scholarly journals Spatial architecture of tumour-infiltrating lymphocytes as a prognostic parameter in resected non-small-cell lung cancer

2020 ◽  
Vol 58 (3) ◽  
pp. 619-628 ◽  
Author(s):  
Giovanni Bocchialini ◽  
Costanza Lagrasta ◽  
Denise Madeddu ◽  
Giulia Mazzaschi ◽  
Davide Marturano ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Resected Nsclc ◽  
Nsclc Patients ◽  
Infiltrating Lymphocytes ◽  
Disease Free

Abstract OBJECTIVES Tumour-infiltrating lymphocytes (TILs) are critically implicated in the clinical outcome and response to immunotherapy in non-small-cell lung cancer (NSCLC) patients. The functional competence of lymphocyte subpopulations is strongly conditioned by their spatial arrangement within the tumour immune microenvironment. The aim of this study was to determine whether the tissue localization of specific TIL subpopulations might have an impact on the risk of recurrence in surgically resected NSCLC. METHODS High-speed scanning of whole slide images was performed on immunohistochemically stained tissue sections from 97 NSCLC patients to assess the number and ratio of CD3+, CD8+ and PD-1+ T-lymphocytes. TIL distribution was computed considering the intratumoural (proximal or distal) and peripheral (invasive margin) localization as well as their location within the fibrotic tissue (immune excluded). The tumour proliferative index was assessed by Ki67 labelling. The impact of TILs number and distribution on clinical-pathological characteristics and outcomes were statistically analysed. RESULTS High density and percentage of proximal CD8+ TILs and low PD-1-to-CD8 ratio had a positive impact on disease-free-survival (P = 0.03) and overall survival (P = 0.003). An inverse correlation was observed between the abundance of intratumoural CD8+ TILs carrying PD-1 inhibitory receptor and cancer cell proliferation. Cases with high compared to low fraction of immune excluded CD8+ TILs had significantly reduced 5-year overall survival (n events: 22 vs 12; P = 0.04) and disease-free survival (n events: 24 vs 16; P = 0.03) rates while the amount of CD3+ and CD8+ TILs located at the invasive margin had a favourable effect on the clinical course. CONCLUSIONS Mapping TIL subpopulations may implement the definition of prognostic parameters in surgically resected NSCLC.

scholarly journals Determination of prognostic factors of surgically treated pathological Stage IIIA non-small cell lung cancer

2020 ◽  
Vol 28 (3) ◽  
pp. 496-504
Author(s):  
Muhammet Sayan
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Disease Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Disease Free

Background: This study aims to identify the prognostic factors in Stage IIIA non-small cell lung cancer and to investigate whether there was a significant difference in terms of overall survival and disease-free survival among the subgroups belonging to this disease stage. Methods: Between January 2010 and December 2018, a total of 144 patients (125 males, 19 females; median age 60 years; range, 41 to 80 years) who were operated for non-small cell lung cancer in our clinic and whose pathological stage was reported as IIIA were retrospectively analyzed. Data including demographic and clinical characteristics of the patients, histopathological diagnosis, the standardized uptake value of the mass on positron emission tomography-computed tomography, tumor diameter, type of surgery, lymph node metastasis status, visceral pleural invasion, and overall and disease-free survival rates were recorded. Results: The median survival was 39 (range, 27.8 to 46.1) months and the five-year overall survival rate was 28%. The mean tumor diameter was 4.3±2.7 cm. The median disease-free survival was 37 (range, 28.1 to 48.6) months and the five-year disease-free survival rate was 26.9%. In the multivariate analysis, overall survival and disease-free survival in T2N2M0 subgroup were significantly worse than the other subgroups. The other poor prognostic factors of survival were the standardized uptake value of the tumor, pneumonectomy, and histopathological subtypes other than squamous cell carcinoma and adenocarcinoma. Parietal pleural invasion was significantly associated with worse disease-free survival rates. Conclusion: Our results showed that there may be significant survival differences between subgroups created by tumor histopathology, lymph node invasion and the type of surgery in a heterogeneous lung cancer stage.

