Author of

• 10912

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  P1.17 - Poster Session 1 - Bronchoscopy, Endoscopy (ID 182)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Pulmonology + Endoscopy/Pulmonary
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10920

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    P1.17-008 - Results of a close surveillance strategy for subjects with pre-invasive endobronchial squamous lesions (ID 2678)

    09:30 - 16:30  |  Author(s): R.A.A. Van Boerdonk
    • Abstract

    Background
    The dismal overall 5-year survival of non-small cell lung cancer (NSCLC) patients is mainly due to advanced stage of disease at time of initial diagnosis in most and the inability to cure metastatic disease in all patients. In contrast, the prognoses of in situ mucosal and small parenchymal lesions are excellent. Early detection strategies might result in the identification of early-stage, (pre-)invasive lesions that are still eligible for curative treatment. The present study was set out to characterize the risk of lung cancer development in a cohort of high-risk subjects harboring pre-invasive endobronchial lesions and to assess the results of surveillance using autofluorescence bronchoscopy (AFB) and computed tomography (CT) scan.

    Methods
    Between November 1995 and December 2012, one hundred and sixty-four at risk individuals with pre-invasive endobronchial lesions were monitored by repeated AFB and CT. During the course of surveillance, progression of lesions to cancer (in situ), recurrences and second primary cancers were treated with different modalities (e.g. endobronchial techniques, surgery, radiotherapy), depending on tumor stage and location. Log-rank tests were performed to examine the relation between baseline characteristics and progression-free and overall survival (PFS and OS, respectively). Cox regression was used for multivariate survival analysis.

    Results
    Demographical and clinical variables of the cohort are shown (Table). At inclusion, 80 individuals were identified with one or more high-grade pre-invasive lesions (severe dysplasia or CIS; HGD), whereas 84 subjects were identified solely with lower grade pre-invasive lesions (LGD). During close surveillance (median follow-up (FU) of 30 months, range 4-152), sixty-one lung cancers were detected (26 CT-detected, 35 AFB-detected cancers) in 55 individuals within a median time to event of 16.5 months. Mean PFS was similar between individuals with radiographically occult lesions vs. FU after surgery for early-stage NSCLC/ENT ca (122.3 vs. 126.9 months, p=0.237) and COPD vs. non-COPD (118.8 vs. 136.8 months, p=0.162). There was a relatively large difference in PFS between LGD and HGD groups (142.6 vs. 93.7 months, p=0.057). Independent risk determinants for OS were indication for surveillance (FU after surgery for early-stage NSCLC/ENT ca vs. radiographically occult lesions, p=0.008) and COPD-status (COPD vs. non-COPD, p<0.001).

    		Referral for radiographically occult lesion	Follow-up after surgery for early-stage NSCLC / ENT ca
    	total
    individuals, n	164	92	72
    Gender
    male	134	72	62
    female	30	20	10
    Age at baseline
    years, mean (range)	64.2 (42-83)	64.8 (42-81)	64.0 (43-82)
    Smoking status
    current smoker	75	44	31
    former smoker	74	36	38
    unknown	15	12	3
    Smoking history
    Pack-years, mean (range)	45 (4-137)	45 (4-120)	40 (15-137)
    COPD-status
    COPD	100	56	44
    non-COPD	45	22	23
    unknown	19	14	5
    AF Bronchoscopies
    Number, mean (range)	7 (1-27)	5 (2-27)	6 (1-18)
    CT-scans
    Number, mean (range)	3 (0-20)	2 (0-20)	3 (0-18)
    No. of detected lung cancers
    During surveillance period	61	29	32
    Parenchymal cancer	21	12	9
    Site-specific lesion progression	24	13	11
    Interval cancer	10	4	6
    Recurrences previous primaries	6	0	6
    Patient outcome
    alive	80	56	24
    died of lung cancer	33	13	20
    died of other/unknown cause	51	23	28

    Conclusion
    Our findings demonstrate that individuals with pre-invasive endobronchial lesions are at high risk of developing (second primary) lung cancers. Combined surveillance using AFB in addition to CT screening facilitated early detection and early (endobronchial) intervention in most patients. Future clinical trials are warranted to determine whether the current approach improves patient outcome.

• 11905

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  P2.20 - Poster Session 2 - Early Detection and Screening (ID 173)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Imaging, Staging & Screening
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11909

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    P2.20-004 - DNA copy number aberrations in endobronchial lesions: a validated predictor for cancer (ID 1166)

    09:30 - 16:30  |  Author(s): R.A.A. Van Boerdonk
    • Abstract

    Background
    Individuals who present with squamous metaplastic and dysplastic lesions are considered at high risk of lung cancer. However, these lesions behave erratically and only a minority progresses towards lung cancer. Therefore, biomarkers need to be discovered that can aid in assessing an individual’s risk for subsequent cancer. We recently identified a DNA copy number aberration (CNA)-classifier, including changes at 3p26.3-p11.1, 3q26.2-29, and 6p25.3-24.3, as a risk predictor for cancer in individuals presenting with endobronchial squamous metaplasia (van Boerdonk et al, AJRCCM, 2011). The current study was set out to validate this classifier in an independent series of endobronchial squamous metaplastic and dysplastic lesions.

    Methods
    DNA copy number profiles (i.e., chromosomal gains and losses) were determined in a set of endobronchial lesions (8 squamous metaplasia (SqM), and 28 dysplasias (Dys) of various grades), identified and biopsied during autofluorescence bronchoscopy, of 36 high-risk subjects using a nested case-control design. Of the 36 patients, 12 cases had a carcinoma in situ or invasive carcinoma at the same site at follow-up (median 11 months, range 4-24), while 24 controls remained cancer-free (median 78 months, range 21-142). DNA copy number profiles were related to lesion outcome. The prediction accuracy of the predefined CNA-based classifier to predict endobronchial carcinoma (in situ) in this series was determined.

    Results
    All SqM and Dys lesions of controls showed no or a relatively low number of CNAs (i.e., quiescent profile with on average 0.2% altered probe features, range 0.0 – 2.4%), while the majority of lesions of cases showed multiple CNAs (i.e. highly aberrant profile with on average 38.8% altered probe features, range 0.0 – 76.7%). The previously defined CNA-classifier demonstrated 92% accuracy for cancer (in situ) prediction in the current series. All nine subjects with CNA-classifier-positive endobronchial lesions at baseline had cancer as final outcome (i.e., a positive predictive value of 100%). The negative predictive value of the classifier was 89%, i.e., all 24 controls and 3 cases were classified as being low-risk.

    Conclusion
    CNAs are a highly accurate biomarker for assessing the progression risk of endobronchial squamous metaplastic and dysplastic lesions. This classifier could assist in selecting subjects with endobronchial lesions who might benefit from more aggressive therapeutic interventions.