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F.I.M. Heralde



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    P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P2.01-001 - Dendritic Cells: Cytokine-Induced Killer Cells Therapy in Advanced Non-Small Cell Lung Cancer: A Case Report of an Aggressive Tumor Relapse (ID 2855)

      09:30 - 09:30  |  Author(s): F.I.M. Heralde

      • Abstract
      • Slides

      Background:
      Cancer has been associated with immuno-surveillance dysfunction resulting to failure in identification and removal of malignant cells, followed by subsequent proliferation. Immune cell therapy aims to restore this immuno-surveillance function and manages micro-metastasis. DC/CIK (dendritic cell/cytokine-induced killer cells) an immune-based-maintenance therapy for advanced non-small cell lung cancer has been reported to improve progression free survival in several studies. Our early study suggested limited advantage of autologous DC vaccination in advanced NSCLC, hence, we proceeded to evaluate the response of a patient with Stage IV NSCLC to DC/CIK.

      Methods:
      The patient, 43-year-old nonsmoker male with family history of maternal breast cancer signed an informed consent to undergo the cell therapy protocol institutionally approved by Ethics Review Board of Lung Center of the Philippines. The patient earlier diagnosed with Stage IV NSCLC in November 2013, underwent chemotherapy of two cycles of Paclitaxel and Carboplatin and subsequently Erlotinib following partial remission. Patient had no severe existing medical condition that affected protocol compliance. The patient enrolled in November 17, 2014, and underwent hematology clearance, hematopoietic stem cell (HSC) mobilization with GCSF injection and leukapheresis. HSC’s recovered from the buffy coat were propagated in-vitro using standard procedures to produce dendritic cells and cytokine induced killer cells. Three DC/CIK treatments were given at three-week intervals consisting of 25-28x10[6] DC primed with mixed peptide antigens based on personalized circulating tumor cell (CTC) RT-PCR profile and 10-20x10[6] CIK. The blood IFN-Y level, CTC count, RT-PCR profile and PET-CT data were obtained.

      Results:
      DC/CIK treatment resulted to initial decline in IFN-Y levels relative to baseline which recovered in levels on the second and third treatment. The CTC count showed reduction in number (i.e., from 229 to 699 and down to one cell/ml) while the RT-PCR profile indicated downregulated expression of three tumor markers (MUC1, Recoverin and p53), obliteration of one marker (KRT19) and emergence of four markers (Brachury, NFYC, S100A14 and MAGE-A3). Meanwhile, the PET-CT results indicated significant regression of bilateral pulmonary nodules and masses; interval resolution of some hypermetabolic lymph nodes and interval increase in others consistent with metastatic lymphadenopathy; osseous metastasis with interval decrease in metabolic activity of bone lesions; and occurrence of patchy reticular and ground glass opacities in right upper and lower lobe with possible infectious or inflammatory nature; and right atrium and pulmonary artery thrombosis. Few days post-PET-CT, patient manifested difficulty of breathing, cough and back pain; initially managed for pneumonia and pulmonary embolism, but showed progressive deterioration. Repeat CT-scan imaging of chest with angiography revealed drastic size increase of right lung mass relative to previous PET-CT scan; while sample biopsy revealed poorly differentiated carcinoma of lung primary. In 28 days post-PET-CT, patient yielded to Acute Respiratory Distress secondary to aggressive tumor in right lung of primary origin.

      Conclusion:
      DC/CIK treatment can be a promising immunobiological maintenance therapy for advanced NSCLC with recognizable molecular and clinical benefit to patients. Optimization of protocol towards anticipative strategies addressing aggressive primary tumor relapse may have to be considered in order to realize its complimentary therapeutic potential.

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    P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P2.04-037 - Frequency of EGFR Mutations in NSCLC Patients of the Lung Center of the Philippines (ID 1257)

      09:30 - 09:30  |  Author(s): F.I.M. Heralde

      • Abstract
      • Slides

      Background:
      In 2014, the Lung Center of the Philippines embarked on a program to offer Epidermal Growth Factor Receptor (EGFR) mutation testing to its Non-Small Cell Lung Carcinoma (NSCLC) patients to support the diagnostic and decision-making capability of its allied oncologists towards anti-EGFR targeted therapy. As previous clinical studies indicated significant benefit from Tyrosine Kinase Inhibitor (TKI) therapies among Asian patients, enrolling patients on a TKI program based on anti-EGFR profile would realize the Lung Center of the Philippines’ objective of providing better chemotherapy to its patients. Meanwhile, early reports showed variable frequency of EGFR mutations among NSCLC patients from two private Philippine hospitals (i.e. San Juan De Dios, 52.3% EGFR positive in 2012 and Saint Luke’s Medical Center, 38.9% EGFR positive in 2015). This study will report the profile of EGFR mutation among NSCLC patients from a government tertiary hospital catering to the general Philippine population.

      Methods:
      Tissue samples from 80 patients clinically diagnosed with NSCLC at stages II to IV via histopathologic sections of biopsy derived specimens, were subjected to EGFR mutation analysis following the Roche EGFR protocol using the Roche EGFR mutation detection kit and the Cobas Quantitative Real Time PCR. The patients’ background data were obtained via a survey questionnaire at the time of sample submission and followed up through telephone interview. The patients were made to execute informed consents following the guidelines of the Institutional Ethics Review Committee of the Hospital.

      Results:
      Out of the 80 NSCLC samples analyzed, 55% (44/80) were from males and 45% (36/80) were from females with a mean age of 61.3 (SD: 11.5) years old. There were 47.5% (38/80) specimens that were positive for EGFR mutations of which 39.5% (15/38) were from males and 60.5% (23/38) were from females. Majority of the EGFR positive patients were non-smokers with only 13.8% (11/80) confirmed to be smokers and only 18.2% (2/11) of the smokers showing positive EGFR mutation. For patients showing positive EGFR mutations, 73.7% (28/38) were Exon 19 deletions, 23.7% (9/38) were Exon 21 L858R, and 2.6% (1/38) was a double mutation comprising Exon 19 deletion and Exon 20 insertion, and is a non-smoker.

      Conclusion:
      EGFR mutation frequency in LCP’s NSCLC patients were midway between the reported values in two Philippine private hospitals and consistent with the reported preponderance among females. Smoking appears not to be a driver for EGFR mutation. Majority of the EGFR mutations detected were on Exon 19 deletion. How these mutation patterns correlate with the chemotherapeutic response would be an important area for future follow-up.

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