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W. Fulp

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    MO05 - Prognostic and Predictive Biomarkers II (ID 95)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO05.03 - A gene expression platform to predict benefit from adjuvant external beam radiation in resected non-small cell lung cancer. (ID 268)

      16:15 - 17:45  |  Author(s): W. Fulp

      • Abstract
      • Presentation
      • Slides

      To date, no personalized decision-making tool exists for adjuvant radiation after resection of non-small cell lung cancer (NSCLC). Our objective was to retrospectively determine if our previously developed 10-gene expression signature, called radiosensitivity index (RSI), would classify patients into radioresistant (RSI-poor) or radiosensitive (RSI-good) using disease-free survival (DFS).

      Inclusion criteria: pathologic AJCC v6 stage III NSCLC at time of resection, negative margins, at a single institution between 2000 and 2012. Neo or adjuvant chemotherapy was required. For radiation group (RT), at least 45 Gy of conformal or intensity-modulated radiation was required. An identical stage group (control) did not receive radiation. Gene expression profiling was conducted on primary lung tumor mRNA. DFS was defined as time-to-recurrence or death from any cause. Predefined cut-point was lowest quartile of calculated RSI. Two-sided log-rank and Cox regression were used.

      Of 144 screened, 95 were eligible (53 RT and 42 control). Demographics: median age 67 yrs, 54% female, 96% white, and 91% current / former smokers. Operations consisted of 56% lobectomy, 26% pneumonectomy, and 18% segmentectomy/wedge. Adjuvant doublet consisted of 48% taxane, 32% gemcitabine, or 20% other. Mean RT dose 54.8 Gy, median follow-up 3.5 yrs. Histology: 64% adenoca, 25% squamous, 10% large-cell. Mean tumor volume 58 cm[3], 77% were pN2, 58% had angiolymphatic invasion and 51% were poorly-differentiated. Mean preoperative PET SUV~max~ was 9.5. No imbalance in clinical factors were observed between RSI-good vs. RSI-poor. On univariate analysis, for RT group, median DFS for RSI-good vs RSI-poor was 5.8 yrs vs. 1.4 yrs, HR 4.2 (95% CI 1.9 – 9.5), p = 0.017. 5-year DFS was 63% vs 22%, p = 0.01. No significant difference was observed for the chemo-only control group, with median DFS for RSI-good vs. RSI-poor: 2.3 vs 2.7 yrs, HR 0.7 (95% CI 0.3 – 1.6), p = 0.98. A test for interaction confirmed that the effect was restricted to the RT group and not the control, with p = 0.04. On multivariate analysis, for the RT group, the RSI was more strongly associated with DFS than any other variable (age, gender, tumor volume, nodal status, baseline SUV~max~, histology, grade, LVI, and operation). After inclusion of covariates, it remained an independent predictive variable with HR 3.8 (95% CI 1.6 – 9.2) p = 0.003. Figure 1

      RSI appears to be predictive for benefit from adjuvant radiation. Additional independent prospective validation is required.

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