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C. Ahn



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    ORAL 22 - Moving Beyond a Smoking Related-Cancer to the Young, Never-smokers and Inherited Disease (ID 117)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      ORAL22.01 - Increasing Incidence of Never Smokers in Non Small Cell Lung Cancer (NSCLC) Patients (ID 707)

      10:45 - 12:15  |  Author(s): C. Ahn

      • Abstract
      • Presentation
      • Slides

      Background:
      It is estimated that 10-15% of lung cancer cases occur in never smokers. The cause of lung cancer in these patients includes many possible environmental factors but the precise cause in a given case is often uncertain. Additionally, there has been significant debate about whether the rate of lung cancer in these never smokers is increasing. Using our institutions’ cancer registry data, our objective was to determine if the proportion of never smokers with lung cancer is increasing.

      Methods:
      We conducted a retrospective study using lung cancer registry data from The University of Texas Southwestern Medical Center in Dallas, Parkland Hospital in Dallas, and Vanderbilt University in Nashville. These registries were queried between 1990 and 2013 for demographic information including gender, age at diagnosis, diagnosis [non small cell lung cancer (NSCLC) or small cell lung cancer (SCLC)], and self-reported smoking history. A total of 10,568 NSCLC cases and 1504 SCLC cases were analyzed. Logistic regression analysis was performed to assess the incidence of never smokers with lung cancer.

      Results:
      The percentage of never smokers increased among NSCLC pts between 1990 and 2013 [Table 1]. Univariate logistic regression demonstrated an increasing proportion of never smokers among NSCLC cases (p < 0.0001 for year) and multivariate logistic regression also demonstrates this increase (p < 0.0001 for year) after controlling for age and gender. Never smokers with NSCLC were more likely to be female (65.3%, p < 0.0001) than males. The increase in the percentage of NSCLC never smokers was seen at both university hospitals and the Dallas county hospital. In contrast, the percentage of never smokers among SCLC cases did not significantly increase during this time period. Table 1: Percentage of never smokers Figure 1



      Conclusion:
      This multi-institution study demonstrates an increasing proportion of never smokers with NSCLC between 1990 and 2013 in a large, geographically and demographically diverse population. Because the biology and, thus, often the treatment options of lung cancer in never smokers differs from that of smokers, further investigation is warranted as to the etiology of the increasing incidence of never-smoker lung cancer.

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    P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P1.01-068 - Randomized Trial of Maintenance Chemotherapy Versus SBRT plus Maintenance Chemotherapy for Advanced NSCLC - Feasibility and Early Outcomes (ID 932)

      09:30 - 17:00  |  Author(s): C. Ahn

      • Abstract
      • Slides

      Background:
      Following first-line chemotherapy, maintenance therapy regimens have shown modest yet statistically significant benefits in progression free survival (PFS). To date, there have been no completed, prospective randomized trials examining the role of locally aggressive therapy in limited metastastic, advanced stage non-small cell lung cancer (NSCLC). We hypothesized that stereotactic body radiotherapy (SBRT) prior to maintenance chemotherapy would further improve PFS. This trial also serves to provide prospective survival data for a population with limited metastatic NSCLC.

      Methods:
      This is a two-arm randomized phase II trial. Eligible patients have stable disease or partial response with limited metastatic disease (defined by six or fewer sites amenable to SBRT) after treatment with up to 6 cycles of first line platinum doublet chemotherapy. Patients are then randomized to investigator’s choice maintenance chemotherapy alone or SBRT to all amenable sites followed by maintenance chemotherapy. The primary endpoint of the study is PFS, with 36 patients required to demonstrate an increase from 4 months in the control arm to 10 months in the experimental arm, with 80% statistical power and a 2-sided significance level of 0.10.

      Results:
      Since May 2014, 11 patients have been enrolled (5 to SBRT + maintenance arm; 6 to maintenance arm). The median number of first-line chemotherapy cycles was four, with the most common regimen carboplatin/paclitaxel followed by carboplatin/pemetrexed. The median number of maintenance chemotherapy cycles was six, the most common agent being pemetrexed followed by bevacizumab. The median number of sites treated with SBRT were two, with the lung the most common anatomic location followed by the adrenal gland. Five patients have progressed to date, three in the maintenance chemotherapy arm and two in the SBRT + maintenance chemotherapy arm. Progression in the maintenance alone arm occurred in original sites of disease in two of three patients. There have been no in-field failures in the SBRT arm. There has been one death due to disease progression in the maintenance chemotherapy arm. No patients have suffered a grade 3 or higher adverse event related to protocol therapy.

