiosurgery deliver more aggressive hypofractionated doses adjacent to the spinal cord. The estimated risk of myelopathy has been calculated as lower than 1% and 10% at 54 and 61 Gy, respectively, when using conventional fractionation of 1.8 to 2 Gy/fraction to the spinal cord. Reports of myelopathy after stereotactic radiosurgery to spinal lesions are rare. The maximum dose delivered should be limited to 13 Gy in a single fraction or 20 Gy in three fractions. Recently, myelopathy has been reported in six of 1,075 patients receiving cyber knife radiosurgery for benign or malignant spinal tumors. In this report, radiation injury occurred over a spectrum of dose parameters that prevented identification of specific dosimetric factors. During 2008, we observed two female patients who developed severe neurologic impairment due to spinal cord lesions after undergoing irradiation of the spine for metastatic breast cancer. The first patient, age 61 years, had a cervical enhancing lesion on the right portion of the C5-C6 spinal cord. She underwent a right quadrantectomy in 2003, followed by chemotherapy and RT for breast cancer. In October 2007, the patient was referred to undergo irradiation (21 Gy fractioned in three doses) and medical therapy with zoledronic acid (Zometa, Novartis Pharmaceuticals UK, Horsham, United Kingdom) for cervical metastases. In June 2008, a magnetic resonance imaging (MRI) scan showed a 2-cm right paramedian intramedullary lesion at C3-C6. A moderate dimensional increase of the lesion was observed after 3 months. A total-body computed tomography scandidnotdemonstrateanyothersystemic lesions.FromOctober2008, the patient experienced a progressive decline in neurological function: at firstmotordeficitanddysesthesia intherightarmfollowedbyprogressive worsening of ambulatory deficit, due to leg paresis. A neurologic examination at admission revealed Brown-Sequard syndrome, right hemiparesis, policynetic reflexes on the right side, ipo-anesthesia with a D4 level on the left side. Autonomous ambulation was not possible. At a new MRI, the lesion appeared hypo in T1, hyperT2, and displayed focal contrast enhancement.

Malignant peripheral nerve sheath tumors of the lateral skull base.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive spindle cell tumors that develop from peripheral nerve sheath cells and account for 5% of all soft tissue sarcomas. MPNSTs involving the lateral skull base are an extremely rare subgroup of these lesions. The article deals with the case of a 51-year-old man with a huge primary MPNST: the disease involved the left frontozygomatic and retroauricolar regions of the scalp with erosion of the outer table of the calvaria and diffuse infiltration of the temporal, infratemporal, and pterygoid fossae. Radical surgery via left transfacial- transparotid approach and reconstruction with microvascular flap were performed. Intraoperative radiotherapy and postoperative radiotherapy were also delivered. Twenty-two months postoperatively, the patient is alive despite recurrence of the tumor in the neck and lung metastases. The article reviews the few series of patients and the small number of case reports of MPNSTs involving the lateral skull base that are available in the English literature describing current concept of pathophysiology, diagnosis, and management of the disease. Although MPNSTs of the lateral skull base have an adverse prognosis, an acceptable survival time and a good quality of life are possible; however, they require an early and correct diagnosis as well as an adequate and aggressive combination therapy.