Glioblastoma is the most frequent and devastating primary malignant brain tumor in adults. Surgery followed by standard radiotherapy with concomitant and adjuvant chemotherapy with temozolomide is ...the standard of care in patients with glioblastoma, however the prognosis remains poor with a median survival in the range of 12-15 months. Common genetic abnormalities in glioblastoma are associated with aberrant activation or suppression of cellular signal transduction pathways and resistance to radiation and chemotherapy. Special attention has been focused on targets such as epidermal growth factor receptor, vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and on pathways such as the phosphatidylinositol-3kinase/Akt/mammalian target of rapamycin and Ras/Raf/mitogen-activated protein-kinase pathways. Several signal transduction inhibitors have been examined in preclinical and clinical malignant glioma trials, including antiangiogenic agents (bevacizumab, enzastaurin), and inhibitors of epidermal growth factor receptor tyrosine kinase (gefitinib and erlotinib), mammalian target of rapamycin (temsirolimus, everolimus) and integrin (cilengitide). Although preliminary clinical results of the use of targeted agents have not translated into significantly better survival, more recent phase II trials are exploring the combination of multitargeted drugs with cytotoxic chemotherapy and radiotherapy in order to overcome the resistance of tumors to single-agent targeted therapies. This review summarizes the current results with cytotoxic and targeted molecular agents in glioblastoma and the development of new chemoradiation strategies under evaluation to increase their effectiveness.
Objectives
The optimal treatment for elderly patients (age > 70 years) with glioblastoma remains controversial. We conducted a prospective trial in 32 consecutive elderly patients with glioblastoma ...who underwent surgery followed by radiotherapy (RT) plus concomitant and adjuvant temozolomide.
Patients and Methods
32 patients 70 years of age or older with a newly diagnosed glioblastoma and a Karnofsky performance status (KPS) ≥ 70 were treated with RT (daily fractions of 2 Gy for a total of 60 Gy) plus temozolomide at the dose of 75 mg/m
2
per day followed by six cycles of adjuvant temozolomide (150–200 mg/m
2
for 5 days during each 28-day cycle). The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS) and toxicity.
Results
The median OS was 10.6 months and the median PFS was 7 months. The 6-month and 12-month survival rates were 91% and 37%, respectively. The 6-month and 12-month PFS rates were 56% and 16%, respectively. In multivariate analysis KPS was the only significant independent predictive factor of survival (
P
= 0.01). Adverse effects were mainly represented by neurotoxicity (40%), which resolved in most cases with the use of steroids, and Grade 3–4 hematologic toxicity in 28% of patients. Chemotherapy was stopped in 2 patients, delayed in 9 patients and reduced in 4 patients.
Conclusions
Standard RT plus concomitant and adjuvant temozolomide is a feasible treatment for elderly patients with newly diagnosed glioblastoma who present with good prognostic factors.
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
O
6-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.
The optimal management of craniopharyngiomas remains controversial. The first-line treatment usually consists of surgical resection. Complete tumor removal provides a high rate of long-term control; ...however, aggressive surgery is associated with significant incidence of complications. Radiotherapy (RT) is currently used in patients after limited surgery and achieves excellent long-term tumor control. Stereotactic radiotherapy, both in the form of radiosurgery (RS) or fractionated stereotactic radiotherapy (FSRT), has been developed as a more accurate technique of irradiation with more precise tumor localization and consequently a reduction in the volume of normal brain irradiated to high radiation doses. We provide a review of published data on outcome of conventional fractionated RT and modern radiation techniques. FSRT is a suitable treatment technique for all sizes of craniopharyngiomas, and efficacy is comparable to conventional RT. Single-fraction stereotactic radiosurgery is usually delivered to small tumors away from critical structures. Longer follow-up is necessary to confirm the excellent tumor control and the potential reduction of long-term radiation toxicity.
Objectives
The optimal treatment for elderly patients (age >70 years) with glioblastoma (GBM) remains controversial. We conducted a prospective trial in 43 consecutive elderly patients with GBM ...treated with hypofractionated radiotherapy (RT) followed by adjuvant temozolomide.
Patients and methods
Forty-three patients 70 years of age or older with a newly diagnosed GBM and a Karnofsky performance status (KPS) ≥ 60 were treated with hypofractionated RT (6 fractions of 5 Gy each for a total of 30 Gy over 2 weeks) followed by up to 12 cycles of adjuvant temozolomide (150–200 mg/m
2
for 5 days during each 28 day cycle). The HRQOL was assessed with the EORTC Quality of Life Questionnaire C30. The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS), toxicity and quality of life.
Results
The median OS was 9.3 months and the median PFS was 6.3 months. The 6 and 12 month survival rates were 86% and 35%, respectively. The 6 and 12 month PFS rates were 55% and 12%, respectively. In multivariate analysis KPS was the only significant independent predictive factor of survival (
P
= 0.008). Neurological deterioration occurred during or after RT in 16% of patients and was resolved in most cases with the use of steroids. Grade 3–4 hematologic toxicity occurred in 28% of patients during the adjuvant chemotherapy treatment with temozolomide. The treatment had no negative effect on HRQOL, however, fatigue (
P
= 0.02) and constipation (
P
= 0.01) scales worsened over time.
Conclusions
Hypofractionated RT followed by temozolomide may provide survival benefit maintaining a good quality of life in elderly patients with GBM. It may represent a reasonable therapeutic approach especially in patients with less favourably prognostic factors.
