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P1.07-035 Circulating Cell-Free Tumor DNA (cfDNA) Testing in Small Cell Lung Cancer
January 2017
revealed that T-DM1 remarkably induced apoptosis and inhibited proliferation. Fluorescence-labeled T-DM1 definitely accumulated to the xenografts in a HER2-selective fashion. Conclusion: T-DM1 treatment could be an attractive therapeutic option in trastuzumab-resistant HER2-positive SCLC where trastuzumab cannot induce enough ADCC activity. Delivery of a cytotoxic agent DM1 to the inside of cells via HER2-mediated internalization is expected and crucial to exert antitumor effect in such ADCC-lacking SCLC cells.
Abstracts
S717
planar scintigraphy of the thorax as well as the SPECT technique .The scintigraphic results were expressed in comparison with soft tissue intake (normal prices <1.5). Results: 111In-OCT was positive in all 10 SCLC patients at the time of diagnosis and progression of the disease. No statistical correlation was found between somatostatin receptors expression at the progression- mainly subtype 2 (SSTR 2)- and survival (p¼0.43), nor TTP (p¼0.25). Also the difference in somatostatin receptors expression during diagnosis and progression had no statistical correlation with survival and TTP. Conclusion: The clinical utility of receptor status characterization obtained with 111In-OCT scintigraphy is rather confined. Our study shows that 111In-OCT scintigraphy, although is a reliable, non-invasive technique to detect primary SLCL and its locoregional or distant metastases, cannot be used as a prognostic or predictive factor in SCLC patients. Keywords: somatostatin receptors, small cell lung cancer
Keywords: HER2, trastuzumab emtansine, SCLC, T-DM1
P1.07-034 Somatostatin Receptors Expression in Small Cell Lung Cancer Patients Topic: Molecular Changes Efimia Boutsikou,1 George Gerasimou,2 Dionisios Spyratos,1 Ellada Eleptheriadou,1 Anna Gotzamani,2 Konstantinos Zarogoulidis1 1 Pulmonary Department, G.Papanikolaou Hospital, Aristotle University of Thessaloniki, Thessaloniki/Greece, 2 nd 2 Clinical Laboratory of Nuclear Medicine, Ahepa Hospital, Thessaloniki/Greece Background: Somatostatin receptors have been described on the membrane of neoplastic cells and their expression has also been demonstrated on small cell lung cancer (SCLC). In this study we examined if the expression of somatostatin receptors at the time of disease progression correlated with survival and time to progression (TTP) of SCLC patients. Methods: 10 patients with SCLC were studied using 111In-octreotide (111In-OCT) scintigraphy at diagnosis and disease progression. Scintigraphic examinations were performed following intravenous (i.v.) injection of 111 MBq 111In-OCT with whole-body scintigraphy and
P1.07-035 Circulating Cell-Free Tumor DNA (cfDNA) Testing in Small Cell Lung Cancer Topic: Molecular Changes Daniel Morgensztern,1 Siddhartha Devarakonda,2 Ashiq Masood,2 Saiama Waqar,3 Alicia Carmack,2 Kimberly Banks,4 Richard Lanman,4 Ramaswamy Govindan3 1Washington University School of Medicine in St. Louis, St. Louis/MO/United States of America, 2Washington University School of Medicine, St. Louis/MO/United States of America, 3Medical Oncology, Washington University School of Medicine, St. Louis/MO/ United States of America, 4Guardant Health, Redwood City/CA/United States of America Background: The diagnosis of small cell lung cancer (SCLC) is often made using fine needle aspiration or small biopsy of tumor specimens that are typically insufficient for next generation sequencing (NGS) analysis. Guardant360 (G360), a blood-based liquid biopsy that analyzes circulating free tumor DNA, may allow the detection of potentially targetable gene abnormalities without the need for repeated tissue biopsies. Methods: Peripheral blood samples from patients with SCLC were collected in two 10 mL tubes. Cell-free DNA was extracted and analyzed by digital sequencing for the detection of single nucleotide variants (SNVs), small Insertions and Deletions (INDELs), Copy Number
S718
Alterations (CNAs), and gene fusions. The Tumor Alterations Relevant for Genomics-Driven Therapy (TARGET) curated database (http://www. broadinstitute.org/cancer/cga/target) was queried for potentially actionable alterations. Results: 240 samples from 227 de-identified patients were collected between June 2014 and June 2016. 