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Jonathan David Spicer
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MA13 - Interventional Pulmonology (ID 914)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Interventional Diagnostics/Pulmonology
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 10:30 - 12:00, Room 206 AC
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MA13.05 - The Canada Lymph Node Sonographic Score: National Validation of a Sonographic Score to Determine Mediastinal Lymph Node Malignancy (ID 12084)
11:00 - 11:05 | Author(s): Jonathan David Spicer
- Abstract
- Presentation
Background
At the time of endobronchial ultrasound (EBUS) staging for Non-Small Cell Lung Cancer (NSCLC), 6 ultrasonic criteria (Fig. 1) are used to assign a Lymph Node Sonographic Score (LNSS) that is predictive of malignancy. The LNSS has not gained widespread use due to lack of research demonstrating its validity and reliability among endoscopists. We hypothesized that LNSS correlates well with the probability of malignancy, potentially guiding decisions for lymph node (LN) biopsy.
a9ded1e5ce5d75814730bb4caaf49419 Method
We conducted a prospective study to assess the validity and reliability of the LNSS. The validation cohort comprised LN that were video-recorded from patients with NSCLC, and assigned a LNSS by an experienced endoscopist. Videos were then circulated to thoracic surgeons and interventional respirologists across Canada, who were asked to assign a score to each LN. All raters had demonstrated proficiency using our online education module, were blinded to staging information, and to each other. Each LN was scored by at least 3 independent raters. Pathological specimens were used as the gold standard for determination of malignancy. Regression, receiver operator curve (ROC), and Gwet’s AC1 analyses were used to test LNSS score performance, discriminatory capacity, and inter-rater reliability.
4c3880bb027f159e801041b1021e88e8 Result
A total of 300 LNs (18% malignant) from 140 patients were analyzed by 11 endoscopists across 7 Canadian centres. LNSS=0 was strongly predictive of benign LN (NPV= 95.69%, OR=49.2, p=0.001). LNSS ≤2.5 (OR=44, p=0.001) was determined as the cutoff for malignancy based on ROC analysis (c= 0.7757, 95%CI: 0.70281-0.84853). Inter-rater reliability for LNSS=0 was 0.8553 (95%CI:0.8158-0.8947, p=0.0001) and 0.46 for LNSS ≤2.5 (95%CI=0.3521-0.5012, p=0.0001).
8eea62084ca7e541d918e823422bd82e Conclusion
The Canada LNSS shows excellent performance in identifying benign LN at the time of EBUS. A cutoff ≤2.5 has the potential to inform decision-making regarding biopsy or repeat biopsy/mediastinoscopy if the initial results are inconclusive. Further teaching and education are required to improve inter-rater reliability.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MTE23 - Surgical Considerations Following Induction Therapy for Stage IIIA Disease (Ticketed Session) (ID 833)
- Event: WCLC 2018
- Type: Meet the Expert Session
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 07:00 - 08:00, Room 201 BD
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MTE23.02 - Surgical Considerations Following Induction Therapy for Stage IIIA Disease (ID 11588)
07:30 - 08:00 | Presenting Author(s): Jonathan David Spicer
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.09 - Pathology (Not CME Accredited Session) (ID 941)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.09-08 - Integrating NGS Information for Staging Multiple Lung Adenocarcinoma: A McGill University Health Centre Retrospective Study. (ID 12635)
16:45 - 18:00 | Author(s): Jonathan David Spicer
- Abstract
Background
The incidence of patients with multiple primary lung adenocarcinoma (MPLC) is increasing and the optimal management of these patients remains unclear. Distinguishing between MPLC and intrapulmonary metastases is at the heart of the diagnostic dilemma. The Comprehensive Histologic Assessment (CHA) relies on microscopic examination including histological subtypes, cytological and stromal features. CHA has shown a good reproducibility but with a non-negligible rate of disagreement, even between expert pathologists. Moreover, predictive biomarker testing has become standard of care for lung cancer patients and the use of Next-Generation Sequencing (NGS) is now widely available. The goal of this study was to evaluate how the NGS information may be integrated in the diagnostic strategy for distinguishing between MPLC and patients with stage III/IV disease.
a9ded1e5ce5d75814730bb4caaf49419 Method
We conducted a retrospective study of all surgical patients with > 1 synchronous lung carcinoma over two years. We identified 59 cases and reviewed initial clinical, pathological and molecular reports. Patients having multifocal lung adenocarcinoma with prominent lepidic component or an adenocarcinoma associated with another histological type were considered as synchronous primaries and not tested for molecular aberrations. The NGS panel analysis using an Illumina miSeq platform included the following genes: AKT1, BRAF, EGFR, ERBB2, FOXL2, GNA11, GNAQ, KIT, KRAS, MET, NRAS, PDGFRA, PIK3A, RET, and TP53.
