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KONSTANTINOS Syrigos
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P09 - Health Services Research/Health Economics - Real World Outcomes (ID 121)
- Event: WCLC 2020
- Type: Posters
- Track: Health Services Research/Health Economics
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P09.59 - Real-World Treatment Patterns and Outcomes for Patients With Advanced Non-Small Cell Lung Cancer in Greece (ID 2529)
00:00 - 00:00 | Presenting Author(s): KONSTANTINOS Syrigos
- Abstract
Introduction
Programmed death receptor-1 inhibitors (PD-1i) are important agents in the treatment of advanced non-small cell lung cancer (NSCLC). In Greece, PD-1i were reimbursed for advanced NSCLC initially as second-line (2L) monotherapy (August 2016) and, subsequently, as first-line (1L) monotherapy (January 2017). This study assessed the demographic characteristics, treatment patterns and outcomes for patients (pts) with NSCLC in Greece.
Methods
In this non-interventional study, data were extracted from the Sotiria Lung Cancer Registry. Included pts have had stage IIIB/IV NSCLC diagnosis and treatment initiation from 15 August 2016 to 14 August 2018. Pts baseline characteristics and treatment patterns were descriptively analyzed. Treatment outcomes were analyzed by measuring the real-world response (rwR), rw progression-free survival (rwPFS), time on treatment (ToT) and overall survival (OS) from 1L therapy initiation.
Results
Of 472 included pts, most were >65 years old (67.6%), male (79.2%), current/ former smokers (90.7%), and had ECOG PS of 0/1 (61.2%). In 1L therapy, 346 (73.3%) pts received chemotherapy-based combinations (combo chemo), 71 (15.0%) chemotherapy monotherapy (mono chemo), 21 (4.6%) tyrosine kinase inhibitors (TKIs) and 18 (3.9%) PD-1i (pembrolizumab). Of pts tested for programmed death-ligand 1 (140, 29.6%), 36 (25.7%) had a tumor proportion score ≥50%, of whom 18 (50.0%) received a PD-1i in 1L therapy. During 1L therapy, pts treated with combo chemo had a median ToT of 2.1 months and 135 (39.0%) achieved rwR; pts treated with mono chemo had a median ToT of 1.2 months and 4 (5.6%) pts achieved rwR. Median rwPFS was 4.2 and 2.2 months and median OS was 19.1 and 4.4 months for combo chemo and mono chemo, respectively. Outcomes were not estimated for 1L TKIs and PD-1i due to small pts numbers. A total of 178 (37.7%) pts received 2L therapy; PD-1i were the most frequently (45.5%) used regimens (nivolumab, 74 pts; pembrolizumab, 7 pts).
Conclusion
In Greek real-world setting, the most widely used 1L therapy in advanced NSCLC was combo chemo, associated with a median OS of 19.1 months. Assessment of newer 1L therapies requires further research with longer observation periods.
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P33 - Pathology - Immunotherapy Biomarker (ID 101)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 2
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P33.02 - Comparison of PD-L1 Protein Expression Between Primary and Metastatic Lesions in Lung Cancer Patients (ID 3550)
00:00 - 00:00 | Author(s): KONSTANTINOS Syrigos
- Abstract
Introduction
PD-L1 expression assessed by IHC is the central companion diagnostic test for immunotherapy. However, most trials have not stipulated the tissue source used to assess expression. Here we assess PD-L1 expression as performed in the “real world” to determine if sampling sites, histologic subtypes, genders and age groups affect the likelihood of high-level expression.
Methods
A retrospective data analysis of the FMI clinical database was conducted on lung cancer cases that were assessed for PD-L1 expression in the context of routine care. All samples were stained with the DAKO 22C3 CDx assay at Foundation Medicine, Inc. (FMI) North Carolina laboratory. PD-L1 expression was evaluated and scored with the Tumor Proportional Score (TPS) methodology; TPS = Number of PD-L1 positive tumor cells / (Total number of PD-L1 positive + PD-L1 negative tumor cells) * 100%. In all tests, two-sided P-values of less than 0.05 were considered significant. Statistical analysis was conducted using Prism 8 software and RStudio version 4.0.1.