7 patients had more than one sample analyzed. During this time period, the number of genes in the panel increased from 54 (10 samples) to 68 (87 samples) and finally to 70 (143 samples). The median time from sample collection to reporting was 13 days (range 8-28 days). Alterations in at least one gene were found in 222 (92.5%) of samples and 210 (92.5%) patients. SNVs in TP53 and RB1 were seen in 72.4% (152/210) and 25.7% (35/136) of patients with detectable alterations respectively. The most common potentially actionable alterations were amplifications of FGFR1 (11.8%) and ERBB2 (7.1%). MYC amplification, which was not considered an actionable alteration by TARGET but has been associated with sensitivity to Aurora kinase inhibitors in pre-clinical studies, was observed in 15.8% of patients. Eight patients had EGFR activating mutations (exon 21 L858R mutation or exon 19 deletion), of which 2 patients also had EGFR T790M mutation, likely representing transformation from NSCLC following targeted therapy with EGFR Tyrosine kinase inhibitors. KIF5BALK and AFAP1-RET fusions were seen in 1 patient each. Conclusion: G360 is a rapid non-invasive NGS platform which may be particularly useful in patients with advanced stage SCLC where tissue samples may be suboptimal for NGS. Due to the limited treatment options in this patient population, the detection of potentially actionable genes through G360 may provide valuable information to guide treatment decisions. Keywords: small cell lung cancer, cfDNA
P1.07-036 Large Cell Neuroendocrine Carcinoma of the Lung: The Mayo Clinic Experience Topic: Pathology Kunlatida Maneenil,1 Ming Liu,2 Alex Adjei,3 Julian Molina,3 Ping Yang2 1Oncology Unit, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok/Thailand, 2Health Sciences Research, Mayo Clinic, Rochester/MN/United States of America, 3Medical Oncology, Mayo Clinic, Rochester/MN/ United States of America Background: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a relatively uncommon, high-grade
Journal of Thoracic Oncology
Vol. 12 No. 1S
neuroendocrine tumor sharing several features with small-cell lung carcinoma (SCLC). LCNEC is considered aggressive, and the optimal treatment strategy and chemotherapy regimen remain undefined. Methods: We retrospectively evaluated a LCNEC patient cohort established from 1997 to 2015 at Mayo Clinic (Minnesota). A diagnosis of LCNEC was made when all WHO classification criteria were present in the tumor section examined. Clinical characteristics, treatment and outcomes were analyzed. Available radiology assessment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Results: The study included 55 LCNEC patients. Median age at diagnosis was 63 years (range: 38-88); two thirds were men; and majority were smokers (94%). Clinical staging was I, II, III or IV in 52.8%, 9.1%, 14.5%, and 23.6% of cases, respectively. Forty-six percent of stage IV patients presented with brain metastases at time of diagnosis (n¼6/13) and 18% (n¼7/ 38) developed brain recurrence in the follow up period. Thirty-nine (71%) patients had surgery and 9 (16%) patients received adjuvant platinum-based chemotherapy. Sixty-five percent of patients with complete resection experienced disease recurrence with 80% recurring within 2 years of resection. Treatment data for first-line palliative chemotherapy were available on 23 patients: 10 received platinum/etoposide and 13 received other regimens. In 19 patients with available imaging; the overall response rate was 52.6% (95% CI, 31.7-72.7) and there was no difference in ORR between platinum/etoposide (ORR¼55.6%) or platinum plus other agents (paclitaxel or pemetrexed; ORR¼55.6%). The median survival time was 26.3 months (95%CI; 18.6-33.9); the 1-, 2-, 3- and 5-year overall survival rates (OS) were 75%, 53%, 36%, and 30%, respectively. Patients who received platinum/etoposide demonstrated longer median time to progression (TTP), and median OS than those who received ‘other’ regimens (14.7 months vs. 7.1 months; p value 0.07, and 28.2 months vs. 21.1 months; p value 0.22, respectively); the differences did not reach conventional statistical significance, likely due to the small sample size. Rigorous pathologic confirmation and genomic analysis are ongoing. Conclusion: LCNEC is associated with a poor prognosis and high recurrence rates after surgery. Advanced LCNEC patients are at high risk for brain metastases, therefore, routine brain imaging surveillance during follow-up may be beneficial. The chemotherapeutic responsiveness of LCNEC patients was intermediate between that of NSCLC and SCLC patients. Future prospective, multicenter, clinical trials are needed to
revealed that T-DM1 remarkably induced apoptosis and inhibited proliferation. Fluorescence-labeled T-DM1 definitely accumulated to the xenografts in a HER2-selective fashion. Conclusion: T-DM1 treatment could be an attractive therapeutic option in trastuzumab-resistant HER2-positive SCLC where trastuzumab cannot induce enough ADCC activity. Delivery of a cytotoxic agent DM1 to the inside of cells via HER2-mediated internalization is expected and crucial to exert antitumor effect in such ADCC-lacking SCLC cells.
