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P. Kosmidis
Moderator of
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MA10 - Facing the Real World: New Staging System and Response Evaluation in Immunotherapy (ID 393)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Radiology/Staging/Screening
- Presentations: 12
- Moderators:P. Kosmidis
- Coordinates: 12/06/2016, 14:20 - 15:50, Stolz 2
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MA10.01 - Validations of the 8th AJCC/UICC Lung Cancer Staging System in a Large North America Cohort (ID 6094)
14:20 - 14:26 | Author(s): L. Yang, Y. Zhou, G. Xiao, A.F. Gazdar, Y. Xie
- Abstract
- Presentation
Background:
The new 8[th] AJCC/UICC lung cancer staging system was developed and validated using the International Association for the Study of Lung Cancer (IASLC) database, which contains 94,708 lung cancer patients worldwide, but only 5% of patients in this database came from North America. The goal of this study is to validate the prognostic performance of this new staging system, focusing on the upgraded "T" and “M” parameters, in North American lung cancer patients.
Methods:
We analyzed 1,163,465 non-small cell lung cancer (NSCLC) cases collected from 2004 to 2013 in the United States in the National Cancer Database (NCDB). After excluding patients with more than one malignant primary tumor or tumor size larger than 10 cm, 545,776 NSCLC patients were included in the final data analysis. We defined 8[th] T and M parameters according to the primary coding guidelines of the Collaborative Staging Manual and Coding Instructions for the new 8[th] AJCC/UICC lung cancer staging system. Kaplan-Meier survival curves and log-rank tests were used to compare survival difference among different stage groups, and Cox regression models were used for multivariate analysis adjusting for potential confounders.
Results:
We validated that the new staging system can provide better survival prognosis for NSCLC patients in the NCDB cohort than the existing 7[th] staging system. The median survival time for T1a is 58 months (N=15,860), for T1b is 47 months (N=78,379), and for T1c is 25 months (N=79,828) (p<2e-16). The median survival time for T2a is 19 months (N=111,925), for T2b is 12 months (N=54,601), for T3 is 10 months (N=105,234), and for T4 is 7 months (N=99,949) (p<2e-16). And the median survival time for M0 is 25 months (N=411,048), for M1a is 8 months (N=49,352), for M1b is 5months (N=42,224), and for M1c is 3 months (N=15,926 cases) (p<2e-16). Multivariate analysis showed that these staging parameters are significantly associated with survival when adjusting other factors.
Conclusion:
Both upgraded “T” and “M” parameters of the 8[th] AJCC/UICC lung cancer staging systems are significantly associated with NSCLC patient survival outcomes using data from the NCDB, indicating a good validation performance in patients from North America.
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MA10.02 - Clinical Staging in the 8th Edition TNM for Lung Cancer is Inaccurate (ID 6362)
14:26 - 14:32 | Author(s): A. Mani, A. Kar, M. Dimartino, J. Mayer, K. Lau
- Abstract
- Presentation
Background:
The new classification for lung cancer refines the T-descriptor criteria into more categories. We examined whether this affects the accuracy of clinical staging, and how this affects the final stage of patients.
Methods:
71 patients underwent resection for primary lung cancer from January 2014 to December 2014. T-component was measured based on the maximum tumour size on CT, PET-CT and histology report. The possible effect on staging based on T-component was compared between both TNMs.
Results:
PET-CT more accurately estimates the pathological size of the tumor (mean difference from histology: CT 3mm (range -1.6 to 2.6cm) and PET-CT 1.3mm (-2 to 2.5cm). Discordance between radiological and pathological T-stage was higher with the 8th edition (7th edition concordance CT 42(59%) and PET-CT 31(43%), 8th edition CT 31(44%) and PET-CT 29(41%) (CT p=0.01; PET-CT p=0.7)). The final stage groupings was also more discrepant in the 8th edition. Concordance was for CT 7th Edition 37(54%) vs 8th Edition 21(31%) (p<0.001), and for PET-CT 34(48%) vs 19(28%) (p<0.001). The discrepancy in stage grouping is contributed significantly by T-stage discordance. In the 30 patients who were not upstaged pathologically by pleural invasion or nodal staging, there is a over 50% increase in inaccuracy of clinical staging in the 8th edition. The CT concordance was 7th edition 24(80%), 8th edition 13(43%) (p<0.001); and for PET-CT 23(77%) vs 10(33%) (p<0.001).
