BACKGROUND: Stage III non-small cell lung cancer (NSCLC) is a highly heterogeneous stage due to its subgroups (IIIA-IIIC) comprising both resectable and unresectable tumors. Accurate determination of the extent of the disease is essential for excluding stage IV and choosing the optimal treatment regimen. Whole body positron emission tomography and computed tomography scan (PET/CT) is recommended as an initial staging imaging in locally advanced NSCLC. Despite international guidelines for NSCLC diagnosis and treatment, they are not always adhered to due to various reasons. Even in such a groundbreaking study, the phase 3 trial PACIFIC investigating the efficacy of durvalumab as consolidation therapy in patients with stage III NSCLC PET/CT was not mandatory. With the premise that whole body PET/CT of the trunk is essential for diagnosing stage III NSCLC, we performed a retrospective study evaluating the relationship of the use of PET/CT versus conventional staging with CT of the chest and abdomen, in terms of survival. METHODS: This retrospective study of stage III NSCLC patients used the Czech lung cancer registry LUCAS, which was established in June 2018. As of the data export (up to February 9, 2022), a total of 703 patients were eligible for the analysis. Overall survival (OS) was compared using Kaplan-Meier analysis and a Cox regression model. Continuous variables were tested using the Mann-Whitney test, and categorical variables using the Pearson's Chi-square or Fisher's exact test. RESULTS: A total of 703 patients were included in the cohort with an average age of 69 years. PET/CT was performed on 354 patients, and conventional staging using chest and abdominal CT on 349 patients. The median OS among patients with PET/CT was 20.9 months [95% confidence interval (CI): 18.1-23.7], and it was statistically significantly higher (P<0.001) than among patients without PET/CT, where the median OS was 9.0 months (95% CI: 7.3-10.6). The observed effect of PET/CT was also statistically significant when comparing individual stages (IIIA, IIIB, IIIC). The multivariate Cox model confirmed the use of PET/CT as an independent prognostic factor. The most common reason for omission of PET/CT was the local or time unavailability of the examination. CONCLUSIONS: Omission of PET/CT can mean a significant decrement in survival for the patients in stage III NSCLC, likely due to poor staging and suboptimal treatment. Routine use of PET/CT is strictly recommended for the optimal management of stage III NSCLC patients even outside the high-income countries.
- Publikační typ
- časopisecké články MeSH
Resekce pokročilejších nemalobuněčných plicních karcinomů stadií II a III bez zajištění další léčbou vede k vysokému procentu recidiv. Samotná neo-/adjuvantní chemoterapie vede pouze k mírnému zlepšení přežití pacientů. Významný pokrok ve snížení šance na recidivu onemocnění přinesla až neoadjuvantní chemoimunoterapie (přičemž některé režimy pokračují i v adjuvantním podávání imunoterapie). Ačkoliv máme jasná data o účinnosti této léčby ze studií fáze III, pořád je řada otázek, na které známe jen částečnou či žádnou odpověď. Tento článek se snaží na některé z nich odpověď na podkladě současných poznatků.
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BACKGROUND/AIM: The aim of this study was to investigate possible association between adverse events of nivolumab therapy and the effectiveness of treatment in patients with non-small cell lung cancer (NSCLC). Focusing on serious adverse events (i.e., those of grade ≥3), we evaluated overall survival (OS), progression-free survival (PFS), as well as objective response rate (ORR) to treatment. PATIENTS AND METHODS: We retrospectively analyzed a set of patients from the TULUNG database of NSCLC treated with nivolumab in eight oncology centers. We evaluated OS data based upon this set. To reduce possible bias, we further evaluated a subgroup of patients treated at the University Hospital in Pilsen, where the occurrence of adverse events, PFS, and ORR were independently examined by two experienced physicians. Survival statistics were evaluated using the Kaplan-Meier method and Cox analysis. RESULTS: We observed significantly greater OS, PFS, and ORR in the group of patients experiencing adverse events upon nivolumab treatment versus in those patients without such events. Although the univariable model analyzing the data set of all patients demonstrated higher OS in patients with serious adverse events, only a nonsignificant trend was observed in the Cox multivariable model. In a subgroup of patients with PFS and ORR evaluation, we did observe significant, favorable effects for patients having had serious adverse effects. CONCLUSION: Patients experiencing severe adverse events show a tendency toward better OS, PFS, and ORR compared to patients without or having only mild adverse events with nivolumab treatment.
- Publikační typ
- časopisecké články MeSH
Operabilní nemalobuněčný plicní karcinom byl dlouhá léta spojen s vysokým procentem recidiv při omezené možnosti neo-/adjuvantní léčby v podobě samotné chemoterapie. V posledních letech byl však na tomto poli zaznamenán velký rozvoj. První studie fáze III přinesly pozitivní data pro adjuvantní užití osimertinibu, atezolizumabu a pembrolizumabu. Další pozitivní výsledky přineslo i neoadjuvantní užití nivolumabu spolu s chemoterapií a perioperační přístup s pembrolizumabem a chemoterapií. Cílem tohoto článku je proto přinést souhrn změn a nových poznatků v této oblasti a poukázat i na některé výzvy, kterým nadále čelíme.
