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Thomas A D’amico
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MA05 - Update on Clinical Trials and Treatments (ID 123)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Mesothelioma
- Presentations: 1
- Now Available
- Moderators:Seiki Hasegawa, Enrico Ruffini, Angel Artal
- Coordinates: 9/08/2019, 13:30 - 15:00, Melbourne (1991)
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MA05.03 - Impact of Time to Surgery on Outcomes in Patients Undergoing Outright Resection for Malignant Pleural Mesothelioma (Now Available) (ID 648)
13:30 - 15:00 | Author(s): Thomas A D’amico
- Abstract
- Presentation
Background
We hypothesized that a longer interval to surgery would be associated with worse overall survival for patients with malignant pleural mesothelioma (MPM).
Method
The National Cancer Database (NCDB) for patients with cT1-3N0-1M0 MPM who underwent surgery without induction therapy. Patients with interval of <1 or >180 days were excluded. Patients were grouped into quartiles based on distribution of time intervals to surgery: Q1 (1-30 days), Q2 (31-50 days), Q3 (51-80 days), and Q4 (>80 days). The primary outcome was overall survival. Secondary outcomes were upstaging to pN2 and margin-positive (>R0) resection rate. Survival was estimated using the Kaplan-Meier and Cox Proportional Hazards methods. Nodal upstaging and >R0 resection rates were modeled with multivariable logistic regression.
Result
A total of 812 patients met study criteria. The median interval from diagnosis to surgery was 52 days. The unadjusted median survival for Q1, 2, 3, and 4 was 16, 19, 20, and 27 months, respectively (log-rank p=0.004). In multivariable analysis, increased time to surgery was not associated with worse overall survival (Table 1), and Q4 (>80 days) was independently associated with improved survival compared to Q1. When modeled as a continuous variable, an increased time to surgery was associated with a small but clinically insignificant increase in survival (AHR 0.997; 95%CI 0.995-0.999; p=0.005). In a multivariable regression of factors predicting pathologic upstaging to N2, increased time to surgery was significantly associated with upstaging (adjusted odds ratio [AOR] for Q4 compared to Q1: 2.26; 95%CI 1.04-5.28). In a separate regression of >R0 resection, an increased interval to surgery was not associated with margin-positive resection (AOR 0.70; 95%CI 0.41-1.21).
Conclusion
An increasing interval from diagnosis to definitive surgery for MPM was not associated with worse overall survival or margin-positive resection, but was associated with higher likelihood of pathologic nodal upstaging in this analysis.
Variable
Adjusted HR
95% CI
P value
Interval (ref:Q1)
Q2
Q3
Q4
1.07
0.96
0.74
0.84-1.36
0.76-1.22
0.58-0.95
0.61
0.75
0.02
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MA08 - Pawing the Way to Improve Outcomes in Stage III NSCLC (ID 127)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:Simon Ekman, Helena A Yu
- Coordinates: 9/08/2019, 15:15 - 16:45, Tokyo (1982)
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MA08.05 - A Multi-Center Analysis of Right vs Left-Sided Pneumonectomy Following Induction Therapy (Now Available) (ID 1178)
15:15 - 16:45 | Author(s): Thomas A D’amico
- Abstract
- Presentation
Background
Previous single-center studies of pneumonectomy following induction therapy for non-small-cell lung cancer (NSCLC) have found a significant perioperative risk associated with right-sided pneumonectomy. We examined the impact of laterality on long-term survival after induction therapy followed by pneumonectomy in a multi-institutional analysis.
Method
Perioperative and long-term outcomes of patients with NSCLC who underwent pneumonectomy following induction chemotherapy with or without radiation from 2000-2016 across 3 institutions were evaluated using multivariable logistic regression, Cox proportional hazards modeling and propensity score-matched analysis. Patients who underwent a completion pneumonectomy or who had M1 disease were excluded from the analysis.
Result
During the study period, 172 patients (right n = 78 [45%], left n = 94 [55%]) met inclusion criteria. Right-sided pneumonectomy was associated with a similar perioperative complication rate (38% [30/78] vs 27% [25/94], p=0.10), and 30-day (13% [10/78] vs 9% [8/94], p=0.36) and 90-day mortality (23% [18/78] vs 13% [12/94], p=0.08) when compared to left-sided pneumonectomy. In multivariable analysis, right-sided pneumonectomy was not found to be a predictor of higher perioperative complications (OR 0.85 [95% CI: 0.33-2.14], p=0.73) or 30-day (OR 2.06 [95% CI: 0.44-9.69], p=0.36) and 90-day mortality (OR 2.06 [95% CI: 0.54-7.88], p=0.29). Overall survival between right and left pneumonectomy was not significantly different in unadjusted (5-year survival 30% [95% CI: 19%-41%] vs 29% [95% CI: 20%-39%], log-rank p=0.77 [Figure]) or multivariable analysis (adjusted hazard ratio, 1.05 [95% CI: 0.63-1.76], p = 0.84). A propensity score-matched analysis of 108 patients balancing baseline characteristics—including pulmonary function, tumor size and stage—was also performed, and found no significant differences in perioperative complication rates (46% [25/54] vs 48% [26/54], p=0.85), 30-day (17% [9/54] vs 7% [4/54], p=0.14) and 90-day mortality (26% [14/54] vs 13% [7/54], p=0.09) between right versus left pneumonectomy, respectively. Overall survival was not significantly different between right- and left-sided pneumonectomy (5-year survival 33% [95% CI: 20%-47%] vs 28% [95% CI: 16%-41%], log-rank p=0.98).
