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D. Jablons
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MA17 - Genetic Drivers (ID 409)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Biology/Pathology
- Presentations: 1
- Moderators:M. Satouchi, G.R. Simon
- Coordinates: 12/07/2016, 14:20 - 15:50, Lehar 1-2
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MA17.01 - Microarray Identification of Genetic Drivers of Brain Metastasis in Lung Adenocarcinoma (ID 3962)
14:20 - 15:50 | Author(s): D. Jablons
- Abstract
- Presentation
Background:
Brain metastasis in non-small cell lung cancer (NSCLC) develop in 20-40% of all patients and represent a major cause of NSCLC morbidity and mortality. The mechanisms driving metastatic potential across the blood-brain-barrier remain poorly understood.
Methods:
Affymetrix microarray was performed on RNA extracted from 75 pairs of snap-frozen primary lung adenocarcinoma and matched normal lung tissue. Changes in gene expression from the primary lung adenocarcinomas that did not ever metastasize to brain over up to 15 years of follow up were compared to the lung adenocarcinomas that ultimately seeded a brain metastasis. From these 75 patients, tissue from 5 paired snap-frozen brain metastases was also available and gene expression changes between the primary lung adenocarcinomas and matched brain metastases were investigated to identify genes and pathways of interest in the development of brain metastasis. Affymetrix Transcriptome Analysis Console software was used for data analysis and interpretation with fold changes >2.0 and p-value of <0.05 for significance.
Results:
From the 75 patients 20 (27%) ultimately developed a brain metastasis from their primary lung adenocarcinoma and 55 (73%) were followed long term without development of brain metastasis. Microarray identified 71 genes that were differentially expressed in lung adenocarcinomas that later produced brain metastasis. S100 calcium binding protein, RAP1GAP, GPR160, and immunoglobins were among the upregulated genes in primary lung adenocarcinomas that developed brain metastasis. Within the matched sets of brain metastasis, hierarchical clustering showed clear distinction in expression patterns comparing brain metastasis verses normal lung, as well as primary adenocarcinomas verses normal lung. 267 genes were identified to be significantly differentially expressed between paired brain metastasis and primary lung adenocarcinomas. Significant changes in focal adhesion, angiogenesis, matrix metalloproteinase pathways, and immunoglobulins were found in the brain metastasis compared with the paired primary lung tumor.
Conclusion:
This study represents the largest microarray analysis of snap frozen pairs of primary lung adenocarcinoma and brain metastasis to date. S100 calcium binding protein, RAP1GAP, GPR160 genes, immunoglobulins, and focal adhesion, angiogenesis, and matrix metalloproteinase pathways were among the upregulated genes in primary lung adenocarcinomas that developed brain metastasis.
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OA19 - Translational Research in Early Stage NSCLC (ID 402)
- Event: WCLC 2016
- Type: Oral Session
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:G. Heller, G. Goss
- Coordinates: 12/07/2016, 11:00 - 12:30, Schubert 3
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OA19.06 - Adjuvant Chemotherapy Decisions Based on Molecular Risk Status Improves Outcomes in Early Stage, Non-Small Cell Lung Cancer (ID 5321)
11:00 - 12:30 | Author(s): D. Jablons
- Abstract
- Presentation
Background:
A clinically certified, 14-gene quantitative PCR expression assay has been found to assess mortality risk more accurately than clinicopathologic criteria in early-stage, non-squamous, non-small cell lung cancer (NSCLC). Clinically validated molecular stratification may provide a more informative approach to identify early stage NSCLC patients who are most likely to benefit from chemotherapy than current National Comprehensive Cancer Network (NCCN) high-risk clinicopathologic features.
Methods:
Prospective molecular risk-stratification by the 14-gene quantitative PCR expression assay was performed on 91 consecutive patients with stage I-IIA non-squamous NSCLC after complete surgical resection at a single institution. Information from molecular risk profiling was used in conjunction with pathologic stage and NCCN criteria to make adjuvant chemotherapy recommendations. Fisher’s exact test was used to compare recurrence rates, and Kaplan-Meier analysis and log-rank tests were used to evaluate differences in disease free survival.
Results:
Median age was 69 years, 57% were female and median follow up was 23±2 months. Among all patients, 33 (36%) met NCCN high-risk criteria for adjuvant chemotherapy and 27 (30%) were molecular high risk. Recommendations for adjuvant chemotherapy were discordant in 18 (55%) of NCCN high-risk patients and in 12 (44%) who were molecular high-risk. Twelve (44%) of molecular high-risk patients agreed to receive adjuvant chemotherapy. Whereas recurrence was observed in 33% of molecular high-risk patients who did not receive adjuvant chemotherapy, none of the molecular high-risk patients who underwent chemotherapy recurred (log-rank p=0.001).
Conclusion:
This prospective single-institution study demonstrates the clinical utility of molecular testing of early-stage NSCLC to supplement pathologic stage and NCCN guidelines in making adjuvant chemotherapy recommendations. Molecular risk scores better differentiated prospective recurrence rates than did NCCN risk criteria. This study provides preliminary evidence that molecular testing followed by adjuvant chemotherapy in molecularly high-risk patients may prevent a significant number of recurrences and improve outcomes.