Conclusion:
We showed that the 8th edition TNM lung cancer staging system was associated with a significant increase in discordance between clinical and pathological staging due to differences in measurement of tumour size and consequently T-stage groupings by different modalities. This has implications for prognostication and clinical trial interpretation especially in patients who do not undergo surgery for pathological stage confirmation.Figure 1
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MA10.03 - Investigating the Potential Utility of the Alternative 9th Edition IASLC Nodal Staging Classification in NSCLC (ID 4491)
14:32 - 14:38 | Author(s): T. Edwards, H. Balata, C. Tennyson, P. Foden, A. Chaturvedi, P. Crosbie, R. Booton, M. Evison
- Abstract
- Presentation
Background:
The IASLC lung cancer staging project recently published recommendations for the 8th edition of the TNM classification of lung cancer. This recommends the same N descriptors be used, however, further analysis of an alternative system (proposed 9[th] Edition) was recommended. The aim of this retrospective study was to assess the utility of this proposed nodal staging system at a large UK tertiary lung cancer centre.
Methods:
Patients who underwent surgical resection for non-small cell lung cancer between 2011-2014 (allowing minimum of 2 years follow-up) were identified from a prospective database (n=1308). Stratification of pathological N-stage as per the IASCLC proposal was performed: N0, single station N1 (N1a), multi-statin N1 (N1b), single station N2 without N1 involvement – skip metastases - (N2a1), single station N2 with N1 involvement (N2a2), multi-station N2 (N2b) and N3. Survival data was obtained from national death registries.
Results:
There a significant effect of N-stage on mortality using Cox proportional hazards regression analysis, using pN0 (n=848) as the reference group and adjusting for sex, age and histology (table 1). There appears to be similar survival outcomes between multi-station N1 (pN1b) and single station N2 skip metastases (pN2a1), and single station N2 with N1 involvement (pN2a2) and multi-station N2 (pN2b).Table 1.
N-stage Hazard Ratio 95% CI p-value pN1a (n=146) 1.68 (1.26, 2.26) 0.001 pN1b (n=55) 2.25 (1.49, 3.39) <0.001 pN2a1 (n=50) 2.24 (1.46, 3.45) <0.001 pN2a2 (n=81) 2.94 (2.15, 4.03) <0.001 pN2b (n=67) 2.99 (2.09, 4.27) <0.001
Conclusion:
The proposed 9[th] edition N-staging classifications appear to add additional insight into prognosis. However, interpretation is limited by the small numbers of patients within the pN1/pN2 sub-groups. 65% of this large cohort were pN0 and acted as the reference group and a further 5% were pNx as no nodes were submitted. Furthermore, the accuracy of pN-staging is reliant on the quality of intra-operative lymph node sampling. Although significant improvements have been made in this timeframe at our centre (published previously), any sub-optimal performance has the potential to affect the validity of the results, particularly if multi-station N2 disease is missed.
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MA10.04 - Discussant for MA10.01, MA10.02, MA10.03 (ID 6948)
14:38 - 14:50 | Author(s): R.U. Osarogiagbon
- Abstract
- Presentation
Abstract not provided
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MA10.05 - Proposals for the Novel Clinical T Categories Based on the Presence of Ground Glass Opacity Component in Lung Adenocarcinoma (ID 6041)
14:50 - 14:56 | Author(s): A. Hattori, T. Matsunaga, K. Takamochi, S. Oh, K. Suzuki
- Abstract
- Presentation
Background:
In lung adenocarcinomas, the histologic lepidic growth pattern tends to correlate with the ground glass opacity (GGO) component, while solid components correspond with invasive adenocarcinoma. The Eighth edition of the TNM staging system suggests that the tumor size be determined according to the invasive size excluding the lepidic component. However, this new concept causes fatal confusion, i.e., tumors are classified into a same T category despite the part-solid or pure-solid appearances provided they showed a same solid component size.
