Showing papers by "Giuseppe Minniti published in 2014"

Fractionated stereotactic radiosurgery for patients with brain metastases

Abstract: Stereotactic radiosurgery (SRS) delivered in 2–5 fractions (multi-fraction SRS) has been employed in patients with brain metastases as an alternative to single-fraction SRS with the aim to reduce late radiation-induced toxicity while maintaining high local control rate. In the present study we have evaluated the efficacy and toxicity of multi-fraction SRS in patients with 1–3 brain metastases. Between March 2006 and October 2012, 135 patients (63 men and 72 women) with 171 brain metastases have been treated with multi-fraction SRS (3 × 9 Gy or 3 × 12 Gy). At a median follow-up of 11.4 months, 16 lesions recurred locally. The 1- and 2-year local control rates were 88 and 72 %, respectively. The 1- and 2-year survival rates were 57 and 25 %, and respective distant failure rates were 52 and 73 %. Seventy-eight percent of patients succumbed to their extracranial disease and 22 % died of progressive intracranial disease. Multivariate analysis showed that melanoma histology was predictive of local failure (p = 0.02; HR 6.1, 95 % CI 1.5–24). Specifically, the 1-year local control rates were 68 % for melanoma, 92 % for breast carcinoma, and 88 % for NSCLC, respectively. Stable extracranial disease (p = 0.004) and Karnofsky performance status (p = 0.01) were predictive of longer survival. Radiologic changes suggestive of radionecrosis occurred in 12 (7 %) out of 171 lesions, with an actuarial risk of 9 % at 1 year and 17 % at 2 years, respectively. In conclusion, multi-fraction SRS appears to be an effective and safe treatment modality for brain metastases. It may represent an alternative to single-dose SRS for patients with large lesions or lesions located near critical structures.

IDH1 mutation and MGMT methylation status predict survival in patients with anaplastic astrocytoma treated with temozolomide-based chemoradiotherapy

Abstract: Several molecular markers have been proposed as predictors of outcome in patients with high grade gliomas. We report a retrospective multicenter study of 97 consecutive adult patients with anaplastic astrocytoma (AA) treated with radiation therapy (RT) plus concomitant and adjuvant temozolomide (TMZ) between October 2004 and March 2012. Correlations between the isocitrate dehydrogenase 1 (IDH1) mutation and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. At a median follow-up time of 46 months (range 12–89 months), median and 5-year overall survival rates were 50.5 months (95 % CI, 37.8–63.2) and 38 % (95 % CI, 25.7–50.7 %), and median and 5-year progression-free survival rates were 36 months (95 % CI, 28.5–44.0) and 22 % (95 % CI, 10–34 %), respectively. IDH1 mutation and MGMT promoter methylation were present in 54 and 60 % of evaluable patients, respectively. Multivariate Cox proportional hazards regression analysis showed that IDH1 mutation (P = 0.001), MGMT methylation (P = 0.01), age < 50 years (P = 0.02), and extent of resection (P = 0.04) were significantly associated with longer survival. Our study confirms the favorable prognostic value of IDH1 mutation and MGMT methylation in patients with AA treated with RT plus concomitant and adjuvant TMZ. The superiority of combined radiochemotherapy over other treatment modalities remains to be demonstrated.

Cytokines, fatigue, and cutaneous erythema in early stage breast cancer patients receiving adjuvant radiation therapy.

Abstract: We investigated the hypothesis that patients developing high-grade erythema of the breast skin during radiation treatment could be more likely to present increased levels of proinflammatory cytokines which may lead, in turn, to associated fatigue. Forty women with early stage breast cancer who received adjuvant radiotherapy were enrolled from 2007 to 2010. Fatigue symptoms, erythema, and cytokine levels (IL-1β, IL-2, IL6, IL-8, TNF-α, and MCP-1) were registered at baseline, during treatment, and after radiotherapy completion. Seven (17.5%) patients presented fatigue without associated depression/anxiety. Grade ≥2 erythema was observed in 5 of these 7 patients. IL-1β, IL-2, IL-6, and TNF-α were statistically increased 4 weeks after radiotherapy (P < 0.05). After the Heckman two-step analysis, a statistically significant influence of skin erythema on proinflammatory markers increase (P = 0.00001) was recorded; in the second step, these blood markers showed a significant impact on fatigue (P = 0.026). A seeming increase of fatigue, erythema, and proinflammatory markers was observed between the fourth and the fifth week of treatment followed by a decrease after RT. There were no significant effects of hormone therapy, breast volume, and anemia on fatigue. Our study seems to suggest that fatigue is related to high-grade breast skin erythema during radiotherapy through the increase of cytokines levels.

Fractionated stereotactic radiosurgery for patients with skull base metastases from systemic cancer involving the anterior visual pathway.

