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M.D.L.L. Gil



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    MINI 13 - Genetic Alterations and Testing (ID 120)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MINI13.13 - Non-Small Cell Lung Cancer (NSCLC) Harboring EGFR Mutations (EGFR-m) and Breast Cancer (BC): A Retrospective Analysis (ID 2857)

      11:55 - 12:00  |  Author(s): M.D.L.L. Gil

      • Abstract
      • Presentation
      • Slides

      Background:
      EGFR-m in NSCLC and its responsiveness to TKI has proved beneficial in a subset of NSCLC patients (p) Breast cancer (BC) represents the most incident neoplasm among women. The co-existence of both EGFR-m-NSCLC and BC has been reported in p with Li-Fraumeni Syndrome. However, no systematic evaluation of the presence of both types of cancers has been performed in the general population.

      Methods:
      We sought to evaluate if EGFR-m-NSCLC associates higher rates of 2[nd] BC than the EGFR-wild type (WT)p. Clinical and molecular characteristics, as well as clinical outcomes of female p visited at our Institution from 2008 to 2014 and harboring both types of tumors were registered.

      Results:
      69/578 female p with EGFR-m were identified. Data on treatment and follow-up of 62p were available. 11/ 62p (17.7%) were diagnosed with both EGFR-m-NSCLC and BC. For EGFR-m-W-p, BC was diagnosed in 3 cases (0.52%) Regarding EGFR-m-NSCLC, age of diagnosis was 65y; 100% of p were Caucasian and never smokers. Del19, L858 and L861Q represented the 72.7%, 27.3% and 9% of EGFR-m. 36.3% had stage IV, 27.2% recurred after surgery and 36.3% initial stages never recurred. 63.6% received a TKI (42.8% erlotinib). 85.7% received TKI as 1[st] line. The overall response rate was 85.7%. 42.8% received subsequent therapies. The cause of death was related to lung cancer in all cases of death (54.5%). mOS was 29 months from the time of LC diagnosis. Regarding BC, the median age of diagnosis was 52y, BC was a prior diagnosis in 90.9%; the stage was 0, I, IIA and IIIA in 18.18%, 27.27%, 45.45% and 9.09%, respectively. After surgery (100%), 36.36% received ET, 36.36% both chemotherapy and ET and 54.54% radiotherapy (RT). 83.33% of p treated with RT developed the LC in the RT field. 90.90% of p never recurred.

      Conclusion:
      Diagnosis of BC appears to be higher in EGFR-m-NSCLC-p than in the general population. Evaluation of the molecular mechanism potentially related to this association is warranted.

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    MINI 15 - Chemotherapy Developments for Lung Cancer (ID 128)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      MINI15.06 - Impact of Three and Further Lines in Advanced Non-Small Cell Lung Cancer Patients According to Molecular Profile: A Retrospective Analysis  (ID 2919)

      17:15 - 17:20  |  Author(s): M.D.L.L. Gil

      • Abstract
      • Presentation
      • Slides

      Background:
      There is little evidence supporting the efficacy of third-line systemic therapy in non-small cell lung cancer (NSCLC) patients (p) with advanced (a) disease, except for erlotinib, and its role is unclear in unselected population. Nonetheless, further-line chemotherapy(CT) is frequently offered in daily clinical practice. We retrospectively analyzed the clinical, pathological characteristics and outcomes of p with aNSCLC who received >3 CT regimens to identify subsets of patients more likely to benefit. The presence of underlying molecular alterations has also been evaluated.

      Methods:
      The study included data from all consecutive p diagnosed with aNSCLC in our Institution from January 2008 to December 2013. Median overall survival (mOS) and progression free survival (PFS) were evaluated with Kaplan-Meier curves and groups were compared using the Log-rank test. Variables analyzed included p tumor and treatment characteristics. Overall response rate(ORR) was calculated according to the RECIST criteria.