Methods:
Between 2008 and 2012, we retrospectively evaluated 719 surgically resected cN0 lung adenocarcinomas that measures 30mm or less in total dimension to assess the prognostic impact on the presence of GGO among the Eighth TNM classification. According to the new T category, it was defined based on the solid component size as follow: Tis; 0 cm (pure-GGO), T1mi; ≤ 5 mm, T1a; 6-10 mm, T1b; 11-20 mm, T1c; 21-30mm. Furthermore, all tumors were classified into 2 groups, i.e., GGO or Solid arms based on the presence of GGO component.
Results:
Of the cases, 133 (18%) were categorized in Tis, 88 (12%) in T1mi, 121 (17%) in T1a, 244 (34%) in T1b and 133 (19%) in T1c, respectively. Multivariate analysis revealed that both a presence of GGO and solid component were independently significant prognostic factors (p=0.007, 0.002). The 5y-overall survival (OS) was 99.2% in Tis, 95.8% in T1mi, 96.5% in T1a, 81.8% in T1b and 66.4% in T1c (p=0.038) with a median follow-up period of 56 months. When we evaluated the impact of T category based on GGO presence, the 5y-OS was significantly different between GGO and Solid arm in each T categories (T1a; 99.0% vs. 95.7%, p=0.045, T1b; 89.8% vs. 73.3%, p=0.004, T1c; 90.0% vs. 62.6%, p=0.046). Furthermore, clinical T categories significantly separated the OS in Solid arm (p=0.015) (T1a vs. T1b; p=0.090, T1b vs. T1c; p=0.037). In contrast, the 5y-OS was approximately 90% or more in GGO arm despite their T categories. Moreover, regarding radiological and pathological correlations, the rates of AIS was only 65% in Tis, and 51% showed invasive adenocarcinoma even in T1mi.
Conclusion:
Clinical T category should be considered based on the presence of GGO on thin-section CT, and tumor size should be applied exclusively to radiological solid lung cancer. In contrast, oncological outcomes of the tumor with GGO component were excellent despite their T categories, which should be described as Tis for pure-GGO, and T1a for part-solid tumor.
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MA10.06 - Centrality Definition in Non Small Cell Lung Cancer. Predictor For Occult Mediastinal Lymph Node Involvment (ID 3993)
14:56 - 15:02 | Author(s): D. Sanchez-Lorente, L. Milla, A. Guirao, R. Guzman, M. Boada, J.M. Gimferrer, G. Sanchez, L. Molins
- Abstract
- Presentation
Background:
Central tumour location is considered as an independent risk factor for occult mediastinal metastases in patients with non-small cell lung cancer (NSCLC) after negative computerized tomography (CT) and integrated positron emission tomography/CT. However, the distinction between a central and a peripheral tumour has not been codified, some authors consider any tumour in the innerthird of the hemithorax to be central, and others in the inner twothirds. The objective of this study is to identify the best centrality tumour definition for detecting occult mediastinal metastasis.
Methods:
We retrospectively reviewed our thoracic surgery database for cases between January 2011 and December 2015. It was identified patients with potentially operable NSCLC screened by CT and PET/CT and they were classified according to tumour location in the inner third, middle third or outer third. The prevalence of occult mediastinal lymph node metastases was analysed in relation to tumour location. Statistical analysis for best centrality definition was performed. Univariable analysis was performed using the Fisher exact test and multivarible analysis using logistic regression.
