DOI: 10.25934/pr00007070
title: Anaplastic Lymphoma Kinase- Brain Prognostic Index (ALK-BPI)  a novel prognostic score for brain metastasized ALK+ Non Small Cell Lung Cancer (NSCLC)

description: Lung cancer is divided nowadays in different subgroups, depending on the biological profile of the cancer cells. The most common type of lung cancer is tobacco related and is usually diagnosed after the age of 50.  An oncogenic driver is a mutation in the human DNA that is almost solely responsible for the development, growth and spread of cancer. One of the first oncogenic drivers to be reported in lung cancer was the fusion of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) (EML4-ALK) in 2007. Subsequently, other gene fusion partners to ALK were identified; EML4 is the most common of these, and ALK-rearrangements are found in 4–7% of non-small cell lung cancer (NSCLC) patients, mostly in younger patients with light or non-smoking history and adenocarcinoma histology. Brain metastases (BM) are common in patients with Non Small Cell Lung Cancer (NSCLC) and are related with a worse prognosis. Around 45% of patients with advanced non oncogenic-driven NSCLC and up to 70% of oncogenic-driven NSCLC develop BM over the course of their disease. In newly diagnosed, metastatic ALK-positive lung cancer, the incidence of BM varies from 20% to 30%, and the overall incidence of postdiagnosis BM increases over time, standing at 23.8% after 1 year, 45.5% after 2 years and 58.4% after 3 years.
Several prognostic scoring systems have been used to aid decision making and for estimating survival for patients with lung cancer and brain metastases. These scores are based on clinical parameters that affect the survival of these patients. The prognosis of patients with brain metastatic ALK-rearranged NSCLC has become significantly better thanks to the introduction of targeted therapies. Some of these targeted therapies, like the second-generation tyrosine kinase inhibitors (TKIs) alectinib and brigatinib are approved as a first-line treatment for spread disease; their use reduces the risk of developing brain metastases. These drugs (TKIs) kill lung cancer cells that have this specific mutation (ALK translocation), and are one of the best examples of personalised cancer medicine. 
We have recently published a Preliminary Study of a Prognostic Tool for Patients with ALK-Rearranged, Non-small Cell Lung Cancer and Brain Metastases, ALK- Brain Prognostic Index (ALK-BPI)  (Cancers, 2020). The variables used for ALK-BPI are sex, performance status ( i.e. the general condition of the patient) and the presence or absence of BM at lung cancer diagnosis. ALK-BPI has two prognostic groups; The good prognosis group had a median overall survival (mOS) of 65.7 months and the poor prognostic group had a mOS of 22.7 months in the publication of our study group in Cancers journal. Therefore, ALK-BPI score is a prognostic tool that can easily be applied for ALK-positive lung cancer patients with BM in daily clinical practice, and that has at least the same, if not better, prognostic value as the Lung-mol Graded Prognostic Assessment (GPA) score. The GPA score is the most validated and most widely used scoring system to date. These scoring systems like Lung-molGPA classify patients in different prognostic categories and help the clinician choose the right treatment for each patient. This means that patients with good prognosis can receive all available treatments and they can live longer with a better quality of life. On the other hand patients in the bad prognostic groups can be identified earlier, have tight follow-up and eventually be included in clinical trials so that we can understand the biology of the disease better and eventually find better treatments in the future. The ALK-BPI score is planned to be validated in a larger cohort consisting of brain metastatic ALK-positive patients receiving ALK-TKI in a first-line setting.
Prognostic scores like ALK-BPI can be used as stratification factors in future randomized clinical trials in order to identify which patients benefit the most from exisiting ALK TKIs, as alectinib, and eventually identify patients who do not respond so well and further research on different treatment approaches that will enhance their prognosis.