Genomics is a powerful tool for mapping tumor progression/evolution with great precision in individuals. Collecting these “N of 1” cases into a common database will help identify common patterns and enable more robust conclusions about cancer diagnosis and progression.

— A. Rose Brannon & Charles L. Sawyers

Why Case Studies Matter in Precision Oncology: Tumor Heterogeneity

The clinical aspects of modern oncology are becoming ever more complex. This is an inevitable outcome of the new era of precision medicine, where patients are increasingly treated with targeted or immunotherapies, which will eventually number in hundreds, compared with the relatively small number of today’s broad-spectrum chemotherapy regiments.

How to keep an oncologist abreast of the new developments and findings that bear light on which drugs to use in which molecular context?  The relative efficacy of new drugs is initially assessed in randomized clinical trials. But the patient population reflected in trials is a relatively small and highly selective sampling of real-world afflicted individuals; to compound this problem, N of 1 studies and full case reports are rarely published because they are not sufficiently “high impact.” Given our new understanding of the heterogeneity of tumors even within a given histology or subtype, and the number of treatments and potential combinations growing at an unprecedented rate, there is no possibility of gaining a full understanding of pathways and drug efficacy through clinical trial results alone.

What is needed is a searchable database that contains information on the genetic alterations in tumors of individual patients, treatments received, and outcomes; also, where relevant and available, the likely mechanisms of resistance (by sequencing and analysis of tumors that recur).

With time, as the collection grows, it will be possible to compare outcomes relative to genetic characteristics for a variety of tumors, discern the efficacy of the treatments, and connect this to the presence or absence of other contributing mutations (as well as to clinicopathological characteristics of tumors). Thus, by finding matches in mutations, treatments, and outcomes, across all tumor types, the database transforms individual anecdotes into the sort of evidence that previously only randomized controlled trials could provide.

Now Live with Sarcoma Central

Rapid Science received generous support from Bayer, EMD Serono, Janssen, and Lilly to develop the tools for our first pilot —  Sarcoma Central, a community of healthcare professionals and researchers — to contribute patient-level data and content for discussion in open and closed groups. The international founding team, World Sarcoma Network, provided early feedback and has now been joined by clinical researchers and physicians in self-organized groups.  Because sarcoma is a rare disease with 90 or more subtypes, it is crucial to engage sarcoma specialists worldwide to compare and contrast patient responses and real-world outcomes to approved drugs, experimental drugs in trial, and combinations thereof. Features of Sarcoma Central include:

• Templates to submit anonymized, patient-level data combining diagnostic and clinical information relevant to outcomes and other topics that participants would like to discuss
• Data submissions also possible via free-text entry of key data, and/or uploaded pdfs; RS staff edits and standardizes data with automated workflow
• An ontologically informed search engine to find outcome matches across histologies, mutations, and treatments
• Convergence with the Collaboration Platform for validated professionals to post and initiate threaded discussions exceptional responders and other matters
• Permission-based open and closed groups that can be created on the fly, based on subtypes, clinical trials, grant proposals, and topics of special interest such as immunotherapy and combination therapies
• Tools for updating cases based on patient observation and progression, or to provide more complete details for an open access audience (see Rapid Science Open).
• “Organic” peer review in the closed community and formal peer review if members wish to push full case details to open access.

Sarcoma Central Founding Members

Project Leaders

• George Demetri, MD, Dana Farber Cancer Institute
• Jean-Yves Blay), MD, PhD Cancéropôle Lyon Rhône-Alpes and University Lyon

Project Advisors

• Hisham Atef, MD, PhD, Cairo University, Egypt
• Jayesh Desai, MD, Royal Melbourne Hospital, Australia
• Hans Gelderblom, MD, PhD, Leiden University Medical Center, The Hague
• Ian Judson, MD, PhD, The Institute of Cancer Research, London
• Akira Kawai, MD, National Cancer Center Hospital, Tokyo
• Robert Maki, MD, PhD, Mt. Sinai Hospital, New York
• Iwona Lugowska, MD, PhD, Maria Sklodowska Curie Memorial Cancer Centre, Warsaw
• Axel Le Cesne, MD, Institut Gustave Roussy, Villejuif Cedex, France
• Margaret von Mehren, MD, Fox-Chase Cancer Center, Philadelphia
• Richard Quek, MD, National Cancer Centre, Singapore
• Piotr Rutkowski, MD, PhD, Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw
• Gary Schwartz, MD, PhD, New York-Presbyterian/Columbia University Medical Center
• Silvia Staccioti, MD, Fondazione IRCCS Istituto Nazionale Tumori, Milan
• David Thomas, MD, PhD, Garvan Institute of Medical Research, Sydney, Australia
• Claudia Valverde, MD, PhD, Hospital Vall d’Hebrón, Barcelona
• Winette van der Graaf, MD, PhD, The Institute of Cancer Research, London