      Results:
      A total of 486 p were included .175 p (36%) received >3 lines (group3+). Table 1 summarized p characteristics. Group 3+included more females (35.4%vs22.8%; p= 0.0041),younger p (58.9vs61.9;p =0.0016), more never-smoker p (26.9%vs18%;p=0.015), less lung (10.9%vs22.2%;p= 0.0020) and heart (4%vs11.6%;p=0.0020) comorbidities, a higher proportion of molecular alterations (EGFR/ALK) (25.7%vs12.9%; p= 0.0005), more adenocarcinoma (68.6%vs55%;p=0.0045) and less brain metastasis (14.3%vs23.5%;p=0.018). ORR to first line was higher in group 3+ (45.8%vs 29%;p=0.0009). 82.3% non-squamous histology were tested for at least one molecular alteration. There were no differences in PFS between both groups. The mOS of p in group 3+ was longer [24.3 m vs. 7.7 m, p<0.0001)], including p with EGFR/ALK/ROS1 wild-type or unknown [21.6 m vs. 7.4 m, p<0.0001) ]. OS was also longer in the group 3+ harboring a molecular alteration [32.2 m vs 12.7m;p=0.0002]. In the univariate analysis the presence of a molecular alteration were related to longer PFS. In univariate analysis having received >3, female gender, age<65 and the presence of molecular alterations were associated with longer OS. In the multivariate analysis >3 therapeutic lines and the presence of molecular alterations were related to longer OS.

      Conclusion:
      P treated with >3 systemic treatments were more likely to respond better, progress later and live longer. This better prognosis could be related to the presence of molecular alteration. However p without or unknown molecular alteration could benefit from receiving subsequent lines.

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    P2.11 - Poster Session/ Palliative and Supportive Care (ID 230)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Palliative and Supportive Care
    • Presentations: 1
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      P2.11-006 - Impact of Different Comorbidities in Clinical and Molecular Characteristics in a Cohort of Non-Small Cell Lung Cancer (NSCLC) Patients (P) (ID 2842)

      09:30 - 09:30  |  Author(s): M.D.L.L. Gil

      • Abstract
      • Slides

      Background:
      The most common comorbid conditions related to Lung Cancer are age- and tobacco-related illnesses, such us cardiovascular disease, chronic obstructive pulmonary disease(COPD) and other malignancies. Different studies have demonstrated and impact in clinical outcome. We retrospectively review the clinical and molecular characteristics, and the outcome related to comorbidities of an homogeneus cohort of advanced NSCLC.

      Methods:
      The study included data from all consecutive p who were diagnosed as having advanced NSCLC at our hospital between January 2008 and December 2013. Overall survival (OS) and progression free survival (PFS) were evaluated with Kaplan-Meier curves and groups are compared using the Log-rank test. Variables analyzed included patient characteristics (age, gender, smoking history, Performance Status by ECOG), tumor characteristics (histology, stage, molecular profile, site of metastasis), treatment characteristics (chemotherapy regimen, total cicles per line, total chemotherapy lines, objective response(ORR) according to the RECIST criteria). Comorbidities analyzed were: COPD, Cardiovascular diseases, Other Cancers and Others.

      Results:
      A total of 580 p were included, 163 p no had comorbidities and 417(71.8%) had at least one. Table 1 summarized patient’s characteristics. Any comorbidity were more frequent in female sex (79.6% vs 64.4%; p0.0002), older patients(mean age 64.3 vs 56.7 yo; p<0.0001), less never-smokers(16.1% vs 25.2; p0.033), less molecular alterations (14.2% vs 22.1%; p0.025) and more squamous histology (25.7% vs 12.9; p0.0043). No differences is ORR, PFS and OS were seen globally. For each comorbidity, COPD was associated to worse ORR (65.9% vs 75.6%; p0.023) and OS (8.1 months vs 14 months; p0.018), and cardiovascular diseases were associated to worse OS (9.1 monthsvs 15.5 months; p<0.0015). In univariate and multivariate analysis COPD, Cardiovascular comorbidity, male sex, age more than 65 yo, and non molecular alteration were related to worse OS. Table 1. Baseline characteristics (N of patients treated with at least one line: 486).