Results:
A total of 359 patients with clinical operable NSCLC were included in our study. Seventy-five (20.9%) tumours were located in the innerthird, 137 (38.2%) in the middlethird and 147 (40.9%) in the outerthird. It was detected 23 patients with N2 disease and negative TC and PET/CT, 8/38 (21.1%) in the innerthird, 6/121 (5.0%) in the middlethird and 9/122 (7.4%) in the outerthird. Defining centrality as tumour located in the innerthird of the hemithorax the incidence of occult N2 was 21.1% and 6.2% for central and peripheral tumour respectively. And defining centrality as tumour located in the inner twothirds the incidence of occult N2 was 8.8% for central tumours and 7.4% for peripheral. Univariable analysis shows statistical differences in occult N2 involvement between central or peripheral defining central lesion as innerthird (p=0.002), but not for central definition of innternal twothirds (p=0.651). In multivariable analysis considering centrality possible defenition, histology, Clinical T factor and Clinical N1 affection, only innerthird as centrality definition was statistical significance predictor factor for occult mediastinal lymph node involvement (p= 0.027)
Conclusion:
Considering the results of our study the best definition for central tumour location is limited to the innerthird of the hemithorax. Given the low rate of occult N2 disease in the middle third location, the systematic evaluation of the mediastinum by ecobronchoscopy and/or mediastinoscopy in this group of patients is not justified.
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MA10.07 - 18F-Fluorodeoxyglucose Positron Emission Tomography Scan in Solid-Type Stage-I Pulmonary Adenocarcinomas: What Cause False-Negative Cases? (ID 4018)
15:02 - 15:08 | Author(s): F. Lococo, C. Galeone, D. Formisano, S. Bellafiore, A. Filice, A. Tartaglione, A. Cesario, C. Rapicetta, F. Fioroni, T. Ricchetti, M. Paci
- Abstract
- Presentation
Background:
False-negative 18F-fluorodeoxyglucose (FDG) uptake can be divided into those cases related to technological limitations of positron-emission tomography (PET) and others related to inherent properties of neoplasms. We aim to clarify possible factors causing false-negative (FN) PET results in solid-type pulmonary adenocarcinomas (PAs).
Methods:
From 01/2007 to 12/2014, among 255 Stage-I NSCLCs we retrospectively review PET/CT-records, clinical information, preoperative thin-section CT-images, and pathological features (classified by the IASLC/ATS/ERS subtyping criteria) of 94 consecutive solid-type Stage-I PA undergone surgical resection at Our Institution. Univariate and multivariate logistic analysis were used to identify and weigh the independent predictors of PET-findings: body weight, blood glucose level, tumor-size, and histological classification.
Results:
There were 58 males and 36 females (mean age= 68.7 yrs, range 42-85). Seventeen lesions (18.1%) were judged as PET-negative and 77 lesions (81.9%) as PET-positive. Overall, mean SUVmax was 8.0 (range 0-35) with higher SUVmax-values (p<0.001) in PA>2cm (mean SUVmax=10.6) than PA<2cm (mean SUVmax=4.8). PET false-negative (FN) results were also differently distributed (27.9% in PA <2cm vs 9.8% in PA>2 cm, p=0.023). When clustering the PA in 2 histological classes (Class-A [“colloid/mucinous/lepidic”] vs Class-B [“micropapillary/solid/acinar/papillary”]), the radiometabolic patterns were significantly different [mean SUVmax 3.8 in Class-A vs 9.9 in Class-B, p<0.001], as reported in Figure 1. Similarly, a different distribution of PET FN-cases was observed (38.7% FN in Class-A vs 7.9% FN in Class-B, p=0.001). Table 1 shows the results of multivariate logistic analysis. Both the tumor-size (cut-off=2cm) and IASLC/ATS/ERS aggregated clusters were clinically relevant factors for determining whether PET results were negative or positive, but only histology was statistically significant (OR:6.1, 95%CI: 1.85-20.15, p=0.003). Figure 1
Conclusion:
Among solid-type lung adenocarcinoma, tumor-size and histopathological findings were significantly associated with FDG-uptake. In particular, it warrants attention that lesions ≤2cm and “colloid/mucinous/lepidic” adenocarcinomas have a tendency for negative PET-findings.