4c3880bb027f159e801041b1021e88e8 Result
Histologically, the majority were considered as MPLC with only four suspected metastases. Twenty-five patients had adenocarcinoma with prominent lepidic component and one case had two different histological differentiations (adenocarcinoma and squamous cell carcinoma). Most of the suspected synchronous primary tumours had different mutations in the separate tumours. Relevant mutations were found in KRAS and P53 genes, with fewer mutations in EGFR, PIK3CA and BRAF genes, in accordance with known frequencies. In 12% of the cases, the NGS was not informative with no molecular mutation in either tumours. One case was reclassified from MPLC to intra-pulmonary metastases and restaged after NGS. For one patient, a TP53 mutation allowed us to reclassify two nodules as metastases from a previous adenocarcinoma originally diagnosed in 2012. In one patient having three separate nodules, different KRAS and TP53 mutations allowed the diagnosis of two nodules as intrapulmonary metastases and one contralateral nodule as synchronous primary adenocarcinoma.
8eea62084ca7e541d918e823422bd82e Conclusion
Although CHA is an efficient method for diagnosing MPLC from intra-pulmonary metastases there are still difficult cases with a risk of misdiagnosis. Integrating NGS analysis in the diagnostic strategy may lead to improved quality and accuracy in the staging of MPLC.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.01-04 - Reducing Time to Molecular Diagnosis for Advanced NSCLC in the Context of a Reference Testing Center (ID 13972)
16:45 - 18:00 | Author(s): Jonathan David Spicer
- Abstract
Background
Testing for mutation of the epidermal growth factor receptor (EGFR) gene is required for treatment of patients with advanced non-small cell lung cancer (NSCLC). First-line treatment with an EGFR tyrosine kinase inhibitor (TKI) in NSCLC patients with an activating EGFR mutation significantly impacts survival. Within the Rossy Cancer Network, the McGill University Health Centre (MUHC) has a supra-regional designation to perform all thoracic surgeries, while the Jewish General Hospital (JGH) is the reference testing center for specialized molecular pathology services. Significant differences in time to TKI therapy were noted between these centers. Our objective was to identify contributing factors to reduce network-wide delays.
a9ded1e5ce5d75814730bb4caaf49419 Method
We used the JGH molecular pathology database to identify all specimens tested for EGFR between 2015 and 2016 and mapped the process steps from diagnostic procedure to start of TKI therapy. We identified process differences and initiated reflex testing at the MUHC; EGFR testing was ordered reflexively by pathologists for all non-squamous NSCLC biopsies and other specimens from known or suspected advanced stage NSCLC.
4c3880bb027f159e801041b1021e88e8 Result
Implementation of reflex testing led to a 13-day reduction from pathology report to EGFR request (Figure 1, BàC). We subsequently identified that MUHC time from molecular results to start of TKI therapy was twice that of the JGH (24 vs 12 mean days). This was due to an additional step requiring integration of faxed molecular results into the patients’ electronic health record.
8eea62084ca7e541d918e823422bd82e Conclusion
We applied lean strategies to reduce time to initiation of targeted therapy. Within our network and in the context of a reference testing center, we identified two critical components that significantly contributed to delays in treatment planning: (i) absence of reflex testing and (ii) unlinked information technology systems. As Quebec moves towards specialized testing centers, it is important to be cognisant of their impact on timely treatment.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.06 - Mesothelioma (Not CME Accredited Session) (ID 955)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.06-33 - Heterogeneity in Care Pathways for Patients with Malignant Pleural Mesothelioma Presenting at a Quaternary Thoracic Oncology Center in Quebec (ID 14346)
16:45 - 18:00 | Author(s): Jonathan David Spicer
- Abstract
Background
Malignant pleural mesothelioma (MPM) is a rare disease for which diagnostic and therapeutic trajectories are ill-defined. We hypothesize that MPM patients experience delays during their diagnostic and therapeutic trajectory with significant heterogeneity in care pathways. Thus, we evaluated management practices at the MUHC over the past 10 years to address the need for a centralized program and dedicated care team.
a9ded1e5ce5d75814730bb4caaf49419 Method
We conducted a retrospective chart review of MPM cases diagnosed at our center from 2006 to 2016. Clinical, pathologic, and treatment variables were collected. We assessed time from first abnormal imaging to definitive diagnosis, time from definitive diagnosis to first treatment and time from definitive diagnosis to palliative care consult. Overall survival was analyzed by Kaplan Meir method.
4c3880bb027f159e801041b1021e88e8 Result
We identified 145 patients over a 10-year period and report outcomes on 92 cases with complete data. Demographic data are presented in Table 1. Overall survival was 1.4% at 5-years for all patients, with a median survival of 1 year following a definitive diagnosis. Forty-five percent of patients underwent an investigational PET/CT scan, 89% of patients had M0 status prior to treatment, of whom 20% developed extra-thoracic metastases. Sixty-three percent of patients received some form of treatment. Eight treatment combinations were identified, irrespective of intent, lymph node involvement, and metastatic status. With regards to delays in care pathway, median time from first abnormal imaging to definitive diagnosis was 34 days (IQR 20.5 to 55), definitive diagnosis to first therapeutic intervention was65 days (IQR 35.8 to 163.8), and definitive diagnosis to palliative consult was 289 days (IQR 3 to 1651).
