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brain_metastases

Brain metastases

Epidemiology

No reliable estimates are available on the incidence in cancer patients. This information is valuable for planning patient care and developing measures that may prevent or decrease the likelihood of metastatic brain disease.

Brain metastases are the most common cause of malignant brain tumours in adults. Of the nearly 1·5 million patients in the USA who received a primary diagnosis of cancer in 2007, about 70 000 of these primary diagnoses are estimated to eventually relapse in the brain 1) 2)).

Between 20% and 40% of all patients with metastatic cancer will have brain metastases at autopsy 3).

Rates of CNS involvement in metastatic cancer are believed to be increasing, possibly owing to better control of systemic disease with novel chemotherapies or improved metastasis detection.

However, controversies exist regarding demographic and clinical profile of brain metastases.

Analysis from the Kentucky and Alberta cancer registries similarly demonstrated the aggressive nature of lung cancer and its propensity for BM at initial presentation. Besides widespread organ involvement, no synchronous organ site predicted BM in lung cancer. BM is a common and important clinical outcome, and use of registry data is becoming more available 4).

Trials

Despite the frequency of brain metastases, prospective trials in this patient population are limited, and the criteria used to assess response and progression in the CNS are heterogeneous 5).

This heterogeneity largely stems from the recognition that existing criteria sets, such as RECIST 6) 7).

Types

Distribution

The majority of brain metastases originate from primary cancers in the lung (40–50%) or breast (15–25%), or from melanoma (5–20%) 9)

They are common in elderly population and mostly due to primary lung. Adenocarcinoma was the most common histology of primary. Majority of lesions has been observed at parietal lobe 10).

Genes involved

Whether brain metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown.

Brastianos et al. detected alterations associated with sensitivity to PI3K/AKT/mTOR, CDK, and HER2/EGFR inhibitors in the brain metastases. Genomic analysis of brain metastases provides an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors, regional lymph nodes, or extracranial metastases 11).

COX2

HBEGF

ST6GALNAC5

HK2

FOXC1

HER2

VEGFA

LEF1

HOXB9

CDH2, KIFC1, and FALZ3

STAT3

αvβ3

HDAC3, JAG2, NUMB, APH1B, HES4, and PSEN1

Clinical Presentation

Presenting symptoms include headache (49%), focal weakness (30%), mental disturbances (32%), gait ataxia (21%), seizures (18%), speech difficulty (12%), visual disturbance (6%), sensory disturbance (6%), and limb ataxia (6%) 12).

Neuropsychological testing demonstrates cognitive impairment in 65% of patients with brain metastases 13) 14) , which might be a result of destruction or displacement of brain tissue by the expanding tumor, peritumoral edema leading to further disruption of surrounding white matter tracts, increased intracranial pressure, and/or vascular compromise.

Diagnosis

Magnetic resonance imaging with contrast enhancement is the imaging procedure of choice to diagnose and characterize brain metastases. Multiple lesions with marked vasogenic edema and mass effect are typically seen in patients with brain metastases. The classical appearance of a metastasis is a solid enhancing mass with well-defined margins and extensive edema. Occasionally, central necrosis produces a ring enhancing mass.


The MR assessment should include T1-weighted images with and without enhancement and T2/FLAIR images. They usually appear as multiple lesions with nodular or annular enhancement and are surrounded by edema. They are hypervascularized and have no restriction of their diffusion coefficient in their necrotic area and contain lipids on 1H spectroscopy. Metastases can be distinguished from primary tumors by the lack of malignant cell infiltration around the tumor 15).

Differential diagnosis

The main differential diagnosis includes primary tumours, abscesses, vascular and inflammatory lesions.

Guidelines

The management of patients with brain metastases has become a major issue due to the increasing frequency and complexity of the diagnostic and therapeutic approaches. In 2014, the European Association of NeuroOncology (EANO) created a multidisciplinary Task Force to draw evidence-based guidelines for patients with brain metastases from solid tumors. Soffietti et al. present these guidelines, which provide a consensus review of evidence and recommendations for diagnosis by neuroimaging and neuropathology, staging, prognostic factors, and different treatment options. Specifically, they addressed options such as surgery, stereotactic radiosurgery/stereotactic fractionated radiotherapy, whole-brain radiotherapy, chemotherapy and targeted therapy (with particular attention to brain metastases from non-small cell lung cancer, melanoma and breast and renal cancer), and supportive care 16).

Treatment

Outcome

Brain metastases are associated with a dismal prognosis. Treatment options for patients with brain metastases (BM) have limited efficacy and the mortality rate is virtually 100%.

Overall prognosis depends on age, extent and activity of the systemic disease, number of brain metastases and performance status. In about half of the patients, especially those with widespread and uncontrolled systemic malignancy, death is heavily related to extra-neural lesions, and treatment of cerebral disease doesn't significantly improve survival.

In such patients the aim is to improve or stabilize the neurological deficit and maintain quality of life. Corticosteroids and whole-brain radiotherapy usually fulfill this purpose. By contrast, patients with limited number of brain metastases, good performance status and controlled or limited systemic disease, may benefit from aggressive treatment as both quality of life and survival are primarily related to treatment of brain lesions.

Strong positive prognostic factors include good functional status, age <65 years, no sites of metastasis outside of the central nervous system (CNS), controlled primary tumor 17), the presence of a single metastasis in the brain, long interval from primary diagnosis to brain relapse, and certain cancer subtypes such as HER2 positive breast cancer brain metastases and EGFR-mutant non-small-cell lung cancer (NSCLC) 18) 19) 20)

Recursive partitioning analysis class

http://rcalc.ccf.org, under the category “Brain Cancer” 21).

It is presently unknown whether patients with brain metastases from heavily pre-treated cancers have a significantly different prognosis than those with less pre-treatment 22).