For many years, operable non-small cell lung cancer has been associated with a high percentage of recurrences with a limited possibility of neo-/adjuvant treatment in the form of chemotherapy alone. However, recent years have seen great development in this field. The first phase III studies yielded positive data for the adjuvant use of osimertinib, atezolizumab and pembrolizumab. Neoadjuvant use of nivolumab together with chemotherapy and perioperative approach with pembrolizumab and chemotherapy also brought other positive results. The aim of this article is therefore to bring a summary of the changes and new findings in this area and to point out some of the challenges we continue to face.
- Klíčová slova
- osimertinib, atezolizumab, pembrolizumab,
- MeSH
- adjuvantní chemoterapie metody MeSH
- anaplastická lymfomová kináza MeSH
- cílená molekulární terapie metody MeSH
- geny erbB-1 MeSH
- humanizované monoklonální protilátky aplikace a dávkování terapeutické užití MeSH
- imunoterapie metody MeSH
- inhibitory kontrolních bodů aplikace a dávkování terapeutické užití MeSH
- inhibitory tyrosinkinasy aplikace a dávkování terapeutické užití MeSH
- lidé MeSH
- nemalobuněčný karcinom plic * patologie terapie MeSH
- neoadjuvantní terapie metody MeSH
- nivolumab aplikace a dávkování terapeutické užití MeSH
- protinádorové látky imunologicky aktivní aplikace a dávkování terapeutické užití MeSH
- protinádorové látky aplikace a dávkování terapeutické užití MeSH
- protokoly protinádorové kombinované chemoterapie aplikace a dávkování terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- abstrakt z konference MeSH
INTRODUCTION: Asthma as a chronic inflammatory disorder has been suggested as a risk factor for endothelial dysfunction (ED), but studies on the association between asthma and cardiovascular disease (CVD) risk are limited. BACKGROUND: We assessed associations of ED with the severity of asthma, eosinophilic inflammation, lung function, and asthma control. METHODS: 52 young asthmatics (median age of 25.22 years) and 45 healthy individuals were included. Demographic, clinical, and laboratory findings were recorded. We evaluated microvascular responsiveness by recording the reactive hyperemia index (RHI) indicating post-occlusive peripheral endothelium-dependent changes in vascular tone using the Itamar Medical EndoPAT2000. VCAM-1, ADMA, high-sensitive CRP (hsCRP), and E-selectin were measured. RESULTS: Asthmatics had considerably lower RHI values (p < 0.001) with a dynamic decreasing trend by asthma severity and higher hsCRP levels (p < 0.001). A substantial increase in hsCRP and E-selectin with asthma severity (p < 0.05) was also observed. We confirmed a higher body mass index (BMI) in asthmatics (p < 0.001), especially in women and in severe asthma. CONCLUSIONS: We demonstrated the progression of CVD in asthmatics and the association of the ongoing deterioration of ED with the inflammatory severity, suggesting that the increased risk of CVD in young asthmatics is dependent on disease severity. The underlying mechanisms of risk factors for CVD and disease control require further study.
- Publikační typ
- časopisecké články MeSH
AIM: This study compared the results of nivolumab treatment in patients with pulmonary adenocarcinomas based upon previous chemotherapeutic regimens. PATIENTS AND METHODS: The data source for this retrospective study was the Czech VILP registry of patients with nivolumab-treated adenocarcinomas in second and higher lines of treatment. In relation to objective response rate, progression-free interval, and overall survival, three comparisons of patient were made: A: Those treated in first line with cisplatin and pemetrexed versus carboplatin with paclitaxel or vinorelbine; B: treatment with cisplatin and pemetrexed versus carboplatin with paclitaxel/vinorelbine and bevacizumab; and C: treatment in previous lines with pemetrexed (first-line cisplatin and pemetrexed plus those treated in second line with pemetrexed) versus treatment with taxane (first-line carboplatin and paclitaxel only plus those treated with second-line docetaxel). RESULTS: We observed no differences in objective response rate or progression-free survival between patients treated with the stated chemotherapeutic regimens. We observed a trend towards better overall survival for patients treated with carboplatin plus taxanes or vinorelbine with/without bevacizumab. CONCLUSION: From our overall survival data, a chemotherapeutic regimen of carboplatin plus taxanes or vinorelbine with/without bevacizumab might be a better partner for immunotherapy than a cisplatin and pemetrexed-based one.
