PURPOSE: Recent papers suggested a correlation between the risk of distant metastasis (DM) and dose outside the PTV, though conclusions in different publications conflicted. This study resolves these conflicts and provides a compelling explanation of prognostic factors. MATERIALS AND METHODS: A dataset of 478 NSCLC patients treated with SBRT (IMRT or VMAT) was analyzed. We developed a deep learning model for DM prediction and explainable AI was used to identify the most significant prognostic factors. Subsequently, the prognostic power of the extracted features and clinical details were analyzed using conventional statistical methods. RESULTS: Treatment technique, tumor features, and dosiomic features in a 3 cm wide ring around the PTV (PTV3cm) were identified as the strongest predictors of DM. The Hazard Ratio (HR) for Dmean,PTV3cm was significantly above 1 (p < 0.001). There was no significance of the PTV3cm dose after treatment technique stratification. However, the dose in PTV3cm was found to be a highly significant DM predictor (HR > 1, p = 0.004) when analyzing only VMAT patients with small and spherical tumors (i.e., sphericity > 0.5). CONCLUSIONS: The main reason for conflicting conclusions in previous papers was inconsistent datasets and insufficient consideration of confounding variables. No causal correlation between the risk of DM and dose outside the PTV was found. However, the mean dose to PTV3cm can be a significant predictor of DM in small spherical targets treated with VMAT, which might clinically imply considering larger PTV margins for smaller, more spherical tumors (e.g., if IGTV > 2 cm, then margin ≤ 7 mm, else margin > 7 mm).
- MeSH
- celková dávka radioterapie * MeSH
- deep learning * MeSH
- lidé středního věku MeSH
- lidé MeSH
- metastázy nádorů MeSH
- nádory plic * patologie radioterapie MeSH
- nemalobuněčný karcinom plic * radioterapie patologie MeSH
- plánování radioterapie pomocí počítače metody MeSH
- prognóza MeSH
- radiochirurgie * metody MeSH
- radioterapie s modulovanou intenzitou metody MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small cell lung cancer (ES-NSCLC), but which patients benefit from stereotactic radiotherapy is unclear. The aim of this study was to analyze prognostic factors for early mortality. METHODS: From August 2010 to 2022, 617 patients with medically inoperable, peripheral or central ES-NSCLC were treated with SABR at our institution. We retrospectively evaluated the data from 172 consecutive patients treated from 2018 to 2020 to analyze the prognostic factors associated with overall survival (OS). The biological effective dose was > 100 Gy10 in all patients, and 60 Gy was applied in 3-5 fractions for a gross tumor volume (GTV) + 3 mm margin when the tumor diameter was < 1 cm; 30-33 Gy was delivered in one fraction. Real-time tumor tracking or an internal target volume approach was applied in 96% and 4% of cases, respectively. In uni- and multivariate analysis, a Cox model was used for the following variables: ventilation parameter FEV1, histology, age, T stage, central vs. peripheral site, gender, pretreatment PET, biologically effective dose (BED), and age-adjusted Charlson comorbidity index (AACCI). RESULTS: The median OS was 35.3 months. In univariate analysis, no correlation was found between OS and ventilation parameters, histology, PET, or centrality. Tumor diameter, biological effective dose, gender, and AACCI met the criteria for inclusion in the multivariate analysis. The multivariate model showed that males (HR 1.51, 95% CI 1.01-2.28; p = 0.05) and AACCI > 5 (HR 1.56, 95% CI 1.06-2.31; p = 0.026) were significant negative prognostic factors of OS. However, the analysis of OS showed that the significant effect of AACCI > 5 was achieved only after 3 years (3-year OS 37% vs. 56%, p = 0.021), whereas the OS in one year was similar (1-year OS 83% vs. 86%, p = 0.58). CONCLUSION: SABR of ES-NSCLC with precise image guidance is feasible for all medically inoperable patients with reasonable performance status. Early deaths were rare in our real-life cohort, and OS is clearly higher than would have been expected after best supportive care.
- MeSH
- analýza přežití MeSH
- kohortové studie MeSH
- lidé MeSH
- malobuněčný karcinom plic * patologie MeSH
- nádory plic * radioterapie chirurgie MeSH
- nemalobuněčný karcinom plic * radioterapie chirurgie MeSH
- radiochirurgie * metody MeSH
- retrospektivní studie MeSH
- staging nádorů MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: Radiotherapy outcome modelling often suffers from class imbalance in the modelled endpoints. One of the main options to address this issue is by introducing new synthetically generated datapoints, using generative models, such as Denoising Diffusion Probabilistic Models (DDPM). In this study, we implemented DDPM to improve performance of a tumor local control model, trained on imbalanced dataset, and compare this approach with other common techniques. METHODS: A dataset of 535 NSCLC patients treated with SBRT (50 Gy/5 fractions) was used to train a deep learning outcome model for tumor local control prediction. The dataset included complete treatment planning data (planning CT images, 3D planning dose distribution and patient demographics) with sparsely distributed endpoints (6-7 % experiencing local failure). Consequently, we trained a novel conditional 3D DDPM model to generate synthetic treatment planning data. Synthetically generated treatment planning datapoints were used to supplement the real training dataset and the improvement in the model's performance was studied. Obtained results were also compared to other common techniques for class imbalanced training, such as Oversampling, Undersampling, Augmentation, Class Weights, SMOTE and ADASYN. RESULTS: Synthetic DDPM-generated data were visually trustworthy, with Fréchet inception distance (FID) below 50. Extending the training dataset with the synthetic data improved the model's performance by more than 10%, while other techniques exhibited only about 4% improvement. CONCLUSIONS: DDPM introduces a novel approach to class-imbalanced outcome modelling problems. The model generates realistic synthetic radiotherapy planning data, with a strong potential to increase performance and robustness of outcome models.
