Patient case: 54-year-old female with lung adenocarcinoma; genetic feature: SND1-BRAF fusion

Clinical trial: Personalized Oncogenomics (POG) Program of British Columbia

Summary: The genomic heterogeneity of cancers implies that to effectively use targeted therapies the investigators will need to assess each individual cancer and match it to a biologically relevant targeted therapy. The investigators will use full genome sequencing to try to identify cancer "drivers" and corresponding drugs that may inhibit these pathways.

Detailed description: Carcinogenesis is an immensely complex process such that even within a histologic cancer subtype - for example adenocarcinoma of the lung or breast - there is significant variability in cancer behaviour and response to therapy. Analyses of individual patients demonstrate unique molecular signatures for every cancer examined. Frequently, multiple different pathways are involved in disease growth and progression and the dominant process varies from person to person and perhaps even within different sites of disease within one person. As well these variations evolve in response to treatment.
  Recognizing genetic aberrations that promote disease facilitates targeted treatment; this has been demonstrated in several small subgroups of cancers in which specific genetic mutations or translocations have been successfully treated with targeted chemotherapy agents. With many recognized mutations and aberrations, personalized evaluation of the genetic signature encoded in DNA and RNA may provide important diagnostic information and potentially enable directed therapy to the appropriate oncologic pathway thereby providing information to help guide chemotherapy choices
  Our initial pilot project demonstrated the feasibility of this approach at our institution (with 100 patients). We now know it is possible to identify and consent patients, sequence the genome and transcriptome, analyze and report abnormalities, and identify potential actionable targets in a clinically relevant time frame.
  The overarching theme of this POG Program is to create a comprehensive cataloguing of somatic cancer mutations and cellular pathway abnormalities that could generate profound insights into genetic patterns that underlie particular cancer phenotypes, and provide valuable prognostic and predictive information.
  Eligible subjects will have several samples analyzed: a fresh tumour biopsy (typically 5 cores are required), a blood sample for normal comparison and archival tumours when available. Comprehensive DNA and RNA sequencing is performed followed by an in-depth bioinformatic analysis to identify somatic mutations, gene expression changes or other abnormalities that might be cancer "drivers" or provide actionable (diagnostic) or druggable targets. The POG team meets every week to discuss the detailed genomic reports for patients, consider additional validation tests when necessary, and debate research questions. The clinicians (typically 5 - 10) come to a consensus on what systemic therapies might be appropriate based on these results. Whenever possible subjects are matched to clinical trials.

Eligibility: Inclusion Criteria:
  -  1. Patients must have histologically or cytologically confirmed diagnosis of cancer; if this is not available but metastatic cancer is virtually certain because of the clinical and radiographic presentation then a POG program biopsy could be done concurrently with a diagnostic biopsy to minimize invasive testing for patients. If the biopsy turned out not to be cancer then the POG analysis may be cancelled.
  2. This cancer must be incurable, as defined by their treating oncologist (generally due to advanced stage).
  3. Patients must agree to provide archival tissue and agree to undergo at least one study specific biopsy at baseline and a blood test for genomic analysis. All subjects will also have a biopsy and blood samples at progression if it could be done safely.
  4. ECOG PS 0 or 1.
  5. Patients may have previously received one line of palliative systemic therapy and/or palliative radiation therapy as needed. In addition, hormone therapy or one line of biologically targeted therapy (such as EGFR inhibitors, BRAF inhibitors, VEGF inhibitors) is permitted and would not count as a line of therapy. Such that a patient could have one line of systemic therapy and one line of hormone or targeted therapy and still be potentially eligible. If the targeted therapy is given concurrently with the systemic chemotherapy that would count as one line of treatment.
  6. Age > 18 years of age.
  7. Patient consent must be obtained according to the BCCA requirements.
  8. Patients must be accessible for follow-up and must be registered at the BCCA. The intention of this program is to serve the population of B.C. such that it is only open to patients currently living and receiving treatment in BC. The ability to track subsequent treatments and outcomes is essential.
  9. Estimated life expectancy of > 6 months.
  Exclusion Criteria:
  -  1. Unable or unwilling to undergo tumour biopsy(s) and/or blood/skin samples for normal DNA.
  2. Significant medical condition that in the opinion of the treating or consenting oncologist renders the subject not suitable for participation.
  3. Unwilling or unable to provide treatment and outcome follow up information to the BCCA investigators.
  4. Patients not currently living in and receiving treatment in BC.

Relevance to patient case: possibly relevant