Showing papers by "Giuseppe Minniti published in 2011"

Stereotactic radiosurgery for brain metastases: Analysis of outcome and risk of brain radionecrosis

Abstract: to investigate the factors affecting survival and toxicity in patients treated with stereotactic radiosurgery (SRS), with special attention to volumes of brain receiving a specific dose (V10 - V16 Gy) as predictors for brain radionecrosis. Two hundred six consecutive patients with 310 cerebral metastases less than 3.5 cm were treated with SRS as primary treatment and followed prospectively at University of Rome La Sapienza Sant'Andrea Hospital. Overall survival, brain control, and local control were estimated using the Kaplan-Meier method calculated from the time of SRS. Univariate and multivariate analysis using a Cox proportional hazards regression model were performed to determine the predictive value of prognostic factors for treatment outcome and SRS-related complications. Median overall survival and brain control were 14.1 months and 10 months, respectively. The 1-year and 2-year survival rates were 58% and 24%, and respective brain control were 43% and 22%. Sixteen patients recurred locally after SRS, with 1-year and 2-year local control rates of 92% and 84%, respectively. On multivariate analysis, stable extracranial disease and KPS >70 were associated with the most significant survival benefit. Neurological complications were recorded in 27 (13%) patients. Severe neurological complications (RTOG Grade 3 and 4) occurred in 5.8% of patients. Brain radionecrosis occurred in 24% of treated lesions, being symptomatic in 10% and asymptomatic in 14%. On multivariate analysis, V10 through V16 Gy were independent risk factors for radionecrosis, with V10 Gy and V12 Gy being the most predictive (p = 0.0001). For V10 Gy >12.6 cm3 and V12 Gy >10.9 cm3 the risk of radionecrosis was 47%. SRS alone represents a feasible option as initial treatment for patients with brain metastases, however a significant subset of patients may develop neurological complications. Lesions with V12 Gy >8.5 cm3 carries a risk of radionecrosis >10% and should be considered for hypofractionated stereotactic radiotherapy especially when located in/near eloquent areas.

Correlation between O6-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide

Abstract: Epigenetic silencing of the O6-methylguanine-DNA-methyltransferase (MGMT) gene by promoter methylation is correlated with improved progression-free survival (PFS) and overall survival (OS) in adult patients with newly diagnosed glioblastoma multiforme (GBM) who receive alkylating agents. The aim of this study is to determine the correlation between MGMT and survival in elderly patients with GBM treated with radiotherapy (RT) and temozolomide (TMZ). Eighty-three patients aged 70 years or older with histologically confirmed GBM treated with RT plus TMZ between February 2005 and September 2009 were investigated in this study. The methylation status of the MGMT promoter was determined by polymerase chain reaction analysis. Median PFS and OS were 7.5 and 12.8 months, respectively. The MGMT promoter was methylated in 42 patients (50.6%) and unmethylated in 41 patients (49.4%). Median OS was 15.3 months in methylated patients and 10.2 months in unmethylated patients (P = 0.0001). Median PFS was 10.5 months in methylated tumors and 5.5 months in unmethylated tumors (P = 0.0001). On multivariate analysis MGMT methylation status emerged as the strongest independent prognostic factor for OS and PFS (P = 0.004 and P = 0.005, respectively). The results of the present study suggest that MGMT methylation status might be an important prognostic factor associated with better OS and PFS in elderly patients with GBM treated with RT and TMZ.

Fractionated stereotactic reirradiation and concurrent temozolomide in patients with recurrent glioblastoma

Abstract: The aim of this paper is to evaluate the efficacy of fractionated stereotactic radiotherapy (FSRT) and concomitant temozolomide (TMZ) as a salvage treatment option in patients with recurrent glioblastoma (GBM). Between May 2006 and December 2009, 36 patients with recurrent GBM received FSRT plus concomitant TMZ at University of Rome La Sapienza, Sant' Andrea Hospital. All patients had Karnofsky performance score ≥60 and were previously treated with standard conformal radiotherapy (RT) (60 Gy) with concomitant and adjuvant TMZ for 6-12 cycles. The median time interval between primary RT and reirradiation was 14 months. At the time of recurrence, all patients received FSRT plus concomitant daily TMZ at the dose of 75 mg/m(2), given 7 days per week from the first day of RT. Radiation dose was 37.5 Gy delivered in 15 fractions over 3 weeks. Median overall survival after FSRT was 9.7 months, and the 6- and 12-month survival rates were 84 and 33%, respectively. The median progression-free survival (PFS) was 5 months, and 6- and 12-month PFS rates were 42 and 8%, respectively. In univariate analysis, KPS (P = 0.04), the interval between primary RT and reirradiation (P = 0.02), and O6-methylguanine-DNA-methyltransferase (MGMT) methylation status at the time of diagnosis (P = 0.009) had an effect on survival; however, in multivariate analysis, only MGMT methylation was statistically significant (P = 0.03). In general, FSRT was well tolerated and the treatment was completed in all patients. Neurological deterioration due to radiation-induced necrosis occurred in three patients (8%). FSRT plus concomitant TMZ is a feasible treatment option associated with survival benefits and low risk of complications in selected patients with recurrent GBM. The potential advantages of combined chemoradiation schedules in patients with recurrent GBM need to be explored in future studies.