      Conclusion:
      This study demonstrates the feasibility of enrolling patients with limited metastatic lung cancer to a randomized trial of local therapy following first-line chemotherapy. To date, all patients have tolerated the administration of SBRT to multiple sites in between first-line and maintenance chemotherapy without any grade 3 or higher adverse events. Continued follow-up will be necessary to determine the efficacy of the experimental arm.

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    P1.11 - Poster Session/ Palliative and Supportive Care (ID 229)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Palliative and Supportive Care
    • Presentations: 1
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      P1.11-003 - New Clinical and Biologic Insight Into Lung Cancer-Associated Cachexia From a Large Cohort Study (ID 1085)

      09:30 - 17:00  |  Author(s): C. Ahn

      • Abstract
      • Slides

      Background:
      Cancer cachexia (CC) is a wasting syndrome without durable palliative intervention observed in 50% of all solid tumors and responsible for 20-30% of all cancer-related deaths. Knowledge of prevalence and survival outcomes for lung CC patients by clinical and pathologic parameters is scarce due to limited series. We provide the largest, most detailed evaluation of lung cancer patients for cachexia, enabling new clinical and biologic insight.

      Methods:
      A retrospective review of 1627 patients with non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) treated at UT Southwestern Medical Center between 1/1/2006 and 12/31/2013 was performed. Patient demographics and tumor characteristics including histology, stage, grade, and size were collected. Each patient was assessed for CC at diagnosis, retrospectively identified by the presence of significant weight loss (>5% loss over 6 months in patients with BMI >= 20; >2% in patients with BMI <20). Overall Survival (OS) was evaluated, and clinicopathologic factors predicting for cachexia development were identified with stepwise logistic regression (SLR).

      Results:
      Overall, CC independently predicted reduced OS on stepwise Cox regression (1.21 OR). 419/1468 (28.5%) of all NSCLC and 57/159 (35.8%) of all SCLC patients had CC. Within NSCLC, CC was documented in 107/350 (30.6%) of squamous carcinomas and 208/761 (27.3%) of adenocarcinomas. CC significantly reduced NSCLC OS across all stages: 21.0 vs. 9.9 months (log-rank P<0.0001). However, CC did not significantly affect SCLC OS: 10.5 vs. 9.9 months (log-rank P=0.46). Prevalence of CC in NSCLC for stages 1, 2, 3, and 4 was 48/309 (15.5%), 16/124 (12.9%), 118/377 (31.3%), and 237/658 (36.0%), respectively. OS for NSCLC -/+ CC for stages 1, 2, 3, and 4 were 67.1 vs. 45.0, 35.4 vs. 37.2, 20.9 vs. 14.3, and 11.4 vs. 6.6 months, respectively (log-rank P=0.0427, =0.5803, =0.0155, <0.0001). OS for squamous histologies -/+ CC for stages 1, 2, 3, and 4 were 56.9 vs. 22.7, 19.3 vs. 19.5, 18.6 vs. 14.3, and 7.8 vs. 5.8 months, respectively. OS for adenocarcinoma histologies -/+ CC for stages 1, 2, 3, and 4 were 86.4 vs. 51.1, 43.9 vs. 23.3, 28.6 vs. 19.2, and 13.0 vs. 8.2 months, respectively. On univariate analysis, grade, stage, tumor size, and tobacco use were significant factors in the development of CC in adenocarcinomas, while stage alone was significant in squamous carcinomas. On SLR, stages 3+4 were associated with increased odds of CC development as compared to stages 1+2 (OR 2.6, P=0.0004) in squamous histologies. On SLR, tumor size >50mm was associated with increased odds of CC development when compared to 0-20 mm (OR 4.3, P<0.0001) in adenocarcinomas.

      Conclusion:
      Cachexia significantly impacts OS in lung cancer, primarily for NSCLC. Fundamental differences of CC prevalence and associated OS were observed for the first time between different histologies and stages. Though CC can manifest in all stages, increased stage and tumor size were independent, significant predictors for CC in squamous and adenocarcinoma populations, respectively. Understanding which clinicopathologic characteristics impact CC prevalence and OS may offer insight into the syndrome’s clinical and biologic underpinnings, providing impetus for novel therapeutics and prediction methods.

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