Image-Guided Radiosurgery and Radiotherapy for Central Nervous Systems Tumors

PICHON RIVIERE, A.; AUGUSTOVSKI, F.; GARCIA MARTI, S.; GLUJOVSKY, D.; ALCARAZ, A.; LOPEZ, A.; BARDACH, A.; CIAPPONI, A; SPIRA, C

Documento de Evaluación de Tecnologías Sanitarias

IECS

Año: 2012 p. 1 - 30

1668-2793

The incidence of primary central nervous system (CNS) tumor in adults is 24.6 every 100,000 individuals in the U.S., with a peak between 75-79 years old. Approximately one third of them are malignant. It is also estimated that there are 100,000-170,000 new brain metastasis cases diagnosed every year in that country. CNS tumors produce signs and symptoms due to brain local invasion, compression of adjacent structures, and/or intracranial pressure. Neuroradiology images are the main diagnostic approach and become critical in preoperative planning. There is a wide range of available treatments aimed at increasing survival and maximizing the patients performance and quality of life where radiotherapy, and particularly radiosurgery and stereotactic radiosurgery (SRS and STR), represent an important tool. Technology In stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) high doses of ionizing radiation are applied to very small fields in order to reduce the tumor and minimize adverse effects. In the case of SRS, radiation is administered in a single session, whereas SRT is performed in several ones. However, in practice, SRT is the term used to refer to both treatments. For better results, it is necessary to adequately identify the area to irradiate using imaging methods (CT scan, MRI or PET) and immobilize the patient to minimize the effect of respiratory movements. There are several technologies available including Gamma Knife, Tomo Therapy and Cyber Knife. Purpose To assess the available evidence on the efficacy, safety and coverage related aspects of radiosurgery and image-guided stereotactic radiotherapy in patients with central nervous system tumors. Methods A bibliographic search was carried out on the main databases: DARE, NHS EED, on Internet general search engines, in health technology evaluation agencies and health sponsors. Priority was given to the inclusion of meta-analysis, systematic reviews, randomized controlled clinical trials, clinical practice guidelines, health technology assessments and financial assessments, and coverage policies from other health systems. Emphasis was made on the most prevalent CNS tumors. Results One meta-analysis, one Cochrane systematic review, one randomized controlled clinical trial, one retrospective study; four clinical practice guidelines; one health technology assessment and six coverage policies were selected. Vestibular Schwannoma/Acoustic Neurinoma One meta-analysis included 37 case series (n= 3,677), where the overall rate of stable disease 92.2% (95% CI: 90.4- 93.7%), regardless of tumor size. The rate of extracranial nerve complications was 4.5%; the overall rate of facial palsy post-SRS was 7.1%; hearing preservation was 59.3%; whereas response regarding tinnitus was poor (17.1%). Glioblastoma Multiforme The meta analysis included 11 patients - n=456 (9 case series; one case control and one randomized prospective study). Overall survival for patients treated with surgery + SRS was 9.5-26 months. The rate of complications was 11.4 % (95% CI: 5.1 ? 23.6%). Meningioma One meta-analysis included 15 case series where 2,734 patients were followed-up between 3.96 and 144 months. The rate of disease stability was 89.0% (95% CI: 84.6?92.3%). The rate of complications (trigeminal nerve dysfunction, diplopia, seizures, hypopituitarism, gait instability, prolonged symptomatic edema requiring treatment and decrease in visual acuity) was 7.0%, with no correlation with tumor size. Brain Metastasis (MTS) One meta-analysis selected 27 studies, 25 case series and two open-label, randomized, controlled trials comparing SRS with another approach (one SRS vs. surgery + whole brain radiotherapy-WBRT-; and the second one SRS vs. SRS + WBRT). A total of 2,679 patients were included. The survival of patients treated with SRS ranged between 5 and 14 months. The overall rate of complications was 10.0%, which included hemorrhage, seizures, radiation symptomatic necrosis, hearing loss and new neurologic deficit, hemiparesis, and visual field deficit. In 2010, a systematic review by Cochrane, evaluated the efficacy of RTCT + radiosurgery (RS) versus WBRT for the treatment of MTS in adults. Two studies which randomized 358 patients were included. Regarding survival, there were no statistically significant differences between the groups the groups. For patients with a single MTS, survival was higher in the TBRT+RS group (6.4 months) vs. WBRT (4.9 months, p=0.04). No significant differences were found as to specific survival due to disease in both groups. When analyzing patients with RPA Class I (patients with better Performance Status and prognosis), a better survival was observed with the combination therapy (11.6 months) vs. WBRT (9.6 months, p=0.04). Clinical practice guidelines Several medical associations support the use of SRS and SRT as a therapeutic option for subjects with 1-3 small brain MTS, good performance status, controlled disease and when surgical resection is not possible. Coverage policies Several U.S. health sponsors support the use of this technology in the CNS tumors analyzed in this document. Costs The cost of radiosurgery treatment is AR$2,000- $40,000 (Argentine pesos, 2012). Conclusions In those patients with brain MTS, two studies of adequate methodological quality suggest that fractioned stereotactic radiotherapy is a good treatment alternative, specially in terms of overall survival, for patients with 1-3 brain MTS, good performance status, and controlled systemic disease when surgery is not plausible. Both the clinical practice guidelines as well as the coverage policies support its use for this condition. For the primary CNS tumors assessed in this document, studies of poor methodological quality suggest that SRS and SRT are the only efficacious alternative when surgery is not possible or as adjuvant therapy, although further studies of good methodological design are required to accurately assess SRS/SRT efficacy in these conditions.