Results
15,028 samples from 7599 male and 7429 female lung cancer patients, were analyzed. Metastatic lesions were more likely to be PD-L1 high (TPS ≥ 50%) compared with primary lesions (33.8%) vs (28.4%) ;(Odds Ratio [OR] 1.28, 95% Confidence Interval [CI] 1.19-1.37; P<.001). This observation was seen in samples from lymph nodes (OR 1.58,95% CI 1.43-1.74; P<.001), pleural fluid (OR 1.48, 95% CI 1.23-1.78;P<.001), soft tissue (OR 1.3, 95% CI 1.08-1.58;P=.007) and adrenal gland (OR 1.7, 95%CI 1.3-2.22; P<.001) but not with those from liver (OR 0.98, 95% CI 0.83-1.16; P=.835), brain (OR 1.00, 95%CI 0.85-1.18; P=.994) and bone (OR 0.83, 95%CI 0.67-1.04; P=.101). Metastatic lesions of patients with non-squamous histology were more likely to have TPS ≥ 50% in comparison with primary tumors (OR 1.37, 95% CI 1.27-1.49; P<.001) but this was not the case for patients with squamous histology (OR 0.83, 95% CI 0.74-1.07; P=.208). Female patients had significantly increased rates of high PD-L1 TPS compared to male patients (OR 1.08, 95% CI 1.01-1.16; P<.027); but this was driven by the higher TPS of lung squamous cell carcinoma female patients (OR 1.24, 95%CI 1.05-1.47; P=.012).
Conclusion
This study demonstrates that PD-L1 expression is associated with the sampling site, histologic type, and gender. Understanding PD-L1 expression distributions may affect trial design and patient care.
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P33.13 - Prognostic and Predictive Value of Complete Blood Count Parameters in Patients with NSCLC Treated with PD-1 Inhibitors (ID 3584)
00:00 - 00:00 | Author(s): KONSTANTINOS Syrigos
- Abstract
Introduction
The advent of immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis has revolutionized the treatment landscape of non-small cell lung cancer (NSCLC), improving outcomes both in the first- and subsequent-line treatment setting. Nevertheless, only a relatively small fraction (15-25%) of patients with advanced NSCLC demonstrates durable and clinically meaningful responses to these agents. As of yet, there remains an urgent need of more accurate and cost-efficient biomarkers of treatment response and prognosis in this challenging population. We herein aimed to investigate the potential value of baseline (pretreatment) values of complete blood count (CBC) levels and indices, including absolute lymphocyte, neutrophil, monocyte, eosinophil and platelet counts (ALC, ANC, AMC, AEC and PLT, respectively), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and myeloid to lymphoid ratio (M:L), as predictors of treatment response and prognosis in patients with advanced NSCLC treated with ICIs.
Methods
The medical records of patients with advanced-stage NSCLC eligible to receive PD-1 inhibitors (nivolumab or pembrolizumab), diagnosed and treated at the Oncology Unit of Sotiria Athens General Hospital from November 2019 until March 2020, were retrospectively reviewed. Baseline demographics, clinicopathological features, molecular profiling results, pretreatment ALC, ANC, AMC, AEC, PLT, NLR, PLR and M:L levels and treatment data were correlated to the following endpoints: treatment response (evaluated at 8-12 weeks after treatment initiation), durable clinical benefit (DCB), defined as absence of disease progression at 6 months, and progression-free survival (PFS).
Results
117 patients were included; mean age (SD) was 66 (9.9) years and the majority of patients were male (78.6%), with positive smoking history (95.7%), performance status (PS) 0-1 (83.8%), adenocarcinoma (54.7%) and stage IV disease (86.1%). 59.8% of patients received nivolumab. Increased PLR (as a continuous variable) and elevated PLT (>400 × 109/L) were both associated with lack of DCB (p=0.033 and p=0.01, respectively). Increased PLR and PLT were also correlated with reduced PFS [HR (95% CI): 1.24 (1.01-1.52); p=0.037 and HR (95% CI): 2.29 (1.19-4.4); p=0.013, respectively]. The significance of increased baseline levels of PLR as an indicator of a worse prognosis was further confirmed in multivariate analysis [HR (95% CI): 0.79 (0.63-0.99); p=0.040].
