Virtual Library
Start Your Search
R. Mudad
Author of
-
+
P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
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): R. Mudad
- 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.
-
+
P3.02b-092 - Central Nervous System (CNS) Responses to Osimertinib in Brain Metastases from Lung Cancer (NSCLC) with T790M: Effectiveness of the 80 Mg Dose (ID 4403)
14:30 - 14:30 | Author(s): R. Mudad
- Abstract
Background:
Patients with progressive CNS metastases from NSCLC who fail radiation therapy (RT) have a poor prognosis and short survival. Systemic chemotherapy is not very effective in controlling CNS metastases that failed RT. Patients with EGFR mutated NSCLC have a higher incidence of CNS metastases on presentation, and during the course of their illness. First and second generation tyrosine kinase inhibitors (TKI) at standard or pulse doses, may produce some clinically significant responses in the brain. Osimertinib is a potent irreversible EGFR TKI selective for activating EGFR and T790M resistance mutations. It has improved CNS penetration compared to older generations TKI. Previous reports have demonstrated the activity of osimertinib in the CNS at 160 mg. We report two patients who had failed RT treatment in the brain, who responded very well to the standard dose of osimertinib at 80 mg.
Methods:
Retrospective review of the charts of two patients was performed.
Results:
A 41-year old man diagnosed with metastatic adenocarcinoma of the lung with bilateral pulmonary nodules and 3 small brain micro metastases in April 2014. His lung biopsy revealed an EGFR Del 19. He was treated with cyberknife to the brain and Afatinib/Bevacizumab with an excellent response that lasted 11 months. Progressive brain metastases developed in May 2015 and treated with whole brain RT (WBRT). Lumbar puncture was negative for leptomeningeal disease. He was continued on Afatinib/Bevacizumab until November 2015, when he progressed in the lungs and the brain. Repeat lung biopsy revealed an EGFR T790M. He was not a candidate for additional RT. He was started on osimertinib at 80 mg in December 2015. Two months later, brain MRI revealed near complete resolution of the lesions, PET scan showed a significant response. Five months later, brain MRI remains negative and he remains in near complete systemic remission. An 84-year old female was diagnosed with multiple brain lesions in January 2015. Work up revealed a right lung mass, biopsy showed adenocarcinoma. She received WBRT. Blood-based cell-free DNA assay (Guardant 360) revealed an EGFR Del 19. She was treated with Erlotinib for 4 months and developed progression in the lungs. Repeat Guardant 360 revealed an EGFR T790M. Osimertinib 80 mg was started. She remains alive at 18 months with an excellent response in the brain .
Conclusion:
These two cases highlight the significant activity of osimertinib in the CNS at the standard 80 mg dose. Prospective studies should confirm this finding.
-
+
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)
-
+
P3.05-009 - Medical Marijuana and Lung Cancer: Patients' Knowledge and Attitude towards Its Use (ID 3994)
14:30 - 14:30 | Author(s): R. Mudad
- Abstract
Background:
Management of cancer-related symptoms in patients with lung cancer can be challengeing. Increasing number of patients have turned to cannabis plant to alleviate those symptoms. Some studies have shown potential benefits, however it is still classified as an illegal schedule I drug in the US. There is a shortage of research on its use in cancer patients. Additionally, there is fear, bias and stigma associated with its use. In this study, we set out to investigate patients' knowledge and views on the use of marijuana.
Methods:
Patients with advanced lung cancer over 18 years of age were included. They had to be receiving systemic intravenous treatment (chemotherapy, immunotherapy, biologic therapy), able to give informed consent and fluent in English. Study was explained by a trained research staff, written informed consent was obtained, and patients were given the survey to fill without assistance. Study was IRB approved.
Results:
A total of 20 patients were enrolled. They were 70% females, 30% males, 15% Hispanic, 5% Asian, 70% white, and 30% black. The majority of patients were symptomatic with 50% having pain, 25% nausea, 30% weight loss, 45% poor appetite and 65% with other symptoms most commonly fatigue. The majority (85%) have heard of the use of medical marijuana for cancer, 40% thought it helped treat the cancer, 75% thought it reduced side effects of treatment, 70% helped with pain, 60% helped with weight gain, and 70% helped with psychological distress. In this group, 82% have considered using marijuana, 70% thought they are able to obtain it. Only 15% said they would smoke it, while 30% would use a vaporized form, and 75% would use it in an edible form. Forty one percent of the patients expressed concerns regarding the legal risk of purchasing marijuana in Florida, while only 23% expressed concerns regarding the legal risk of using it. One hundred percent of the patients felt it should be legally available to cancer patients, and 100% expressed the need for a trusted educational resource for learning about Marijuana use. Overall, 94% of the patients would consider using it if legalized.
Conclusion:
To our knowledge, this is the first study focusing on lung cancer patients and their awareness regarding a highly controversial and currently illegal substance. Patients are interested in a robust educational resource regarding its benefit or lack thereof. More research focusing on this modality for palliation of symptoms in lung cancer patients is urgently needed.
