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E. Nadal
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MINI 12 - Biomarkers and Lung Nodule Management (ID 109)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:J.M. Siegfried, H.I. Pass
- Coordinates: 9/07/2015, 16:45 - 18:15, 401-404
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MINI12.01 - A Novel Serum 4-MicroRNA Signature for Lung Cancer Detection (ID 585)
16:45 - 16:50 | Author(s): E. Nadal
- Abstract
- Presentation
Background:
Early detection of lung cancer using low-dose CT led to a 20% reduction in mortality. However, this strategy has several limitations including high false-positive rates, potential over-diagnosis, and the potential harm associated with radiation exposure. The aim of this study was to identify differentially-expressed miRNAs in the serum of non-small cell lung cancer (NSCLC) patients that might be a clinically-useful tool for lung cancer early detection.
Methods:
We performed miRNA expression profile analysis using TaqMan OpenArray Human panel in a discovery set of 70 serum samples obtained at lung tumor resection including lung adenocarcinoma (AD) and lung squamous carcinoma (SCC) and 22 non-cancer subjects (NC). To construct the diagnostic signature, the miRNA candidates were selected based upon the following criteria: miRNAs significantly up-regulated (adjusted t-test p < 0.001) in the NSCLC tissue and serum as compared to normal lung tissue and NC serum respectively, not overexpressed in circulating blood cells and with Area Under the Curve (AUC) > 0.840 for discriminating stage I LC from NC in the receiver-operating characteristic (ROC) plots. Selected serum miRNAs were then validated by quantitative PCR using an independent validation set of serum samples from LC patients (n=84) and NC (n=23).
Results:
Sixty miRNAs were significantly up-regulated and 31 were down-regulated in the serum from NSCLC patients versus NC (adjusted p<0.001). Four miRNAs (miR-193b, miR-301, miR-141 and miR-200b) were selected for validating their diagnostic value in an independent cohort. A diagnostic signature was obtained by logistic regression based upon the expression values of these 4 serum miRNAs in the discovery set. This miRNA signature generated an AUC of 0.985 (95% CI 0.961 – 1.000, p < 0.001) for detecting NSCLC (all stages) and of 0.989 (95% CI 0.967 – 1.000, p < 0.001) for detecting stage I NSCLC in the discovery set. In the test set, the diagnostic utility of this miRNA signature was validated and exhibited an AUC of 0.993 (95% CI 0.979 – 1.000, p < 0.001).
Conclusion:
We identified a serum 4-miRNA signature that discriminated with high accuracy lung cancer patients from NC. Further prospective validation of this miRNA signature is warranted using an independent cohort of serum samples from patients who participated in a lung cancer screening program.
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MINI 33 - Radiotherapy and Complications (ID 164)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
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MINI33.11 - Locally Advanced NSCLC Elderly Patients Assessed by Multidimensional Geriatric Assessment and Treated with Concurrent Chemoradiation (ID 2867)
18:30 - 18:35 | Author(s): E. Nadal
- Abstract
Background:
Despite the increasing number of elderly patients (p) with unresectable stage III NSCLC p presenting to our clinic, there is no consensus on the therapeutic approach to these p. The comprehensive geriatric assessment (CGA) and the comorbidity measurement are relevant tools to identify p who may benefit from tolerable combinations of concurrent chemoradiation (CRT).
Methods:
Elderly p (≥75 years) with stage III NSCLC underwent multidimensional geriatric assessment (MGA) that incorporated validated instruments to assess comorbidity, polypharmacy, functional status, geriatric syndromes (GS), mood, cognition and vulnerability. P were classified according to the MGA results into 3 risk groups: (1) fit p: independent in all ADL and IADL, no comorbidities and absence of GS; (2) vulnerable p: <3 comorbidities and/or <3 IADL but no ADL disability and absence of GS; (3) dependent p: ≥3 disabilities or presence of GS. P classified into group 1 and 2 were considered candidates for antitumoral treatment, whereas patients into group 3 were candidates to best support care. Clinical, GA and follow-up data were prospectively collected. Overall survival (OS) was calculated using Kaplan-Meier method and the median follow-up time was 13.5 months.
