Positron Emission Tomography 18F-Fluorodeoxyglucose Uptake and Prognosis in Patients with Surgically Treated, Stage I Non-small Cell Lung Cancer: A Systematic Review

Background18F-fluorodeoxyglucose (FDG) uptake holds potential as a noninvasive biomarker in patients with non-small cell lung cancer (NSCLC). We aimed to investigate the association between tumor FDG uptake and survival in patients with surgically resected, stage I NSCLC.MethodsWe used systematic methods to identify studies for inclusion, assess methodological quality, and abstract relevant data about study design and results.ResultsOur literature search identified 1578 citations, of which nine retrospective, cross-sectional studies met eligibility criteria. In all studies, higher degrees of FDG uptake in the primary tumor were associated with worse overall or disease free survival after 2 to 5 years of follow-up, but these differences were statistically significant in only five studies. Across studies, the median overall or disease free survival was 70% for patients with higher FDG uptake compared with 88% for patients with lower FDG uptake. In three studies that performed multivariable analysis, the adjusted hazard of death or recurrence was 1.9 to 8.6 times greater in patients with higher FDG uptake.ConclusionCurrent evidence suggests that increasing tumor FDG uptake is associated with worse survival in patients with stage I NSCLC. FDG uptake has the potential to be used as a biomarker for identifying stage I patients who are at increased risk of death or recurrence and therefore could identify candidates for participation in future trials of adjuvant therapy

A Phase II First-Line Study of Gemcitabine, Carboplatin, and Bevacizumab in Advanced Stage Nonsquamous Non-small Cell Lung Cancer

Background:Bevacizumab improves responses and progression-free survival when added to first-line paclitaxel/carboplatin or cisplatin/gemcitabine for patients with advanced nonsquamous non-small cell lung cancer. This study was designed to evaluate toxicities and efficacy of gemcitabine/carboplatin/bevacizumab.Methods:Patients with untreated advanced nonsquamous non-small cell lung cancer, with no evidence of brain metastases and not on anticoagulation were eligible. Patients received gemcitabine 1000 mg/m2 on days 1 and 8; carboplatin area under the curve 5 day 1; and bevacizumab 15 mg/kg day 1 every 3 weeks for up to six cycles. Bevacizumab was then continued every 3 weeks until disease progression or unacceptable toxicity.Results:From July 2006 to December 2008, 48 patients were enrolled: 23 (48%) men, 25 (52%) women, and 19 (40%) never smokers. One patient never received therapy and is not included in the analysis. Median cycle number was 8 (1–42) with 37 patients (78.7%) completing ≥4 cycles of three drugs. Dose reductions occurred in 34 (72.3%) patients. Grade 3/4 toxicities included neutropenia (47%/15%), thrombocytopenia (11%/15%), anemia (6%/0%), dyspnea (6%/2%), bacterial pneumonia (4%/0%), and hypertension (4%/2%). No neutropenic fevers occurred. One patient died of hemoptysis. Grade 3 bleeding occurred in three other patients. There were seven (14.9%) partial responses. Median time to first event (progression/death/toxicity requiring discontinuation) was 6.4 months (95% confidence interval: 4.8–7.9 months). The median overall survival (OS) was 12.8 months (95% confidence interval: 10.0–16.5). The OS is 57% at 1 year and 10% at 2 years.Conclusions:Although perhaps skewed by a high proportion of nonsmokers and women, treatment with gemcitabine/carboplatin/bevacizumab has an acceptable toxicity profile with promising median OS despite a low response rate