New Book: Current Research in Brain Cancer

Current Research in Brain Cancer

by Carmen Ferguson (Editor)

$150.00

Buy

Brain cancers occur when an abnormal growth of cells occurs in the brain. Some types of brain cancer are medulloblastomaastrocytomameningiomas, etc. A form of astrocytoma called glioblastoma is the most aggressive form of brain cancer. Symptoms of brain cancer include headaches, vomiting, seizures, altered vision and mental changes. It is diagnosed using computed tomography (CT) or magnetic resonance imaging (MRI) scans and the result is confirmed usually through a biopsy. The treatment of brain cancer may involve a combination of chemotherapy, radiation therapy and surgery. No therapy has yet shown any progress in increasing life expectancy in people with malignant gliomas. However, cancer immunotherapy is being actively studied. Research is also being pursued in the use of vesicular stomatitis virus and retroviral replicating vectors as management strategies for brain cancer. The objective of this book is to give a modern perspective on brain cancer. Different approaches, evaluations, methodologies and advanced studies on brain cancer have been included in this book. Students, researchers, experts and all associated with neurology, neuroscience, surgical oncology, clinical oncology and radiation oncology will benefit alike from this book.

Non small cell lung cancer intracranial metastases radiosurgery

Non small cell lung cancer intracranial metastases radiosurgery

Multisession radiosurgery (M-GKS) may be an effective alternative for large brain metastases from Non small cell lung cancer (NSCLC). Specifically, severe radiation induced toxicity (≥ grade 3) did not occur in M-GKS for large-volume metastases. Although the long-term effects and results from larger samples remain unclear, M-GKS may be a suitable palliative treatment for preserving neurological function 1).

Traditionally, whole brain radiotherapy (WBRT) has been the cornerstone of Non small cell lung cancer intracranial metastases treatment, but its indication is a matter of debate. A randomized trial has shown that for patients with a poor prognosis, WBRT does not add quality of life (QoL) nor survival over the best supportive care. In recent decades, stereotactic radiosurgery (SRS) has become an attractive non-invasive treatment for patients with BM. Only the BM is irradiated to an ablative dose, sparing healthy brain tissue. Intracranial recurrence rates decrease when WBRT is administered following SRS or resection but does not improve overall survival and comes at the expense of neurocognitive function and QoL. The downside of SRS compared with WBRT is a risk of radionecrosis (RN) and a higher risk of developing new BM during follow-up. Currently, SRS is an established treatment for patients with a maximum of four BM. Several promising strategies are currently being investigated to further improve the indication and outcome of SRS for patients with BM: the effectivity and safety of SRS in patients with more than four BM, combining SRS with systemic therapy such as targeted agents or immunotherapy, shared decision-making with SRS as a treatment option, and individualized isotoxic dose prescription to mitigate the risk of RN and further enhance local control probability of SRS.

The review of Hartgerink et al., discusses the current indications of SRS and future directions of treatment for patients with BM of NSCLC with focus on the value of SRS 2).


Radiosurgery for multiple BMs is controversial, yet patients with EGFR Non small cell lung cancer intracranial metastases and Anaplastic lymphoma kinase non small cell lung cancer may be uniquely suited to benefit from this approach. These results support single and multiple courses of radiosurgery without WBRT for patients with oncogene-addicted NSCLC with four or more BMs 3).

References

1)

Park K, Kim JW, Chung HT, Paek SH, Kim DG. Single-Session versus Multisession Gamma Knife Radiosurgery for Large Brain Metastases from Non-Small Cell Lung Cancer: A Retrospective Analysis. Stereotact Funct Neurosurg. 2019 May 22:1-7. doi: 10.1159/000496154. [Epub ahead of print] PubMed PMID: 31117101.
2)

Hartgerink D, van der Heijden B, De Ruysscher D, Postma A, Ackermans L, Hoeben A, Anten M, Lambin P, Terhaag K, Jochems A, Dekker A, Schoenmaekers J, Hendriks L, Zindler J. Stereotactic Radiosurgery in the Management of Patients With Brain Metastases of Non-Small Cell Lung Cancer: Indications, Decision Tools and Future Directions. Front Oncol. 2018 May 9;8:154. doi: 10.3389/fonc.2018.00154. eCollection 2018. Review. PubMed PMID: 29868476; PubMed Central PMCID: PMC5954030.
3)

Robin TP, Camidge DR, Stuhr K, Nath SK, Breeze RE, Pacheco JM, Liu AK, Gaspar LE, Purcell WT, Doebele RC, Kavanagh BD, Rusthoven CG. Excellent Outcomes with Radiosurgery for Multiple Brain Metastases in ALK and EGFR Driven Non-Small Cell Lung Cancer. J Thorac Oncol. 2018 May;13(5):715-720. doi: 10.1016/j.jtho.2017.12.006. Epub 2017 Dec 19. PubMed PMID: 29269007.

