The 10-year survival rate for patients with metastatic melanoma is less than 10%. Although surgery and radiation therapy have a role in the treatment of metastatic disease, systemic therapy is the mainstay of treatment for these patients. After decades of failed attempts to improve treatment outcomes, recent successes with ipilimumab and vemurafenib have ushered in a new era in systemic therapy. Both ipilimumab and vemurafenib are associated with significant improvements in overall survival of patients in randomized phase III trials, an end point that had proven elusive so far. These breakthroughs not only provide more treatment options for patients with melanoma but also spur the investigation of a new generation of drugs for cancer therapy in general. This article reviews both the current systemic treatment options for metastatic melanoma and promising investigational approaches.
"This report shows that VMAT can deliver effective and efficient WBRT with either HA, SIB, or both in patients with BMs. The ability to do this is becoming more important as melanoma patients are living longer with new targeted therapies  that can even cross the blood brain barrier and have efficacy in the brain. The resulting increase in progression free survival means avoiding WBRT toxicity is even more important. "
[Show abstract][Hide abstract] ABSTRACT: Purpose
Volumetric modulated arc therapy (VMAT) can deliver intensity modulated radiotherapy (IMRT) like dose distributions in a short time; this allows the expansion of IMRT treatments to palliative situations like brain metastases (BMs). VMAT can deliver whole brain radiotherapy (WBRT) with hippocampal avoidance and a simultaneous integrated boost (SIB) to achieve stereotactic radiotherapy (SRT) for BMs. This study is an audit of our experience in the treatment of brain metastases with VMAT in our institution.
Methods and materials
Metastases were volumetrically contoured on fused diagnostic gadolinium enhanced T1 weighted MRI/planning CT images. Risk organs included hippocampus, optic nerve, optic chiasm, eye, and brain stem. The hippocampi were contoured manually as one paired organ with assistance from a neuroradiologist. WBRT and SIB were integrated into a single plan.
Thirty patients with 73 BMs were treated between March 2010 and February 2012 with VMAT. Mean follow up time was 3.5 months. For 26 patients, BMs arose from primary melanoma and for the remaining four patients from non-small cell lung cancer (n= 2), primary breast cancer, and sarcoma. Mean age was 60 years. The male to female ratio was 2:1. Five patients were treated without hippocampal avoidance (HA) intent. The median WBRT dose was 31 Gy with a median SIB dose for BMs of 50 Gy, given over a median of 15 fractions. Mean values for BMs were as follows: GTV = 6.9 cc, PTV = 13.3 cc, conformity index = 8.6, homogeneity index = 1.06. Mean and maximum hippocampus dose was 20.4 Gy, and 32.4 Gy, respectively, in patients treated with HA intent. Mean VMAT treatment time from beam on to beam off for one fraction was 3.43 minutes, which compared to WBRT time of 1.3 minutes. Twenty out of 25 assessable lesions at the time of analysis were controlled. Treatment was well tolerated; grade 4 toxicity was reported in one patient. The median overall survival was 9.40 months
VMAT for BMs is feasible, safe and associated with a similar survival times and toxicities to conventional SRT+/−WBRT. The advantage of VMAT is that WBRT and SRT can be delivered at the same time on one machine.
[Show abstract][Hide abstract] ABSTRACT: Morphological and physiological characteristics of leaves from plant species collected in steppe communities in the various climatic zones in Eurasia were compared. The changes in leaf structure correlated with the major climatic factors. The mean thickness of leaves increased with increasing mean temperature of July and decreasing mean precipitation, which corresponded to aridity increase. The increased leaf thickness correlated with an increase in the specific leaf weight. The content of chlorophylls (a + b) in leaves greatly varied with plant habitats, whereas the chlorophyll a/b ratio remained unchanged. The chlorophyll content in leaf tissues had a general tendency to decrease with increasing leaf thickness. The leaf chlorophyll content positively correlated (R
2 = 0.77) with the proportion of chlorenchyma in leaf tissues. It is concluded that steppe plants adapt to climate aridization at the structural level by increasing the proportion of protective heterotrophic components of the leaf without changing the functional activity of photosynthetic tissues.
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