Conclusion
Higher pre-treatment levels of PLR may independently predict a worse prognosis in advanced NSCLC patients treated with PD-1 inhibitors. Furthermore, lower PLT and PLR values may be useful as predictors of DCB in this setting. Further prospective studies are warranted to confirm these findings.
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P36 - Pathology - Prognosis (ID 106)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P36.11 - Clinicopathological Features of Long-Term Survivors in Lung Cancer (ID 3730)
00:00 - 00:00 | Author(s): KONSTANTINOS Syrigos
- Abstract
Introduction
Lung cancer (LC) is the leading cause of cancer-related death worldwide. Despite recent progress in the diagnosis and treatment of this lethal disease, the majority of patients are diagnosed at an advanced and inoperable disease stage, which portends a poor prognosis. Although two-year survival rates of advanced-stage LC remain disappointingly low, a small group of patients manage to survive for a longer period. The goal of this study was to reveal potential clinicopathological predictors of long-term survival in this setting.
Methods
The medical records of 45 patients with advanced LC, diagnosed and treated at the Oncology Unit of Sotiria Athens General Hospital between January 1st 2015 and December 31st 2018 were retrospectively reviewed. Twenty-five (25) of these patients presented an overall survival (OS) of at least two years since diagnosis and were described as long-term survivors (LTS). Their demographic, clinicopathological and treatment data were compared with those of twenty (20) short-term survivors (STS), who died in less than 2 years.
Results
The majority of patients in both groups were male (27/45, 60%), with stage IV disease (84.4%). Mean age of LTS and STS was 66,4 years (SD: 7,4 years) and 66,2 years (SD: 8,8 years), respectively. Gender, age, smoking history, co-morbidities, disease stage, number and location of metastases and histological type of tumor were all similarly distributed between STS and LTS groups. In contrast, statistically significant differences were observed with regard to performance status (PS) (p=0.002), number of treatment lines received (p<0.001), administration of immunotherapy (p=0,01) and radiotherapy (p=0,002) and response to first-line treatment (p=0,020).
Conclusion
Long-tern survival in our study was associated with good PS at baseline and administration of more aggressive treatment. The independent prognostic value of the above parameters remains to be confirmed in larger prospective studies. Notably, given the rarity of LTS in LC, prospective validation of their clinicopathological features may be a challenging task.
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P38 - Pathology - Pathology/Staging (ID 108)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P38.13 - Cytology-Histology Concordance for Diagnosis, Histological Subtyping and Molecular Profiling of Lung Cancer (ID 3721)
00:00 - 00:00 | Author(s): KONSTANTINOS Syrigos
- Abstract
Introduction
Cytological samples are often the only diagnostic material available for confirmation of lung cancer (LC) diagnosis. The aim of the present study was to evaluate cytology-histology concordance for diagnosis, histological subtyping and molecular profiling of LC, and to determine the factors which may affect sample adequacy or diagnostic concordance.
Methods
118 patients with histologically or cytologically confirmed LC were retrospectively studied. Clinicopathological features of patients were correlated with the type of biological samples obtained (histological or cytological) and the sampling methods used. Concordance between histological and cytological diagnosis and adequacy of samples were also correlated with the above parameters.
Results
The majority of patients were male (58.5%), with positive smoking history (82.2%), non-small cell histological subtype of tumor (72%) και advanced disease stage (66.9%). Histological and cytological samples were adequate for evaluation in 94/100 (94%) and 85/88 cases (96.6%), respectively and were positive for malignancy in 87/100 (87%) and 57/88 cases (64.8%), respectively. Cytology-histology concordance with regard to the diagnosis of malignancy was 52.9%. In the positive for malignancy subgroup, high cytology-histology concordance (96.9%) was observed with regard to histological subtyping of tumor. Molecular testing was performed in 30/118 cases (25.4%), most commonly using histological samples (23/30, 76.7%); 28/30 of these samples (93.3%) were adequate for evaluation. Cytology-histology concordance for a positive for malignancy diagnosis was correlated with small cell histological subtype (p=0.047) in univariate but not in multivariate analysis.
