Role of the total mutation burden (TMB) and tumor-infiltrating lymphocytes (TILs) on the development of second primary cancer after complete resection of non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21092-e21092
Author(s):  
Marie-Pier Gauthier ◽  
Maryam Karimi ◽  
Stefan Michiels ◽  
Lesley Seymour ◽  
Elisabeth Brambilla ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Genomic Instability ◽  
Early Stage ◽  
Performance Status ◽  
Tumor Infiltrating Lymphocytes ◽  
Tumor Stage ◽  
Second Primary ◽  
Early Stage Lung Cancer ◽  
Risk Of Death ◽  
Resected Nsclc

e21092 Background: Risk of developing SPC after complete surgical resection of NSCLC has been reported to be 3-6% per person-year. We hypothesized that genomic instability, as assessed by high TMB, and the absence of TILs in the primary tumor might be associated with SPC. Methods: The LACE [Lung Adjuvant Cisplatin Evaluation])-BIO database was used, which includes 3 randomized trials. TMB and TILs were analyzed on FFPE specimens. TMB was categorized into tertiles (high > 7.8 mutations/MB, moderate i.e. > 4 and < = 7.8, low < 4) and TILs as marked vs. other. Associations on competing time-to-event endpoints (SPC, and death without developing SPC) were evaluated using the Fine and Gray model stratified by trail and adjusted on treatment, age, gender, tumor stage, nodal stage, histology, performance status and surgery type. Results: TMB and TILs assessments were available for 879 patients without missing clinical covariates; 85 patients had marked TILs. During follow-up, 47 SPCs had been observed and 392 deaths without developing SPC. Regarding TMB, a significant association was found between low TMB and death without SPC (sub-distribution hazard ratio SHR = 1.36(1.06-1.74), see Table), suggesting a higher risk of death without SPC among patient with low TMB compared to those with moderate TMB; no strong effect was observed for SPC. Regarding TILs, a trend was observed between marked TILS and a lower risk of death (SHR = 0.70 [0.47-1.04]) but to a lesser extent for SPC (SHR = 0.80 [0.28-2.28]). Conclusions: This is the first study of the effect of genomic instability (measured by TMB) and host immune response (measured by TILs) in completely resected NSCLC on competing events of SPC and death, suggesting associations between TMB, TILs and death-without-SPC . There was no statistically significant association with SPC. However, the number of SPCs was small; these findings requires validation in other early stage lung cancer cohorts. [Table: see text]

Efficacy and toxicity hypofractionated radiotherapy for centrally located non-small cell lung cancer

2021 ◽  
pp. 1-4
Author(s):  
Tanzeel Janjua ◽  
Fei Sun ◽  
Katy Clarke ◽  
Pete Dickinson ◽  
Kevin Franks ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cox Regression ◽  
Early Stage ◽  
Performance Status ◽  
Small Cell ◽  
Small Cell Lung ◽  
Early Stage Lung Cancer ◽  
Cox Regression Analysis

Abstract Aim: Centrally located early-stage non-small cell lung cancer in patients who are unfit for surgery are treated with fractionated radiotherapy. We present the outcomes of a moderately hypofractionated accelerated dose regimen of 50 Gy in 15 fractions from a single centre in the UK. Materials and methods: Electronic case notes and radiotherapy records of lung cancer patients treated between January 2014 and December 2016 were retrospectively reviewed. Adult Comorbidity Evaluation-27 score was used to evaluate comorbidities. Mean lung doses and percentage of lung receiving more than 20 Gy were calculated for all patients. Survival outcomes were estimated using Kaplan–Meier curves. Results: Fifty-three patients were included in the study; the median follow-up was 20.2 months. 87% of patients had stage I disease. There was no 30-day post-treatment mortality. Ninety-day mortality rate after radiotherapy was 3.8%. Grade 2 pneumonitis was seen in five patients while no grade 3 or 4 pneumonitis was observed. The median progression-free survival (PFS) and overall survival (OS) were 18.5 months and 28.2 months, respectively. The estimated 1 and 2 years PFS were 62.3% and 41.3%, respectively, and OS were 77.4% and 56.6%, respectively. Worsening performance status was associated with worse survival on cox regression analysis. Disease relapsed in 36% of patients. 7.5% of patients with relapsed disease had infield recurrence. Findings: 50 Gy in 15 fractions radiotherapy for central early-stage lung cancer is a feasible choice that requires further randomised trials.

