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Iskalni niz: "ključne besede" (non-small-cell lung cancer) .

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1.
Local control and survival after stereotactic body radiation therapy of early-stage lung cancer patients in Slovenia
Karmen Stanič, Jasna But-Hadžić, Jan Žagar, Martina Vrankar, 2023, izvirni znanstveni članek

Povzetek: Background. Stereotactic body radiation therapy (SBRT) precisely and non-invasively delivers ablative radiationdose to tumors in early-stage lung cancer patients who are not candidates for surgery or refuse it. The aim of researchwas to evaluate local control, overall survival (OS), local progression free survival (LPFS), distant metastases free survival(DMFS), disease free survival (DFS) and toxicity in early-stage lung cancer patients treated with SBRT in a single tertiarycancer centre.Patients and methods. We retrospectively evaluated medical records and radiation treatment plan parametersof 228 tumors irradiated in 206 early-stage lung cancer patients between 2016 and 2021 at the Institute of OncologyLjubljana.Results. After 25 months of median follow up, 68 of 206 (33%) patients died. Median OS was 46 months (CI 36 −56),1-year, 2-year and 3-year OS were 87%, 74% and 62% and 5-year OS was 31%. A total of 45 disease progressions havebeen identified in 41 patients. Local progress only was noticed in 5 (2%) patients, systemic progress in 32 (16%) andcombined systemic and local in 4 (2%) patients. Local control rate (LCR) at 1 year was 98%, at 2 and 3 years 96%and 95% at 5 years. The 1-, 2- and 3-year LPFS were 98%, 96% and 94%, respectively and 5-year LPFS was 82%. One,2-, 3- and 5-year DFS w ere 89%, 81%, 72% and 49%, respectively. Among 28 toxicities recorded only one was Grade4 (pneumonitis), all others were Grade 1 or 2. No differences in LCR, LPFS, DFS were found in univariate analysis com-paring patient, tumor, and treatment characteristics. For OS the only statistically significant difference was found inpatients with more than 3 comorbidities compared to those with less comorbidities.Conclusions. Early lung cancer treated with SBRT at single tertiary cancer centre showed that LCR, LPFS, DFS, DMFSand OS were comparable to published studies. Patients with many comorbidities had significantly worse overallsurvival compared to those with less comorbidities. No other significant differences by patient, tumor, or treatmentcharacteristics were found for DMFS, LPFS, and DFS. Toxicity data confirmed that treatment was well tolerated.
Ključne besede: stereotactic body radiotherapy, early-stage lung cancer, lung cancer
Objavljeno v DiRROS: 25.07.2024; Ogledov: 29; Prenosov: 13
.pdf Celotno besedilo (326,62 KB)
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Real-world outcomes, treatment patterns and T790M testing rates in non-small cell lung cancer patients treated with first-line first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors from the Slovenian cohort of the REFLECT study
Nina Turnšek, Rok Devjak, Natalija Edelbaher, Ilonka Osrajnik, Mojca Unk, Dušanka Vidovič, Tina Jerič, Urška Janžič, 2022, izvirni znanstveni članek