The aim of this study was to evaluate local control and survival rates after stereotactic radiosurgery (SRS) plus whole-brain radiotherapy (WBRT) for the treatment of multiple brain metastases from ...non-small cell lung cancer (NSCLC).
Between June 2004 and September 2008, sixty-six patients with multiple brain metastases from NSCLC were enrolled in this prospective study. All patients were required to have 2-3 brain metastases and Karnofsky performance status (KPS) > or = 70. WBRT treatment dose was 30 Gy in 10 fractions followed by SRS. A matched control population treated with WBRT alone to a dose of 30 Gy in 10 fractions was used for comparison.
The median survival was 10.3 months in the WBRT plus SRS group and 7.2 months in the WBRT group (p=0.005). The 6-month and 12-month survival rates were 90% and 38% in the SRS plus WBRT group and 84% and 19% in the WBRT group (p=0.01). Stable extracranial disease and KPS were significant predictive factors of survival in both groups (p=0.001). Death due to neurological causes occurred in 18% and 35% of patients treated with WBRT plus SRS and WBRT (p=0.02), respectively. Disease control in the brain was 10 months in the SRS plus WBRT group and 7 months in the WBRT group (p=0.001); the 6-month and 12-month control rates were 82% and 42% for WBRT plus SRS, and 75% and 18% for WBRT (p=0.001), respectively. The 6-month and 12-month control rates of treated lesions (local control) were 90% and 47% in the WBRT group, and 100% and 93% in the WBRT plus SRS group (p=0.001).
WBRT plus SRS is a safe, minimally invasive and well-tolerated treatment for patients with up to three brain metastases from NSCLC. The treatment is associated with longer survival and better disease control in comparison with WBRT alone. Survival benefits need to be confirmed by large randomized studies.
Radiotherapy (RT) is often employed in patients with acromegaly refractory to medical and/or surgical interventions in order to prevent tumour regrowth and normalize elevated GH and IGF-I levels. It ...achieves tumour control and hormone normalization up to 90% and 70% of patients at 10–15 years. Despite the excellent tumour control, conventional RT is associated with a potential risk of developing late toxicity, especially hypopituitarism, and its role in the management of patients with GH-secreting pituitary adenomas remains a matter of debate. Stereotactic techniques have been developed with the aim to deliver more localized irradiation and minimize the long-term consequences of treatment, while improving its efficacy. Stereotactic irradiation can be given in a single dose as stereotactic radiosurgery (SRS) or in multiple doses as fractionated stereotactic radiotherapy (FSRT). We have reviewed the recent published literature on stereotactic techniques for GH-secreting pituitary tumors with the aim to define the efficacy and potential adverse effects of each of these techniques.
Adenoid cystic carcinoma (ACC) of Bartholin's gland is an extremely rare tumor of the female genital tract, representing about 5%-15% of Bartholin's gland malignancies. Approximately 80 cases have ...been reported in the literature. The authors describe the case of a 54-year-old woman with locally advanced ACC of Bartholin's gland treated with surgery and adjuvant radiotherapy (RT). She underwent radical hemivulvectomy associated with ipsilateral inguinal and femoral lymph node dissection. Subsequently, she received postoperative three-dimensional conformal RT. Total dose prescribed was 56 Gy in 28 fractions of two Gy each. After 20 months of follow up, there was no evidence of local failure or distant progression.
Purpose
The authors report acute toxicity in 14 patients with locally advanced head and neck squamous cell carcinoma treated with radiotherapy and cetuximab.
Materials and methods
Data collection was ...performed prospectively on patients treated from September 2007 to March 2009. Treatment consisted of 64.8–70 Gy radiotherapy in conventional fractions and cetuximab.
Results
Two out of 14 patients did not complete the planned combined treatment; radiotherapy was temporarily suspended in six other patients. Seven of 12 patients received cetuximab until the end of radiotherapy. Treatment breaks were principally due to severe acute cutaneous or mucous toxicity. Any grade acneiform rash occurred in all patients. In-field G3-4 cutaneous toxicity occurred in five (36%) patients and G3-4 mucous toxicity in seven (50%). One patient died of sepsis.
Conclusions
In our experience, severe acute toxic reactions are common in patients treated with radiotherapy and concurrent cetuximab, resulting in frequent breaks or incomplete treatment with potential reduction in disease control.
Our aim was to retrospectively analyse a series of patients with anal cancer treated with curative intent at a single institute in terms of survival and local disease control.
Forty-two patients with ...anal cancer were treated with primary radiotherapy with or without concurrent chemotherapy. The influence of the prognostic factors on overall (OS), disease-free (DFS), disease-specific (DSS), colostomy-free (CFS) and metastasis-free (MFS) survival was evaluated.
Nine patients had stage I, 15 stage II, four stage IIIA and 14 stage IIIB disease. Tumour progression/ persistence occurred in five patients (12%). The 5-year OS, DSS, DFS, CFS and MFS were 72.7%, 84.2%, 85.7%, 81.1% and 87.1%, respectively. On univariate analysis, T stage emerged as highly significant for OS, DSS, CFS and DFS, whereas N status was a significant prognostic factor for DSS. On multivariate analysis, T stage was a significant prognostic factor for OS and CFS.
Our data support the view that combined chemoradiation treatment of anal cancer is feasible and may provide survival benefits with an acceptable rate of adverse effects. We should consider T and N stages as important prognostic factors for survival.
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