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MA10.08 - Discussant for MA10.05, MA10.06, MA10.07 (ID 7086)
15:08 - 15:20 | Author(s): A. Onn
- Abstract
- Presentation
Abstract not provided
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MA10.09 - Comparison between CT Scan Evaluation Criteria and PERCIST for Evaluation of Immune Check-Point Inhibitors Response (ID 6227)
15:20 - 15:26 | Author(s): G. Rossi, C. Genova, S. Morbelli, E. Rijavec, G. Barletta, F. Biello, C. Maggioni, S. Mennella, M.G. Dal Bello, R. Distefano, M. Bauckneht, G. Cittadini, F.D. Merlo, G. Sambuceti, F. Grossi
- Abstract
- Presentation
Background:
Immune check-point inhibitors (ICPIs) exert their activity by blocking inhibitory signaling and therefore enhancing T-cell activity against tumor cells; however, this peculiar mechanism of action might lead to many difficulties in evaluating clinical response with the usual CT imaging due to inflammatory patterns that could confuse the evaluation. The aim of this study was to assess the role of FDG-PET to support clinical decision based on CT scan.
Methods:
From May 2015 to April 2016, 74 patients with advanced pretreated NSCLC received at least one dose of nivolumab (3 mg/Kg every 14 days) within a single-institutional translational research trial. Among these, 58 patients were evaluable for response assessment. The patients underwent CT scan and FDG-PET every four cycles and, in case of progressive disease, an additional evaluation was performed after two further cycles in order to confirm it. We evaluated the response to treatment by CT scan with RECIST criteria, Immuno-related Response Criteria (irRC), WHO criteria and immunoRECIST criteria, while the metabolic response has been determined with PERCIST criteria. Finally, we determined the concordance in terms of response between CT evaluation criteria and metabolic response obtained with PERCIST; concordance was calculated with kappa value.
Results:
Our findings showed a low concordance of all CT scan evaluation criteria to PERCIST, the best concordance being between PERCIST and RECIST (K=0.500) and the worst agreement being between PERCIST and irRC (K=0.295) . In particular, PERCIST seems to underestimate the progressive disease (PD). In fact, between 46% and 55% of patients, defined in progression with CT evaluation criteria were considered in stable metabolic disease (SMD) by PERCIST; among these, 50% of patients in the RECIST PD group and 80% of RECIST SD patients were alive at 6 months. Furthermore, in our sample, between 9% and 18% of patients were considered in progression with CT evaluation criteria when they were in partial response with PERCIST; these patients were still alive with a survival similar to those who defined in partial response with RECIST (>9 months).
Conclusion:
FDG-PET evaluation by PERCIST could not be helpful when SMD is reported, in fact, patients that have a RECIST PD maintain a poor prognosis compared to RECIST SD between the patients define as SMD. Conversely, PERCIST evaluation could be informative when it define a partial response, specially when RECIST criteria show a PD.
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MA10.10 - [18F]-FDG-PET/CT Early Response to Nivolumab in NSCLC (ID 6211)
15:26 - 15:32 | Author(s): D. Bellevre, G. Petyt, G. Collet, C. Hossein-Foucher, S. Baldacci, A. Baranzelli, F. Semah, A.B. Cortot
- Abstract
- Presentation
Background:
Nivolumab is approved for treatment of squamous and non-squamous advanced NSCLC. Since nivolumab restores antitumor immunity, it is not clear whether 18F-FDG-PET/CT is able to distinguish response from tumor progression. We evaluated early metabolic patterns of response to nivolumab in advanced NSCLC patients.
Methods:
We retrospectively reviewed PET/CT scans and paired CT scans from 22 patients with advanced NSCLC who received nivolumab 3mg/kg every 2 weeks and performed PET/CT before and after 4 infusions of nivulomab. Total Lesion Glycolysis (TLG) and Metabolic Tumor Volume (MTV) of every lesion up to 5 per patient were measured on baseline and follow-up PET/CT. Percentage changes in MTV (ΔMTV) and TLG (ΔTLG) between the two PET/CT were calculated. Patients were classified into responders (nivolumab for >6 months), non responders (nivolumab ≤6 months) or having pseudo-progression (PP, nivolumab and clinical benefit >6 months despite initial progressive disease according to RECIST criteria)
Results:
Among 22 patients, 6 (27%) were responders, 15 (68%) were non-responders and 1 (4.5%) had PP. Baseline MTV and TLG were significantly lower in responders than in non-responders (medians 27 vs. 63 mL, p=0.03 and 124 vs. 254 g, p=0.04, respectively). After 4 infusions of nivolumab, metabolic parameters were significantly lower in responders than in non-responders (median MTV : 2 vs. 148 mL, p=0.001 and median TLG : 6 vs. 835 g, p=0.002). Mean ΔMTV and ΔTLG were both -88% in responders, and +236% and +312% respectively in non-responders, which was significantly different (p=0.0005). The only patient with PP had lower ΔMTV (+11%) and ΔTLG (+41%) than non-responders patients.
