User Tools

Site Tools


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 Features

Diagnosis

Differential diagnosis

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 12).

Treatment

Outcome

Recurrence

Case series

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)
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.
brain_metastases.txt · Last modified: 2019/09/10 19:25 by administrador