Correlation between outcomes and tumor size in >7 cm T4 non-small cell lung cancer patients: A tumor size-based comparison study

2021 ◽  
Vol 29 (8) ◽  
pp. 784-791
Author(s):  
Volkan Erdoğu ◽  
Necati Çitak ◽  
Celal B Sezen ◽  
Levent Cansever ◽  
Cemal Aker ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Tumor Size ◽  
Disease Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Lung Cancer Patients ◽  
Disease Free

Background We investigated whether all size-based pathological T4N0–N1 non-small cell lung cancer patients with tumors at any size >7 cm had the same outcomes. Methods We reviewed non-small cell lung cancer patients with tumors >7 cm who underwent anatomical lung resection between 2010 and 2016. A total of 251 size-based T4N0–N1 patients were divided into two groups based on tumor size. Group S ( n = 192) included patients with tumors of 7.1–9.9 cm and Group L ( n = 59) as tumor size ≥10 cm. Results The mean tumor size was 8.83 ± 1.7 cm (Group S: 8.06 ± 0.6 cm, Group L: 11.3 ± 1.6 cm). There were 146 patients with pathological N0 and 105 patients with pathological N1 disease. Mean overall survival and disease-free survival were 64.2 and 51.4 months, respectively. The five-year overall survival and disease-free survival rates were 51.2% and 43.5% (five-year OS; pT4N0:52.7%, pT4N1:47.9%, DFS; pT4N0:44.3%, pT4N1: 42.3%). No significant differences were observed between T4N0 and T4N1 patients in terms of five-year OS or DFS ( p = 0.325, p = 0.505 respectively). The five-year overall survival and disease-free survival rates were 52% and 44.6% in Group S, and 48.5% and 38.9% in Group L. No significant difference was observed between the groups in terms of five-year overall survival or disease-free survival ( p = 0.699, p = 0.608, respectively). Conclusions Above 7 cm, any further increase in tumor size in non-small cell lung cancer patients had no significant effect on survival, confirming it is not necessary to further discriminate among patients with tumors in that size class.

scholarly journals Tumor Mutation Burden as a Biomarker in Resected Non–Small-Cell Lung Cancer

2018 ◽  
Vol 36 (30) ◽  
pp. 2995-3006 ◽  
Author(s):  
Siddhartha Devarakonda ◽  
Federico Rotolo ◽  
Ming-Sound Tsao ◽  
Irena Lanc ◽  
Elisabeth Brambilla ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Tumor Mutation Burden ◽  
Resected Nsclc ◽  
Mutation Burden ◽  
Disease Free

Purpose The survival benefit with adjuvant chemotherapy for patients with resected stage II-III non–small-cell lung cancer (NSCLC) is modest. Efforts to develop prognostic or predictive biomarkers in these patients have not yielded clinically useful tests. We report findings from the Lung Adjuvant Cisplatin Evaluation (LACE)-Bio-II study, in which we analyzed next-generation sequencing and long-term outcomes data from > 900 patients with early-stage NSCLC treated prospectively in adjuvant landmark clinical trials. We used a targeted gene panel to assess the prognostic and predictive effect of mutations in individual genes, DNA repair pathways, and tumor mutation burden (TMB). Methods A total of 908 unmatched, formalin-fixed, paraffin-embedded, resected lung cancer tumor specimens were sequenced using a targeted panel of 1,538 genes. Stringent filtering criteria were applied to exclude germline variants and artifacts related to formalin fixation. Disease-free survival, overall survival, and lung cancer—specific survival (LCSS) were assessed in Cox models stratified by trial and adjusted for treatment, age, sex, performance score, histology, type of surgery, and stage. Results Nonsynonymous mutations were identified in 1,515 genes in 908 tumor samples. High nonsynonymous TMB (> 8 mutations/Mb) was prognostic for favorable outcomes (ie, overall survival, disease-free survival, and LCSS) in patients with resected NSCLC. LCSS benefit with adjuvant chemotherapy was more pronounced in patients with low nonsynonymous TMBs (≤ 4 mutations/Mb). Presence of mutations in DNA repair pathways, tumor-infiltrating lymphocytes, TP53 alteration subtype, and intratumor heterogeneity was neither prognostic nor predictive. Statistically significant effect of mutations in individual genes was difficult to determine due to high false-discovery rates. Conclusion High nonsynonymous TMB was associated with a better prognosis in patients with resected NSCLC. In addition, the benefit of adjuvant chemotherapy on LCSS was more pronounced in patients with low nonsynonymous TMBs. Studies are warranted to confirm these findings.

