Study Suggests Prognostic Molecular Assay More Accurate than Conventional NCCN Criteria in Stratifying Risk in Early-Stage NSCLC Patients
Building on earlier retrospective validation studies, a team of Thoracic Oncology Program researchers, demonstrated in a small prospective study the clinical utility of a 14-gene expression assay in stratifying risk among non-small cell lung cancer (NSCLC) patients. In a recently published paper in the journal Clinical Lung Cancer, lead author Gavitt Woodard, M.D., a general surgery research resident in the Thoracic Oncology Laboratory, and coauthors David M. Jablons, M.D. (pictured second) and Michael Mann, M.D., (pictured 3rd) began to address a key question regarding widespread use of the assay known as Pervenio Lung RS*: Will this assay succeed in a prospective cohort of patients at better identifying high risk patients who might benefit from additional, potentially life-saving therapy than the criteria currently listed in published guidelines, as it has in previous retrospective training and independent validation studies?
The paper looked at the first 52 patients whose tumors were analyzed prospectively with the Pervenio Lung RS assay at UCSF, and asked whether or not the test accurately categorized the patients as high or low risk. In addition, it directly compared the relative success of the molecular assay to the success of the published National Comprehensive Cancer Network (NCCN) guidelines for differentiating high risk. Those guidelines currently rely on their criteria to determine candidacy for chemotherapy based entirely on risk, so an improvement in risk stratification has important implications for clinical practice.
Michael Mann, M.D., a Clinical Professor of Surgery at UCSF, was encouraged by the study's findings. "The results are striking. All of the recurrences were observed among the molecular high risk patients. In other words, none of the low risk patients recurred. Even though traditional staging continued to classify all of these patients as “early stage” – meaning that their chances of surgical cure should be very high - there was an overall 12% recurrence rate within just a short, 15-month mean follow-up."
"That is why an assay that better stratifies risk is so desperately needed by clinicians: we know from previous studies that high risk patients are the most likely to benefit from post-operative chemotherapy that can prevent recurrence and subsequent death. In this small cohort, the molecular test far outperformed the NCCN guidelines in identifying those high risk patients: one third of the recurrences occurred among patients who had been classified by NCCN criteria as low risk (again compared to 0% of the Pervenio low risk patients), including patients that NCCN called low risk, but that Pervenio identified as high risk."
"Overall, molecular risk assessment was discordant from NCCN criteria in 14 of 23 patients in stages Ib and IIa (61%). Importantly, in this critical category of Stage Ib-IIa patients, patients for whom these criteria are the only guideposts to determine treatment, a higher percentage of NCCN low risk patients recurred (20%) than of NCCN high risk patients (11%), whereas recurrences were only observed among Pervenio high risk patients in this critical subgroup."
Co-author David Jablons, M.D., leader of the Thoracic Oncology Program at the Hellen Diller UCSF Comprehensive Cancer Center, said of the results, “this study suggests that treatment decisions would have been better guided by Pervenio than by conventional NCCN guidelines in this prospectively tested, completely independent cohort of patients. This is a strong demonstration, albeit in a small cohort, of the assay’s ultimate clinical utility.”
The assay had previously been validated in some of the largest studies ever published on the molecular analysis of early stage lung cancer. In a series of international retrospective studies, the molecular assay was used to determine risk of post-operative death in roughly 1,500 patients. As in this prospective cohort of UCSF patients, the molecular assay successfully differentiated risk, and outperformed published NCCN high risk criteria.
*Drs Jablons and Mann serve as consultants to Life Technologies, which markets the Pervenio Lung RS