Abstracts
S717
planar scintigraphy of the thorax as well as the SPECT technique .The scintigraphic results were expressed in comparison with soft tissue intake (normal prices <1.5). Results: 111In-OCT was positive in all 10 SCLC patients at the time of diagnosis and progression of the disease. No statistical correlation was found between somatostatin receptors expression at the progression- mainly subtype 2 (SSTR 2)- and survival (p¼0.43), nor TTP (p¼0.25). Also the difference in somatostatin receptors expression during diagnosis and progression had no statistical correlation with survival and TTP. Conclusion: The clinical utility of receptor status characterization obtained with 111In-OCT scintigraphy is rather confined. Our study shows that 111In-OCT scintigraphy, although is a reliable, non-invasive technique to detect primary SLCL and its locoregional or distant metastases, cannot be used as a prognostic or predictive factor in SCLC patients. Keywords: somatostatin receptors, small cell lung cancer
Keywords: HER2, trastuzumab emtansine, SCLC, T-DM1
P1.07-034 Somatostatin Receptors Expression in Small Cell Lung Cancer Patients Topic: Molecular Changes Efimia Boutsikou,1 George Gerasimou,2 Dionisios Spyratos,1 Ellada Eleptheriadou,1 Anna Gotzamani,2 Konstantinos Zarogoulidis1 1 Pulmonary Department, G.Papanikolaou Hospital, Aristotle University of Thessaloniki, Thessaloniki/Greece, 2 nd 2 Clinical Laboratory of Nuclear Medicine, Ahepa Hospital, Thessaloniki/Greece Background: Somatostatin receptors have been described on the membrane of neoplastic cells and their expression has also been demonstrated on small cell lung cancer (SCLC). In this study we examined if the expression of somatostatin receptors at the time of disease progression correlated with survival and time to progression (TTP) of SCLC patients. Methods: 10 patients with SCLC were studied using 111In-octreotide (111In-OCT) scintigraphy at diagnosis and disease progression. Scintigraphic examinations were performed following intravenous (i.v.) injection of 111 MBq 111In-OCT with whole-body scintigraphy and
P1.07-035 Circulating Cell-Free Tumor DNA (cfDNA) Testing in Small Cell Lung Cancer Topic: Molecular Changes Daniel Morgensztern,1 Siddhartha Devarakonda,2 Ashiq Masood,2 Saiama Waqar,3 Alicia Carmack,2 Kimberly Banks,4 Richard Lanman,4 Ramaswamy Govindan3 1Washington University School of Medicine in St. Louis, St. Louis/MO/United States of America, 2Washington University School of Medicine, St. Louis/MO/United States of America, 3Medical Oncology, Washington University School of Medicine, St. Louis/MO/ United States of America, 4Guardant Health, Redwood City/CA/United States of America Background: The diagnosis of small cell lung cancer (SCLC) is often made using fine needle aspiration or small biopsy of tumor specimens that are typically insufficient for next generation sequencing (NGS) analysis. Guardant360 (G360), a blood-based liquid biopsy that analyzes circulating free tumor DNA, may allow the detection of potentially targetable gene abnormalities without the need for repeated tissue biopsies. Methods: Peripheral blood samples from patients with SCLC were collected in two 10 mL tubes. Cell-free DNA was extracted and analyzed by digital sequencing for the detection of single nucleotide variants (SNVs), small Insertions and Deletions (INDELs), Copy Number
S718
Alterations (CNAs), and gene fusions. The Tumor Alterations Relevant for Genomics-Driven Therapy (TARGET) curated database (http://www. broadinstitute.org/cancer/cga/target) was queried for potentially actionable alterations. Results: 240 samples from 227 de-identified patients were collected between June 2014 and June 2016. 