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Esmo 2010 Powerpoint Slides Esmo 2010 Powerpoint Slides Presentation Transcript

  • Clinicopathologic characteristics and survival outcomes of five subtypes of adenocarcinoma that has been associated with histological characteristics of EML4-ALK NSCLC Sai-Hong Ignatius Ou, MD PhD Associate Clinical Professor Chao Family Comprehensive Cancer Center Department of Medicine, Division of Hematology-Oncology University of California Irvine Medical Center, Orange, CA 92868
  • Background
    • ALK translocation in NSCLC has recently been discovered
    • At least 9 EML4-ALK fusion transcripts in NSCLC described
    • Usually ALK +ve NSCLC are found in young, never-smokers, with adenocarcinoma but only constitutes about 3-5% of all NSCLC
    • Several adenocarcinoma histological subtypes have been associated with ALK +ve NSCLC including signet ring carcinoma (SRC), acinar carcinoma, papillary carcinoma, mixed adenocarcinoma, and even BAC
    • An ALK inhibitor (Crizotinib-PF02341066) has significant clinical activity in ALK +ve NSCLC
  • Objective
    • We investigated clinicopathologic characteristics and survival outcome of several rare adenocarcinoma subtypes to see if any one or more of the adenocarcinoma subtypes closely matches those described for ALK + ve NSCLC
  • Methods
    • Adenocarcinoma of the lung diagnosed from 1989 to 2006 were abstracted from the California Cancer Registry (CCR)
    • Smoking status were abstracted from subgroup of patients within 3 regional CCR using a text mining algorithm
    • Univariate analysis were performed by log-rank using Kaplan-Meier method
    • Multivariate analysis were performed by Cox proportional hazards model
  • Results
    • A total of 59501 cases were analyzed including
      • 50089 cases of adenocarcinoma
      • 7171 cases of BAC
      • 1241 cases of papillary carcinoma
      • 379 cases of acinar carcinoma
      • 359 cases of mixed adenocarcinoma
      • 262 cases of signet ring carcinoma
  • < 0.0001 152 (42.3) 35 (9.8) 51 (14.2) 39 (10.9) 82 (22.8) 16 (6.1) 13 (5.0) 54 (20.6) 129 (49.2) 50 (19.1) 319 (25.7) 95 (7.7) 170 (13.7) 375 (30.2) 282 (22.7) 184 (48.6) 47 (12.4) 43 (11.4) 26 (6.9) 79 (20.8) 3139 (43.8) 403 (5.6) 658 (9.2) 1171 (16.3) 1800 (25.1) 9174 (18.3) 2610 (5.2) 8315 (16.6) 18409 (36.8) 11581 (23.1) AJCC stage I II III IV Unknown < 0.0001 86 (24.0) 126 (35.1) 86 (24.0) 6 (1.7) 55 (15.3) 2 (0.8) 24 99.2) 131 (50.0) 3 (1.2) 102 (38.9) 204 (16.4) 411 (33.1) 189 (15.2) 16 (1.3) 421 (33.9) 61 (16.1) 208 (54.9) 89 (23.5) 4 (1.1) 17 (4.5) 2119 (29.6) 1840 (25.7) 614 (8.6) 55 (0.8) 2543 (35.5) 2635 (5.3) 11484 (22.9) 21743 (43.4) 794 (1.6) 13433 (26.8) Tumor differentiation Well Moderate Poor Undifferentiated Unknown 0.0001 255 (71.0) 20 (5.6) 37 (10.3) 47 (13.1) 0 (0.0) 190 (72.5) 19 (7.3) 31 (11.8) 21 (8.0) 1 (0.4) 875 (70.5) 86 (6.9) 108 (8.7) 169 (13.6) 3 (0.2) 290 (76.5) 23 (6.1) 30 (7.9) 34 (9.0) 2 (0.5) 5226 (72.9) 481 (6.7) 646 (9.0) 800 (11.2) 18 (0.3) 37677 (75.2) 3695 (7.4) 4310 (8.6) 4215 (8.4) 192 (0.4) Ethnicity Caucasian African-American Hispanic Asian Other < 0.0001 149 (41.5) 210 (58.5) 146 (55.7) 116 (44.3) 592 (47.7) 649 (52.3) 166 (43.8) 213 (56.2) 2958 (41.3) 4213 (58.8) 26062 (52.0) 24027 (48.0) Gender Male Female < 0.0001 1 (0.3) 21 (5.9) 65 (18.1) 115 (32.0) 101 (28.1) 56 (15.6) 13 (5.0) 24 (9.2) 64 (24.4) 80 (30.5) 65 (24.8) 16 (6.1) 20 (1.6) 86 (6.9) 253 (20.4) 386 (31.1) 386 (31.1) 110 (8.9) 3 (0.8) 24 (6.3) 61 (16.1) 142 (37.5) 111 (29.3) 38 (10.0) 66 (0.9) 327 (4.6) 1095 (15.3) 2197 (30.6) 2569 (35.8) 917 (12.8) 666 (1.3) 3516 (7.0) 9852 (19.7) 16198 (32.3) 14822 (29.6) 5035 (10.1) Age category 0-39 40-49 50-59 60-69 70-79 80+ < 0.0001 21 (1-62) 5.5 (1-58) 17 (1-115) 31 (3-98) 28 (1-151) 9 (1-109) Median f/u time (95%CI) < 0.0001 68 (48-85) 64 (40-80) 67 (46-82) 66 (47-83) 69 (49-83) 67 (46-83) Median age (95% CI) 359 262 1241 379 7171 50089 N p Mixed adenoCA SRC Papillary carcinoma Acinar carcinoma BAC AdenoCA
  • Smoking status according to adenoCA subtype
  • Kaplan-Meier survival curves by adenoCA subtypes
  • Cox analysis < 0.0001 < 0.0001 < 0.0001 (1.792-1.966) (2.220-2.392) (3.460-3.720) 1.000 1.877 2.305 3.588 AJCC stage* I II III IV < 0.0001 < 0.0001 < 0.0001 (1.126-1.221) (1.318-1.426) (1.226-1.437) 1.000 1.173 1.370 1.327 Tumor differentiation* Well Moderate Poor Undifferentiated 0.4782 < 0.0001 0.4714 (0.978-1.048) (0.784-0.838) (0.957-1.021) 1.000 1.013 0.810 0.988 Ethnicity Caucasian African American Asian Hispanic < 0.0001 (0.813-0.843) 1.000 0.828 Gender Male Female < 0.0001 (1.011-1.013) 1.012 Age 0.0006 0.0182 < 0.0001 0.0019 0.0029 (0.653-0.889) (0.688-0.966) (0.812-0.866) (0.848-0.963) (1.069-1.382) 1.000 0.762 0.815 0.838 0.903 1.215 Histology Adenocarcinoma Acinar carcinoma Mixed adenocarcinoma BAC Papillary carcinoma Signet-ring cell carcinoma p 95% Confidence Interval Hazard Ratio
  • Conclusions
    • Acinar carcinoma subtype has the best OS
    • Signet ring carcinoma (SRC) subtype had the worst OS
    • Adenocarcinoma subtypes are heterogeneous
    • SRC had the highest proportion of never-smokers
    • All adenocarcinoma subtypes is a favorable prognostic factor in OS when compared to adenocarcinoma
    • SRC is an independent unfavorable prognostic factor after factoring in age, gender, ethnicity, stage, tumor differentiation, period of diagnosis and treatment (surgery, radiation, chemotherapy)