Assessment of prognostic factors in patients with metastatic epidural spinal cord compression (MESCC) from solid tumor after surgery plus radiotherapy: a single institution experience.

PURPOSE: To identify potential prognostic factors predicting functional outcome and survival after surgery followed by radiotherapy for metastatic spinal cord compression due to solid tumors. METHODS: 531 consecutive patients with metastatic epidural spinal cord compression (MESCC) were treated at our institution. Surgery followed by radiation therapy was performed in 151 patients (30%) with various histological diagnoses. Three different surgical procedures were performed: minimal resection with or without instrumented fixation, curettage, and total tumorectomy. Within 1 month after surgery, RT was performed, delivering a total dose of 30-36 Gy (3 Gy per fraction). Ten potential prognostic factors were investigated for relationship with functional outcome and survival. RESULTS: Clinical remission of pain was obtained in 91% of patients and 94 (62.5%) had recovery of neurological deficit. Recurrence in the same site of treatment occurred in nine (6%) patients. Median survival was 14 months (range 0-52 months); OS at 1, 2, and 3 years was 43.6, 37, and 21.5%, respectively. Survival was significantly associated with the histology of primary tumor (P < 0.001) and visceral metastases (P < 0.001) in the whole group; for histology, the prognostic factors statistically significant were other bone metastases in breast cancer, control of primary tumor, and the absence of visceral metastases in NSCLC and kind of surgery in the other. CONCLUSIONS: The key element for successful treatment of MESCC is multidisciplinary care of the patient, which includes all of those prognostic factors that have been, until now, analyzed and compared. In our set of patients treated for vertebral metastases, PS, time to development of symptoms, and the presence of visceral metastases affected functional outcome and survival.

Early surgical experience with minimally invasive percutaneous approach for patients with metastatic epidural spinal cord compression (MESCC) to poor prognoses.

PURPOSE: This study was designed to assess the impact of minimally invasive surgery (MIS) for the treatment of patients with metastatic epidural spinal cord compression (MESCC) and vertebral body fracture, in terms of feasibility, clinical improvement, and morbidity. METHODS: Twenty-five consecutive patients with diagnosis of MESCC from solid primary tumors were treated between January 2008 and June 2010 at our institution. All patients, after multidisciplinary assessment, were considered with poor prognosis because of their disease's extension and/or other clinical conditions. Mini-invasive percutaneous surgery was performed in all patients followed by radiotherapy within 2 weeks postoperatively. Clinical outcome was evaluated by modified visual analog scale for pain, Frankel Scale for neurologic deficit, and magnetic resonance imaging or computed tomography scan. RESULTS: Clinical remission of pain was obtained in the vast majority of patients (96%). Improvement of neurological deficit was observed in 22 patients (88%). No major morbidity or perioperative mortality occurred. The average hospital stay was 6 days. Local recurrence occurred in two patients (8%). Median survival was 10 (range, 6-24) months. Overall survival at 1 year was 43%. CONCLUSIONS: For patients with MESCC and body fracture, with limited life expectancy, minimally invasive spinal surgery followed by radiotherapy, is feasible and provides clinical benefit in most of patients, with low morbidity. We believe that a minimally invasive approach can be an alternative surgical method compared with more aggressive or demanding procedures, which in selected patients with metastatic spinal cord compression with poor prognosis could represent overtreatment.

Vertebral metastases reirradiation with volumetric-modulated arc radiotherapy.

PURPOSE: To assess the feasibility, acute toxicity, clinical improvement, local control and survival for spinal metastatic patients re-irradiated using volumetric-modulated-arc-radiotherapy (VMAT). METHODS AND MATERIALS: Between February 2009 and November 2010, 31 patients were treated. Surgery was performed in six before re-irradiation. The clinical target volume (CTV) was defined as the whole vertebrae with recurrence excluding the central section of spinal canal. Planning target volume was defined as CTV+0-5mm in the three directions. Dose was prescribed in order to have biological equivalent dose to the spinal cord from the two courses lower than 120 Gy(2) to 1 cc of the volume. Clinical improvement, toxicity and recurrence were evaluated. All patients had back pain before treatment and 15 (48%) neurological deficit. RESULTS: Clinical remission of pain was obtained in 29 patients (93%). Neurological improvement was observed in 73% of patients. No acute or late toxicities were recorded. No recurrence occurred. Median survival was 10 months (range 6-24). At the last follow-up 19 patients (61%) were alive and 12 (39%) dead from systemic disease progression. The 1 and 2 year survival were 55% and 35%, respectively. CONCLUSION: In patients with spinal metastases recurrence re-irradiation with VMAT is feasible and provides clinical benefit in most patients.

A role for the transcription factor HEY1 in glioblastoma.

Abstract Glioblastoma multiforme (GBM), the highest-grade glioma, is the most frequent tumour of the brain with a very poor prognosis and limited therapeutic options. Although little is known about the molecular mechanisms that underlie glioblastoma formation, a number of signal transduction routes, such as the Notch and Ras signalling pathways, seem to play an important role in the formation of GBM. In the present study, we show by in situ hybridization on primary tumour material that the transcription factor HEY1, a target of the Notch signalling pathway, is specifically up-regulated in glioma and that expression of HEY1 in GBM correlates with tumour-grade and survival. In addition, we show by chromatin immunoprecipitations, luciferase assays and Northern blot experiments that HEY1 is a bona fide target of the E2F family of transcription factors, connecting the Ras and Notch signalling pathways. Finally, we show that ectopic expression of HEY1 induces cell proliferation in neural stem cells, while depletion of HEY1 by RNA interference reduces proliferation of glioblastoma cells in tissue culture. Together, these data imply a role for HEY1 in the progression of GBM, and therefore we propose that HEY1 may be a therapeutic target for glioblastoma patients. Moreover, HEY1 may represent a molecular marker to distinguish GBM patients with a longer survival prognosis from those at high risk.

Fractal dimension as a quantitator of the microvasculature of normal and adenomatous pituitary tissue.

It is well known that angiogenesis is a complex process that accompanies neoplastic growth, but pituitary tumours are less vascularized than normal pituitary glands. Several analytical methods aimed at quantifying the vascular system in two-dimensional histological sections have been proposed, with very discordant results. In this study we investigated the non-Euclidean geometrical complexity of the two-dimensional microvasculature of normal pituitary glands and pituitary adenomas by quantifying the surface fractal dimension that measures its space-filling property. We found a statistical significant difference between the mean vascular surface fractal dimension estimated in normal versus adenomatous tissues (P = 0.01), normal versus secreting adenomatous tissues (P = 0.0003), and normal versus non-secreting adenomatous tissues (P = 0.047), whereas the difference between the secreting and non-secreting adenomatous tissues was not statistically significant. This study provides the first demonstration that fractal dimension is an objective and valid quantitator of the two-dimensional geometrical complexity of the pituitary gland microvascular network in physiological and pathological states. Further studies are needed to compare the vascular surface fractal dimension estimates in different subtypes of pituitary tumours and correlate them with clinical parameters in order to evaluate whether the distribution pattern of vascular growth is related to a particular state of the pituitary gland.

Calvarial metastases as clinical presentation of renal cell carcinoma: report of two cases and review of the literature.

Calvarium is a frequent target site of involvement for common neoplasms. Some cases of calvarial metastases have been reported in literature as secondary lesions from renal cell carcinoma (RCC), but only five cases have been described concerning calvarial mass as the first clinical presentation of this kind of tumor. In this report, we discuss the clinical aspects of two further cases we observed, in which the renal cell carcinoma was found thanks to the histological examination of a calvarial mass after surgery. We also briefly review the literature.