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P2.04 - Poster Session with Presenters Present (ID 466)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.04-039 - Long-Term Risk of Recurrence in Benign Pleural Solitary Fibrous Tumors: A Single Institution Review (ID 5782)
14:30 - 15:45 | Author(s): D. Jablons
- Abstract
Background:
Solitary fibrous tumor (SFT) is a rare tumor of submesothelial origin that can occur in the abdomen, extremities, trunk, head, neck and pleura. Pleural SFTs are defined as benign or malignant based on the number of mitoses and the presence of pleomorphism, hemorrhage, or necrosis. There is limited data in the literature regarding the recurrence risk of benign pleural SFT and the need for long-term follow up in these patients.
Methods:
A single institution retrospective chart review was performed on all surgically resected primary pleural SFTs between 1992 and 2015. Preoperative clinical information, pathologic tumor characteristics, and long-term recurrence and survival data were collected.
Results:
There were 29 primary pleural SFTs resected between 1992 and 2015. Patients had a mean age of 60 years and there were 16 men (55%) and 13 women (45%). Fourteen (48%) presented with symptoms, including two patients with paraneoplastic syndromes, and the other 15 tumors (52%) were found incidentally on imaging. There were six giant SFTs defined as size greater than 15 cm, with two of six giant SFTs undergoing preoperative embolization to aid surgical resection. Otherwise, there were no neoadjuvant or adjuvant treatments in any patient. There was no perioperative 30-day mortality (0%). Mean follow up time was 77 months, during which 4 (14%) patients recurred and 21 of 29 patients (72%) were alive at last follow up. Three of the 8 deaths occurred in patients with recurrent disease. Among the 19 benign pleural SFTs, 2 (11%) recurred at 5 and 9 years postoperatively and 2 of the 6 malignant SFTs (33%) recurred at 4 and 15 years postoperatively. Margin status was known in 25 cases, of which 21 (84%) were negative and 4 (16%) were positive. There were no recurrences in patients with known negative margins.
Conclusion:
This study represents one of the largest contemporary single institution reviews of outcomes of pleural SFT. While benign pleural SFTs were less likely to recur than malignant pleural SFTs, benign pleural SFTs with positive or unknown margin status remain at risk for recurrence up to a decade following resection and require ongoing long-term follow up and surveillance imaging.
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P3.01 - Poster Session with Presenters Present (ID 469)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.01-013 - Case Report of Melanotic Schwannoma: A Challenging Diagnosis Made Clear through Genetic Testing (ID 4943)
14:30 - 15:45 | Author(s): D. Jablons
- Abstract
Background:
Melanotic schwannomas (MS) are tumors associated with the Carney complex of hyperpigmentation, myxomas, and endocrine overactivity. They most frequently arise from spinal nerve roots and present a diagnostic challenge due to their lack of characteristic pathologic features. We present the case of an otherwise healthy 35-year-old man who presented with nocturnal dyspnea and ptosis. Imaging identified a large 8.1 x 9.2 x 8.4 cm mass in the right apical posterior mediastinum. Core biopsy was consistent with melanoma, although no primary site could be identified. The patient underwent complete R0 resection of an encapsulated posterior thoracic inlet mass adherent to the sympathetic chain and apical parietal pleura. Surgical pathology showed nests of large pleomorphic epithelioid cells with prominent nucleoli and abundant intracytoplasmic pigment consistent with the initial diagnosis of melanoma. The actual diagnosis of melanontic schwannoma was made only when the tumor was sent for molecular testing and a rare mutation was identified.
Methods:
Oncogene sequencing (UCSF-Syapse) was performed on surgically resected formalin-fixed and paraffin embedded tumor. Single nucleotide variations, copy number changes, and rearrangements were detected using a hybridization-based enrichment assay of approximately 500 oncogenes commonly implicated in the development of neoplasia. Of the genes assayed, entire coding regions were analyzed in 429 genes with additional analysis of selected introns in 42 genes.
Results:
Based on standard hematoxyalin and eosin (H&E) stains as well as S-100 and Melan-A positivity on immunohistochemistry (IHC) stains, the specimen was originally diagnosed as melanoma. The initial diagnosis was also supported by a Ki-67 proliferative index of 15%. Molecular testing uncovered a rare PRKAR1A mutation inconsistent with melanoma and consistent with melanotic schwannoma. No other mutations were identified. PRKAR1A mutations are known to occur in up to 70% of Carney complex patients but have never been known to occur in melanoma.
Conclusion:
Standard techniques of H&E and IHC staining with their potential to misdiagnose two similar tumor histologies are outdated in the context of 21st century technology. Modern precision medicine and molecular diagnostics enable the clear distinction of histologically similar tumors. The speed and low cost of sequencing technology has advanced to recommend its frequent use in cases such as this where a diagnosis is not entirely clear.
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WS04 - Mesothelioma Workshop (Ticketed Session) (ID 416)
- Event: WCLC 2016
- Type: Workshop
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 12/04/2016, 08:00 - 11:00, Stolz 2
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WS04.01 - Debate - Extrapleural Pneumonectomies Should be Performed for Pleural Mesothelioma (ID 6981)
08:00 - 11:00 | Author(s): D. Jablons
- Abstract
- Presentation
Abstract not provided
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