Harpole, David H.

7008 Background: Fluoro-deoxyglucose positron emission tomography (FDG-PET) is recommended for diagnosis and staging of known or suspected NSCLC. Meta-analyses examining the accuracy of FDG-PET to diagnose lung cancer demonstrated high sensitivity 94% and specificity 83% but were performed in select centers. The purpose of this study is to evaluate the accuracy of FDG-PET to diagnose NSCLC and examine enrolling site differences in the national prospective ACOSOG Z4031 trial. Methods: 1,074 patients with clinical stage I (cT1-2N0M0) known or suspected NSCLC were enrolled between 2004 and 2006 in the Z4031 study and underwent surgical resection. The final diagnosis was determined by pathological examination. FDG-PET results were abstracted from radiology interpretations included in the case report forms. FDG-PET avidity was categorized based on either radiologist description or reported maximum standard uptake value (SUV). The four categories were: not avid and not cancerous (SUV=0), low avidity and likely not cancerous (SUV>0 and <2.5), avid and probably cancerous (SUV>2.5 and <5) and highly avid and likely cancerous (SUV>5). Sensitivity analysis of FDG-PET diagnostic accuracy was performed for varying levels of avidity and by preoperative lesion size. Differences in accuracy by enrolling site were examined. Results: There were 51 enrolling sites in 39 cities with 969 eligible participants. Preoperative FDG-PET results were available for 682 participants. Lung cancer prevalence was 83%. FDG-PET sensitivity was 82% (95% CI: 79-85), and specificity was 31% (95% CI: 23-40). Positive and negative predictive values were 85% and 26%, respectively and accuracy improved with lesion size. There were 80 false positive scans and 69% were granulomas. False negative scans occurred in 101 patients (11were ≤10mm) with adenocarcinoma, squamous, bronchoalveolar cell and neuroendocrine tumors responsible for 64%, 12%, 10% and 8% of false negative results, respectively. Specificity did not differ between the 8 sites with >25 patients (p=0.74). Conclusions: In a national surgical population with clinical stage I NSCLC, FDG-PET to diagnose lung cancer performed poorly compared to published studies. Reasons for poor test performance should be explored.

Abstract Background: Fluoro-deoxyglucose positron emission tomography (FDG-PET) scans are used for diagnosis and staging of known or suspected non-small cell lung cancer (NSCLC). Single institution studies examining the impact of avidity on survival have reported mixed results. The purpose of this study is to evaluate the association between FDG-PET avidity and survival in the national prospective ACOSOG Z4031 trial in patients with pathological Stage I NSCLC. Methods: Between 2004 and 2006, 1074 patients with known or suspected clinical stage I (cT1-2N0M0) NSCLC were enrolled in the ACOSOG Z4031 trial and underwent surgical resection. FDG-PET results were abstracted from radiology interpretations included in the case report forms. FDG-PET avidity was categorized based on either radiologist description or reported maximum standard uptake value (SUV). The four categories were: 1) not avid and not cancerous (SUV=0), 2) low avidity and likely not cancerous (SUV&gt;0 and &lt;2.5), 3) avid and probably cancerous (SUV≥2.5 and &lt;5) and 4) highly avid and likely cancerous (SUV≥5). The lesion was classified as avid if in categories 3 or 4. The final diagnosis was determined by pathological examination and all cause mortality was reported. Cox proportional hazard regression was used to assess the impact of FDG-PET avidity on survival. The covariates used in the model included pStage, gender, age, race, and preoperative lesion size. Kaplan-Meier survival curves were calculated and the log-rank test was used to determine differences in survival based on FDG-PET avidity. Results: There were 51 enrolling sites in 39 cities with 969 eligible participants. Preoperative FDG-PET results were available for 540 participants with NSCLC and 81% had FDG-PET avid or highly avid lesions. 400 patients had pStage I NSCLC and the 5 year survival was 70% with 95%CI (65%, 75%). FDG-PET avidity, male gender, age, and lesion size negatively impacted survival. FDG-PET avidity in pStage I disease still negatively impacted survival (p=0.03) when controlling for lesion size. The 5 year survival for Stage I disease was 80% with 95%CI (68%, 88%) in FDG-PET negative patients and 67% with 95% CI (61%, 72%) in FDG-PET positive patients (p=0.02). Conclusions: In a national surgical population with pathological stage I NSCLC, FDG-PET avidity negatively impacted five year survival, independently of lesion size. Further work should be done to determine if chemotherapy would be beneficial in patients with PET avid lesions and pStage I NSCLC. Citation Format: Eric L. Grogan, Stephen A. Deppen, Heidi Chen, Karla V. Ballman, Francys C. Verdial, Melinda C. Aldrich, Paul A. Decker, David H. Harpole, Robert J. Cerfolio, Robert J. Keenan, David R. Jones, Thomas A. D'Amico, Joseph B. Shrager, Bryan F. Meyers, Joe B. Putnam. FDG-PET avidity negatively impacts survival in pStage I NSCLC in the ACOSOG Z4031 trial. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-296. doi:10.1158/1538-7445.AM2013-LB-296

Purpose Adjuvant chemotherapy for resected non–small-cell lung cancer (NSCLC) is now accepted on the basis of several randomized clinical trials (RCTs) that demonstrated improved survival. Although there is strong evidence that adjuvant chemotherapy is effective in stages II and IIIA NSCLC, its utility in stage IB disease is unclear. This report provides a mature analysis of Cancer and Leukemia Group B (CALGB) 9633, the only RCT designed specifically for stage IB NSCLC. Patients and Methods Within 4 to 8 weeks of resection, patients were randomly assigned to adjuvant chemotherapy or observation. Eligible patients had pathologically confirmed T2N0 NSCLC and had undergone lobectomy or pneumonectomy. Chemotherapy consisted of paclitaxel 200 mg/m 2 intravenously over 3 hours and carboplatin at an area under the curve dose of 6 mg/mL per minute intravenously over 45 to 60 minutes every 3 weeks for four cycles. The primary end point was overall survival. Results Three hundred-forty-four patients were randomly assigned. Median follow-up was 74 months. Groups were well-balanced with regard to demographics, histology, and extent of surgery. Grades 3 to 4 neutropenia were the predominant toxicity; there were no treatment-related deaths. Survival was not significantly different (hazard ratio [HR], 0.83; CI, 0.64 to 1.08; P = .12). However, exploratory analysis demonstrated a significant survival difference in favor of adjuvant chemotherapy for patients who had tumors ≥ 4 cm in diameter (HR, 0.69; CI, 0.48 to 0.99; P = .043). Conclusion Because a significant survival advantage was not observed across the entire cohort, adjuvant chemotherapy should not be considered standard care in stage IB NSCLC. Given the magnitude of observed survival differences, CALGB 9633 was underpowered to detect small but clinically meaningful improvements. A statistically significant survival advantage for patients who had tumors ≥ 4 cm supports consideration of adjuvant paclitaxel/carboplatin for stage IB patients who have large tumors.