Molecular Tumor Board: The University of California San Diego Moores Cancer Center Experience

Abstract

Objective. DNA sequencing tests are enabling physicians to interrogate the molecular profiles of patients' tumors, but most oncologists have not been trained in advanced genomics. We initiated a molecular tumor board to provide expert multidisciplinary input for these patients. Materials and Methods. A team that included clinicians, basic scientists, geneticists, and bioinformatics/pathway scientists with expertise in various cancer types attended. Molecular tests were performed in a Clinical Laboratory Improvement Amendments environment. Results. Patients (n 5 34, since December 2012) had received a median of three prior therapies. The median time from physician order to receipt of molecular diagnostic test results was 27 days (range: 14-77 days). Patients had a median of 4 molecular abnormalities (range: 1-14 abnormalities) found by next-generation sequencing (182-or 236-gene panels).Seventy-four genes were involved, with 123 distinct abnormalities. Importantly, no two patients had the same aberrations, and 107 distinct abnormalities were seen only once. Among the 11 evaluable patients whose treatment had been informed by molecular diagnostics, 3 achieved partial responses (progression-free survival of 3.4 months, $6.5 months, and 7.6 months).The most common reasons for being unable to act on the molecular diagnostic results were that patients were ineligible for or could not travel to an appropriately targeted clinical trial and/or that insurance would not cover the cognate agents. Conclusion. Genomic sequencing is revealing complex molecular profiles that differ by patient. Multidisciplinary molecular tumor boards may help optimize management. Barriers to personalized therapy include access to appropriately targeted drugs. The Oncologist 2014;19:631-636Implications for Practice: Our study relates our experience with the initiation of molecular tumor board meetings, which are a new vehicle for managing patients with complex malignancies on whom molecular diagnostics have been performed. This experience could be of significant importance to oncologists who are increasingly faced with advanced molecular diagnostic data, yet have minimal training in genomics. Our article should help clinicians to handle practical issues related to setting up and efficiently utilizing molecular tumor board meetings. We also aim at helping oncologists and health care systems understand and address practical, logistical, and scientific issues, such as the challenges associated with interpretation of molecular testing for patients with advanced cancer. INTRODUCTIONTechnological developments in genomic sequencing are advancing at a breathtaking rate. These tests are rapidly being made available in the clinic, potentially facilitating a personalized treatment strategy [1][2][3][4]. The collaboration between biologists who interpret and confirm the functional relevance of molecular abnormalities and clinicians who assess relationships to cancer prognosis and response to therapy has led to the discovery of the activity of molecu...

Precision Oncology: The UC San Diego Moores Cancer Center PREDICT Experience

“…The median time from genomic results until treatment initiation was 2.3 months (95% CI, 1.8-3.5), often because physicians initiated testing before patients had failed their prior therapy to have a plan available in case of failure (18). The median time elapsed from the biopsy used for molecular testing until therapy initiation after tumor profiling results was 8.4 months (95% CI, 6.8-11.2).…”

“…The most common reasons that patients were treated with an unmatched therapy were patient or physician choice, or that matching drug(s) were unavailable because there was no local clinical trial(s) for which the patient was eligible or no insurance coverage for off-label drug use (17,18).…”

“…In addition to deploying larger panels, the potential for actionability has increased because targeted pharmaceuticals have rapidly entered the clinical arena. However, many patients may not be treated, despite the presence of theoretically druggable abnormalities in their malignancies, often because off-label approved medications may be difficult to acquire, and clinical trials have strict eligibility and are often restricted geographically to a few centers (18)(19)(20).…”

De l’exome à l’avatar : vers une « oncologie de précision » ?

“…On se retrouvera donc de plus en plus dans la situation où, après analyse de l'ADN de la tumeur, plusieurs possibilités de traitement sont ouvertes. Par ailleurs, l'expérience à ce jour indique que le taux de succès est faible, seuls 10 à 20 % des interventions suggérées par la génomique s'avérant efficaces [2,3]. Il devient donc très important d'avoir des indications complémentaires pour faire le meilleur choix, et le passage par un test sur un avatar portant la tumeur du patient est indubitablement une option intéressante, d'autant que les études rapportées dans cette chronique montrent toutes une bonne cohérence entre efficacité sur l'avatar et réponse chez le patient [5][6][7][8].…”

“…C'est d'ailleurs l'objectif de l'essai SAFIR02 qui démarre et inclura cette fois le séquençage NGS d'un large panel de gènes. Une autre étude, menée à l'Université de Californie, vient de faire l'objet d'une publication [3] dont les résultats sont un peu plus positifs -mais l'effectif est bien moindre et le recul insuffisant. Dans ce cas, sur 21 patients dont l'ADN tumoral a été étudié avec un panel de 236 gènes (le test Foundation one de l'entre-prise Foundation Medicine 2 ), et qui pouvaient en principe bénéficier d'un traitement ciblé, 12 ont été effectivement traités avec seulement trois résultats positifs.…”