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VBCC - May 2013, Volume 4, No 4 - AACR Annual Meeting
Charles Bankhead

Washington, DC—A positive fluorodeoxyglucose-positron emission tomography (FDG-PET) scan distinguished patients with high-risk stage I non–small-cell lung cancer (NSCLC) who may benefit from adjuvant chemotherapy, a retrospective review of a large database showed.
The increased uptake of FDG was associated with a median 5-year survival rate of 67% compared with 80% for patients with stage I NSCLC. Subgroup analysis showed that the survival difference was attributable to patients with high-risk stage IA disease, according to a study presented at the 2013 American Association for Cancer Research annual meeting.

“FDG-PET avidity was negatively associated with survival in resected stage I non–small-cell lung cancer,” said Eric L. Grogan, MD, MPH, Assistant Professor of Thoracic Sur­gery, Vanderbilt University Medical Center, Nashville, TN. “Observations were similar in academic and community centers, meaning the results appear to be broadly applicable. FDG-PET might be useful for determining which patients with pathologic stage IA non–small-cell lung cancer might benefit from adjuvant chemotherapy,” Dr Grogan noted.

Surgery remains the primary treatment modality for stage I NSCLC. Whereas patients with stages II and III disease clearly benefit from adjuvant therapy, the results are mixed but are generally negative for stage I. The evidence suggests that chemotherapy may offer some survival advantages for patients with stage IB NSCLC, but the evidence also has consistently shown that adjuvant chemotherapy adds only toxicity to patients with stage IA NSCLC, Dr Grogan continued.

Nonetheless, the survival data for stage I NSCLC suggest the existence of a high-risk subgroup of stage I cancers, namely, stage IA. Overall, pathologic stage I NSCLC has a 5-year median survival rate of 67%, which is substantially lower than in other early-stage cancers, explained Dr Grogan. A likely contributing factor is the lack of accuracy for clinical staging. Ap­proxi­mately 30% of patients with clinical stage I disease are found to have nodal involvement at surgery, reclassifying the disease as stage II or III.

“There is an urgent need to identify this subgroup of patients with stage I non–small-cell lung cancer that is at high risk of recurrence,” said Dr Grogan.

FDG-PET avidity has proved to be a marker of poorer survival in NSCLC, but minimal data for the association have involved patients with pathologic stage I disease. In an effort to resolve the uncertainty, investigators reviewed data from an American College of Surgeons Oncology Group study that examined “proteomic” markers in serum for the detection of NSCLC.

From 2004 to 2006, patients with known or suspected clinical stage I NSCLC underwent surgical resection at 51 sites in 39 cities. The pathologic results showed that 80% of the lesions were malignant and 20% were benign.

Of the 969 patients who were eligible for this trial, 682 had FDG-PET imaging, including 400 patients with pathologic stage I NSCLC. Each scan was reviewed by experienced independent radiologists, who characterized lesions by standard uptake value and by FDG-PET avidity. The lesions’ avidity was categorized on a scale of 1 (standard uptake value = 0, not cancer) to 4 (standard uptake value ≥5.0, high avidity/likely cancer).

The primary outcome was all-cause mortality, and FDG-PET avidity–defined differences in survival were reflected in Kaplan-Meier survival curves.

Overall, 314 (78%) FDG-PET scans demonstrated avidity. Pathology showed that 275 (69%) patients had stage IA NSCLC and 125 (31%) had stage IB disease.
Stage IA disease was associated with significantly better 5-year survival compared with stage IB disease (P = .015). In addition, a positive FDG-PET scan predicted worse survival (P = .02).

Subgroup analysis showed that the FDG-PET results were influenced by differences in patients with stage IA disease. FDG-PET avidity predicted significantly worse survival in pathologic stage IA NSCLC (P = .013), but not in pathologic stage IB disease.

Multivariate analysis showed that a positive FDG-PET scan increased the survival hazard ratio (HR) by almost 80% (HR, 1.78; P = .04). Older age (HR, 1.04; P <.01) and lesion size (HR, 1.02; P = .02) were the only other independent predictors of survival.

The interaction between FDG-PET results and pathologic stage showed that a positive scan more than doubled the survival HR in patients with stage IA disease, but had no effect on survival in patients with stage IB NSCLC. Older age was the only other significant factor in the analysis
(age, 74 years vs 60 years; HR, 1.61; P <.01).

Despite the reliance on a retrospective analysis of data and the evaluation of an outcome that was not the primary end point, the varied nature of participating centers, radiologists, and PET equipment provided a reasonable facsimile of the diversity found in clinical practice, which should help make the results broadly applicable.

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