Conclusion:
In NSCLC, objective response and disease progression upon nivolumab usually translate into early and clear-cut patterns of change in PET/CT. Early PET/CT may help to distinguish progression from pseudo-progression.
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MA10.11 - Comparison among Different Radiological Criteria for Assessing Response to Nivolumab in Advanced Non-Small Cell Lung Cancer (ID 6181)
15:32 - 15:38 | Author(s): F. Grossi, G. Rossi, E. Rijavec, G. Barletta, F. Biello, C. Maggioni, S. Mennella, M.G. Dal Bello, R. Distefano, G. Cittadini, F.D. Merlo, C. Genova
- Abstract
- Presentation
Background:
Immune check-point inhibitors have dramatically changed the management of advanced non-small cell lung cancer (NSCLC); however, their mechanism of action creates concerns on the most appropriate method to determine radiological responses to this drug class. The aim of this study is to compare a set of different evaluation criteria for patients receiving nivolumab for advanced NSCLC.
Methods:
Patients with pre-treated advanced NSCLC were enrolled in a single-institutional translational research study in the San Martino Hospital – National Institute for Cancer Research, Genova, Italy and received nivolumab (3 mg/kg every 14 days). Computed tomography (CT) was performed at baseline and after every 4 administrations. The assessments were performed according to Immune-related response criteria (irRC), response evaluation criteria in solid tumors (RECIST 1.1), World Health Organization (WHO), and immune-related RECIST (irRECIST), which are recently proposed based on the original RECIST with the following differences derived by irRC: 1) new lesions do not automatically define progressive disease (PD), but are added to the target lesions count; 2) PD has to be confirmed with a subsequent CT-scan after 2 additional cycles. The concordance among the different criteria was determined with Cohen’s kappa coefficient (K).
Results:
Fifty-two patients were eligible: median age= 70 years (44-85); male/female: 70%/30%; current or former smokers= 87%; non-squamous/squamous histology= 79%/21%; median number of cycles= 6 (4-29). The following responses were observed:
Generally, the concordance between first evaluation and best response was good for all the criteria (K ranging from 0.783 to 0.839); the concordance between irRECIST and irRC was high (K= 0.828) and RECIST 1.1 had a good concordance with IRC (K= 0.734), irRECIST (K= 0.767), and WHO (0.766).Partial Response Stable Disease Progressive Disease First evaluation (4 cycles) RECIST 1.1 4 (7.7%) 19 (36.5%) 29 (55.8%) irRC 3 (5.8%) 23 (44.2%) 26 (50%) WHO 3 (5.8%) 20 (38.5%) 29 (55.8%) irRECIST 4 (7.6%) 24 (46.2%) 24 (46.2%) Best Response Partial Response Stable Disease Progressive Disease RECIST 1.1 9 (17.3%) 14 (26.9%) 29 (55.8%) irRC 8 (15.4%) 19 (36.5%) 25 (48.1%) WHO 7 (13.5%) 17 (32.7%) 28 (53.8%) irRECIST 11 (21.2%) 18 (34.6%) 23 (44.2%)
Conclusion:
The different response assessment methods were generally concordant. Since response is more easily assessed with irRECIST than with irRC, the former might be proposed as an appropriate method of response evaluation.
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MA10.12 - Discussant for MA10.09, MA10.10, MA10.11 (ID 7069)
15:38 - 15:50 | Author(s): P.R. Mohapatra
- Abstract
- Presentation
Abstract not provided
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