Author of

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  P3.18 - Poster Session 3 - Pathology (ID 177)

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

  • 12776

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    P3.18-007 - Metastatic sites with a major component of solid pattern pulmonary adenocarcinoma are associated with shorter survival with systemic therapy and infrequent EGFR mutations (ID 1790)

    09:30 - 09:30  |  Author(s): T.D. Clay
    • Abstract

    Background
    The predominant histologic subtype according to the IASCL/ATS/ERS classification has been associated with prognosis in patients undergoing curative surgical resection. It is recommended in the IASLC/ATS/ERS classification that histologic patterns present in small specimens be recorded in the final histopathology report. We investigated the relationship between histologic patterns in metastatic sites, overall survival and EGFR and KRAS mutations.

    Methods
    We identified patients who underwent surgical resection of non-small cell lung carcinoma in metastatic sites from 2000 to 2011. One biopsy site was selected per patient. A pathologist reviewed all slides to confirm the diagnosis of metastatic lung adenocarcinoma, recording all adenocarcinoma histologic patterns present. EGFR and KRAS mutations were scanned by high resolution melting, and confirmed by Sanger sequencing. Clinical data were extracted from the medical records.

    Results
    The 100 patients comprised 66 males, with a median age of 64 years. 85% had stage IV disease, and 15% had unresected stage III disease with mediastinal lymph node sampling. Most were current or former smokers (79%) of ECOG 0/1 (67%). Just over half the patients received systemic therapy (56%). The overall median survival was 10.2 months (95% CI 8.1 – 12.2 months). Metastatic sites included brain (30%), pleura (25%), bone/skeletal muscle (20%), and lymph nodes (mediastinal 18%; chest wall/neck 7%). It was possible in each biopsy to identify a major histologic pattern (Table 1). For patients receiving systemic therapy, survival was significantly shorter for those with a major component of solid pattern tumour in metastases compared to those with major acinar or micropapillary patterns in metastases (Table 1). No survival difference was noted on the basis of ECOG, stage, EGFR or KRAS mutations. For patients who did not receive systemic therapy, the major histologic pattern showed no association with overall survival (Table 1). Worse ECOG was the only significant factor in determining outcome (ECOG 0/1 vs 2+ – hazard ratio 2.18 (1.14 – 4.16, p=0.018)). EGFR mutations were significantly associated with major non-solid pattern histology in metastases (Fisher’s exact = 0.006). No association was observed by KRAS mutation status (Table 1).

    The major histologic component in sites of metastatic adenocarcinoma – overall survival by the use of systemic therapy; presence of EGFR and KRAS mutations (*Comparison across 4 histological types; OS - overall survival, CI - confidence interval, HR - hazard ratio)

    Solid Micropapillary Acinar Papillary Comments Major Pattern 50% 20% 29% 1% Mutations present n = 50 n = 20 n = 29 n = 1 n=100 EGFR mutation, n (column %) 2 (4%) 5 (25%) 4 (14%) 1 (100%) Fisher's exact = 0.006 * KRAS mutation, n (column %) 18 (36%) 5 (25%) 9 (31%) 0 Fisher's exact = 0.789* Systemic Therapy Given n = 29 n = 13 n = 13 n = 1 n=56 Median OS, months (95% CI) 9.4 (8.3 - 12.2) 18.9 (11.6 - 24.4) 15.9 (10.7 - 24.7) Solid vs MPA HR 0.33 (0.16 - 0.67, p = 0.002) Solid vs Acinar HR 0.32 (0.15 - 0.67, p=0.003) No Systemic Therapy n = 21 n = 7 n = 16 n = 0 n=44 Median OS, months (95% CI) 4.3 (3.3 - 7.4) 4.7 (1.5 - 11.5) 4.4 (1.9 - 16.9) No significant differences

    Conclusion
    Our results suggest that patients with a major component of solid pattern tumour in metastatic sites may be more resistant to systemic therapy as evidenced by shorter overall survival in comparison to those with major micropapillary and acinar pattern tumour in metastases. Furthermore, major solid pattern metastases are unlikely to harbour EGFR mutations. These findings require validation in larger patient cohorts.