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H. Dienemann
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MA 06 - Lung Cancer Biology I (ID 660)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Biology/Pathology
- Presentations: 1
- Moderators:N. Motoi, Keith M Kerr
- Coordinates: 10/16/2017, 15:45 - 17:30, Room 501
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MA 06.06 - Assessment of RANK Prevalence and Clinical Significance in the NSCLC European Thoracic Oncology Platform Lungscape Cohort (ID 10006)
15:45 - 17:30 | Author(s): H. Dienemann
- Abstract
- Presentation
Background:
Receptor Activator of Nuclear Factor κappa-B (RANK) is a pathway involved in bone homeostasis. Recent evidence suggests that RANK signalling may also play a role in bone metastasis, and primary breast and lung cancers. The European Thoracic Oncology Platform (ETOP) Lungscape project allows evaluation of the prevalence of RANK expression and its clinical significance in a cohort of surgically-resected NSCLCs.
Method:
RANK expression was assessed on tissue microarrays (TMAs) using immunohistochemistry. Up to 4 cores per patient were analysed based on sample acceptance criteria. An H-Score (staining intensity + % cells stained) was used to assess RANK expression (positivity), as defined by at least 1 core with any degree of positive staining. Prevalence of RANK positivity and its association with clinicopathological characteristics, other cancer-related biomarkers (IHC ALK/MET/PTEN/PD-L1 expression and EGFR/KRAS/PIK3CA mutations) and patient outcome [Relapse-free Survival (RFS), Time-to-Relapse (TTR), Overall Survival (OS)] was explored in a subset of the ETOP Lungscape cohort. The prevalence of RANK overexpression (proportion of positive cancer cells ≥50%) was also investigated.
Result:
RANK expression was assessed in patients from 3 centers, a total of 402 from the 2709 patients of the Lungscape cohort, with median follow-up 44 months; 32.6% female, 40.8/54.2/5.0% adenocarcinomas (AC)/squamous cell carcinomas (SCC)/other, 44.8/28.4/26.9% with stage I/II/III, 20.6/57.7/18.9% current/former/never smokers (and 2.7% with unknown smoking status). Median was 74 months for both RFS and OS, while median TTR was not reached. Prevalence of RANK positivity was 26.6% (107 of the 402 cases), with 95% confidence interval (95%CI):22.4%-31.2%; significantly higher in AC: 48.2% (79 of 164 cases), 95%CI:40.3%-56.1%; vs SCC: 9.2% (20 of 218 cases), 95%CI:5.7%-13.8%; (p<0.001). RANK positivity was more frequent in females (38.9% vs 20.7% in males, p<0.001) and tumors≤4cm (30.7% vs 21.1% in tumors>4cm, p=0.031). Significant associations were also detected between RANK and PTEN expression in AC (RANK positivity 57.4% in PTEN expression vs 30.5% in PTEN loss; p=0.0011) and with MET status in SCC (RANK positivity 27.8% in MET+ vs 7.6% in MET-; p=0.016). No association with outcome was found. RANK overexpression was identified in 43 (10.7%; 95%CI: 7.9%-14.1%) cases.
Conclusion:
In this early-stage NSCLC cohort, RANK positivity (26.6% overall) is found to be significantly more common in adenocarcinomas (48.2%), females, patients with tumors of smaller size, with PTEN expression (in SCC) and MET positivity (in AC). No prognostic significance of RANK expression was found. Analysis of additional cases is ongoing and results will be presented.
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P3.05 - Early Stage NSCLC (ID 721)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Early Stage NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.05-007 - Potential of CYFRA 21-1 and CEA to Predict Adjuvant Chemotherapy Benefit in Early-Stage Squamous Cell Lung Cancer (ID 9303)
09:30 - 16:00 | Author(s): H. Dienemann
- Abstract
Background:
Tumor markers (TMs), cytokeratin 19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA), which have demonstrated prognostic value in early-stage non-small cell lung cancer (NSCLC), may also predict which patients are suitable candidates for adjuvant chemotherapy (adCHT).
Method:
Presurgical serum samples collected during an observational study of patients with stage I-II NSCLC were analyzed for CYFRA 21-1 and CEA via electrochemiluminescence immunoassay (Elecsys[®]; Roche Diagnostics). Recurrence-free survival (RFS) was analyzed using Kaplan Meier methods and a Cox proportional hazards model. A TM-based risk score was generated with RFS as the endpoint and the log10 of CYFRA 21-1 and CEA values as independent risk predictors. RFS was compared for patients who received adCHT versus surgery alone, with patients stratified as high versus low risk based on pathological disease stage (I vs II), the TM-based risk score, and clinical characteristics (age, gender, smoking status, disease stage, Eastern Cooperative Oncology Group performance status).