      No comorbidities (N=163) Any comorbididy (N=417) p-value
      Median age Gender (Female) Smoking history (%) -never -former -current -not reported EGFR mut/ ALK translocation Histology -NOS -Adenocarcinoma -Squamous -Adenosquamous -LCC -LCC-NE Site of metastasis -Lung -Brain -Bone -Liver -Adrenal gland 56.7(11.0) 105(64.4) 41(25.2) 63(38.7) 58(35.6) 1(0.6) 36(22.1) 22(13.5) 109(66.9) 21(12.9) 1(0.6) 9(5.5) 1(0.6) 59(36.2) 35 (21.5) 59(36.2) 23(14.1) 25(15.3) 64.3(9.8) 332(79.6) 67(16.1) 209(50.1) 138(33.1) 3(0.7) 59(14.2) 60(14.4) 228(54.7) 107 (25.7) 7(1.7) 8(1.9) 6(1.4) 159(38.1) 96(23.0) 131(31.4) 50(12.0) 53(12.7) <0.0001 <0.0001 0.033 0.025 0.0043 0.70 0.74 0.28 0.49 0.99


      Conclusion:
      Comorbidities are frequent in patients with advanced NSCLC p, and are age and tobacco related. Patients with COPD have a worse ORR and OS, and patients with Cardiovascular comorbidities have worse OS. In our knowledge, is the first study that relates comorbidities in NSCLC to molecular alterations.

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    P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P3.04-046 - Prevalence of ROS1, HER2, and BRAF Alterations in a Cohort of Advanced Non-Small Cell Lung Cancer (NSCLC) Patients (P) Triple Negative (TN) (ID 2711)

      09:30 - 09:30  |  Author(s): M.D.L.L. Gil

      • Abstract
      • Slides

      Background:
      During the last years, new predictive and less frequent biomarkers have emerged in NSCLC, such as ROS1 translocation (ROS1t), HER2 mutations (HER2m) and BRAF mutations (BRAFm). We analyze retrospectively the frequency, clinical and tumor characteristics of NSCLC p TN( EGFR, KRAS and ALK wild-type).

      Methods:
      The study included data from all consecutive non-squamous and non-smokers squamous TN advanced NSCLC p diagnosed at our hospital from December 2008 to July 2014

      Results:
      101 p were included. The table below summarizes p characteristics. ROS1t were found in 4.9% p and were found more in female gender (100%), non-smokers(100%), stage IV (100%), adenocarcinoma histology (100%) and p had more lung metastasis(50% vs 34.2%), brain metastasis (50%vs 38.5%) and pleural/pericardial effusions (50% vs 12.8%). HER2m was found in 1 p (1.25%). Female, non-smoker and adenocarcinoma histology. BRAFm were found in 2 p ( 3.2%), one male and one female, smokers and adenocarcinoma histology. Valid results range from 85.6% to 96.2% for biopsy samples and from 78.2% to 81.4% for citology samples.

      TOTAL(N101) ROS1(N81) BRAF(N80) HER2(N80)
      Mean age 61 58 63 63
      Gender Male Female 65(64,3%) 36(35,6%) 57(70,3%) 24(29,6%) 52 (65%) 28(35%) 52(65%) 28(35%)
      Smoking history Current Former Never 38(37,6%) 41(40,5%) 22(21,7%) 32(39,5%) 37(45,6%) 12(14,8%) 33(41,2%) 31(38,7%) 16(20%) 33(41,2%) 31(38,7%) 16(20%)
      Histology Adenocarcinoma Squamous NOS LCC 88(87,1%) 5(4,9%) 6(5,9%) 2(1,9%) 72(88,8%) 3(3,7%) 6(7,4%) 0 71(88,7%) 2(2,5%) 5(6,2%) 2(2,5%) 71(88,7%) 2(2,5%) 5(6,2%) 2(2,5%)
      Sample CItology Biopsy 29(28,7%) 72(71,2%) 27(33,3%) 54(66,6%) 23 (28,7%) 57 (71,2%) 23 (28,7%) 57 (71,2%)
      Site metastasis Lung Bone Brain Liver 33(32,6%) 28(27,7%) 30(29,7%) 9(8,9%) 28(34,5%) 21(25,9%) 25(30,8%) 5(6,1%) 25(31,2%) 22(27,5%) 27(33,7%) 7(8,7%) 25(31,2%) 22(27,5%) 27(33,7%) 7(8,7%)


      Conclusion:
      ROS1t, HER2m and BRAFm have emerged as targetable oncogenic drivers in NSCLC. Although the prevalence is low (1%–2%), could be increased selecting by clinical and molecular characteristics. Citology samples could be useful to detect these molecular alterations.

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