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• W2286095810 abstract "Brain metastases are a common complication of advanced stage non-small cell lung cancer (NSCLC), with an estimated incidence at initial diagnosis of 10–20%, increasing to up to 40% in the two years following diagnosis [Carolan et al., 2005Carolan H Sun A Bezjak A et al.Does the incidence and outcome of brain metastases in locally advanced non-small cell lung cancer justify prophylactic cranial irradiation or early detection?.Lung Cancer. 2005; 49: 109-115Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar]. Palliative whole brain radiotherapy (WBRT) has been the mainstay of treatment for patients with multiple brain metastases, extending survival to 3-6 months. However, despite WBRT approximately 50% of patients die with symptoms of intracranial progression. Attempts to increase the treatment efficacy by dose-escalation of WBRT [Murray et al., 1997Murray KJ Scott C Greenberg HM et al.A randomized phase III study of accelerated hyperfractionation versus standard in patients with unresected brain metastases: a report of the Radiation Therapy Oncology Group (RTOG) 9104.Int J Radiat Oncol Biol Phys. 1997; 39: 571-574Abstract Full Text PDF PubMed Scopus (261) Google Scholar], or by focal radiation dose increase [Hoskin et al., 1990Hoskin PJ Crow J Ford HT The influence of extent and local management on the outcome of radiotherapy for brain metastases.Int J Radiat Oncol Biol Phys. 1990; 19: 111-115Abstract Full Text PDF PubMed Scopus (106) Google Scholar], have proven unsuccessful. Similarly, the concurrent use of radiation sensitizers has failed to result in improved outcome of WBRT. Recent studies have focussed on the tolerability and efficacy of the combination of WBRT and chemotherapy, e.g. with temozolomide, gefitinib and erlotinib. However, thus far randomized phase III studies are lacking for most chemotherapeutic agents, and available data are mostly from phase I/II studies. Stereotactic radiosurgery (SRS) is characterized by the high-precision delivery of a single fraction of high-dose radiotherapy. SRS techniques generate a rapid dose fall-off outside the target volume, thereby sparing the normal brain tissue and allowing for high biologically equivalent doses to be precisely delivered. SRS is generally considered to be the preferred treatment for patients with a limited number (1–3) of brain metastases in any location of the brain, including the brainstem. Several published series have shown that SRS is highly effective in both single and multiple brain metastases, with local control rates of 70–90% and median survival rates of between 6 and 12 months being reported. The superiority of SRS over WBRT, however, has only been demonstrated for patients with a single brain metastasis. A randomized trial has been performed by the RTOG, where 333 patients with 1-3 brain metastases were assigned to WBRT alone or WBRT plus SRS [Andrews et al., 2004Andrews DW Scott CB Sperduto PW et al.Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial.Lancet. 2004; 363: 1665-1672Abstract Full Text Full Text PDF PubMed Scopus (1797) Google Scholar]. The overall trial failed to show a significant improvement in median overall survival, but patients with a single metastasis had improved survival (6.5 vs. 4.9 months, p=0.05) and functional autonomy after WBRT and SRS. Although a randomized comparison between neurosurgery and radiosurgery is lacking, the results of both approaches are comparable and SRS is considered to be a non-invasive alternative to surgery, with less morbidity and mortality. In recent years, neurosurgery generally has been reserved for space-occupying lesions with a diameter of >3 cm, and for cases where pathological confirmation is required. Whether SRS should be delivered as a sole modality or in combination with WBRT for primary brain metastases remains a controversial issue. The rate of development of new brain metastases after SRS is dependent on the number of brain metastases treated, but also on the quality of pre-treatment imaging as high-resolution, double-contrast MRI scans can detect additional small metastases in a considerable number of patients. A multi-institutional study [Sneed et al., 2002Sneed PK Suh JH Goetsch SJ et al.A multiinstitutional review of radiosurgery alone vs radiosurgery with whole brain radiotherapy as the initial management of brain metastases.Int J Radiat Oncol Biol Phys. 2002; 53: 519-526Abstract Full Text Full Text PDF PubMed Scopus (427) Google Scholar] showed that the upfront addition of whole brain radiotherapy (WBRT) to SRS decreased the intracranial failure rate, but as a result of efficient salvage therapy, this failed to have a significant impact on the survival of patients. A recently reported randomized trial in patients with 1-4 brain metastases has confirmed the above findings [Aoyama et al., 2006Aoyama H Shirato H Tago M et al.Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial.JAMA. 2006; 295: 2483-2491Crossref PubMed Scopus (1531) Google Scholar], with a 1 year actuarial rate of developing new brain metastases of 42% in the WBRT plus SRS group and 64% in the SRS-alone group (p=0.003). However, not all intracranial relapses were symptomatic and salvage therapy was required in 15% and 43% of patients after WBRT plus SRS and after SRS only, respectively. Furthermore, in the majority of patients salvage SRS could be performed, sparing patients from the potential side effects of WBRT. In the light of these findings, most authors advise to use SRS as a single modality without upfront WBRT for the primary treatment of brain metastases. Recent years have witnessed a shift towards more aggressive treatment for patients with a synchronous presentation of NSCLC and a single brain metastasis. This approach seems particularly valuable for patients presenting with a thoracic stage I NSCLC, where combined surgical treatment of the brain metastasis and the primary tumor has resulted in survival rates that are similar to stage I patients [Billing et al., 2001Billing PS Miller DL Allen MS et al.Surgical treatment of primary lung cancer with synchronous brain metastases.J Thorac Cardiovasc Surg. 2001; 122: 548-553Abstract Full Text PDF PubMed Scopus (150) Google Scholar; Hu et al., 2006Hu C Chang EL Hassenbusch 3rd, SJ et al.Nonsmall cell lung cancer presenting with synchronous solitary brain metastasis.Cancer. 2006; 106: 1998-2004Crossref PubMed Scopus (112) Google Scholar]. The reported high efficacy of stereotactic body radiotherapy (SBRT) for early stage NSCLC nowadays allow for a non-invasive, but still aggressive treatment regiment in this subset of patients with combined SBRT for the primary tumor and SRS for the brain metastasis. The results of such an aggressive approach, however, were far less favourable for patients with more advanced thoracic stages. Radiotherapy facilities for delivering radiosurgery have been increasing rapidly in recent years and the introduction of non-invasive patient immobilization techniques, e.g. the use of frameless radiosurgery have made SRS a well tolerable, patient-friendly technique that can be performed on an outpatient basis. The toxicity of SRS is only very limited with fatigue, and local alopecia being the most commonly encountered side effects. At the VUmc Amsterdam, SRS for patients with primary or recurrent brain metastases from NSCLC has been performed since the early 1990's. Well over a hundred patients have been treated and the results of this series with respect to patterns of failure and toxicity will be presented during the meeting." @default.
• W2286095810 created "2016-06-24" @default.
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• W2286095810 date "2007-08-01" @default.
• W2286095810 modified "2023-10-18" @default.
• W2286095810 title "M18-01: Whole brain radiotherapy and stereotactic radiosurgery for brain metastases from NSCLC" @default.
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