Povzetek: Background. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective treatments for EGFR mutation-positive (EGFRm) non-small cell lung cancer (NSCLC). However, routine clinical practice is different between countries/institutions. Patients and methods. The REFLECT study (NCT04031898) is a retrospective medical chart review that explored real-life treatment and outcomes of EGFRm NSCLC patients receiving first-line (1L) first-/second-generation (1G/2G) EGFR TKIs in 8 countries. This study included adult patients with documented advanced/metastatic EGFRm NSCLC with 1L 1G/2G EGFR TKIs initiated between Jan 2015 – Jun 2018. We reviewed data on clinical characteristics, treatments, EGFR/T790M testing patterns, and survival outcomes. Here, we report data from 120 medical charts in 3 study sites from Slovenia. Results. The Slovenian cohort (median age 70 years, 74% females) received 37% erlotinib, 32% afatinib, 31% gefitinib. At the time of data collection, 94 (78%) discontinuations of 1L TKI, and 89 (74%) progression events on 1L treatment were reported. Among patients progressing on 1L, 73 (82%) were tested for T790M mutation yielding 50 (68%) positive results, and 62 (85%) received 2L treatment. 82% of patients received osimertinib. Attrition rate between 1L and 2L was 10%. The median (95% CI) real-world progression free survival on 1L EGFR TKIs was 15.6 (12.6, 19.2) months; median overall survival (95% CI) was 28.9 (25.0, 34.3) months. Conclusions. This real-world study provides valuable information about 1G/2G EGFR TKIs treatment outcomes and attrition rates in Slovenian EGFRm NSCLC patients. The reduced attrition rate and improved survival outcomes empha-size the importance of 1L treatment decision.
Ključne besede: real-world study, non-small cell lung cancer, epidermal growth factor receptor, lung cancer
Objavljeno v DiRROS: 25.07.2024; Ogledov: 19; Prenosov: 6
.pdf Celotno besedilo (543,78 KB)

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Clinical outcomes in stage III non-small cell lung cancer patients treated with durvalumab after sequential or concurrent platinum-based chemoradiotherapy : single institute experience
Martina Vrankar, Karmen Stanič, Staša Jelerčič, Eva Ćirić, Ana Lina Vodušek, Jasna But-Hadžić, 2021, izvirni znanstveni članek

Povzetek: Chemoradiotherapy (ChT-RT) followed by 12-month durvalumab is the new standard treatment for unresectable stage III non-small cell lung cancer. Survival data for patients from everyday routine clinical practice is scarce, as well as potential impact on treatment efficacy of sequential or concomitant chemotherapy and the us-age of gemcitabine.Patients and methods. We retrospectively analysed unresectable stage III NSCLC patients who were treated with durvalumab after radical concurrent or sequential chemotherapy (ChT) from December 2017 and completed treat-ment until December 2020. We assessed progression free survival (PFS), overall survival (OS) and toxicity regarding baseline characteristic of patients.Results. Eighty-five patients with median age of 63 years of which 70.6% were male, 56.5% in stage IIIB and 58.8% with squamous cell carcinoma, were included in the analysis. Thirty-one patients received sequential ChT only, 51 patients received induction and concurrent ChT and 3 patients received concurrent ChT only. Seventy-nine patients (92.9%) received gemcitabine and cisplatin as induction chemotherapy and switched to etoposide and cisplatin during con-current treatment with radiotherapy (RT). Patients started durvalumab after a median of 57 days (range 12–99 days) from the end of the RT and were treated with the median of 10.8 (range 0.5–12 months) months. Forty-one patients (48.2%) completed treatment with planned 12-month therapy, 25 patients (29.4%) completed treatment early due to the toxicity and 16 patients (18.8%) due to the disease progression. Median PFS was 22.0 months, 12- and estimated 24-month PFS were 71% (95% CI: 61.2–80.8%) and 45.8% (95% CI: 32.7–58.9%). With the median follow-up time of 23 months (range 2–35 months), median OS has not been reached. Twelve- and estimated 24-month OS were 86.7% (95% CI: 79.5–93.9%) and 68.6% (95% CI: 57.2–79.9%).Conclusions. Our survival data are comparable with published research as well as with recently published real-world reports. Additionally, the regimen with gemcitabine and platinum-based chemotherapy as induction treatment was efficient and well tolerated.
Ključne besede: non-small cell lung cancer, stage III, chemoradiotherapy, durvalumab, acute toxicity
Objavljeno v DiRROS: 23.07.2024; Ogledov: 9; Prenosov: 5
.pdf Celotno besedilo (394,39 KB)

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Nanoscale transformations of amphiboles within human alveolar epithelial cells
Ruggero Vigliaturo, Maja Jamnik, Goran Dražić, Marjetka Podobnik, Magda Tušek-Žnidarič, Giancarlo Della Ventura, Günther Redhammer, Nada Žnidaršič, Simon Caserman, Reto Gieré, 2022, izvirni znanstveni članek