Fractionated stereotactic conformal radiotherapy for large benign skull base meningiomas

Abstract: to assess the safety and efficacy of fractionated stereotactic radiotherapy (FSRT) for large skull base meningiomas. Fifty-two patients with large skull base meningiomas aged 34-74 years (median age 56 years) were treated with FSRT between June 2004 and August 2009. All patients received FSRT for residual or progressive meningiomas more than 4 centimeters in greatest dimension. The median GTV was 35.4 cm3 (range 24.1-94.9 cm3), and the median PTV was 47.6 cm3 (range 33.5-142.7 cm3). Treatment volumes were achieved with 5-8 noncoplanar beams shaped using a micromultileaf collimator (MLC). Treatment was delivered in 30 daily fractions over 6 weeks to a total dose of 50 Gy using 6 MV photons. Outcome was assessed prospectively. At a median follow-up of 42 months (range 9-72 months) the 3-year and 5-year progression-free survival (PFS) rates were 96% and 93%, respectively, and survival was 100%. Three patients required further debulking surgery for progressive disease. Hypopituitarism was the most commonly reported late complication, with a new hormone pituitary deficit occurring in 10 (19%) of patients. Clinically significant late neurological toxicity was observed in 3 (5.5%) patients consisting of worsening of pre-existing cranial deficits. FSRT as a high-precision technique of localized RT is suitable for the treatment of large skull base meningiomas. The local control is comparable to that reported following conventional external beam RT. Longer follow-up is required to assess long term efficacy and toxicity, particularly in terms of potential reduction of treatment-related late toxicity.

Frameless linac-based stereotactic radiosurgery (SRS) for brain metastases: analysis of patient repositioning using a mask fixation system and clinical outcomes

Abstract: To assess the accuracy of patient repositioning and clinical outcomes of frameless stereotactic radiosurgery (SRS) for brain metastases using a stereotactic mask fixation system. One hundred two patients treated consecutively with frameless SRS as primary treatment at University of Rome Sapienza Sant'Andrea Hospital between October 2008 and April 2010 and followed prospectively were involved in the study. A commercial stereotactic mask fixation system (BrainLab) was used for patient immobilization. A computerized tomography (CT) scan obtained immediately before SRS was used to evaluate the accuracy of patient repositioning in the mask by comparing the isocenter position to the isocenter position established in the planning CT. Deviations of isocenter coordinates in each direction and 3D displacement were calculated. Overall survival, brain control, and local control were estimated using the Kaplan-Meier method calculated from the time of SRS. The mean measured isocenter displacements were 0.12 mm (SD 0.35 mm) in the lateral direction, 0.2 mm (SD 0.4 mm) in the anteroposterior, and 0.4 mm (SD 0.6 mm) in craniocaudal direction. The maximum displacement of 2.1 mm was seen in craniocaudal direction. The mean 3D displacement was 0.5 mm (SD 0.7 mm), being maximum 2.9 mm. The median survival was 15.5 months, and 1-year and 2-year survival rates were 58% and 24%, respectively. Nine patients recurred locally after SRS, with 1-year and 2-year local control rates of 91% and 82%, respectively. Stable extracranial disease (P = 0.001) and KPS > 70 (P = 0.01) were independent predictors of survival. Frameless SRS is an effective treatment in the management of patients with brain metastases. The presented non-invasive mask-based fixation stereotactic system is associated with a high degree of patient repositioning accuracy; however, a careful evaluation is essential since occasional errors up to 3 mm may occur.