scholarly journals Torque Teno Virus load in lung cancer patients correlates with age but not with tumor stage

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252304
Author(s):  
Dirk Stefani ◽  
Balazs Hegedues ◽  
Stephane Collaud ◽  
Mohamed Zaatar ◽  
Till Ploenes ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Stage Iv ◽  
Tumor Stage ◽  
Plasma Dna ◽  
Early Stage Lung Cancer ◽  
Lung Cancer Patients ◽  
Stage Iv Lung Cancer ◽  
Stage Lung Cancer

Background Torque teno virus (TTV) is a ubiquitous non-pathogenic virus, which is suppressed in immunological healthy individuals but replicates in immune compromised patients. Thus, TTV load is a suitable biomarker for monitoring the immunosuppression also in lung transplant recipients. Since little is known about the changes of TTV load in lung cancer patients, we analyzed TTV plasma DNA levels in lung cancer patients and its perioperative changes after lung cancer surgery. Material and methods Patients with lung cancer and non-malignant nodules as control group were included prospectively. TTV DNA levels were measured by quantiative PCR using DNA isolated from patients plasma and correlated with routine circulating biomarkers and clinicopathological variables. Results 47 patients (early stage lung cancer n = 30, stage IV lung cancer n = 10, non-malignant nodules n = 7) were included. TTV DNA levels were not detected in seven patients (15%). There was no significant difference between the stage IV cases and the preoperative TTV plasma DNA levels in patients with early stage lung cancer or non-malignant nodules (p = 0.627). While gender, tumor stage and tumor histology showed no correlation with TTV load patients below 65 years of age had a significantly lower TTV load then older patients (p = 0.022). Regarding routine blood based biomarkers, LDH activity was significantly higher in patients with stage IV lung cancer (p = 0.043), however, TTV load showed no correlation with LDH activity, albumin, hemoglobin, CRP or WBC. Comparing the preoperative, postoperative and discharge day TTV load, no unequivocal pattern in the kinetics were. Conclusion Our study suggest that lung cancer has no stage dependent impact on TTV plasma DNA levels and confirms that elderly patients have a significantly higher TTV load. Furthermore, we found no uniform perioperative changes during early stage lung cancer resection on plasma TTV DNA levels.

scholarly journals Treatment and survival of second primary early-stage lung cancer, following treatment of head and neck cancer in the Netherlands

Lung Cancer ◽  
2016 ◽  
Vol 94 ◽  
pp. 54-60 ◽  
Author(s):  
Alexander V. Louie ◽  
Ronald A. Damhuis ◽  
Cornelis J. Haasbeek ◽  
Andrew Warner ◽  
Danielle Rodin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Head And Neck Cancer ◽  
The Netherlands ◽  
Head And Neck ◽  
Neck Cancer ◽  
Early Stage ◽  
Second Primary ◽  
Early Stage Lung Cancer ◽  
Stage Lung Cancer

Adjuvant Chemotherapy in Completely Resected Non–Small-Cell Lung Cancer

2005 ◽  
Vol 23 (14) ◽  
pp. 3270-3278 ◽  
Author(s):  
Katherine M.W. Pisters ◽  
Thierry Le Chevalier
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Randomized Trials ◽  
Performance Status ◽  
Small Cell ◽  
Small Cell Lung ◽  
Risk Of Death ◽  
Resected Nsclc