Result:
227 patients were included (stage I: 69%; male: 67%; median age: 65 years; adenocarcinoma [ADC]: 47%, squamous-cell carcinoma [SCC]: 40%, mixed histology: 13%); 70 received adCHT (84% with a platinum-based regimen). Median follow-up was 58.8 months. Median RFS for all patients was 76.3 months (81.0 and 68.6 months for ADC and SCC, respectively). All high-risk patients, defined by TMs or clinical characteristics (but not stage alone), had a worse prognosis, irrespective of treatment received. A similar pattern was seen in patients with SCC, whereas stage and clinical characteristics (but not TMs) were prognostic in patients with ADC. All high-risk patients (defined by any method) derived an RFS benefit from adCHT versus surgery alone (stage HR 2.7, p = 0.002; TMs HR 2.1, p = 0.018; clinical characteristics HR 3.2, p = 0.001). However, in all low-risk patients, RFS was similar regardless of whether they received adCHT or not. High-risk SCC patients also derived an RFS benefit from adCHT versus surgery alone (stage HR 4.9, p = 0.004; TMs HR 9.4, p = 0.002; clinical characteristics HR 9.0, p = 0.003), whereas those with low-risk SCC did not. In patients with ADC, none of the methods used were able to predict which patients might benefit from adCHT.
Conclusion:
Baseline CYFRA 21‑1 and CEA levels may provide further information beyond clinical characteristics that could help clinicians to decide which patients with early-stage SCC should receive adCHT. Further evaluation of these biomarkers is warranted.
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P3.05-008 - Potential of CYFRA 21-1 and HE4 to Detect Recurrence in Patients with Early-Stage Lung Adenocarcinoma (ID 9876)
09:30 - 16:00 | Author(s): H. Dienemann
- Abstract
Background:
The Tumor markers (TMs) cytokeratin 19 fragment (CYFRA 21-1) and human epididymis protein 4 (HE4) have each been shown to be useful in diagnosis, prognosis and monitoring of NSCLC, but their combination has not been investigated. The objective of this analysis was to evaluate the ability of CYFRA 21-1 and HE4 to predict relapse in patients with adenocarcinoma (ADC).
Method:
In an observational study of adult patients with stage I-IIIA ADC, serum samples were prospectively collected prior to surgery and during follow-up at 3, 6, 12, 18 and 24 months and then every 6-12 months up to 5 years post-R0 resection. Patients could receive an adjuvant therapy of either radiotherapy or chemotherapy (not both) according to their clinical situation and local best practice. In a post hoc analysis, CYFRA 21-1 and HE4 levels from these samples were measured via electrochemiluminescence immunoassay (Elecsys[®]; Roche Diagnostics). All cases of disease recurrence were verified by imaging. The diagnostic performance of CYFRA 21-1, HE4 and their combination was assessed by the Receiver Operating Characteristic (ROC) and corresponding area under the curve (AUC). The combination of both TMs was based on the weighted sum of the logarithmized (base 10) markers. Weights were derived from a logistic regression model which included the log10 of CYFRA 21-1 and HE4 as independent variables and relapse (yes/no) as a dependent variable.
Result:
117 patients were included in the post hoc analysis (stage I/II/IIIA: 64%/21%/15%; male: 55%; median age: 63 years), providing a total of 623 TM measurements. All patients had received surgery for ADC; 34 patients (29%) also received adjuvant chemotherapy and 16 patients (14%) received radiation. Blood samples were collected for a median follow-up of 37 months. At this timepoint, 31 patients (26%) had experienced disease recurrence. Median recurrence-free survival was 80.2 months. Both CYFRA 21‑1 and HE4 were able to detect recurrence (AUC and corresponding 95% confidence interval [CI]): 76.6% [66.9–86.3%] and 73.7% [64.1–83.4%], respectively), but this increased with the combination (AUC 79.0%, 95% CI 69.4–88.6%). At a sensitivity of 80%, the respective specificities (95% CI) for CYFRA 21‑1, HE4 and the combination were 56.0% (51.9–60.1%), 49.1% (45.0–53.2%), and 70.1% (66.2–73.7%).
Conclusion:
Serial measurements of serum CYFRA 21‑1 and HE4 levels could provide a valuable alternative method for follow-up monitoring and recurrence detection in patients with early-stage ADC, which would trigger imaging if elevated.