Léčba metastazujícího karcinomu prsu s pozitivitou receptoru pro lidský epidermální růstový faktor (human epidermal growth factor receptor, HER) prochází v současné době velkým rozvojem co do nabídky léčiv i jejich účinku. Uvádíme kazuistiku 45leté pacientky s metastazujícím HER pozitivním nádorem prsu, silně předléčené chemoterapií antracykliny a taxany a po anti-HER léčbě pertuzumabem, trastuzumabem i lapatinibem s rozsáhlým symptomatickým postižením plic a pohrudnice. Léčbou trastuzumab deruxrtecanem bylo u této pacientky ve třetí linii paliativní léčby dosaženo parciální remise a významného klinického zlepšení stavu. Zatím účinek trvá 18 měsíců a pokračujeme v udržovací léčbě stejnou dávkou 5,4 mg/kg tělesné hmotnosti. Nezaznamenali jsme žádné závažné projevy toxicity G3/4, ani kardiální, ani hematologické. Léčba trastuzumab deruxtecanem je velmi účinnou možností s přijatelnou toxicitou i u silně předléčených pacientek.
The treatment of metastatic HER-positive breast cancer is currently undergoing great development in terms of the range of drugs and their effect. We present the case report of a 45-year-old female patient with HER-positive metastatic breast cancer, heavily pretreated with anthracycline and taxanes chemotherapy and after anti-HER treatment with pertuzumab, trastuzumab and lapatinib and with extensive symptomatic involvement of the lungs and pleura. Treatment with trastuzumab deruxtecan in this patient in the third line of palliative treatment resulted in a partial remission and significant clinical improvement. So far, the effect lasts 18 months and we continue the maintenance treatment with the same dose 5.4 mg/kg body weight. We did not observe any serious G3/4 manifestations of either cardiac or hematological toxicity. Treatment with trastuzumab deruxtecan is a very effective option with acceptable toxicity even in heavily pretreated patients.
- Klíčová slova
- Transtuzumab deruxtexan,
- MeSH
- antracykliny terapeutické užití MeSH
- dospělí MeSH
- geny erbB-2 * účinky léků MeSH
- humanizované monoklonální protilátky škodlivé účinky terapeutické užití MeSH
- kardiotoxicita diagnostické zobrazování farmakoterapie prevence a kontrola MeSH
- lidé MeSH
- nádory pánve radioterapie sekundární MeSH
- nádory plic radioterapie sekundární MeSH
- nádory prsu * chirurgie diagnóza farmakoterapie genetika MeSH
- přežití MeSH
- taxoidy terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Imunoterapie checkpoint inhibitory prokázala pozoruhodný přínos v léčbě řady onkologických diagnóz včetně karcinomu plic. Standardně je indikována léčba inhibitory receptoru programované buněčné smrti 1 / ligandu programované buněčné smrti 1 (programmed cell death protein 1 / programmed cell death-ligand 1, PD-1/PD-LI) v monoterapii, jako kombinovaná imunoterapie s inhibitory cytotoxického antigenu 4 asociovaného s T lymfocyty (cytotoxic T-lymphocyte antigen 4, CTLA-4) nebo v kombinaci s jinými léčebnými modalitami, např. chemoterapií či radioterapií. Tento článek si klade za cíl představit aktuální možnosti léčby karcinomu plic durvalumabem - pětiletá data studie PACIFIC a tříletá data studie CASPIAN.
Immunotherapy with checkpoint inhibitors has demonstrated remarkable therapeutic benefits in many oncological diagnoses, including lung cancer. Treatment with programmed cell death protein 1 / programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors can be indicated in various ways: as monotherapy, combination immunotherapy with cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors or in combination with other treatment modalities as chemotherapy or radiotherapy. This article aims to present current treatment options of lung cancer with durvalumab - the five-year data of the PACIFIC trial and the three-year data of the CASPIAN trial.