EGFR Non small cell lung cancer intracranial metastases

EGFR Non small cell lung cancer intracranial metastases

Advances in our understanding of genomic alterations in lung cancer have led to the discovery of several driver mutations in non small cell lung cancer 1). The most common are the EGFR activating mutations, which are present in 50% of patients of Asian descent and in 10%–15% of white patients with NSCLC of adenocarcinoma histology 2).

Huang et al., investigated whether tumor mutation status (EGFRKRASALKROS1BRAF) and treatment history were associated with survivalafter neurosurgery.

They reviewed the electronic health records of 104 non small cell lung cancer (NSCLC) patients with genomic profiling who underwent neurosurgical resection for symptomatic brain metastases at an academic institution between January 2000 and January 2018.

They used multivariate Cox proportional hazards models to evaluate the association between overall survival (OS) after neurosurgery and clinico-pathological factors including mutation status.

Mean age of patients in this study was 61 (±12) years, and 44% were men. The median OS after neurosurgery was 24 months (95% confidence interval: 18-34). Our multivariate analysis showed that the presence of an EGFR mutation in the tumor was significantly associated with improved OS (hazard ratio [HR] 0.214 p = 0.029), independent of tyrosine kinase inhibitor (TKI) use. Presence of KRAS, ALK, ROS1 and BRAF alterations were not associated with survival (all p > 0.05). Conversely, older age (HR: 1.039; p=0.029), a history of multiple brain irradiation procedures (HR 9.197; p < 0.001) and presence of extracranial metastasis (HR 2.556; p = 0.016) resulted in increased risk of mortality.

Patients requiring surgical resection of an EGFR mutated NSCLC brain metastasis had an associated improved survival compared to patients without this mutation, independent of TKI use. Decreased survival was associated with older age, multiple prior brain radiation therapies and extracranial metastasis 3).


Activating mutations in the epidermal growth factor receptor (EGFR) predict for prolonged progression-free survival in patients with advanced non-small cell lung cancer (NSCLC) treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) versus chemotherapy.


A group of patients with non-small cell lung cancer (NSCLC) have tumors that contain an inversion in chromosome 2 that juxtaposes the 5′ end of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the 3′ end of the anaplastic lymphoma kinase (ALK) gene, resulting in the novel fusion oncogene EML4-ALK


Multi-institutional analysis demonstrated that the use of upfront EGFR-TKI, and deferral of radiotherapy, is associated with inferior OS in patients with EGFR-mutant NSCLC who develop brain metastases. SRS followed by EGFR-TKI resulted in the longest OS and allowed patients to avoid the potential neurocognitive sequelae of WBRT. A prospective, multi-institutional randomized trial of SRS followed by EGFR-TKI versus EGFR-TKI followed by SRS at intracranial progression is urgently needed 4).

References

1)

Zer A, Leighl N. Promising targets and current clinical trials in metastatic non-squamous nsclc. Front Oncol. 2014;4:329. doi: 10.3389/fonc.2014.00329.
2)

Chan BA, Hughes BG. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Transl Lung Cancer Res. 2015;4:36–54.
3)

Huang Y, Chow KKH, Aredo JV, Padda SK, Han SS, Kakusa BW, Gephart MH. EGFR mutation status confers survival benefit in non-small cell lung cancer patients undergoing surgical resection of brain metastases: a retrospective cohort study. World Neurosurg. 2019 Jan 30. pii: S1878-8750(19)30210-4. doi: 10.1016/j.wneu.2019.01.112. [Epub ahead of print] PubMed PMID: 30710723.
4)

Magnuson WJ, Lester-Coll NH, Wu AJ, Yang TJ, Lockney NA, Gerber NK, Beal K, Amini A, Patil T, Kavanagh BD, Camidge DR, Braunstein SE, Boreta LC, Balasubramanian SK, Ahluwalia MS, Rana NG, Attia A, Gettinger SN, Contessa JN, Yu JB, Chiang VL. Management of Brain Metastases in Tyrosine Kinase Inhibitor-Naïve Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer: A Retrospective Multi-Institutional Analysis. J Clin Oncol. 2017 Apr 1;35(10):1070-1077. doi: 10.1200/JCO.2016.69.7144. Epub 2017 Jan 23. PubMed PMID: 28113019.
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