NEW YORK (GenomeWeb) – A study published online this week in The Lancet Oncology suggests mutation patterns in seven genes may help predict outcomes for individuals with follicular lymphoma.
Starting from an existing clinical risk model known as the "Follicular Lymphoma International Prognostic Index" (FLIPI), investigators from Germany, Canada, and the US searched for additional, prognostically-informative mutations across 74 genes in more than 150 individuals with follicular lymphoma.
Mutation patterns in seven genes offered hints about patients' progression-free survival over five years, prompting the team to add these genes to a revamped prognostic model dubbed m7-FLIPI.
In the original patient group and validation experiments involving 107 more individuals with follicular lymphoma, m7-FLIPI distinguished between high- and low-risk groups more accurately than FLIPI alone, the study's authors reported.
"The m7-FLIPI could be extremely significant for the medical community, changing the story for high-risk patients who are currently destined to not respond well to standard treatment," co-senior author Randy Gascoyne, scientific director of the British Columbia Cancer Agency's Centre for Lymphoid Cancer, said in a statement.
Though many individuals with follicular lymphoma respond well to treatment, roughly one-quarter of patients fall into a high-risk group with far worse outcomes. At the moment, the FLIPI model places roughly half of those with follicular lymphoma into a high-risk group, the researchers explained, even though most of those patients won't experience relapse.
To refine predictions of treatment success for newly diagnosed follicular lymphoma patients, the team took a retrospective look at gene mutation patterns and patient outcomes in a group of 151 individuals with stage III or IV follicular lymphoma who were recruited in Germany between early 2000 and fall 2010.
"We set out to determine, at the time of diagnosis, which patients' disease will have sustained responses after treatment and whether new genetic data could help inform which patients are at risk for developing progressive lymphoma so clinicians would be able to offer these high-risk patients more effective therapies," Gascoyne explained.
Using Agilent SureSelect targeted capture enrichment coupled with Illumina sequencing, he and his colleagues sequenced the protein-coding regions of 74 suspicious genes in formalin-fixed, paraffin-embedded tumor samples taken from each individual prior to treatment.
The team then searched for genes that were more likely to be mutated in participants with poor or favorable outcomes over a median of 7.7 years of follow-up, during which the patients were treated with combination chemotherapy.
Indeed, mutational patterns in seven genes improved prognostic predictions for the patients.
When this information was added into FLIPI, the researchers identified 43 individuals in a high-risk group that had a five-year, "failure-free" survival rate of 38 percent. In contrast, they saw a failure-free survival rate of more than 77 percent for those classified in the low-risk group by m7-FLIPI.
Meanwhile, the m7-FLIPI test placed almost a quarter of the 107 follicular lymphoma patients in the study's validation cohort into the high-risk group, which had just 25 percent progression-free survival over five years compared to 68 percent in the low-risk group.
The researchers found that the m7-FLIPI test could accurately predict progression-free survival between 64 percent and 72 percent of the time, while true predictions of poor outcomes were 78 percent in the training cohort and 68 percent in the validation group.