Povzetek: Amphibole asbestos is related to lung fibrosis and several types of lung tumors. The disease-triggering mechanisms still challenge our diagnostic capabilities and are still far from being fully understood. The literature focuses primarily on the role and formation of asbestos bodies in lung tissues, but there is a distinct lack of studies on amphibole particles that have been internalized by alveolar epithelial cells (AECs). These internalized particles may directly interact with the cell nucleus and the organelles, exerting a synergistic action with asbestos bodies (AB) from a different location. Here we document the near-atomic- to nano-scale transformations induced by, and taking place within, AECs of three distinct amphiboles (anthophyllite, grunerite, “amosite”) with different Fe-content and morphologic features. We show that: (i) an Fe-rich layer is formed on the internalized particles, (ii) particle grain boundaries are transformed abiotically by the internal chemical environment of AECs and/or by a biologically induced mineralization mechanism, (iii) the Fe-rich material produced on the particle surface does not contain large amounts of P, in stark contrast to extracellular ABs, and (iv) the iron in the Fe-rich layer is derived from the particle itself. Internalized particles and ABs follow two distinct formation mechanisms reaching different physicochemical end-states.
Ključne besede: amphiboles, human alveolar epithelial cells, asbestos, lung cancer, nanoscale investigation, acS/TEM-EDXS, dual-EELS, asbestos-related tumors
Objavljeno v DiRROS: 16.07.2024; Ogledov: 60; Prenosov: 27
.pdf Celotno besedilo (4,53 MB)
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Consolidation radiotherapy for patients with extended disease small cell lung cancer in a single tertiary institution : impact of dose and perspectives in the era of immunotherapy
Karmen Stanič, Martina Vrankar, Jasna But-Hadžić, 2020, izvirni znanstveni članek

Povzetek: Consolidation radiotherapy (cRT) in extended disease small cell lung cancer (ED-SCLC) showed improved 2-year overall survival in patients who responded to chemotherapy (ChT) in CREST trial, however results of two meta - analysis were contradictive. Recently, immunotherapy was introduced to the treatment of ED-SCLC, making the role of cRT even more unclear. The aim of our study was to access if consolidation thoracic irradiation improves survival of ED-SCLC patients treated in a routine clinical practice and to study the impact of cRT dose on survival. We also discuss the future role of cRT in the era of immunotherapy. Patients and methods. We retrospectively reviewed 704 consecutive medical records of patients with small cell lung cancer treated at the Institute of Oncology Ljubljana from January 2010 to December 2014 with median follow up of 65 months. We analyzed median overall survival (mOS) of patients with ED-SCLC treated with ChT only and those treated with ChT and cRT. We also compared mOS of patients treated with different consolidation doses and performed univariate and multivariate analysis of prognostic factors. Results. Out of 412 patients with ED-SCLC, ChT with cRT was delivered to 74 patients and ChT only to 113 patients. Patients with cRT had significantly longer mOS compared to patients with ChT only, 11.1 months (CI 10.1%12.0) vs. 7.6 months (CI 6.9%8.5, p < 0.001) and longer 1-year OS (44% vs. 23%, p = 0.0025), while the difference in 2-year OS was not significantly different (10% vs. 5%, p = 0.19). The cRT dose was not uniform. Higher dose with 45 Gy (in 18 fractions) resulted in better mOS compared to lower doses 30%36 Gy (in 10%12 fractions), 17.2 months vs. 10.3 months (p = 0.03) and statistically significant difference was also seen for 1-year OS (68% vs. 30%, p = 0.01) but non significant for 2-year OS (18% vs. 5%, p = 0.11). Conclusions. Consolidation RT improved mOS and 1-year OS in ED-SCLC as compared to ChT alone. Higher dose of cRT resulted in better mOS and 1-year OS compared to lower dose. Consolidation RT, higher number of ChT cycles and prophylactic cranial irradiation (PCI) were independent prognostic factors for better survival in our analysis. For patients who received cRT, only higher doses and PCI had impact on survival regardless of number of ChT cycles received. Role of cRT in the era of immunotherapy is unknown and should be exploited in further trials.
Ključne besede: radiotherapy, small lung cancer, clinical cases, immunotherapy
Objavljeno v DiRROS: 16.07.2024; Ogledov: 77; Prenosov: 34
.pdf Celotno besedilo (458,53 KB)