Recurrence

1)
FG Davis, TA Dolecek, BJ McCarthy, JL Villano Toward determining the lifetime occurrence of metastatic brain tumors estimated from 2007 United States cancer incidence data Neuro Oncol, 14 (2012), pp. 1171–1177
2)
American Cancer Society Cancer Facts & FiguresAmerican Cancer Society, Atlanta, GA (2007
3)
Sawaya R, Bindal RK, Lang FF, Abi-Said D. 2nd ed. New York: Churchill Livingstone; 2001. Metastatic brain tumors.
4)
Villano JL, Durbin EB, Normandeau C, Thakkar JP, Moirangthem V, Davis FG. Incidence of brain metastasis at initial presentation of lung cancer. Neuro Oncol. 2014 Jun 2. pii: nou099. [Epub ahead of print] PubMed PMID: 24891450.
5)
NU Lin, EQ Lee, H Aoyama, et al. Challenges relating to solid tumour brain metastases in clinical trials, part 1: patient population, response, and progression. A report from the RANO group Lancet Oncol, 14 (2013), pp. e396–e406
6)
EA Eisenhauer, P Therasse, J Bogaerts, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) Eur J Cancer, 45 (2009), pp. 228–247
7)
P Therasse, SG Arbuck, EA Eisenhauer, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada J Natl Cancer Inst, 92 (2000), pp. 205–216
8) , 9)
Schouten LJ, Rutten J, Huveneers HA, Twijnstra A. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer. 2002;94:2698–2705.
10)
Saha A, Ghosh SK, Roy C, Choudhury KB, Chakrabarty B, Sarkar R. Demographic and clinical profile of patients with brain metastases: A retrospective study. Asian J Neurosurg. 2013 Jul;8(3):157-61. doi: 10.4103/1793-5482.121688. PubMed PMID: 24403959.
11)
Brastianos PK, Carter SL, Santagata S, Cahill DP, Taylor-Weiner A, Jones RT, Van Allen EM, Lawrence MS, Horowitz PM, Cibulskis K, Ligon KL, Tabernero J, Seoane J, Martinez-Saez E, Curry WT, Dunn IF, Paek SH, Park SH, McKenna A, Chevalier A, Rosenberg M, Barker FG 2nd, Gill CM, Van Hummelen P, Thorner AR, Johnson BE, Hoang MP, Choueiri TK, Signoretti S, Sougnez C, Rabin MS, Lin NU, Winer EP, Stemmer-Rachamimov A, Meyerson M, Garraway L, Gabriel S, Lander ES, Beroukhim R, Batchelor TT, Baselga J, Louis DN, Getz G, Hahn WC. Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets. Cancer Discov. 2015 Sep 26. [Epub ahead of print] PubMed PMID: 26410082.
12)
Posner JB. Neurologic Complications of Cancer. Vol. 37. Philadelphia: Davis FA; 1995. Paraneoplastic Syndromes; p. 311.
13)
Chang EL, et al. A pilot study of neurocognitive function in patients with one to three new brain metastases initially treated with stereotactic radiosurgery alone. Neurosurgery. 2007;60:277–283.
14)
Mehta MP, et al. Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases. J Clin Oncol. 2003;21:2529–2536
15)
Grand S, Pasteris C, Attye A, Le Bas JF, Krainik A. The different faces of central nervous system metastases. Diagn Interv Imaging. 2014 Oct;95(10):917-31. doi: 10.1016/j.diii.2014.06.014. Review. PubMed PMID: 25023732.
16)
Soffietti R, Abacioglu U, Baumert B, Combs SE, Kinhult S, Kros JM, Marosi C, Metellus P, Radbruch A, Villa Freixa SS, Brada M, Carapella CM, Preusser M, Le Rhun E, Rudà R, Tonn JC, Weber DC, Weller M. Diagnosis and treatment of brain metastases from solid tumors: guidelines from the European Association of Neuro-Oncology (EANO). Neuro Oncol. 2017 Feb 1;19(2):162-174. doi: 10.1093/neuonc/now241. PubMed PMID: 28391295.
17)
Gaspar L, et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 1997;37:745–751.
18)
Melisko ME, Moore DH, Sneed PK, De Franco J, Rugo HS. Brain metastases in breast cancer: clinical and pathologic characteristics associated with improvements in survival. J Neurooncol. 2008;88:359–365.
19)
Eichler AF, et al. Survival in patients with brain metastases from breast cancer: the importance of HER-2 status. Cancer. 2008;112:2359–2367.
20)
Eichler AF, et al. EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer. Neuro Oncol. 2010;12:1193–1199.
21)
Barnholtz-Sloan JS, Yu C, Sloan AE, Vengoechea J, Wang M, Dignam JJ, Vogelbaum MA, Sperduto PW, Mehta MP, Machtay M, Kattan MW. A nomogram for individualized estimation of survival among patients with brain metastasis. Neuro Oncol. 2012 Jul;14(7):910-8. doi: 10.1093/neuonc/nos087. Epub 2012 Apr 27. PubMed PMID: 22544733; PubMed Central PMCID: PMC3379797.
22)
Lanier CM, McTyre E, LeCompte M, Cramer CK, Hughes R, Watabe K, Lo HW, O'Neill S, Munley MT, Laxton AW, Tatter SB, Ruiz J, Chan MD. The number of prior lines of systemic therapy as a prognostic factor for patients with brain metastases treated with stereotactic radiosurgery: Results of a large single institution retrospective analysis. Clin Neurol Neurosurg. 2017 Dec 27;165:24-28. doi: 10.1016/j.clineuro.2017.12.021. [Epub ahead of print] PubMed PMID: 29289917.
brain_metastases.txt · Last modified: 2018/01/02 20:42 by administrador