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E. Haura
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-012 - Longitudinal Monitoring of ctDNA EGFR Mutation Burden from Urine Correlates with Patient Response to EGFR TKIs: A Case Series (ID 5717)
14:30 - 14:30 | Author(s): E. Haura
- Abstract
Background:
Circulating tumor DNA (ctDNA) are short DNA fragments released into the systemic circulation by rapid cell turnover, and excreted into the urine. Urinary ctDNA-based detection of oncogenic mutations is a non-invasive modality that can help in clinical decision-making, especially when tissue biopsies are not available. When conventional imaging modalities are inconclusive, quantitative assessment of systemic ctDNA burden has the potential to assess response to therapy. In this case series we assessed EGFR mutation status at baseline and at intervals following administration of tyrosine kinase inhibitor (TKI) therapy to determine whether EGFR systemic mutation load correlated with disease burden and therapeutic response.
Methods:
Four patients on anti-EGFR (TKI) were prospectively monitored for quantitative assessment of systemic mutant allele burden of activating and resistance EGFR mutations (Exon 19 deletions, L858R and T790M) in urine. EGFR mutations were quantitatively interrogated by short footprint mutation enrichment PCR followed by next-generation sequencing assays. Systemic mutant allele burden was compared to assessment of tumor burden computed by standard imaging modalities.
Results:
Patients 1, 2, and 3 were originally diagnosed with EGFR-positive NSCLC. Targeted molecular testing of systemic urine ctDNA revealed high EGFR mutation burden and the presence of the T790M resistance mutation at the time of progression on TKI therapy (>550 copies/10[5] genome equivalents (GEq)). Interestingly, the extent of radiographic progression in patient 3 was not completely clear, and urinary T790M along with clinical assessment of pain helped determine progression prior to obtaining pleural effusion results. After initiation of a 3[rd] generation TKI (patient 1: ASP8273, patients 2 and 3: osimertinib), all patients experienced an appreciable decrease in the EGFR mutation burden, which was consistent with clinical improvement prior to radiographic imaging. Patient 4 presented with multiple lung nodules at diagnosis and a high systemic L858R mutant allele burden (>550 copies/100,000 GEq). Two months after initiation of first-line TKI, the main lesion and lymph nodes slightly improved, but the lung nodules progressed. The high systemic L858R burden persisted at the same level as pre-therapy.
Conclusion:
Urinary ctDNA-based quantitative assessment of systemic EGFR mutant allele burden is a non-invasive molecular diagnostic testing modality that correlates with tumor burden and response to therapy.
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P3.05 - Poster Session with Presenters Present (ID 475)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Palliative Care/Ethics
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.05-010 - Developing Tools for a Successful Thoracic Rapid Tissue Donation Program (ID 3722)
14:30 - 14:30 | Author(s): E. Haura
- Abstract
Background:
Advances in cancer treatment have been made through the use of human tumor tissues from patients with refractory disease. Rapid Tissue Donation (RTD) provides an opportunity to gain insight into treatment-resistant cancers by analyzing tissue from primary tumors and metastasis within 24 hours following a patient’s death. The discussion of participation is a delicate process that must consider inherent communication challenges. Prospective patients may perceive their physician’s recruitment efforts for RTD as a sign of loss of hope. Companions may be distressed by the offer. This study examined the decision making of participating in a RTD program for patients with advanced stage lung cancer and their companion.
Methods:
After a physician-guided introduction of the RTD program, participants with stage 4 lung cancer (n=9) and their companions (n=8) were consented to participate in a qualitative, semi-structured interview assessing their decision making process and barriers and benefits of enrolling in the program, perceptions of the RTD brochures and satisfaction with the recruitment process. Companions participated in independent and joint interviews assessing their perceptions of patients’ decision to enroll in the program. Coders reviewed the verbatim transcripts of the interviews and applied qualitative thematic analysis to identify emerging themes.
Results:
The majority of patients chose to enroll in the RTD program as an opportunity to give back to science and upon learning organ donation was not an option for them. All patients had good relationships with their physician and this was a deciding factor for participation. Patients had limited concerns about participation and wanted to be sure their loved ones were not burdened by the process. Companions had more concerns about logistics but all supported patients’ decisions. All participants were comfortable with the recruiting process and their physician’s initiation and subsequent discussion of the program. Several patients indicated that they did not plan to inform extended family members. Two companions reported feeling distressed during a clinical discussion concerning the patients’ participation. Patients and their companions approved of the brochure’s content, including references to death, but often objected to the use of language depicting cancer as a “battle” or “fight”.
Conclusion:
Implementation of an RTD program requires monitoring of the complex communication processes that occur at both interpersonal and institutional levels. Additional research during the ongoing accrual process will continue to assess physician perspectives and seek methods honoring the wishes of patients and companions. R21 CA 194932-01 (NCI)
