- What is TOPOGRAPH?
- TOPOGRAPH (Therapy-Oriented Precision Oncology Guidelines for Recommending Anti-cancer PHarmaceuticals) is an independent, oncologist-led effort of cataloguing literature and evidence to streamline the process of recommending drug treatments in precision cancer medicine. This resource is intended to help oncologists find relevant literature when making treatment decisions for patients with advanced or metastatic cancer, using contemporary genomic profiling results and other assays. Currently, TOPOGRAPH provides contents with reference to the Australian public health system. This resource is actively maintained as part of a nation-wide precision oncology program.
- Why do we need another knowledge base?
-
There are a number of precision oncology knowledgebases (KBs) available, such as
OncoKB
, Cancer genome interpreter
, PMKB
, JAX CKB
, CIViC
, and ClinVar.
Efforts in harmonisation of different KBs for variant interpretation have also been established.
Most other publicly available KBs focus on delineating the significance of genomic alterations found through a diagnostic assay (e.g., comprehensive genomic profiling).
In contrast, TOPOGRAPH addresses the real-world need of oncologists by focusing on the treatment selection aspects (hence "therapy-oriented").
TOPOGRAPH uses literature and evidence to understand the implications on a treatment (drug or drug combination) in the presence of a biomarker, identified by methods of molecular profiling and/or other assays (tests).
TOPOGRAPH is designed differently from other databases.
To make this resource useful in clinics, TOPOGRAPH considers both accessibility (with respect to approval and reimbursement) and maturity of a drug (with respect to its stage of development, as well as the outcomes of relevant clinical trials) more closely.
These aspects are important to consider when making rational clinical decisions about targeted cancer therapies.
More general discussions about the rationale behind this resource can be found here .
- Why are AMP/ASCO/CAP or ESCAT criteria not used for cataloguing the therapies?
- The AMP/ASCO/CAP criteria (Li et al. J Mol Diagn 2017) was purposed to annotate clinically relevant variants from diagnostic molecular profiling. The ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) (Mateo et al. Ann Oncol. 2018) criteria was designed for ranking genomic alterations as targets in precision oncology. While both AMP/ASCO/CAP and ESCAT criteria provide valuable frameworks for evidence assessment, neither criteria can represent drug resistance/lack of drug activity succinctly, which is also important in clinical decision-making. TOPOGRAPH adapts a grading/numbering system similar to OncoKB but defines a different set of literature criterias to align more closely with the needs of oncologists in practice (See Literature assessment criteria).
- Can TOPOGRAPH be used for assessing the oncogenicity of a variant?
- TOPOGRAPH is not intended for interpreting the pathogenicity of gene variants in cancer. Expertise in molecular pathology and other resources should be consulted for this task, in addition to bioinformatic analysis, before TOPOGRAPH is used to assess whether a therapy is relevant in the presence of a variant or a biomarker. Established therapeutic guidelines should always be consulted.
- What is the latest database version?
- The latest version of the database is 20240413 (AU). See Change log.
- What are the terms of using TOPOGRAPH?
-
The contents provided by TOPOGRAPH may be used freely in academic and research settings.
Neither Garvan Institute of Medical Research or Omico accepts responsibility about the inaccuracies or incompleteness of the curation content.
FOR RESEARCH USE ONLY While TOPOGRAPH is designed as a clinical reference, the content is currently intended for research use only. Data from this website may not be used in a commercial setting. Data is shared under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) Licence.
- Can I ask for advice about treatment or refer a patient?
- TOPOGRAPH only provides information about targeted therapies and cannot accept patient referrals. For Australian patients, please send referrals to the Molecular Screening and Therapeutics (MoST) program for genomic screening and/or participation in biomarker-matched clinical trials if clinically appropriate.
- Is there an analytic tool or a clinical trial matching function?
- A suite of online tools is being developed for matching patients to Australian find cancer trials based on results of comprehensive genomic profiling.
- How do I cite TOPOGRAPH in a scienfitic paper?
- Lin FP, Thavaneswaran S, Grady JP, Ballinger M, Kansara M, Oakes SR, Desai J, Lee CK, Simes J, and Thomas DM. Criteria-based curation of a therapy-focused compendium to support treatment recommendations in precision oncology. npj Precis Oncol 2021; 5: 58. doi: 10.1038/s41698-021-00194-z
- How do I report errors or make suggestions about the website/database?
- Please contact Frank Lin for website issues and corrections of curated contents.
Curation strategy of TOPOGRAPH.
ANZCTR: Australia and New Zealand Clinical Trial Registry.
KB: knowledge base.
To make this resource more accessible in the clinic, a cascade decision algorithm has been proposed to facilitate the process of shared decision-making between a physician and a patient:
- Biomarker-driven therapies should always be considered alongside other therapeutic options not selected based on biomarker, and supportive care.
- Participation in a clinical trial is always considered the best clinical practice, if one is accessible.
- T1 therapies are recommended with exception of when a concomitant, high-level resistance biomarker is present (i.e., Tier R1) or known failure of treatment after previously exposure, intolerance, or toxicity to another drug in the same therapeutic class.
- Off-label use of T2 therapies may be considered appropriate in selected circumstances.
- T3/4 therapies are not generally recommended outside clinical trial settings, given lack of compelling clinical data to support its use.
- In exceptional circumstances where treatment options are limited for a given cancer type, off-label access of therapies with lower tier (T3/4) may be considered appropriate, if the potential value of accessing a therapy outweighs the potential harms.
