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- Makrakis, D, et al.
(författare)
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Effect of body tissue composition on the outcome of patients with metastatic non-small cell lung cancer treated with PD-1/PD-L1 inhibitors
- 2023
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 18:2, s. e0277708-
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Tidskriftsartikel (refereegranskat)abstract
- Obesity and sarcopenia have been reported to affect outcomes in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). We analyzed prospective data from 52 patients with non-oncogene driven metastatic NSCLC treated with ICIs. Body tissue composition was calculated by measuring the fat and muscle densities at the level of 3rd lumbar vertebra in each patient computed tomography scan before ICI initiation using sliceOmatic tomovision. We converted the densities to indices [Intramuscular Fat Index (IMFI), Visceral Fat Index (VFI), Subcutaneous Fat Index (SFI), Lumbar Skeletal Muscle Index (LSMI)] by dividing them by height in meters squared. Patients were dichotomized based on their baseline IMFI, VFI and SFI according to their gender-specific median value. The cut-offs that were set for LMSI values were 55 cm2/m2 for males and 39 cm2/m2 for females. SFI distribution was significantly higher (p = 0.040) in responders compared to non-responders. None of the other variables affected response rates. Low LSMI HR: 2.90 (95% CI: 1.261–6.667, p = 0.012) and low SFI: 2.20 (95% CI: 1.114–4.333, p = 0.023) values predicted for inferior OS. VFI and IMFI values did not affect survival. Subcutaneous adipose and skeletal muscle tissue composition significantly affected immunotherapy outcomes in our cohort.
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- Rounis, K, et al.
(författare)
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Correlation of Clinical Parameters with Intracranial Outcome in Non-Small Cell Lung Cancer Patients with Brain Metastases Treated with Pd-1/Pd-L1 Inhibitors as Monotherapy
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:7
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Tidskriftsartikel (refereegranskat)abstract
- There is a paucity of biomarkers for the prediction of intracranial (IC) outcome in immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients (pts) with brain metastases (BM). We identified 280 NSCLC pts treated with ICIs at Karolinska University Hospital, Sweden, and University Hospital of Heraklion, Greece. The inclusion criteria for response assessment were brain metastases (BM) prior to ICI administration, radiological evaluation with CT or MRI for IC response assessment, PD-1/PD-L1 inhibitors as monotherapy, and no local central nervous system (CNS) treatment modalities for ≥3 months before ICI initiation. In the IC response analysis, 33 pts were included. Non-primary (BM not present at diagnosis) BM, odds ratio (OR): 13.33 (95% CI: 1.424–124.880, p = 0.023); no previous brain radiation therapy (RT), OR: 5.49 (95% CI: 1.210–25.000, p = 0.027); and age ≥70 years, OR: 6.19 (95% CI: 1.27–30.170, p = 0.024) were associated with increased probability of IC disease progression. Two prognostic groups (immunotherapy (I-O) CNS score) were created based on the abovementioned parameters. The I-O CNS poor prognostic group B exhibited a higher probability for IC disease progression, OR: 27.50 (95% CI: 2.88–262.34, p = 0.004). Age, CNS radiotherapy before the start of ICI treatment, and primary brain metastatic disease can potentially affect the IC outcome of NSCLC pts with BM.
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- Skribek, M, et al.
(författare)
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Outcome of Patients with NSCLC and Brain Metastases Treated with Immune Checkpoint Inhibitors in a 'Real-Life' Setting
- 2020
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- There is lack of data addressing the intracranial (IC) efficacy of immune checkpoint inhibitors (ICIs) on brain metastases (BM) in non-small cell lung cancer (NSCLC). This patient category is underrepresented in randomized clinical trials. We retrospectively collected clinical data on patients with non-oncogenic driven NSCLC with BM who were treated with ICIs at two medical oncology institutes in Sweden and Greece from 2016 to 2019. IC efficacy was assessed in patients who had not received local treatment for BM less than three months prior to the initiation of ICIs and had adequate radiological evaluation. We screened 280 patients, of which 51 had BM. BM was an independent predictor for inferior PFS (HR = 2.27; 95% CI, 1.53–3.36) but not OS (HR = 1.58; 95% CI, 0.97–2.60) for the whole patient population. IC response assessment was done on 33 patients. IC objective response rate (ORR) was 24.2%. The presence of neurological symptoms related to BM did not affect IC ORR (p = 0.48). High PD-L1 levels from extracranial biopsies were not a predictive factor for IC ORR (p = 0.13). ICIs are active in NSCLC patients with BM regardless of the presence of neurological symptoms and can achieve durable IC disease stabilization in a subgroup of patients.
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- Tsakonas, G, et al.
(författare)
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ALK-Brain Prognostic Index-Preliminary Study of a Prognostic Tool for Patients with ALK-Rearranged, Non-small Cell Lung Cancer and Brain Metastases
- 2020
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Disease-specific Graded Prognostic Assessment (DS-GPA) is the most validated prognostic tool for patients with brain metastasized lung cancer. The Lung-molGPA scoring system was recently introduced for oncogenic-driven brain metastasized lung cancer, but has not yet been validated in cohorts including only ALK-translocated tumors. Methods: We designed a retrospective cohort study consisting of 44 patients with brain metastasized ALK-positive, non-small cell lung cancer (NSCLC) who were treated between January 2009 and November 2019 at Karolinska University Hospital in Stockholm, Sweden. Information about demographics and clinicopathological parameters were collected. Predictors of overall survival (OS) were identified by Cox regression analyses. A bootstrap validation with 1000 samples was performed in order to compare the different prognostic scores. Results: The variables found to independently influence OS in the multivariate analysis, i.e., PS, sex and brain metastases at diagnosis, were used as prognostic variables in our new prognostic index (ALK-BPI). Patients were divided into two prognostic groups. The median OS was 65.7 months for the good prognostic group and 22.7 months for the poor prognostic group (p = 0.0068). In the univariate analysis of the different prognostic scores, ALK-BPI performed better than the others (HR = 3.6; 95% CI: 1.3–9.9). The mean C-statistics of the different prognostic scores were compared to each other, and no significant difference was observed. Conclusion: We propose the ALK-BPI score as a new prognostic tool that can easily be applied for ALK-positive lung cancer patients with brain metastases in daily clinical practice, as it has at least the same prognostic value as Lung-molGPA.
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