- Klíčová slova
- durvalumab,
- MeSH
- analýza přežití MeSH
- imunoterapie MeSH
- klinické zkoušky, fáze III jako téma MeSH
- kombinovaná farmakoterapie MeSH
- lidé MeSH
- monoklonální protilátky aplikace a dávkování ekonomika MeSH
- multicentrické studie jako téma MeSH
- nádory plic * farmakoterapie radioterapie MeSH
- protinádorové látky imunologicky aktivní * aplikace a dávkování ekonomika MeSH
- randomizované kontrolované studie jako téma MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- MeSH
- lidé MeSH
- nádory plic * radioterapie MeSH
- protonová terapie * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Radioterapie je klíčovou léčebnou modalitou v léčbě karcinomu plic napříč všemi stadii. V průběhu nemoci je radioterapie klinicky přínosná až u 77 % pacientů.1 Celosvětově je ovšem „prozářenosť daleko nižší, v České republice absolvuje radioterapii zhruba 25 % pacientů s bronchogenním karcinomem.2 Pokročilé techniky radioterapie, jako jsou IMRT (intensity modulated radiotherapy) a IGRT se zohledněním dýchacích pohybů (image guided radiotherapy), umožňují redukovat dávku na srdce a zdravou plíci, snižují riziko postradiační pneumonitidy a prodlužují přežití.3
Radiotherapy is the basic treatment modality in lung cancer across all its stages. There is a therapeutic benefit in settings up to 77 per cent, but the worldwide use is lower, in the Czech Republic about 25 percent. The advanced radiotherapeutic techniques, such as IMRT (intensity modulated radiotherapy) and IGRT with monitoring of respiratory motion (image guided radiotherapy), enable to reduce a dose to the organs at risk (heart, contralateral lung), the risk of pneumonitis and they prolong the survival.
- MeSH
- adenokarcinom plic diagnostické zobrazování farmakoterapie radioterapie MeSH
- celková dávka radioterapie MeSH
- chemoradioterapie metody MeSH
- frakcionace dávky záření MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- malobuněčný karcinom plic farmakoterapie radioterapie MeSH
- nádory plic * farmakoterapie radioterapie MeSH
- nemalobuněčný karcinom plic farmakoterapie radioterapie MeSH
- paliativní péče metody MeSH
- radioterapie * metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- chemoradioterapie metody MeSH
- lidé MeSH
- nádory plic * farmakoterapie radioterapie MeSH
- radioterapie metody MeSH
- Check Tag
- lidé MeSH
Plicní karcinomy jsou celosvětově nejčastěji diagnostikovanými nádorovými onemocněními. Radioterapie může být indikována v jejich léčebném algoritmu za určitých okolností v jakémkoliv stadiu onemocnění s odpovídajícím léčebným záměrem. Jedná se o velmi dynamicky se rozvíjející disciplínu, která promptně zařazuje do svých léčebných postupů nejmodernější zobrazovací metody, nejnovější poznatky z radiobiologie a rovněž moderní technologie sloužící k přesnému dodání dávky do cílového objemu.
Lung cancers are the most commonly diagnosed cancers worldwide. Radiotherapy may be indicated in their treatment algorithm under certain circumstances at any stage of the disease with an appropriate treatment intent. It is a very dynamically developing discipline that promptly adopts the most modern imaging methods, the latest radiobiological knowledge, as well as modern technology used to accurately deliver the dose to the target volume.
BACKGROUND: Autophagy is a crucial factor contributing to radioresistance during radiotherapy. Although Lys05 has proven its ability to improve the results of radiotherapy through the inhibition of autophagy, molecular mechanisms of this inhibition remain elusive. We aimed to describe the molecular mechanisms involved in Lys05-induced inhibition of autophagy. MATERIALS AND METHODS: Radioresistant human non-small cell lung carcinoma cells (H1299, p53-negative) and methods of quantitative phosphoproteomics were employed to define the molecular mechanisms involved in Lys05-induced inhibition of autophagy. RESULTS: We confirmed that at an early stage after irradiation, autophagy was induced, whereas at a later stage after irradiation, it was inhibited. The early-stage induction of autophagy was characterized mainly by the activation of biosynthetic and metabolic processes through up- or down-regulation of the critical autophagic regulatory proteins Sequestosome-1 (SQSTM1) and proline-rich AKT1 substrate 1 (AKT1S1). The late-stage inhibition of autophagy was attributed mainly to down-regulation of Unc-51 like autophagy-activating kinase 1 (ULK1) through phosphorylation at Ser638. CONCLUSION: This work contributes to emerging phosphoproteomic insights into autophagy-mediated global signaling in lung cancer cells, which might consequently facilitate the development of precision medicine therapeutics.
- MeSH
- aminochinoliny farmakologie MeSH
- autofagie * MeSH
- fosfoproteiny analýza metabolismus MeSH
- fosforylace MeSH
- lidé MeSH
- nádorové buňky kultivované MeSH
- nádory plic farmakoterapie metabolismus patologie radioterapie MeSH
- nemalobuněčný karcinom plic farmakoterapie metabolismus patologie radioterapie MeSH
- polyaminy farmakologie MeSH
- proteom analýza metabolismus MeSH
- radiosenzibilizující látky farmakologie MeSH
- signální transdukce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