scholarly journals Protein Kinase D1 Is Increased in Tumor Tissue, Correlates With Advanced Tumor Features and Worse Prognosis of Non-Small Cell Lung Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382093412
Author(s):  
Jing Yao ◽  
Yan Jiang ◽  
Shuang Geng ◽  
Li Sun
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Protein Kinase ◽  
Small Cell Lung Cancer ◽  
Disease Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Protein Kinase D1 ◽  
Disease Free

Objective: This study aimed to assess protein kinase D1 expression and its association with tumor characteristics as well as prognosis in patients with non-small cell lung cancer. Methods: Protein kinase D1 expression in tumor tissues and adjacent tissues from 172 patients with non-small cell lung cancer who underwent surgical resection were analyzed by immunohistochemical staining. Based on the total immunohistochemical score, protein kinase D1 expression was classified as protein kinase D1 high expression (further divided into protein kinase D1 high+++, protein kinase D1 high++, and protein kinase D1 high+ expressions) and protein kinase D1 low expression. Clinical characteristics of patients with non-small cell lung cancer were acquired from the database. Accumulating disease-free survival and overall survival were calculated based on patients’ relapse/survival status. Results: Protein kinase D1 expression was increased in tumor tissues compared to adjacent tissues ( P < .001). Tumor protein kinase D1 high expression correlated with poorer pathological differentiation ( P = .041), increased tumor size ( P = .003), the presence of lymph node metastasis ( P = .001), and elevated tumor, nodes and metastases stage ( P < .001). Besides, both accumulating disease-free survival and overall survival were decreased in patients with tumor protein kinase D1 high expression compared to patients with tumor protein kinase D1 low expression ( P = .010 for disease-free survival and P = 0.005 for overall survival). Moreover, they were lowest in patients with tumor protein kinase D1 high+++ expression, followed by patients with tumor protein kinase D1 high++ expression, then patients with tumor protein kinase D1 high+ expression, and highest in patients with tumor protein kinase D1 low expression ( P < .001 for disease-free survival and P = .001 for overall survival). Notably, higher tumor protein kinase D1 expression was an independent predictive factor for decreased disease-free survival ( P = .001) and overall survival ( P = .004). Conclusions: Protein kinase D1 might be a potential marker to identify patients with non-small cell lung cancer with worse tumor features and prognosis.

scholarly journals Can G8 Scoring in Patients with Geriatric Lung Cancer Help to Determine Curative Treatment?

2020 ◽  
pp. 1-7
Author(s):  
Şule Karabulut Gül ◽  
Hüseyin Tepetam
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Elderly Patients ◽  
Small Cell Lung Cancer ◽  
Disease Free Survival ◽  
Small Cell ◽  
Curative Treatment ◽  
Small Cell Lung ◽  
Free Survival ◽  
Disease Free