Abstract: Background: To analyze the tumor control, survival outcomes, and toxicity after stereotactic radiosurgery (SRS) for skull base metastases from systemic cancer involving the anterior visual pathway. Patients and methods: We have analyzed 34 patients (23 females and 11 males, median age 59 years) who underwent multi-fraction SRS for a skull base metastasis compressing or in close proximity of optic nerves and chiasm. All metastases were treated with frameless LINAC-based multi-fraction SRS in 5 daily fractions of 5 Gy each. Local control, distant failure, and overall survival were estimated using the Kaplan-Meier method calculated from the time of SRS. Prognostic variables were assessed using log-rank and Cox regression analyses. Results: At a median follow-up of 13 months (range, 2–36.5 months), twenty-five patients had died and 9 were alive. The 1-year and 2-year local control rates were 89% and 72%, and respective actuarial survival rates were 63% and 30%. Four patients recurred with a median time to progression of 12 months (range, 6–27 months), and 17 patients had new brain metastases at distant brain sites. The 1-year and 2-year distant failure rates were 50% and 77%, respectively. On multivariate analysis, a Karnofsky performance status (KPS) >70 and the absence of extracranial metastases were prognostic factors associated with lower distant failure rates and longer survival. After multi-fraction SRS, 15 (51%) out of 29 patients had a clinical improvement of their preexisting cranial deficits. No patients developed radiation-induced optic neuropathy during the follow-up. Conclusions: Multi-fraction SRS (5 x 5 Gy) is a safe treatment option associated with good local control and improved cranial nerve symptoms for patients with a skull base metastasis involving the anterior visual pathway.

Chemoradiation for anaplastic oligodendrogliomas: clinical outcomes and prognostic value of molecular markers

Abstract: Combination of procarbazine, lomustine and vincristine (PCV) with radiation therapy (RT) has been associated with longer survival in patients with anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA), especially in those with chromosome 1p/19q codeletion. We report a multicenter retrospective study of 84 consecutive adult patients with AO and AOA treated with RT plus concomitant and adjuvant temozolomide (TMZ) between February 2004 and January 2011. Correlations between chromosome 1p/19q codeletion, isocitrate dehydrogenase1 (IDH1) mutation, and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. For all 84 patients the median overall survival (OS) and progression-free survival rates were 55.6 and 45.2 months, respectively. Grade 3 or 4 hematological toxicity occurred in 17 % of patients. Chromosome 1p/19q codeletion was detected in 57 %, IDH1 mutation in 63 %, and MGMT promoter methylation in 74 % of evaluable patients. In multivariate analysis the presence of chromosome 1p/19q codeletion was associated with significant survival benefit (median OS 34 months in noncodeleted tumors and not reached in codeleted tumors; HR 0.16, 95 % CI 0.03-0.45; P = 0.005). IDH1 mutation was also of prognostic significance for longer survival (P = 0.001; HR 0.20, 95 % 0.06-0.41), whereas MGMT promoter methylation was only of borderline significance. The study indicates that RT with concomitant and adjuvant TMZ is a relatively safe treatment associated with longer survival in patients with 1p/19q codeleted and IDH1 mutated tumors. Results from ongoing randomized studies will be essential to clarify if RT plus TMZ may provide survival as good as or better than RT combined with PCV for patients with AO and AOA.

Whole brain reirradiation and concurrent temozolomide in patients with brain metastases

Abstract: A second course of whole brain radiation therapy (WBRT) has been employed in selected patients with progressive brain metastases providing favorable symptomatic palliation with acceptable toxicity, although its efficacy and safety remain matter of debate. In the present study we have evaluated the outcomes in patients with progressive intracranial disease treated with WBRT reirradiation and concurrent temozolomide between October 2010 and May 2013. Data were obtained from a prospectively maintained database including patients with brain tumors treated with radiotherapy at Sant’Andrea Hospital. We identified 27 patients (10 males and 17 females) with a median age of 54 years who received WBRT reirradiation at a dose of 25 Gy in ten fractions plus concomitant daily temozolomide administered orally at a dose of 75 mg/m2. At the time of repeat WBRT all patients had a KPS ≥ 60. The primary disease sites were lung (n = 18) and breast (n = 9). The median overall survival after the second course of WBRT was 6.2 months and the median time to progression was 5.5 months. Eight patients experienced complete resolution of symptoms, 9 patients had a significant improvement, and 6 patients had no change in their neurologic function. Four patients had further deterioration after reirradiation. Overall, 85 % of patients improved or maintained their neurologic status. No severe acute toxicity during or after the second course of WBRT reirradiation was observed. On multivariate analysis with the Cox proportional hazards model, stable or absent extracranial metastases (p = 0.005) and response to treatment (p = 0.01) were independent favorable prognostic factors for survival. The median and 12-month survival rates were 12 months and 50 % in patients with stable or absent extracranial disease and 4.6 months and 7 % in those with progressive extracranial disease (p = 0.001). In conclusion, in the respect to the small number of treated patients, repeat WBRT plus concomitant temozolomide may be a treatment option in selected patients with multiple brain metastases to improve or maintain neurological conditions and quality of life with acceptable toxicity. The favorable effects of concomitant temozolomide on survival remain unclear.

Radiation therapy for older adults with glioblastoma: radical treatment, palliative treatment, or no treatment at all?