Table 1. Demographics and treatment characteristics of patients diagnosed with MPM at the McGill University Health Center over a 10-year period. Characteristics Overall Sample size 92 Age Number (%) Median (IQR) 72 (62-79.5) Female Gender, n (%) 19 (20.7) Previous or current smoker, n (%) 36 (39.1) Asbestos Exposure No 20 (21.7) Yes 36 (39.1) Unknown 36 (39.1) Type of MPM Biphasic 9 (9.8) Desmoplastic 3 (3.3) Epitheliod 67 (72.8) Sarcomatoid 3 (3.3) Not otherwise specified 10 (10.9) Treatment No 28 (30.4) Yes 58 (63.0) Unknown 6 (6.5) Treatment Course Chemotherapy only 8 (13.8) Chemo & Radiotherapy 5 (8.6) Radiotherapy only 15 (25.9) Surgery only 10 (17.2) Trimodality therapy 7 (12.1) Surgery and Chemo 7 (12.1) Surgery and Radiotherapy 4 (6.9) Concurrent therapy 2 (3.4) Intent at first treatment Curative 31 (53.4) Palliative 24 (41.4) Unknown 3 (5.2)
8eea62084ca7e541d918e823422bd82e Conclusion
Overall outcomes for MPM patients presenting at our center are equivalent to historical controls. However, significant heterogeneity and delays exist during the patient trajectory. A centralized approach to diagnosis and treatment may lead to a more efficient and beneficial trajectory for these patients.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 965)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.16-03 - CheckMate 816: A Phase 3 Trial of Neoadjuvant Nivolumab Plus Ipilimumab or Chemotherapy vs Chemotherapy in Early-Stage NSCLC (ID 12599)
16:45 - 18:00 | Author(s): Jonathan David Spicer
- Abstract
Background
Approximately 20–25% of patients with NSCLC are diagnosed with early or localized disease, which has a relapse rate of 30–80% with surgery. Although neoadjuvant chemotherapy can reduce the risk of relapse, it only provides a pathological complete response (pCR; no viable tumor cells) rate of 4%. The neoadjuvant setting presents abundant tumor-associated neoantigens derived from the primary tumor that may allow immunotherapy to prime a long-lasting immune response. Clinical trial results support the use of immuno-oncology agents as neoadjuvant treatment for early-stage NSCLC. In a pilot study in patients with untreated, surgically resectable early-stage (stage I–IIIA) NSCLC, nivolumab (a fully human PD-1 immune checkpoint inhibitor antibody) administered as neoadjuvant treatment (3 mg/kg for 2 cycles during the 4 weeks prior to surgery) induced a pCR in 10% of patients and a major pathological response (MPR; ≤10% residual viable tumor cells in resected primary tumor) in 45% of patients, did not delay surgery, and was associated with an acceptable safety profile. Combining immuno-oncology agents with distinct mechanisms of action, such as PD-1 and CTLA-4 inhibitors, offers the possibility of a synergistic response and may improve antitumor activity compared with either agent alone. The combination of an immuno-oncology agent and chemotherapy may also offer synergistic activity, given that chemotherapy results in tumor cell death and subsequent antigen release that can activate an immune response. Promising results have been noted with nivolumab plus ipilimumab (a CTLA-4 immune checkpoint inhibitor antibody) and nivolumab plus chemotherapy in patients with treatment-naïve stage IIIB/IV NSCLC in the multicohort phase 1 CheckMate 012 study. CheckMate 816 (NCT02998528) is a phase 3 study evaluating nivolumab plus ipilimumab, nivolumab plus platinum-doublet chemotherapy, and platinum-doublet chemotherapy as neoadjuvant treatment for early-stage NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
Approximately 642 patients aged ≥18 years with early-stage (stages IB–IIIA) resectable NSCLC, ECOG performance status 0–1, pulmonary function capable of tolerating lung resection, and available lung tumor tissue will be enrolled in North America, South America, Europe, Asia, and Africa. Patients are ineligible if they have active autoimmune disease or had received prior treatment with immune checkpoint inhibitors. Patients will be randomized (1:1:1) to receive neoadjuvant nivolumab plus ipilimumab, nivolumab plus platinum-doublet chemotherapy, or platinum-doublet chemotherapy. Primary endpoints are event-free survival and pCR. Key secondary endpoints are overall survival and MPR (<10% residual tumor in lung and lymph nodes). The start date was January 2017. The estimated primary completion date is May 2023.
4c3880bb027f159e801041b1021e88e8 Result
Section not applicable
8eea62084ca7e541d918e823422bd82e Conclusion
Section not applicable
6f8b794f3246b0c1e1780bb4d4d5dc53