Conclusion
Cytology-histology concordance for histological subtyping of tumor among cases positive for malignancy was high, despite the relatively low overall concordance. No independent correlation was observed between any of the clinicopathological parameters evaluated and the presence of inadequate samples or diagnostic discordance.
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P75 - Immunotherapy (Phase II/III Trials) - Misc. Topics (ID 248)
- Event: WCLC 2020
- Type: Posters
- Track: Immunotherapy (Phase II/III Trials)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P75.04 - Advanced Lung Cancer Inflammation Index (ALI), Neutrophil-to-Lymphocyte Ratio (NLR), and PD-(L)1 Inhibitor Efficacy in NSCLC (ID 3415)
00:00 - 00:00 | Author(s): KONSTANTINOS Syrigos
- Abstract
Introduction
Improved biomarkers of immune checkpoint inhibitor (ICI) efficacy are a main objective of research in thoracic oncology currently. The neutrophil-to-lymphocyte ratio (NLR) and advanced lung cancer inflammation (ALI) index (body mass index*serum albumin/NLR) reflect systemic inflammation and are easily reproducible in clinical practice.
Methods
The potential value of ALI and NLR as immunotherapy (IO) biomarkers was analyzed in a discovery cohort of 348 advanced NSCLC patients treated with PD-(L)1 inhibitors in the Heidelberg University Hospital, followed by validation in an independent cohort of 590 patients with similar characteristics from 25 cancer centers in Greece (experimental cohorts). An additional control cohort of 444 therapy-naive NSCLC patients treated with first-line platinum-based chemotherapy without subsequent targeted or IO drugs from Heidelberg was also examined in order to discern predictive from prognostic effects. ALI and NLR were dichotomized at the bibliographic cut-offs of 18 and 5, respectively, which corresponded to the median value of our untreated patients (18.03 and 5.00). The relationship of overall survival from start of IO treatment (OS) with other parameters was analyzed with Cox regression models, including calculation of the Harrel’s C-index in both ICI-treated cohorts for validation of results.
Results
High ALI values (>18) were significantly associated with longer OS for patients receiving ICI monotherapy in both the training (hazard ratio (HR)=0.43, 95% confidence interval (CI) 0.31-0.61, p<0.0001, n=245) and validation cohorts (HR=0.70, 95% CI 0.52-0.95, p=0.0236, n=507). In contrast, no relationship between ALI and OS was observed for patients treated with chemoimmunotherapy (HR=1.10 with p=0.82, and HR=0.83 with p=0.74 in the two cohorts, respectively). In the control cohort of chemotherapy, the association between ALI and OS was less pronounced compared to the discovery cohort (HR=0.70, 95% CI 0.58-0.85, p=0.0003), and showed a significant interaction with the type of treatment (ICI vs. chemotherapy, p<0.0001) in combined analysis of the two cohorts. The relationships of NLR and PD-L1 tumor proportion score (TPS, absent vs. 1-49 vs. 50-100) with OS were significant also in case of ICI monotherapy only (HR=0.50 with p<0.0001, and HR=0.75 with p=0.013, respectively, in the training cohort), but not with chemoimmunotherapy (p>0.70 for both markers in both cohorts). Among patients treated with ICI monotherapy in both experimental cohorts (n=752), the effect of ALI on OS (HR=0.51, p=6*10‑10) was stronger than that of the NLR (HR=0.55, p=3*10-8) and PD-L1 TPS (HR=0.71, p=10-4). In a multivariable analysis for OS together with other parameters significant in univariable testing, ALI emerged as an independent predictor with the strongest impact (HR=0.48 with p=0.002 for high ALI, HR=0.62 with p=0.005 for first- vs. subsequent-line immunotherapy, HR=0.79 with p=0.023 for higher PD-L1 TPS, and HR=0.83 with p=0.45 for low NLR).
Conclusion
The ALI score is a powerful prognostic and predictive biomarker for patients with advanced NSCLC treated with PD-(L)1 inhibitors alone, but not in combination with chemotherapy. Its association with outcome appears to be stronger than that of other widely used parameters, such as the PD-L1 TPS and NLR, and could therefore facilitate more accurate predictions. Reliable markers for chemoimmunotherapy outcomes remain an unmet need in NSCLC.