Results:
From July 2008 to November 2014, 54 elderly p with stage III NSCLC were identified. The median age was 80 years (74-87) and most p (93%) were males. The most common histological subtype was squamous cell carcinoma (54%), followed by adenocarcinoma (28%) and NOS (18%). MGA classified 20 p (37%) as fit, 23 p (43%) as vulnerable and 11 p (20%) as dependent. Median number of comorbidities: 4 (0-11); median number of drugs: 6 (0-12); median Karnofsky: 80% (60-100); median Barthel: 95 (80-100); Lawton-Brody Scale (<4/≥4): 18%/82%; Pfeiffer (<4/≥4): 89%/11%; Yesavage test (0/≥1): 54%/46%; 1 (0-10); median GS: 1 (1-3); VES-13 (<3/≥3): 50%/50%. Risk groups 1 and 2 had significantly better median OS (20 and 17.5 months, respectively) as compared with group 3 (7.7 months, p=0.004). The number of p treated with concurrent CRT was higher among fit patients (14; 70%) as compared with group 2 (8; 35%) and 3 (0; 0%). Some fit and vulnerable p did not receive concurrent CRT due to patient and physician decision, tumor not amenable for radiotherapy or comorbid conditions. P treated with concurrent CRT received conventional 3D thoracic radiotherapy (2 Gy/fraction) in combination with carboplatin AUC 2.5 and vinorelbine 15 mg/m2 on days 1, 8, 21 and 29. Overall response rate was 68%. Median OS was 22 months (95% CI 10.6 – 33.6). There were no differences in OS when comparing risk groups 1 and 2 (p=0.446). Adverse events (G3-4): neutropenia, 2p (9%); anemia, 1p (4.5%); thrombocytopenia 1p (3%); febrile neutropenia, 1p (3%); pneumonia, 1p (3%); tracheo-bronchial infection, 3p (14%); asthenia 2p (9%); anorexia 1p (4.5%); diarrhea, 1p (4.5%); radiation pneumonitis, 3p (14%) and oesophagitis 0p (0%). Three p (14%) died due to radiation pneumonitis and 1 p (3%) due to a respiratory infection.
Conclusion:
MGA may help in the selection of elderly p for concurrent CRT and appeared to be a valuable tool to avoid undertreatment of those p.
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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-015 - Malignant Pleural Mesothelioma: Observational and Retrospective Analysis of Spanish Database (BEMME). The Spanish Lung Cancer Group (SLCG) (ID 2355)
09:30 - 09:30 | Author(s): E. Nadal
- Abstract
Background:
Malignant Pleural Mesothelioma (MPM) is a rare but aggressive malignancy of the pleura, with a strong causal link to asbestos exposure. Although in Spain asbestos was banned in 2002, it is estimated that occupationally related deaths due to MPM will continue to occur until 2040. BEMME (Base Epidemiológica Mesotelioma Maligno en España) is an observational and retrospective study sponsored by the Spanish Lung Cancer Group that aimed to characterize the patient’s and tumour’s features as well as the treatment modalities of patients diagnosed with mesothelioma in Spain.
Methods:
Clinical records of patients with malignant pleural and peritoneal mesothelioma were retrospectively reviewed to collect epidemiological data, diagnostic tests, treatment modalities and survival data into an electronic and anonymous database. Thirty-five Spanish hospitals participated in the project and 570 mesothelioma patients were included in the BEMME database. Here we present a descriptive analysis of MPM patients based upon these data.
Results:
From January 2008 to December 2013, 538 patients (p) had MPM. Most patients were males (77%) and 74% of patients were ≥ 60 years (60-70y: 33%, >70y: 41%). Most patients (49%) had a performance status 1 at diagnosis. Only 32% of patients were recorded as positive for asbestos exposure and 77% of patients were never-smokers. Dyspnoea (35%) and thoracic pain (26%) were reported as the most frequent symptoms at diagnosis. Epithelioid was the most frequent histological subtype (63%), followed by sarcomatoid (12%), biphasic (8%) and not specified (17%). Disease stages at diagnosis were: stage I, 7%; stage II, 9%; stage III, 17%; stage IV, 45%; not specified, 22%. Surgery was performed in 41p: extrapleural neumonectomy 16p, extended pleurectomy 15p and partial pleurectomy 10p. Palliative pleurodesis was performed in 22% of patients. A total of 70% of patients received chemotherapy (55% palliative, 11 neoadjuvant and 6% adjuvant). The median overall survival (OS) for all patients was 13.2 months (95% CI 12.2 – 15.2). There were no statistically significant differences in OS according to age, gender and asbestos exposure. In the univariate analysis, higher stage (III-IV vs. I-II, p=0.0003) and non-epithelioid subtype (non-epithelioid vs. epithelioid, p=0.00001) were significantly associated with shorter OS.
Conclusion:
In Spain, most MPM patients are diagnosed at advanced stages and are treated with palliative modalities: mainly chemotherapy and pleurodesis. Stage and histologic subtype were prognostic factors for survival. BEMME database is a helpful tool to describe the therapeutic strategies employed in MPM patients in Spain.