Objective: The median age at diagnosis of lung cancer is 70 years and there are limited data in the literature regarding the treatment of elderly patients. In elderly patients, comorbid diseases, poor performance, and toxicity may lead to a surge in physicians' curative treatment and may remain untreated. The aim of this study was to evaluate the results of treatment in patients older than 70 years whose performances were evaluated by using Geriatric 8 score and to find out the response to curative treatment. Materials and Methods: 124 patients over 70 years of age were evaluated retrospectively. 68 patients with early stage or locally advanced non-small cell lung cancer who were inoperable but not suitable for stereotactic radiotherapy were evaluated retrospectively. Geriatric 8 (G8) screening test was used to identify elderly cancer patients who could benefit from curative treatment. Patients received curative chemoradiotherapy or radiotherapy alone. Results: In all patients (68), overall survival (83% for 1 year, 66% for 2 years) was median 18 months and disease free survival (58% for 1 year, 34.1% for 2 years) was median 14 months. As the G8 score increased, a statistically significant increase was observed in overall and disease free survival. Having weight loss or not, presence of accompanying disease, having good or bad health situation, having body mass index above and below 21, and the usage number of medications below or above 3 affects overall and disease free survival. When only the patients who received radiochemotherapy (n = 43) were evaluated, the mean survival (free of the ECOG performance score) was 12.8 months with G8 score less than 14 and 29.17 months with G8 score 14 and above and were statistically significant (p = 0.000). Conclusion: When making a treatment decision, clinical evaluation should be performed well in patients older than 70 years with non-small cell lung cancer (NSCLC). In our study, overall survival and disease free survival were found to be better in patients with a G8 score above 14. Therefore, we think that it may be appropriate to use curative concurrent radio chemotherapy in selected patients with high G8 score and not to decide on biological age in elderly patients.

scholarly journals Interleukin polymorphisms associated with overall survival, disease-free survival, and recurrence in non-small cell lung cancer patients

2015 ◽  
Vol 54 (S1) ◽  
pp. E172-E184 ◽  
Author(s):  
Nicholas T. Woods ◽  
Alvaro N. Monteiro ◽  
Zachary J. Thompson ◽  
Ernest K. Amankwah ◽  
Nina Naas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Lung Cancer Patients ◽  
Disease Free

scholarly journals Acceptability and feasibility of S-1 plus cisplatin adjuvant chemotherapy for completely resected non-small cell lung cancer: an open-label, single arm, multicenter, phase 2 trial

2020 ◽  
Author(s):  
Shugo Uematsu ◽  
Atsushi Sano ◽  
Kazutoshi Isobe ◽  
Kazuhiro Usui ◽  
Jun Matsumoto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Adjuvant Chemotherapy ◽  
Adverse Events ◽  
Disease Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Disease Free

Abstract Background Although platinum-based chemotherapy is accepted as adjuvant chemotherapy for resectable advanced non-small cell lung cancer (NSCLC), its completion rate is low due to severe adverse events. S-1 plus cisplatin is associated with relatively low toxicity and an unimpaired quality of life, and has been used for unresectable advanced lung cancer. We investigated the acceptability and feasibility of combination therapy with S-1 plus cisplatin as postoperative adjuvant chemotherapy following complete resection of pathological stage II-IIIA NSCLC. Methods Enrolled patients received oral S-1 at a dose depending on their body weight twice daily for 21 days with intravenous cisplatin 60 mg/m2 on day 8, with 1 cycle comprising 5 weeks and 4 cycles. Patients received standard precautions against adverse events and received standard treatment when adverse events occurred. The primary endpoint was completion rate; secondary endpoints included safety, status of drug administration, disease-free survival, and overall survival. Results A total of 19 patients [14 men, 5 women; mean age, 59.1 years; mean body surface area, 1.688 m2; 17 with an Eastern Cooperative Oncology Group performance status (PS) of 0 and 2 with a PS of 1; 7 (36.8%) with stage II disease and 12 (63.2%) with stage IIIA disease] were enrolled. The rate of completion of 4 cycles was 68.4%. Grade 3 adverse events that occurred in ≥10% of patients included neutropenia (21.1%), nausea (21.1%), and anorexia (15.8%). No grade 4 adverse events, febrile neutropenia, or treatment-related deaths occurred. The mean relative dose intensity was 79% for S-1 and 80% for cisplatin. The 2-year disease-free survival rate was 42.1%, and 2-year overall survival rate was 83.3%. Conclusion This study demonstrated the acceptability and feasibility of using S-1 plus cisplatin as adjuvant chemotherapy.

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