Objectives, challenges and opportunities of new IASLC Molecular Database Project
Reviewed by Emily Henderson, B.Sc.Mar 31 2021
A new Molecular Database Project initiated by the International Association for the Study of Lung (IASLC) will accelerate the understanding of lung cancer biology, clinical care and care delivery on a global scale and will improve the prognosis and optimal treatment of lung cancer across time and space, according to an editorial in the Journal of Thoracic Oncology, an official journal of the IASLC. The editorial can be viewed here: https://www.jto.org/article/S1556-0864(21)01781-0/fulltext.
In the editorial, the IASLC Staging and Prognostic Factors Committee's Molecular Sub-Committee, and committee members, emphasized that there is great opportunity, with the emergence of molecular biomarkers of disease behavior, to improve treatment and survival.
"Biomarker testing, the portal to personalized treatment of lung cancer, has splintered a once seemingly monolithic disease into fragments of genomic and proteomic disease subsets with widely different, but generally improving, treatment and survival expectations," the committee wrote in the editorial.
Staging serves three main purposes: communication, prognostication and direction of treatment. The Tumor (T), Node (N), and Metastasis (M) system is a strictly anatomy-based communication of the extent of cancer and, by inference, its likely effects on quality of life and death (prognosis), which then informs the choice of treatment modalities. Since its introduction between 1966 and 1968, the TNM staging system has facilitated communication about lung cancer across time and space, bridging geographic, linguistic, healthcare infrastructural, socioeconomic and cultural differences. The system has gone through seven revisions, each designed to improve its utility in identifying anatomic clusters of patients with similar prognoses, and, indirectly, improve its practical utility in guiding treatment.
As of December 2020, nine genomic/protein markers could be used to select US Food and Drug Administration (FDA)-approved treatment for stage IV lung cancer (EGFR, ALK, BRAFV600E, ROS1, NTRK, MET exon 14 skipping, and RET mutations; PD-L1 Tumor Proportion Score of > 50%; and microsatellite instability high or mismatch repair deficient tumors). Drugs targeting two other biomarkers, mutations of ERBB2 and KRASG12C, received FDA breakthrough therapy designation for fast-tracked clinical development.
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"This trend will only increase with time along with the list of prognostic and predictive markers," the editorial states.
Objectives of the molecular database project include:
- Provide a global platform for a deeper, broader understanding of the value of molecular testing, and targeted therapy for prognostication, prediction and treatment selection across the full spectrum of TNM stage.
- Evaluate novel single or multiple prognostic markers that could add biological information. regarding the outcome of patients in the different TNM stages. These novel prognostic factors would add to the current clinical gold-standard criteria and would be formally considered using criteria developed by the Prognostic Factors Subcommittee, and the Minimal Standards Working Group.
- Create evidence in a set of highly characterized lung cancers with complete clinical, pathologic and staging information to support the role of biomarkers in lung cancer diagnosis, prognosis and treatment selection, across the stage spectrum.
- Create evidence to support advocacy for routine genomic testing where appropriate.
- Define important research questions that might be the focus of observational studies, pragmatic trials and clinical trials of existing and emerging biomarkers and therapeutics.
- Invite applications for projects to analyze the molecular database.
Individuals and groups interested in contributing data to the IASLC Staging Project can download the appropriate forms and instructions from the IASLC website. Application forms are available at http://www.iaslc.org. Click the Research & Education tab and go to Staging Project.