Surgery alone has long been the standard treatment for patients with operable non–small-cell lung cancer (NSCLC). However, despite complete resection, 5-year survival rates have been disappointing, with about 50% of patients eventually suffering relapse and death from disease. Randomized trials conducted in the 1980s hinted at a survival benefit for postoperative cisplatin-based regimens, but they were underpowered. A meta-analysis published in 1995 found a nonsignificant 13% reduction in the risk of death associated with cisplatin-based chemotherapy, with an increase of survival of 5% at 5 years. This led to renewed interest in adjuvant chemotherapy in resected NSCLC. Thousands of patients have been included in a new generation of randomized trials in the last 10 years. Most of these recent studies have now been reported and several have demonstrated a clear survival advantage for patients treated with platin-based adjuvant therapy. These results also suggest a greater benefit with modern two-drug regimens. In view of the most recent data, postoperative platin-based chemotherapy can now be considered the standard of care for completely resected NSCLC patients with good performance status.

scholarly journals Stereotactic Body Radiation Therapy for Patients with Pulmonary Interstitial Change: High Incidence of Fatal Radiation Pneumonitis in a Retrospective Multi-Institutional Study

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 257 ◽  
Author(s):  
Hiroshi Onishi ◽  
Hideomi Yamashita ◽  
Yoshiyuki Shioyama ◽  
Yasuo Matsumoto ◽  
Kenji Takayama ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Stereotactic Body Radiation Therapy ◽  
Radiation Pneumonitis ◽  
Early Stage ◽  
Performance Status ◽  
Stage I ◽  
Normal Lung ◽  
Early Stage Lung Cancer ◽  
Stereotactic Body Radiation

Pretreatment pulmonary interstitial change (PIC) has been indicated as a risk factor of severe radiation pneumonitis (RP) following stereotactic body radiation therapy (SBRT) for early-stage lung cancer, but details of its true effect remain unclear. This study aims to evaluate treatment outcomes of SBRT for stage I non-small cell lung cancer in patients with PIC. A total of 242 patients are included in this study (88% male). The median age is 77 years (range, 55–92 years). A total dose of 40–70 Gy is administered in 4 to 10 fractions during a 4-to-25 day period. One, two, and three-year overall survival (OS) rates are 82.1%, 57.1%, and 42.6%, respectively. Fatal RP is identified in 6.9% of all patients. The percent vital capacity <70%, mean percentage normal lung volume receiving more than 20 Gy (>10%), performance status of 2–4, presence of squamous cell carcinoma, clinical T2 stage, regular use of steroid before SBRT, and percentage predicting forced expiratory volume in one second (<70%) are associated with worse prognoses for OS. Our results indicate that fatal RP frequently occurs after SBRT for stage I lung cancer in patients with PIC.

scholarly journals Anticipating EGFR Targeting in Early Stages of Lung Cancer: Leave No Stone Unturned

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2685
Author(s):  
Lorenzo Belluomini ◽  
Silvia Teresa Riva ◽  
Michele Simbolo ◽  
Riccardo Nocini ◽  
Ilaria Trestini ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Early Stage ◽  
Target Therapy ◽  
Complete Response ◽  
Early Stage Lung Cancer ◽  
Early Stages ◽  
Resected Nsclc ◽  
Egfr Mutant ◽  
The Impact

 Background: The current treatment landscape of early stage lung cancer is rapidly evolving, particularly in EGFR mutant non-small cell lung cancer (NSCLC), where target therapy is moving to early stages. In the current review, we collected the available data exploring the impact of EGFR targeting in both neoadjuvant and adjuvant settings, underlying lights and shadows and discussing the existing open issues. Methods: We performed a comprehensive search using PubMed and the proceedings of major international meetings to identify neoadjuvant/adjuvant trials with EGFR tyrosine kinase inhibitors (TKIs) in NSCLC. Results: Limited data are available so far about the activity/efficacy of neoadjuvant TKIs in EGFR mutant NSCLC, with only modest downstaging and pathological complete response rates reported. Differently, the ADAURA trial already proposed osimertinib as a potential new standard of care in resected NSCLC harboring an activating EGFR mutation. Conclusion: Anticipating targeted therapy to early stage EGFR mutant NSCLC presents great opportunities but also meaningful challenges in the current therapeutic/diagnostic pathway of lung cancer care. Appropriate endpoint(s) selection for clinical trials, disease progression management, patients’ and treatment selection, as well as need to address the feasibility of molecular profiling anticipation, represent crucial issues to face before innovation can move to early stages. 

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