7 patients had more than one sample analyzed. During this time period, the number of genes in the panel increased from 54 (10 samples) to 68 (87 samples) and finally to 70 (143 samples). The median time from sample collection to reporting was 13 days (range 8-28 days). Alterations in at least one gene were found in 222 (92.5%) of samples and 210 (92.5%) patients. SNVs in TP53 and RB1 were seen in 72.4% (152/210) and 25.7% (35/136) of patients with detectable alterations respectively. The most common potentially actionable alterations were amplifications of FGFR1 (11.8%) and ERBB2 (7.1%). MYC amplification, which was not considered an actionable alteration by TARGET but has been associated with sensitivity to Aurora kinase inhibitors in pre-clinical studies, was observed in 15.8% of patients. Eight patients had EGFR activating mutations (exon 21 L858R mutation or exon 19 deletion), of which 2 patients also had EGFR T790M mutation, likely representing transformation from NSCLC following targeted therapy with EGFR Tyrosine kinase inhibitors. KIF5BALK and AFAP1-RET fusions were seen in 1 patient each. Conclusion: G360 is a rapid non-invasive NGS platform which may be particularly useful in patients with advanced stage SCLC where tissue samples may be suboptimal for NGS. Due to the limited treatment options in this patient population, the detection of potentially actionable genes through G360 may provide valuable information to guide treatment decisions. Keywords: small cell lung cancer, cfDNA
P1.07-036 Large Cell Neuroendocrine Carcinoma of the Lung: The Mayo Clinic Experience Topic: Pathology Kunlatida Maneenil,1 Ming Liu,2 Alex Adjei,3 Julian Molina,3 Ping Yang2 1Oncology Unit, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok/Thailand, 2Health Sciences Research, Mayo Clinic, Rochester/MN/United States of America, 3Medical Oncology, Mayo Clinic, Rochester/MN/ United States of America Background: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a relatively uncommon, high-grade
Journal of Thoracic Oncology
Vol. 12 No. 1S
neuroendocrine tumor sharing several features with small-cell lung carcinoma (SCLC). LCNEC is considered aggressive, and the optimal treatment strategy and chemotherapy regimen remain undefined. Methods: We retrospectively evaluated a LCNEC patient cohort established from 1997 to 2015 at Mayo Clinic (Minnesota). A diagnosis of LCNEC was made when all WHO classification criteria were present in the tumor section examined. Clinical characteristics, treatment and outcomes were analyzed. Available radiology assessment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Results: The study included 55 LCNEC patients. Median age at diagnosis was 63 years (range: 38-88); two thirds were men; and majority were smokers (94%). Clinical staging was I, II, III or IV in 52.8%, 9.1%, 14.5%, and 23.6% of cases, respectively. Forty-six percent of stage IV patients presented with brain metastases at time of diagnosis (n¼6/13) and 18% (n¼7/ 38) developed brain recurrence in the follow up period. Thirty-nine (71%) patients had surgery and 9 (16%) patients received adjuvant platinum-based chemotherapy. Sixty-five percent of patients with complete resection experienced disease recurrence with 80% recurring within 2 years of resection. Treatment data for first-line palliative chemotherapy were available on 23 patients: 10 received platinum/etoposide and 13 received other regimens. In 19 patients with available imaging; the overall response rate was 52.6% (95% CI, 31.7-72.7) and there was no difference in ORR between platinum/etoposide (ORR¼55.6%) or platinum plus other agents (paclitaxel or pemetrexed; ORR¼55.6%). The median survival time was 26.3 months (95%CI; 18.6-33.9); the 1-, 2-, 3- and 5-year overall survival rates (OS) were 75%, 53%, 36%, and 30%, respectively. Patients who received platinum/etoposide demonstrated longer median time to progression (TTP), and median OS than those who received ‘other’ regimens (14.7 months vs. 7.1 months; p value 0.07, and 28.2 months vs. 21.1 months; p value 0.22, respectively); the differences did not reach conventional statistical significance, likely due to the small sample size. Rigorous pathologic confirmation and genomic analysis are ongoing. Conclusion: LCNEC is associated with a poor prognosis and high recurrence rates after surgery. Advanced LCNEC patients are at high risk for brain metastases, therefore, routine brain imaging surveillance during follow-up may be beneficial. The chemotherapeutic responsiveness of LCNEC patients was intermediate between that of NSCLC and SCLC patients. Future prospective, multicenter, clinical trials are needed to