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A.V. Louie



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    MINI 18 - Radiation Topics in Localized NSCLC (ID 139)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      MINI18.08 - A Systematic Review of Comparative Effectiveness Studies of Surgery versus SABR in Early Stage Lung Cancer: How Good Is the Data? (ID 1549)

      16:45 - 18:15  |  Author(s): A.V. Louie

      • Abstract
      • Presentation
      • Slides

      Background:
      Three prospective randomized control trials (RCTs) comparing stereotactic ablative radiotherapy (SABR) and surgery in early stage non-small cell lung cancer (ES-NSCLC) failed to complete accrual. Numerous other comparative effectiveness studies have been published, but such studies may be more prone to bias, and conclusions may vary based on study quality. The goal of this study was to perform a systematic review of comparative effectiveness studies that compare both treatment modalities in this patient population, to assess study quality and conclusions.

      Methods:
      In accordance with PRISMA guidelines, a systematic review was conducted on studies reporting on comparative outcomes of surgery versus SABR for ES-NSCLC. Studies published in the English language over a 10-year period (April 2006-March 2015) were identified using PUBMED with an inclusive search strategy, using the National Library of Medicine’s medical subject headings. Eligible study designs included RCTs, population analyses, match pair comparisons, propensity-match score comparisons, retrospective case-control series, decision analyses, and cost-effectiveness analyses. Letters, editorial and systematic reviews were excluded. Abstracts identified were independently reviewed by two investigators to determine eligibility, with discrepancies settled by a third investigator. Using a standardized data abstraction form, study, patient, tumor, and treatment characteristics were abstracted. As patients undergoing surgery and SABR often differ in their baseline characteristics, we determined the proportion of studies reporting statistical adjustment for baseline characteristic imbalances (e.g. matching in patient studies, sensitivity analyses in modeling studies). The Fisher’s exact test was used to determine if there was an association between the use of statistical adjustment and differences in overall survival (OS) findings.

      Results:
      Of the 568 studies identified by our search strategy, 22 were eligible for analysis. Primary study design was retrospective (n=11), population-based (n=7), or model-based (n=4). Most patient studies (n=17) reported on a statistical adjustment for differences in baseline characteristics, with propensity score matching (n=12) being the most common technique employed. All studies, except for 1, reported details of the type of surgery performed. SABR doses employed ranged from 30 Gy in 1 fraction, to 60 Gy in 3 fractions. The weighted average pathologic confirmation of malignancy rate for SABR patients was 72% (range 22-100%). Of the 20 studies reporting on overall survival, 12 found that SABR and surgery were equal, or sensitive to variability in baseline patient, treatment, or tumor factors. The remaining 8 studies reported an overall survival benefit of surgery over SABR, however, 4 of these studies did not employ statistical adjustments for baseline characteristics. In the other 4 studies reporting overall survival superiority of surgery when controlling for various co-variates, at least one other recurrence endpoint (local, regional, or distant) was found to be equal between surgery and SABR. All but 2 studies stated in their conclusion that future clinical trials are warranted to investigate the role of SABR in the potentially operable ES-NSCLC patient.

      Conclusion:
      A systematic review of the comparative effectiveness literature indicates that the results of well-controlled studies comparing surgery and SABR argue for clinical equipoise. Results of a pooled analysis of two international RCTs that closed prematurely are expected shortly.

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    MINI 32 - Topics in Localized Lung Cancer (ID 166)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      MINI32.14 - Primary Early-Stage Lung Cancer Following Head and Neck Cancer: A Population Based Study of Treatment and Survival in the Netherlands (ID 1433)

      18:30 - 20:00  |  Author(s): A.V. Louie

      • Abstract
      • Presentation
      • Slides

      Background:
      Second primary lung cancer (SPLC) is an important cause of death in survivors of head and neck squamous cell cancer (HNSCC). The goal of this Dutch population study was to compare treatment patterns and outcomes in early-stage SPLC after HNSCC.

      Methods:
      Details on all patients in a population of 16 million diagnosed with lung cancer between 1997 and 2011 were obtained from the Netherlands Cancer Registry. After excluding patients with a history of other malignancies, patients were dichotomized with a primary lung cancer or a SPLC after HNSCC. The latter included oral cavity, oropharynx, larynx, and hypopharynx sub-sites. Baseline characteristics of early-stage primary and SPLC were compared using the chi-square, fisher’s exact, or t-test, where appropriate. After stratifying patients into five consecutive 3-year time periods, the Chi-Square Trend test was used to determine trends in treatment patterns over time. Overall survival was calculated using the Kaplan-Meier method, and the log-rank test used to assess differences in survival. 30- and 90-day treatment related mortality were calculated. To assess for stage migration due to routine availability of PET-staging, as well as the availability of stereotactic ablative radiotherapy (SABR), outcomes were analyzed before and after 2005. All statistical tests were two-sided and considered significant when p<0.05.

      Results:
      Of the 153,330 lung cancer patients, 19,501 with a history of a non-HNSCC primary cancer were excluded from the analysis. Of the 133,829 remaining patients, 2,556 (2%) represented a SPLC following HNSCC. SPLC patients were more likely to present in stage I (27% versus 16%, p<0.01) rather than stage IV (34% versus 44%, p<0.01). For early-stage SPLC, initial HNSCC anatomical subsites were most commonly larynx (53%) and oral cavity (24%). Treatment for early-stage SPLC included surgery (53%), radiotherapy (RT, 33%), or best supportive care (14%). The proportion of RT patients undergoing SABR was unknown. When compared to surgery, early-stage SPLC patients receiving any-form of RT tended to be older, with more advanced T-stage disease, poorly differentiated histology, and lower rates of pathologic diagnosis (all p<0.01). The proportion of all early-stage lung cancer patients receiving surgery over time remained stable in the primary setting (range: 59-63%, p=0.69), but decreased for early-stage SPLC patients (range: 68-42%, p<0.01). The use of RT increased over time for both primary (range: 21-30%, p<0.01) and early-stage SPLC patients (range: 23-43%, p<0.01). 30- and 90-day treatment related mortality rates were higher in surgical versus RT patients in both pre-2005 (3.8%, 8.6% versus 4.0%, 8.0%) and post-2005 (2.3%, 4.0% versus and 0%, 3.2%) eras. Overall, early-stage SPLC surgical patients had improved survival when compared to RT patients (p<0.01). In the post 2005 era, however, survival was similar for these two modalities (p=0.13).

      Conclusion:
      In survivors of HNSCC who develop early-stage SPLC, RT deserves attention as an alternative gold standard to surgery. Previous studies indicated that a majority of RT delivered for early-stage NSCLC after 2006 was SABR [Palma D, 2010]. Despite negative selection of poorer baseline characteristics, use of RT resulted in comparable survival and lower post-treatment mortality when compared to surgery in the modern era.

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