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Care of patients with non-small-cell lung cancer stage III : the Central European real-world experience
Milada Zemanova, Robert Pirker, Luboš Petruželka, Zuzana Zbozínkova, Mirjana Rajer, Krisztina Bogos, Gunta Purkalne, Vesna Ceriman, Subhash Chaudhary, Igor Richter, 2020, izvirni znanstveni članek

Povzetek: Background. Management of non-small-cell lung cancer (NSCLC) is affected by regional specificities. The present study aimed at determining diagnostic and therapeutic procedures including outcome of patients with NSCLC stage III in the realworld setting in Central European countries to define areas for improvements. Patients and methods. This multicentre, prospective and non-interventional study collected data of patients with NSCLC stage III in a web-based registry and analysed them centrally. Results. Between March 2014 and March 2017, patients (n=583) with the following characteristics were entered: 32% females, 7% never-smokers; ECOG performance status (PS) 0, 1, 2 and 3 in 25%, 58%, 12% and 5%, respectively; 21% prior weight loss; 53% squamous carcinoma, 38% adenocarcinoma; 10% EGFR mutations. Staging procedures included chest X-ray (97% of patients), chest CT (96%), PET-CT (27%), brain imaging (20%), bronchoscopy (89%), endobronchial ultrasound (EBUS) (13%) and CT-guided biopsy (9%). Stages IIIA/IIIB were diagnosed in 55%/45% of patients, respectively. N2/N3 nodes were diagnosed in 60%/23% and pathologically confirmed in 29% of patients. Most patients (56%) were treated by combined modalities. Surgery plus chemotherapy was administered to 20%, definitive chemoradiotherapy to 34%, chemotherapy only to 26%, radiotherapy only to 12% and best supportive care (BSC) to 5% of patients. Median survival and progression-free survival times were 16.8 (15.3;18.5) and 11.2 (10.2;12.2) months, respectively. Stage IIIA, female gender, no weight loss, pathological mediastinal lymph node verification, surgery and combined modality therapy were associated with longer survival. Conclusions. The real-world study demonstrated a broad heterogeneity in the management o f stage III NSCLC in Central European countries and suggested to increase the rates of PET-CT imaging, brain imaging and invasive mediastinal staging.
Ključne besede: diagnostic procedures, multimodality treatment, non-small-cell cancer, lung cancer
Objavljeno v DiRROS: 12.07.2024; Ogledov: 80; Prenosov: 43
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Mobocertinib in patients with EGFR exon 20 insertion-positive non-small cell lung cancer (MOON) : an international real-world safety and efficacy analysis
Oliver Illini, Felix Carl Saalfeld, Petros Christopoulos, Michaël Duruisseaux, Anders Vikström, Nir Peled, Ingel Demedts, Elizabeth Dudnik, Anna Eisert, Urška Janžič, Katja Mohorčič, Marija Ivanović, Sayed M. S. Hashemi, 2024, izvirni znanstveni članek

Povzetek: EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade ≥3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24–45). The response rate in treatment-naïve patients was 27% (95% CI, 8–58). The median progression-free and overall survival was 5 months (95% CI, 3.5–6.5) and 12 months (95% CI, 6.8–17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.
Ključne besede: medicina, non-small cell lung cancer, EGFR exon 20 inhibitors, mobocertinib, real-world data, exon 20 insertion
Objavljeno v DiRROS: 19.06.2024; Ogledov: 111; Prenosov: 73
.pdf Celotno besedilo (1,93 MB)
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