Breaking oncological paradigms
James Fleck1 & Gabriel Macedo2: Anticancerweb 28(10), 2020
At first, Precision Medicine seemed like fiction, but it gradually became clinically useful for dealing with some types of tumor for which there was no standard treatment or for patients who expressed disease progression after two or more previous unsuccessful treatments. The cornerstone was the identification of a mutation (germline or somatic) that could become a biological target or a predictive biomarker for a new pharmacological action (actionability) in a specific tumor type. Some initial disappointment was due to the low percentage of actionable mutations identified in rare tumors or refractory diseases. More recently, some cutting-edge cancer drugs with a focus on genetic biomarkers, rather than any specific type of cancer, have gained approval and changed the way we diagnose and treat malignant tumors, creating the new tumor-agnostic cancer treatment scenario. Currently, an increasing number of clinical trials are using next-generation sequencing (NGS) to recruit eligible patients, which has resulted in important advances in the understanding of tumor molecular biology, also helping in the development of new anticancer drugs. The new therapeutic options must be considered under a highly qualified multidisciplinary supervision, which has been responsible for the development of Molecular Tumor Board (MTB) concept in highly qualified cancer centers, worldwide.
A Molecular Tumor Board should follow some basic rules: The multidisciplinary team must meet regularly, preferably through videoconferences, which is time saving and allows for participation of experts from multiple institutions. A well-designed administrative profile must be implemented to optimize cost efficiency. Continuous knowledge translation must be sought not only to increase data availability, but also to improve technical education. Surgeons should be informed about the acquisition of sufficient tissue, as well as the proper handling of the material at the time of diagnostic biopsy. An ad hoc report must be provided including the NGS results in the context of each patient's specific clinical assessment. The multidisciplinary team should categorize molecular analysis results according to levels of evidence, preferably supported by prospective randomized trials and FDA approval. Several international classifications and harmonized clinical interpretations from knowledgebases (https://search.cancervariants.org/#*) are already available and the report must clearly specify which one was used. MTB generally fosters very specific and sensitive questions, asking for a comprehensive assessment of the board, which should include various specialties, such as clinical oncologists, cancer surgeons, pathologists, molecular biologists, geneticists, bioethicists, bioinformaticians, research coordinators, pharmacists, data managers, among others. The growing availability of data will soon require improvements in bioinformatics and, eventually, the use of artificial intelligence. A long-term ICER / QALY analysis will indicate the best way to face global health burden, and MTB may come to play an essential role in personalized clinical assessment of cancer patients, improving indices like NNT (number needed to treat) and NNH (number needed to harm). Participation of all stakeholders should be encouraged, generating collective intelligence. The methodology will be standardized soon and the indications expanded, making precision medicine accessible to everyone.
1. James Fleck, MD, PhD is a Full Professor of Clinical Oncology at the Department of Internal Medicine FAMED – UFRGS
2. Gabriel Macedo, MSc, PhD is the Precision Medicine Program – Coordinator at Hospital de Clínicas de Porto Alegre
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8. Photo by National Cancer Institute on Unsplash