I přes zlepšení vyšetření k určení klinického stadia, operační techniky a zavedení adjuvantní chemoterapie a případně radioterapie u stadií II a III nemalobuněčného plicního karcinomu (NSCLC) dochází u velkého počtu operovaných pacientů k recidivám onemocnění. Vzhledem k průlomovým výsledkům imunoterapie u pokročilých stadií NSCLC se logicky nabízely studie zkoumající její případný přínos i u operovaných nemocných. První studie se zabývaly jejím užitím v adjuvantním podání po chemoterapii, kde již prokázal přínos atezolizumab ve studii fáze III. V nedávné době bylo publikováno i tiskové prohlášení o pozitivních datech pro pembrolizumab ve stejné indikaci. Následovaly studie s neoadjuvantní imunoterapií, které ve stadiích fáze III přešly povětšinou na režim chemoimunoterapie (s případným pokračováním imunoterapie adjuvantně). Recentně vyšlo tiskové prohlášení o pozitivních výsledcích nivolumabu spolu s chemoterapií v neoadjuvantním podání. Je proto vysoce pravděpodobné, že se tyto léčebné modality v blízké době promítnou do standardních léčebných režimů.
Despite improvements in staging, surgical techniques, and the introduction of adjuvant chemotherapy for stage II and III non-small cell lung cancer (NSCLC), a large number of operated patients have recurrences of the disease. Due to the breakthrough results of immunotherapy in advanced stages of NSCLC, studies examining its potential benefits in operated patients were logically started. The first studies looked at the use of adjuvant immunotherapy after chemotherapy, where they had already shown the benefits of atezolizumab in a phase III study. A press release on positive data for pembrolizumab in the same indication has also been published recently. This was followed by studies with neoadjuvant immunotherapy, which in the phase III trials mostly switched to the chemoimmunotherapy regimen (with possible continuation of immunotherapy in adjuvant administration). Recently, there was a press release on the positive results of nivolumab with neoadjuvant chemotherapy. It is therefore highly likely that these treatment modalities will translate into standard treatment regimens in the near future.
- MeSH
- adjuvantní chemoterapie metody MeSH
- imunoterapie metody MeSH
- lidé MeSH
- nemalobuněčný karcinom plic * farmakoterapie MeSH
- neoadjuvantní terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND/AIM: Due to some interconnectedness at the molecular level, this study assessed the possible influence of laboratory parameters associated with systemic inflammatory environment on programmed death-ligand 1 (PD-L1) expression in non-small cell lung carcinoma (NSCLC). PATIENTS AND METHODS: We assessed effects of c-reactive protein (CRP), albumin, haemoglobin, neutrophil, and lymphocyte levels on PD-L1 expression in NSCLC. Patient data were obtained retrospectively from LUCAS, the Czech registry of patients with lung carcinomas. Correlations of two continuous parameters (PD-L1 expression and laboratory parameters) were analysed by correlation coefficient. Differences in continuous parameters between two or more groups were tested by Mann-Whitney or Kruskal-Wallis tests. Independence of two categorical parameters was tested by chi-square test. RESULTS: We demonstrated no influence of the investigated laboratory parameters on PD-L1 expression in NSCLC, either in continuous or categorical division of variables. CONCLUSION: Inflammatory laboratory parameters at time of NSCLC diagnosis are unlikely to affect the determination of PD-L1 expression.
- MeSH
- antigeny CD274 analýza MeSH
- C-reaktivní protein analýza MeSH
- hemoglobiny analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidský sérový albumin analýza MeSH
- lymfocyty imunologie MeSH
- nádorové biomarkery analýza MeSH
- nádory plic imunologie patologie MeSH
- nemalobuněčný karcinom plic imunologie patologie MeSH
- neutrofily imunologie MeSH
- registrace MeSH
- retrospektivní studie MeSH
- senioři MeSH
- staging nádorů MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Programmed death-ligand 1 (PD-L1) expression is a standard predictor in the selection of immunotherapy for locally advanced/advanced non-small cell lung cancer (NSCLC). However, comedication with corticosteroids or non-steroidal anti-inflammatory drugs (NSAIDs) may influence the effectiveness of this treatment as documented in several previous studies. Due to certain molecular linkages between PD-L1 and corticosteroids or NSAIDs, we therefore addressed the question of whether there is a relationship between PD-L1 expression in NSCLC and the use of this comedication. METHODS: This is a retrospective study using the Czech tumor registry LUng CAncer focuS (LUCAS), from which patient data were drawn. Independence of two categorical parameters was tested by Pearson's chi-square test. RESULTS: In our group of 1,148 patients, we observed no significant relationship between PD-L1 expression and the use of corticosteroids or NSAIDs. CONCLUSIONS: According to our data, treatment with corticosteroids or NSAIDs during biopsy does not affect the expression of PD-L1 and it is therefore not necessary to take this treatment into account in this regard.
- Publikační typ
- časopisecké články MeSH