Abstract: The incidence of glioblastoma in older adults has increased over the last few decades. Current treatment includes surgery, radiotherapy, and chemotherapy, but optimal disease management remains a matter of debate. Both standard (60 Gy in 30 daily fractions) and hypofractionated radiotherapy (30–40 Gy in 10–15 daily fractions) have been employed with a similar survival benefit. Recent randomized studies indicate that chemotherapy with the alkylating agent temozolomide is a safe and effective therapeutic option for patients aged 60 years or older with newly diagnosed glioblastoma, suggesting that it should be a sufficient treatment for patients presenting with a methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter gene. The addition of concomitant temozolomide chemotherapy, adjuvant temozolomide chemotherapy, or both to postoperative radiotherapy, which is the standard treatment for adults with glioblastoma, has been associated with a survival benefit for older patients with a good performance status; however, aggressive treatment in this population may be associated with a high risk of neurological toxicity and deterioration of quality of life. Survival stratification according to age, MGMT promoter methylation status, and neurological status may be useful for clinical decision making and designing randomized trials for adequately evaluating the optimal combination of radiotherapy and chemotherapy for older patients with glioblastoma.

Image-Guided Hypofractionated Radiotherapy in Low-Risk Prostate Cancer Patients

Abstract: Aim. To evaluate efficacy and toxicity of image-guided hypofractionated radiotherapy (HFRT) in the treatment of low-risk prostate cancer. Outcomes and toxicities of this series of patients were compared to another group of 32 low-risk patients treated with conventional fractionation (CFRT). Methods. Fifty-nine patients with low-risk prostate cancer were analysed. Total dose for the prostate and proximal seminal vesicles was 60 Gy delivered in 20 fractions. Results. The median follow-up was 30 months. The actuarial 4-year overall survival, biochemical free survival, and disease specific survival were 100%, 97.4%, and 97.4%, respectively. Acute grade 1-2 gastrointestinal (GI) and genitourinary (GU) toxicity rates were 11.9% and 40.7%, respectively. Grade 1 GI and GU late toxicity rates were 8.5% and 13.6%, respectively. No grade ≥2 late toxicities were recorded. Acute grade 2-3 GU toxicity resulted significantly lower () in HFRT group compared to the CFRT group. The cumulative 4-year incidence of grade 1-2 GU toxicity was significantly higher () for HFRT patients. Conclusions. Our study demonstrated that hypofractionated regimen provided excellent biochemical control in favorable risk prostate cancer patients. The incidence of GI and GU toxicity was low. However, HFRT presented higher cumulative incidence of low-grade late GU toxicity than CFRT.

Glioblastoma multiforme and hepatitis B: do the right thing(s).

Abstract: OBJECTIVE: Hepatitis B virus (HBV) reactivation is a well-known complication related to immunosuppression. Clinical manifestations of HBV relapse range from self-limiting anicteric hepatitis to acute he - patic failure. Temozolomide (TMZ) is an alkylating agent used for the treatment of glioblastoma multi - forme (GBM), the most common and deadliest of malignant primary brain tumors. CASE REPORT: We report the case of a 52-year old man with a history of serological positivity for hepatitis B surface antigen (HBsAg) who was diagnosed with GBM. Since the tumor was multi - focal and thus inoperable, the patient received radiotherapy with concomitant TMZ and corti - costeroids, without a prophylactic therapy for HBV infection. Acute hepatitis developed five months later the beginning of anticancer thera - py. We started antiviral entecavir, which led to a decrease of HBV-DNA titer to 20 IU/ml, allowing the prosecution of theTMZ therapy. CONCLUSIONS: Up to now only four other cases of HBV relapse during TMZ therapy have been reported in literature. These cases under - line the need of HBV screening and antiviral pro - phylaxis before startingTMZ administration .

P08.17repeat stereotactic radiosurgery (srs) for recurrent brain metastases.

Abstract: OBJECTIVES: SRS for brain metastases is an effective treatment for brain metastases with a reported survival of 7-14 months. Local control is in the range of 70-90% at 12 months, with a proportion of patients who recurs locally we have evaluate the efficacy of repeat stereotactic radiosurgery (SRS) as salvage treatment in patients with recurrent brain metastases. PATIENTS AND METHODS: Between May 2008 and December 2012, twenty-seven patients received repeat SRS for a recurrent brain metastasis at University of Rome Sapienza, Sant'Andrea Hospital. All patients had Karnofsky Performance Score ≥ 60 and were previously treated with single-fraction SRS. The median time interval between primary SRS and reirradiation was 13.5 months. At the time of recurrence all patients received multi-fraction SRS (7-8 Gy x 3) RESULTS: Median overall and 12-month survival rates after repeat multifraction SRS were 10.3 months and 37%, respectively. Six patients were alive at the of analysis. The 6-month and 12-month local control rates were 90% and 72%. KPS > 70 (p = 0.04) and presence of extracranial disease (p = 0.01) were significant prognostic factor associated with longer survival. In general the treatment was well tolerated with relatively low treatment-related toxicity. Radionecrosis occurred in 7 reirradiated lesions, and was associated with neurological deterioration in 3 of them. CONCLUSION: Multi-fraction SRS is a feasible treatment option associated with good local control and acceptable radiation-induced toxicity in selected patients with recurrent brain metastases.