Like travelers who roam curious lands, oncologists who delve into tumor genetics may find themselves in need of local guides, experts who will put them on the right path. As far as oncologists are concerned, the right path is the one that leads to an effective therapy, but in difficult-to-treat cases, the path to the best treatment plan may diverge from familiar trails, with the twists and turns following the contours of a tumor’s unique genomic landscape.
To make such landscapes less forbidding and the paths through them less tortuous, oncologists may consult with other experts such as basic scientists, geneticists, and bioinformatics scientists. Such a pathfinding exercise has, in fact, been carried out. At the University of California, San Diego Moores Cancer Center, researchers put together an advisory group, a tumor board, to analyze the results of molecular profiles.
As explained by the researchers, who presented their work in the May 5 online issue of The Oncologist, the tumor board convened medical, surgical, and radiation therapy oncologists; biostatisticians; radiologists; pathologists; clinical geneticists; basic and translational science researchers; and bioinformatics and pathway analysis specialists. These multidisciplinary experts were then charged with discussing the intricacies of tumor genetics and tailoring a personalized treatment plan for difficult-to-treat patients. These patients were struggling with advanced cancer, had exhausted standard therapies, or were receiving treatments that physicians feared would become ineffective.
The 34 patients in the study had received a median of three prior therapies. In addition, they had a median of four molecular abnormalities found by next-generation sequencing (182- or 236-gene panels).
“We found 74 genes with 123 aberrations involved in cancer growth,” said Razelle Kurzrock, M.D, director of the Center for Personalized Cancer Therapy at the Moores Cancer Center. “No two patients had the same aberrations, and 107 distinct anomalies were seen only once.”
"Cancer can be different in every patient," added Barbara Parker, M.D., Moores Cancer Center deputy director for Clinical Affairs. “Standard therapy can be very efficient for many patients, but for those who do not respond to conventional treatment, we need to find alternatives that will work for their disease.” In particular, it may be necessary to individualize therapy to a patient’s genetic makeup if that patient does not respond to standard care or appears to have disease that has become drug resistant.
The study, as detailed in “Molecular Tumor Board: The University of California San Diego Moores Cancer Center Experience,” focused on 11 “evaluable” patients whose treatment had been informed by molecular diagnostics: three of these patients 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, noted the study’s authors, 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.”
“We have found that molecular diagnostics play an important role in patient care when paired with the expertise of a molecular tumor board,” said Maria Schwaederle, PharmD, lead author and a researcher in the Center for Personalized Cancer Therapy. “However, the immense complexity of tumors and their genomic aberrations will require sophisticated computer technologies for optimal interpretation.”
In addition to the interpretive challenges posed by next-generation sequencing, there are more mundane if equally consequential difficulties. As indicated in the study’s conclusion, “Barriers to personalized therapy include access to appropriately targeted drugs.”