Preventing Head and Neck Tumors the Genetic Way
Genetic Variants in the PI3K/PTEN/AKT/mTOR Pathway Predict Head and Neck Cancer Patient Second Primary Tumor/Recurrence Risk and Response to Retinoid ChemopreventionHildebrandt MA, Lippman SM, Etzel CJ, et al
Clin Cancer Res. 2012;18:3705-3713
SummaryIn the Retinoid Head and Neck Second Primary trial, patients with head and neck squamous cell cancer (HNSCC) and a high risk for tumor recurrence or of developing a second primary were randomly assigned to receive placebo or to the chemopreventive agent 13-cis-retinoic acid (13-cRA). Unfortunately, this study failed to demonstrate a statistically significant favorable effect of active chemoprevention on the risk for recurrence.
Hildebrandt and colleagues explored a possible relationship between specific genetic variations in HNSCC and risk for recurrence or development of a second primary as well as response to this chemoprevention strategy.
Retrospective analysis of tumors from 440 participants from the original trial showed not only a highly statistically significant relationship between the presence of a particular genotype panel and the risk for recurrence or relapse, but also a 73% reduction in the risk for relapse or recurrence if this patient population received 13-cRA rather than placebo (median event-free survival > 93 months vs 75.1 months, respectively; P = .01; hazard ratio, 0.27 [95% confidence interval, 0.11-0.68]).
ViewpointCancers of the head and neck region pose a unique set of challenges for the oncology community. Although the majority of these cancers can be cured by local treatment with surgery and/or radiotherapy, in certain well-defined settings, the risk for disease recurrence or development of a second primary cancer in the head and neck region is quite high. As a result, there has been a long-standing interest in the development of an effective chemopreventive strategy after definitive ("curative") management of the primary lesion.
Considerable data support the potential for 13-cRA to be an effective chemopreventive therapeutic approach, but the largest randomized trial, comprising 1190 patients with early-stage disease, failed to demonstrate its utility in preventing recurrence or secondary primaries.
The current analysis must at this time be considered hypothesis-generating rather than definitive, owing to the retrospective nature of the investigation. However, it indicates it may be possible to define a unique genetic profile of an early-stage HNSCC that suggests a particularly high risk for recurrence -- and whose risk can potentially be substantially reduced after administration of 13-cRA.
Further research in the area of risk assessment as it relates to an individual cancer's genetic profile in HNSCC is clearly warranted.