Radiation techniques for acromegaly

Abstract: Radiotherapy (RT) remains an effective treatment in patients with acromegaly refractory to medical and/or surgical interventions, with durable tumor control and biochemical remission; however, there are still concerns about delayed biochemical effect and potential late toxicity of radiation treatment, especially high rates of hypopituitarism. Stereotactic radiotherapy has been developed as a more accurate technique of irradiation with more precise tumour localization and consequently a reduction in the volume of normal tissue, particularly the brain, irradiated to high radiation doses. Radiation can be delivered in a single fraction by stereotactic radiosurgery (SRS) or as fractionated stereotactic radiotherapy (FSRT) in which smaller doses are delivered over 5-6 weeks in 25-30 treatments. A review of the recent literature suggests that pituitary irradiation is an effective treatment for acromegaly. Stereotactic techniques for GH-secreting pituitary tumors are discussed with the aim to define the efficacy and potential adverse effects of each of these techniques.

Palonosetron for the prevention of chemotherapy-induced nausea and vomiting in glioblastoma patients treated with temozolomide: a phase II study

Abstract: Purpose Chemotherapy-induced nausea and vomiting (CINV) is a side effect related to administration of the adjuvant temozolomide (TMZ) in patients affected by glioblastoma. After chemoradiotherapy, adjuvant TMZ is administered as an oral multiple-day regimen, and TMZ-associated CINV may interfere with the continuation of chemotherapy, with potentially negative consequences on clinical efficacy. The aim of the present study was to investigate the efficacy of palonosetron for prevention of CINV-induced by adjuvant TMZ.

Hypofractionated Radiotherapy with or without IGRT in Prostate Cancer: Preliminary Report of Acute Toxicity

Abstract: Background: To evaluate the acute tolerance to hypofractionated schedule of patients with prostate cancer. Patients and Methods: We treated 62 patients with intermediate risk prostate cancer. All patients were treated with a total dose of 43.8 Gy on seminal vesicles and 54.75 Gy on prostate, 3.65 Gy per fraction, three times a week for a total of 5 weeks. All patients underwent neoadjuvant, concomitant and adjuvant hormonal therapy. Thirty-six patients were submitted to image-guided radiation therapy (IGRT). Results: Median follow-up was 15 months (range 3- 33 months). Toxicities during the treatment were: grade 1-2 gastrointestinal (GI) toxicity, 22.6%; grade 1-2 genitourinary (GU) toxicity, 51.6%. Toxicities 3 months after the end of the treatment were grade 1-2 GI 6.5%, grade 1-2 GU 9.7%. No statistical difference was observed comparing acute toxicity in patients treated with or without IGRT. Conclusion: This study showed that the hypofractionation schedule used is well tolerated, with a low rate of acute grade 1-2 GI toxicity and without major grade (≥3) acute toxicity. Longer follow- up is needed to determine if this low rate of acute toxicity will be translated in a low rate of late toxicity. The different sensitivity of different tissues to fractionation changes can be quantified through the α/β ratio in the linear- quadratic model (1). The α/β ratio parameter is an indication of the fractionation sensitivity of a particular cell type. In general α/β is high (≥10 Gy) for early-responding normal tissues (skin and mucosa) and most tumors and low (<5 Gy) for late-responding normal tissue (spinal cord and bone). One implication of different α/β ratios for tumor cells and normal tissue is that it may be possible to increase the therapeutic ratio. Specifically, if α/β for prostate cancer is lower than the nearby normal tissues, then therapeutic advantage can be gained by using fewer, larger fractions (2). In 1999, Brenner and Hall (3) calculated the α/β ratio of prostate tumor after radiotherapy, using the linear-quadratic model and the obtained α/β value was 1.5 Gy (95% confidence interval, CI=0.8-2.2 Gy). Another matter is the α/β of the rectum and bladder. The α/β values of the rectal late-responding tissues have been found to be between 3 and 6 Gy, most probably around 5 Gy (4-5). Hypofractionation would, thus, reduce early side effects (if overall treatment time is left constant) or this gain in therapeutic index could be used to shorten overall treatment time. If the prostate tumor α/β ratio is lower than that for late rectal tissues, hypofractionated therapies could be designed with larger dose/fraction, fewer fractions, but not shortening the overall treatment too drastically, in order to maintain acute toxicity rates. It has been suggested that much rectal injury is actually a result of acute toxicity, which would fit in with a high α/β value for late rectal injury (7, 8). According to these postulations, in 2007 we started a prospective study at our institution using an hypofractionated schedule (365 cGy for 15 fractions/3weeks) for patients with intermediate risk prostate cancer and here we have preliminarily analyzed the tolerance of this regimen in term of compliance and acute toxicity.