Meyers, Bryan F.

7524 Background: A multicenter study (Z4032) compared sublobar resection (SR) to sublobar resection with brachytherapy (SRB) for stage I NSCLC. Local recurrence (LR) and overall survival (OS) rates at 3-years (3-yr) were similar between arms (see abstract 113613). This analysis combines arms, and evaluates the effect of factors previously reported to impact oncological outcomes after SR. Methods: 213 patients (pts) were evaluable for analysis. LR was defined as recurrence at the staple line (local progression), same lobe away from the staple line, or within hilar nodes. Factors assessed for impact on 3-yr outcomes were: resection type (wedge/segmentectomy), margin size (<1cm /≥1cm), margin:tumor ratio (<1/ ≥1), tumor size (≤2cm/>2cm) and staple line cytology (+/-). Results: LR occurred in 27/213 (12.6%) pts and included local progression in 12/213 (5.6%). OS rate at 3-yr was 152/213 (71.4%). Trends favored the use of segmentectomy, margin:tumor ratio≥1, tumor size ≤2cm and negative staple line cytology; no factor reached statistical significance at 3-yr. The only factor significantly (p=0.02) associated with decreased 3-yr LR was margin size ≥1cm (8.3%) compared to margin<1cm (19.3%). Conclusions: SR is a good option for high-risk pts with NSCLC. The 3-yr OS rate of 71.4% and local progression rate of 5.6% are useful benchmarks to compare to other therapies. A resection margin of at least 1 cm is desirable. Clinical trial information: NCT00107172. [Table: see text]

7502 Background: Prior studies suggest that adjuvant brachytherapy reduces local recurrence (LR) after sublobar resection (SR) for NSCLC. A multicenter randomized study was undertaken in patients (pts) with stage I NSCLC ≤3cm comparing SR to SR with brachytherapy (SRB). Methods: High-risk operable patients with NSCLC were randomized to SR or SRB. Brachytherapy involved placement of I125 seeds incorporated into Vicryl sutures or into Vicryl mesh placed over the staple line. Wedge or segmental resection was allowed. The primary endpoint was time to local recurrence (LR) defined as recurrence within the primary tumor lobe at the staple line (local progression), away from the staple line or within hilar nodes. The trial was designed to have 90% power to detect a hazard ratio (HR) of 0.315 in favor of the SRB arm using a one-sided α of 0.05 with a sample size of 100 eligible pts per arm. Follow-up CT scans were obtained serially for 36 months. Results: 224 pts were randomized; 213 (109 SR,104 SRB) were eligible. Median (range) age was 71 (49-87) yrs; 94 (44%) were male. No differences were found in baseline characteristics. Adverse events, previously reported, were not different between arms. Median (range) follow-up was 4.06 (0.04, 5.0) yrs. There was no difference between arms in time to LR (HR = 0.87; 5% CI: 0.41, 1.86, p=0.72) or to LR or death (LRD) (HR = 0.81, 95% CI: 0.50, 1.32, p=0.40). There was no difference between arms in pattern of LR (table). In subgroups of pts with potentially compromised surgical margin (margin < 1cm; margin:tumor ratio <1; positive staple line cytology) SRB did not reduce LR or LRD at 3-yrs. Overall 3-yr survival was similar for SR (71%) and SRB (72%) (p=0.81). Conclusions: LR remains a concern after sublobar resection. However, local progression at the staple line was low. This trial demonstrated that adjuvant brachytherapy does not impact oncologic outcomes. Clinical trial information: NCT00107172. [Table: see text]

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 A major concern with sublobar resection (SR) for non–small-cell lung cancer (NSCLC) is high local recurrence (LR). Adjuvant brachytherapy may reduce LR This multicenter randomized trial compares SR to SR with brachytherapy (SRB). Patients and Methods High-risk operable patients with NSCLC ≤ 3 cm were randomly assigned to SR or SRB. The primary end point was time to LR, where LR included recurrence at the staple line (local progression), in the primary tumor lobe away from the staple line, and in ipsilateral hilar nodes. The trial was designed to have a 90% power to detect a hazard ratio (HR) of 0.315 in favor of SRB, using a one-sided type I error rate of 0.05 with a sample size of 100 eligible patients in each arm. Results Two hundred twenty-four patients were randomly assigned; 222 patients were evaluable for intent-to-treat analysis. Median age was 71 years (range, 49 to 87 years). No differences were found in baseline characteristics. Median follow-up time was 4.38 years (range, 0.04 to 5.59 years). There was no difference in time to LR (HR, 1.01; 95% CI, 0.51 to 1.98; log-rank P = .98) or in the types of LR. Local progression occurred in only 17 (7.7%) of 222 patients. In patients with potentially compromised margins (margin < 1 cm, margin-to-tumor ratio < 1, positive staple line cytology, wedge resection, nodule size > 2.0 cm), SRB did not reduce LR, although trends favored the SRB arm. This was most marked in 14 patients with positive staple line cytology (HR, 0.22; P = .24). Three-year overall survival rates were similar for patients in the SR (71%) and SRB (71%) arms (P = .97). Conclusion Brachytherapy did not reduce LR after SR. This finding may have been related to closer attention to parenchymal margins by surgeons participating in this study.