Conclusion
In this multi-center analysis, right-sided pneumonectomy after induction therapy was not associated with significantly higher perioperative mortality rates or worse long-term survival when compared to a left-sided pneumonectomy.
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-89 - Neoadjuvant Pembrolizumab in Early Stage Non-Small Cell Lung Cancer (NSCLC): Toxicity, Efficacy, and Surgical Outcomes (ID 1941)
10:15 - 18:15 | Author(s): Thomas A D’amico
- Abstract
Background
Pembrolizumab is a programmed death receptor-1 masking antibody approved for advanced NSCLC in program death receptor ligand-1 high tumors, and in chemotherapy combinations. This trial studies the effect of neoadjuvant pembrolizumab on surgical tolerability (primary endpoint), tumor response, side effects, and immune biomarkers in blood and tumor.
Method
Baseline PET/CT, brain imaging, histologic diagnosis NSCLC, and surgical consultation were required for eligibility. Patients with stage T > 3 cm and N0, N1, or resectable N2 NSCLC received neoadjuvant pembrolizumab 200 mg every 21 days 2 cycles prior to pre-operative chest CT scan followed by standard surgery. Adjuvant chemotherapy was strongly encouraged but not required. After completion of standard chemotherapy, 4 cycles of adjuvant pembrolizumab 200 mg every 21 days was offered. Blood for immune profiling of circulating immune cells was collected at baseline, after cycle 2 pembrolizumab, after surgery, and after adjuvant pembrolizumab. Excess tumor was disaggregated for tumor infiltrating lymphocytes, regulatory immune cells, and tumor cells, and viably stored for later analysis. We report clinical outcomes of tumor response and surgical outcomes.
Result
Study activated 31/1/2017, last enrollment 6/2/2019, and last surgery 19/3/2019. 35 patients signed consent and 30 received at least 1 dose pembrolizumab: 2 withdrew consent, 3 screen failed. Characteristics of 30 treated patients (%): male 16 (53), adenocarcinoma 10 (33), squamous 17 (57), other histology 3 (10), and stages 1B 8 (27), IIA 8 (27), IIB 6 (20), IIIA 8 (27). Planned surgery completed for 25/30 (83%). Reasons for not undergoing surgery: distant metastatic disease (1 brain metastases, 2 pleural metastases), 1 would not tolerate required pneumonectomy, 1 N3 nodal disease. Surgeries performed: video-assisted thoracic surgery (VATS) lobectomy 12, thoracotomy lobectomy 9, VATS pneumonectomy 2, thoracotomy pneumonectomy 1, and VATS bilobectomy and chest wall resection 1. All surgery was performed within range 38-77 days (median 48 days) after cycle 1 day 1 pembrolizumab. Data will be presented for toxicities neoadjuvant pembrolizumab, surgical outcomes, and neoadjuvant pembrolizumab RECIST responses, and pathologic responses. Some major pathologic responses (< 10% viable tumor) and at least 2 pathologic CRs were observed.
Conclusion
Two doses of neoadjuvant pembrolizumab was tolerable and produced major or complete pathologic responses in some tumors. Neoadjuvant pembrolizumab is tolerable and is an ideal platform to investigate mechanisms of immune resistance and sensitivity in early stage NSCLC.
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P2.06 - Mesothelioma (ID 170)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.06-03 - Timing of Surgery After Induction Therapy for Malignant Pleural Mesothelioma: A National Analysis (ID 649)
10:15 - 18:15 | Author(s): Thomas A D’amico
- Abstract
Background
The safe window to offer surgery following induction chemotherapy for malignant pleural mesothelioma (MPM) is unknown.
Method
The National Cancer Database (NCDB) was queried for patients with cT1-3N0-1M0 MPM undergoing induction chemotherapy followed by definitive surgery. Patients with induction radiation, missing survival data, and time to surgery <1 or >180 days were excluded. Patients were stratified into quartiles based on time from chemotherapy to surgery: Q1 (<85 days), Q2 (85-100 days), Q3 (101-120 days), and Q4 (>120 days). The primary outcome was overall survival, and secondary outcomes were pN2 disease and margin-positive (>R0) resection. Survival was modeled with Kaplan-Meier and Cox Proportional Hazards, and upstaging and >R0 resection with multivariable logistic regression.
Result
A total of 205 patients were included, with a median time from induction therapy to surgery of 104 days. There was no difference in unadjusted median survival between the groups: 23 (Q1), 25 (Q2), 25 (Q3), and 20 (Q4) months (log-rank p=0.92). In multivariable regression, increasing time to surgery was not associated with survival examined by quartile (Table) or as a continuous variable (adjusted hazard ratio [AHR] 1.00; 95% confidence interval [CI] 0.99-1.01). Increasing time to surgery was also not associated with increased pathologic upstaging to N2 (adjusted odds ratio [AOR] for Q4 vs. Q1: 1.22; 95%CI 0.33-4.65). In a multivariable regression, increased time from chemotherapy to surgery was not associated with >R0 resection (AOR 0.81; 95%CI 0.23-2.87 for Q4 vs. Q1).
Conclusion
Increased time from induction therapy to surgery for MPM was not associated with worse survival, nodal upstaging, or margin-positive resection in this study. Patients with MPM can be safely offered surgery even three months after induction chemotherapy.
Variable
Adjusted HR
95% CI
P value
Interval (ref:Q1)
Q2
Q3
Q4
0.83
0.92
1.08
0.49-1.40
0.55-1.53
0.61-1.92
0.49
0.74
0.79
