Andrews, D. W. 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 363, 1665-1672

University of Rochester, Rochester, New York, United States
The Lancet (Impact Factor: 45.22). 06/2004; 363(9422):1665-72. DOI: 10.1016/S0140-6736(04)16250-8
Source: PubMed


Brain metastases occur in up to 40% of all patients with systemic cancer. We aimed to assess whether stereotactic radiosurgery provided any therapeutic benefit in a randomised multi-institutional trial directed by the Radiation Therapy Oncology Group (RTOG).
Patients with one to three newly diagnosed brain metastases were randomly allocated either whole brain radiation therapy (WBRT) or WBRT followed by stereotactic radiosurgery boost. Patients were stratified by number of metastases and status of extracranial disease. Primary outcome was survival; secondary outcomes were tumour response and local rates, overall intracranial recurrence rates, cause of death, and performance measurements.
From January, 1996, to June, 2001, we enrolled 333 patients from 55 participating RTOG institutions--167 were assigned WBRT and stereotactic radiosurgery and 164 were allocated WBRT alone. Univariate analysis showed that there was a survival advantage in the WBRT and stereotactic radiosurgery group for patients with a single brain metastasis (median survival time 6.5 vs 4.9 months, p=0.0393). Patients in the stereotactic surgery group were more likely to have a stable or improved Karnofsky Performance Status (KPS) score at 6 months' follow-up than were patients allocated WBRT alone (43% vs 27%, respectively; p=0.03). By multivariate analysis, survival improved in patients with an RPA class 1 (p<0.0001) or a favourable histological status (p=0.0121).
WBRT and stereotactic boost treatment improved functional autonomy (KPS) for all patients and survival for patients with a single unresectable brain metastasis. WBRT and stereotactic radiosurgery should, therefore, be standard treatment for patients with a single unresectable brain metastasis and considered for patients with two or three brain metastases.

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Available from: Minesh P Mehta, Mar 02, 2015
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    • "Une décennie plus tard, l'impact de la radiochirurgie (radiothérapie stéréotaxique focalisée délivrée en une seule séance) a été évaluée dans la prise en charge des métastases cérébrales (une à trois) avec des résultats également satisfaisants en termes de survie et de contrôle local par comparaison à ceux de l'irradiation pancérébrale seule [14] "
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    ABSTRACT: Surgical excision of brain metastases has been well evaluated in unique metastases. Two randomized phase III trial have shown that combined with adjuvant whole brain radiotherapy, it significantly improves overall survival. However, even in the presence of multiple brain metastases, surgery may be useful. Also, even in lesions amenable to radiosurgery, surgical resection is preferred when tumors displayed cystic or necrotic aspect with important edema or when located in highly eloquent areas or cortico-subcortically. Furthermore, surgery may have a diagnostic role, in the absence of histological documentation of the primary disease, to rule out a differential diagnosis (brain abscess, lymphoma, primary tumor of the central nervous system or radionecrosis). Finally, the biological documentation of brain metastatic disease might be useful in situations where a specific targeted therapy can be proposed. Selection of patients who will really benefit from surgery should take into account three factors, clinical and functional status of the patient, systemic disease status and characteristics of intracranial metastases. Given the improved overall survival of cancer patients partially due to the advent of effective targeted therapies on systemic disease, a renewed interest has been given to the local treatment of brain metastases. Surgical resection currently represents a valuable tool in the armamentarium of brain metastases but has also become a diagnostic and decision tool that can affect therapeutic strategies in these patients.
    Full-text · Article · Jan 2015 · Cancer/Radiothérapie
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    • "During the past few decades stereotactic radiosurgery (SRS) has become more common, either as a boost in combination with whole brain radiation, or used alone. The randomized RTOG-9508 study found that adding SRS to whole brain irradiation improved local control rates [2]. SRS uses very intense treatments such as 15–24 Gy in a single fraction [3] [4], which results in ablation of tissue inside the target zone and excellent tumor control. "
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    ABSTRACT: Brain metastases are a common problem, managed with surgery, stereotactic radiosurgery (SRS), whole brain irradiation (WBI), or a combination. SRS targets individual tumors with large dosages of radiation. There is a trend toward using more SRS and less WBI, due to a reduction in cognitive damage, shorter treatment course, and improved tumor control. In conventional radiation a total dose of radiation is frequently divided over time into several smaller “fractions”, which helps spare normal tissues such as the brain. Two doses of 10 Gy each given on separate days will result in 45% less damage to normal brain tissue than a single dose of 20 Gy, according to the linear quadratic model for biologically effective dose (BED). Unfortunately, standard fractionation also reduces the effective dose to the tumor. It would therefore be highly beneficial to be able to fractionate the dose to the normal brain, but not fractionate the tumor dose. When a tumor is irradiated, there are dozens of beams that pass through the skull and converge on the tumor, also irradiating healthy brain tissue in the beam paths. If multiple tumors are irradiated, there are areas of brain that are overlapped by beams that are targeting separate tumors. If these tumors were treated on separate days, then on any given day portions of normal brain may only see the radiation beams for one tumor instead of 2 or more. That is how spatial fractionation of multiple metastases works. By treating groups of tumors on separate days the beams are spread out over time, reducing areas of beam overlap, and effectively fractionating the dose to healthy brain. Yet, each tumor still receives a single treatment. The hypothesis is that an array of metastases may be divided into 2–5 different groups that are treated on different days such that the BED to normal brain tissue is minimized. This should benefit patients by reducing side effects, allowing greater numbers of tumors to be treated, and making retreatment safer. An algorithm is discussed, which places the largest tumors and tumors situated close together into different groups. Modifications for axial beam delivery systems such as helical tomotherapy are discussed.
    Full-text · Article · Oct 2014 · Medical Hypotheses
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    • "Stereotactic radiosurgery (SRS) delivers a single high dose of irradiation to the target volume while avoiding the surrounding normal tissues. A randomized trial conducted by the RTOG (22) showed that the addition of SRS to WBRT was superior to WBRT alone in patients with a newly diagnosed single brain lesion. A survival benefit was not seen for patients with two or three metastatic lesions, although local brain control was significantly improved with the addition of SRS. "
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    ABSTRACT: Brain metastases (BM) are a common and lethal complication of non-small cell lung cancer (NSCLC), which portend a poor prognosis. In addition, their management implies several challenges including preservation of neurological and neurocognitive function during surgery or radiation-therapy, minimizing iatrogenic complications of supportive medications, and optimizing drug delivery across the blood-brain barrier. Despite these challenges, advancements in combined modality approaches can deliver hope of improved overall survival and quality of life for a subset of NSCLC patients with BM. Moreover, new drugs harnessing our greater understanding of tumor biology promise to build on this hope. In this mini-review, we revised the management of BM in NSCLC including advancements in neurosurgery, radiation therapy, as well as systemic and supportive therapy.
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