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L. Bacon
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MA 20 - Recent Advances in Pulmonology/Endoscopy (ID 685)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Pulmonology/Endoscopy
- Presentations: 1
- Moderators:C. Lee, S. Sasada
- Coordinates: 10/18/2017, 14:30 - 16:15, F205 + F206 (Annex Hall)
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MA 20.12 - Longitudinal Evaluation of Pulmonary Function in Patients with Advanced NSCLC Treated with Concurrent Chemo-Radiotherapy (ID 10197)
15:45 - 15:50 | Author(s): L. Bacon
- Abstract
- Presentation
Background:
Patients with locally advanced Non-small cell lung cancer (aNSCLC) receive standard treatment with concurrent chemo-radiotherapy (CCRT). Different studies have tried to identify the changes in lung function after radiation exposition due to the high risk of pulmonary toxicity. The aim of this work is to evaluate lung function with a broad spectrum of respiratory tests as an objective way of assessing lung injury in patients with locally aNSCLC treated with CCRT.
Method:
A prospective study was conducted from June 2013 to July 2015. Fifty-two patients with locally advanced and oligometastatic NSCLC were included. The candidates received treatment with CCRT at the Instituto Nacional de Cancerología (Mexico). Participants were evaluated at baseline, end of RT, week 6, 12, 24 and 48 post-RT through forced spirometry with bronchodilator, body plethysmography, carbon monoxide diffusing capacity (DLCO), arterial blood gases, impulse oscillometry, 6-minute walk test and exhaled fraction of NO (FeNO). The study was registered in clinicaltrials.gov (NCT01580579).
Result:
Before treatment, 34.7% patients presented airflow obstruction (post-BD FEV~1~/FVC < 70%) which remained constant after RT (33.3%). For baseline results, the median of the % of the predictive value in FEV~1 ~post-BD was 97% (79-108), FVC 105% (90-116), TLC 101% (91-111) and DLCO 77% (55-103). At the end of CCRT, FEV~1 ~and FVC showed a significant reduction of 10% within week 12-48 (p=0.0004, p= 0.0005). TLC declined after week 6 post-RT, with a maximum drop of 15% at week 48 (p=0.0015). DLCO changes occurred from RT start to week 48, decreasing up to 20% at week 12 (p=0.0001). FeNO increased, exceeding 20% of its initial/baseline value with a peak at week 6 post-RT. Eighteen patients (34.7%) were hypoxemic (SO2 <90%) at the beginning of the trial, oxygen saturation had a statistically significant reduction at week 6 and week 48 (p<0.03, p<0.01). No significant differences were found in impulse oscillometry and 6-minute walk test. The results of the respiratory tests that decreased with the CCRT did not return to baseline at the end of follow-up.
Conclusion:
Regardless of pre-existing lung damage, the reduction in FEV~1~, FVC, DLCO, TLC and SO2 may represent increased inflammation, tissue remodeling and modification in gas exchange, however further studies are required. The nadir of the lung function occurred at 12 weeks from CCRT initiation. Increased FeNO values may represent a non-invasive marker of airway inflammation that correlates with RT lung injury mechanisms.
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P1.09 - Mesothelioma (ID 695)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.09-013 - Profiling Response to Chemotherapy in Malignant Pleural Mesothelioma Among Hispanics (MeSO-CLICaP) (ID 10430)
09:30 - 09:30 | Author(s): L. Bacon
- Abstract
Background:
Malignant pleural mesothelioma (MPM) is a rare malignant disease, and the understanding of molecular pathogenesis has lagged behind other malignancies.
Method:
A series of 53 formalin-fixed, paraffin-embedded tissue samples with clinical annotations were retrospectively tested for BAP1 and PI3K mutations and for mRNA expression of TS and EGFR. Immunohistochemistry staining for CD26 (dipeptidyl-peptidase IV, DPP-IV) and Fibulin3 (Fib3) proteins were also performed. Outcomes like progression free survival (PFS), overall survival (OS) and response rate (ORR) were recorded and evaluated according to biomarkers. Cox model was applied to determine variables associated with survival.
Result:
Median age was 58 years (range 36-76), 27 (51%) were men, 89% were current or former smokers, and six patients had previous contact with asbestos. 77% had a baseline ECOG 0-1 and almost all patients (n=52/98%) received cisplatin or carboplatin plus pemetrexed (Pem) as first line; 58% of them were treated with Pem as maintenance for a mean of 4.7 +/-2.8 cycles. 53.5% and 41.5% of patients were positive for CD26 and fibulin-3, while 49% and 43.4% had low levels of EGFR and TS mRNA, respectively. The majority of epithelioid and biphasic types expressed CD26 (p=0.008), Fibulin3 (0.013) and had lower levels of TS mRNA (p=0.008). Mutations in PI3K (c.1173A> G, c.32G> C and c.32G> T) were found in 5 patients and only one patient had a mutation in BAP1 (c.241T> G). First line PFS were significantly longer in CD26+ (p=0.0001), in those with low EGFR mRNA expression (p=0.001), in patients with positive Fib3 (p=0.006) and lower TS mRNA expression (p=0.0001). OS were significantly higher in patients with CD26+ (p=0.0001), EGFR- (p=0.001), Fib3 + (p=0.0002) and low TS mRNA expression level (p=0.0001). Multivariate analysis found that CD26+ (p=0.012), Fib3 (p=0.020) and TS mRNA levels (p=0.05) were independent prognostic factors.
Conclusion:
CD26, Fib3 and TS were prognostic factors significantly associated with improved survival in patients with advanced MPM.
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P3.09 - Mesothelioma (ID 725)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.09-010b - Predicting Response to First Line Chemotherapy in Pleural Mesothelioma: A Random Forest Tree Model (Meso-CLICaP) (ID 10389)
09:30 - 09:30 | Author(s): L. Bacon
- Abstract
Background:
Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy. Multidisciplinary treatment including surgery, radiation therapy and adjuvant chemotherapy has been established as the cornerstone of management prolonging progression free survival (PFS). Although beneficial, this treatment strategy has morbidity and mortality. Therefore, selection of patients who benefit from this treatment strategy is crucial for maximizing clinical benefit.
Method:
A random forest tree model was build for the prediction of response to first line chemotherapy among Hispanic patients with MPM. Variables evaluated included sex, age, ECOG performance status, smoking history, exposure to asbestos and histology. Based on these characteristics, patients were classified by responders (partial or complete response) and non-responders (stable disease or disease progression). In order to validate the results, a random subset of 70% of the sample was used to construct the model and the remaining 30% was utilized as an independent validation cohort. Predictions were compared to each patient’s treatment response and operational characteristics for the validation cohort model and receiver operational curves were computed.
Result:
A total of 153 patients were included. Median age was 59 years old (r, 33-84), 60 (39%) were females, 127 (83%) had an ECOG performance score of 0-1 and 127 (83%) had an epithelioid histological subtype. In terms of expositional hazards, 107 (70%) were smokers (24% current/46% former), whereas 61 (40%) presented active exposure to asbestos. In terms of survival, median overall survival (OS) was 25 months (95%CI 23.4-29.4) and median PFS after first line chemotherapy was 6.97 months (95%CI 5.83-8.57). An objective response was observed in 74 patients (48%; complete response in 7/5%). In terms of operational characteristics, the validated model obtained a 0.992 AUC, a sensitivity of 100% and a specificity of 95% for detecting responders and non-responders to first line chemotherapy.
Conclusion:
Selection of responders to first line treatment based on clinical variables can accurately be achieved. These results could lead to better selection of Hispanic patients for aggressive and morbid treatments.
