Treatment of brain metastases: Review of phase III randomized controlled trials

Abstract The optimal management of brain metastases remains controversial. Both whole brain radiotherapy (WBRT) and local treatment [surgery (S) or radiosurgery (RS)] are the cornerstones of treatment. The role of systemic therapy is also being explored. Randomized controlled trials (RCT) have tried to assess the individual and combined effects of different therapeutic strategies. (1) RCT in oligometastatic patients: WBRT alone vs. local treatment+WBRT. Combined treatment may improve both overall survival and local control in patients with a single metastasis, but it also leads to a local control benefit in patients with two to four lesions. Exclusive local treatment vs. WBRT plus local treatment. The addition of WBRT to local treatment may result in improved local control, improved freedom from new brain metastases and improved overall brain control. S+WBRT vs. RS+WBRT. There is no evidence of superiority of a combined treatment over the other one. (2) RCT addressing the point of improving WBRT outcome: differences in WBRT fractionation do not significantly alter outcome of treatments. Only a few systemic drugs may cause some significant advantages. (3) RCT that assessed neurocognitive impairment and quality of life: the baseline cognitive performance of most patients is significantly impaired. Intracranial tumor control is an essential factor in stabilizing neurocognitive function. The data on neurocognitive toxicity related to WBRT are still contradictory. Impairment of both neurocognitive function and quality of life of patients with brain metastases needs to be further addressed in RCT

Stereotactic radiotherapy for early stage non-small cell lung cancer

Stereotactic body radiotherapy (SBRT) represents a consolidated treatment option for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). The clinical evidence accumulated in the past decade supports its use as an alternative to surgery with comparable survival outcomes. Due to its limited toxicity, SBRT is also applicable to elderly patients with very poor baseline pulmonary function or other severe comorbidities. Recent comparative studies in operable patients raised the issue of the possible use of SBRT also for this subgroup, with quite promising results that still should be fully confirmed by prospective trials with long-term follow-up. Aim of this review is to summarize and discuss the major studies conducted over the years on SBRT and to provide data on the efficacy and toxicity of this radiotherapy technique for stage I NSCLC. Technical aspects and quality of life related issues are also discussed, with the goal to provide information on the current role and limitations of SBRT in clinical practice

Is clinical radiosensitivity a complex genetically controlled event?

New insights into molecular mechanisms responsible for cellular radiation response are coming from recent basic radiobiological studies. Preliminary data supporting the concept of clinical radiosensitivity as a complex genetically controlled event are available, and it seems reasonable to hypothesize that genes encoding for proteins implicated in known radiation-induced pathways, such as DNA repair, could influence normal tissue and tumor response to radiotherapy. Such genes could be considered as candidates for experimental studies and as targets for innovative therapies. Variants that could influence individual radiosensitivity have been recently identified, and specific Single Nucleotide Polymorphisms have been associated to the development of different radiation effects on normal tissues. Allelic architecture of complex traits able to modify phenotypes is difficult to be established, and different grades of interaction between common or rare genetic determinants may be present and should be considered. Many different experimental strategies could be investigated in the future, such as analysis of multiple genes in large irradiated patient cohorts strictly observed for radiation effects or identification of new candidate genes, with the aim of identifying factors that could be employed in predictive testing and individualization of radiation therapy on a genetic basis