1. Treatment patterns and real-world evidence for stage III non-small cell lung cancer in Central and Eastern EuropeMilada Zemanova, Marko Jakopović, Karmen Stanič, Małgorzata Łazar-Poniatowska, Martina Vrankar, Petronela Rusu, Tudor Ciuleanu, Davorin Radosavljevic, Krisztina Bogos, Sergiusz Nawrocki, 2020, original scientific article Abstract: The aim of this project was to collect real-world evidence and describe treatment patterns for stage III non-small cell lung cancer in Central and Eastern Europe. Based on real-world evidence, an expert opinion was developed, and the unmet needs and quality indicators were identified. Patients and methods. A systematic literature search and a multidisciplinary expert panel of 10 physicians from 7 countries used a modified Delphi process to identify quality indicators and unmet needs in patients with stage III non-small cell lung cancer. The profound questionnaire was used to characterize treatment patterns used for stage III non-small cell lung cancer, and a systematic review identified patterns in Central and Eastern Europe. The first questionnaire was completed by a group of medical oncologists, radiation oncologists and pneumologists. The panel of experts attended an in-person meeting to review the results of the questionnaire and to process a second round Delphi. An additional survey was then compiled and completed by the panel. Results. A complete consensus was reached by the panel of experts on a set of evidence-based clinical recommendations. The experience-based questionnaire generated a highly variable map of treatment patterns within the region. A list of unmet needs and barriers to quality care were developed with near-unanimous consent of the panel of experts. Conclusions. The current landscape of diagnostic and therapeutic approaches in Central and Eastern European countries is highly variable. We identified several significant barriers, mainly related to the availability of diagnostic and imaging methods and low rates of chemoradiotherapy with curative intention as initial treatment for unresectable stage III NSCLC.
Keywords: non-small cell lung cance, stage III, treatment patterns, Delphi method
Published in DiRROS: 16.07.2024; Views: 18; Downloads: 7
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2. 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 immunotherapyKarmen Stanič, Martina Vrankar, Jasna But-Hadžić, 2020, original scientific article Abstract: 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.
Keywords: radiotherapy, small lung cancer, clinical cases, immunotherapy
Published in DiRROS: 16.07.2024; Views: 10; Downloads: 4
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3. ▫$[^{18}\mathrm F]$▫FDG PET immunotherapy radiomics signature (iRADIOMICS) predicts response of non-small-cell lung cancer patients treated with pembrolizumabDamijan Valentinuzzi, Martina Vrankar, Nina Boc, Valentina Ahac, Žiga Zupančič, Mojca Unk, Katja Škalič, Ivana Žagar, Andrej Studen, Urban Simončič, Jens C. Eickhoff, Robert Jeraj, 2020, original scientific article Keywords: medical physics, medical imaging, oncology
Published in DiRROS: 15.07.2024; Views: 44; Downloads: 7
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5. Immune RECIST criteria and symptomatic pseudoprogression in non-small cell lung cancer patients treated with immunotherapyMartina Vrankar, Mojca Unk, 2018, review article Abstract: Uncommon responses during immunotherapy is a new challenging issue in oncology practice. Recently, new criteria for evaluation of response to immunotherapy immune response evaluation criteria solid tumors (iRECIST) were accepted. According to iRECIST, worsening of performance status (PS) accompanied to pseudoprogression reflects most probably the true progression of the malignant disease. Methods. A systematic review of the literature was made by using several electronic database with the following search criteria: symptomatic pseudoprogression, atypical response, immunotherapy and lung cancer. Results. In the literature, we identified five reports of seven patients treated with immunotherapy that met the inclusion criteria. We also report our experience of patient with pseudoprogression and almost complete response after one dose of immunotherapy. Conclusions. As seen from our review, iRECIST criteria might be insufficient in distinguishing true progression from pseudoprogression in some patients with advanced NSCLC treated with immunotherapy. More precise assessment methods are urgently needed.
Keywords: symptomatic pseudoprogression, atypical response, immunotherapy, lung cancer
Published in DiRROS: 11.06.2024; Views: 94; Downloads: 31
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6. Long-term survival of locally advanced stage III non-small cell lung cancer patients treated with chemoradiotherapy and perspectives for the treatment with immunotherapyMartina Vrankar, Karmen Stanič, 2018, original scientific article Abstract: Standard treatment for patients with inoperable locally advanced non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (CCRT). Five-year overall survival rates range between 15 and 25%, while long term survival data are rarely reported. Patients and methods A total of 102 patients with stage III NSCLC treated between September 2005 and November 2010 with induction chemotherapy and CCRT were included in this long term survival analysis. All patients were tested for PD-L1 status and expression of PD-L1 was correlated with overall survival (OS), progression free survival (PFS) and toxicities. Results The median OS of all patients was 24.8 months (95% CI 18.7 to 31.0) with 10 year-survival rate of 11.2%. The median OS of patients with PD-L1 expression was 12.1 months (95% CI 0.1 to 26.2), while in patients with negative or unknown PD-L1 status was significantly longer, 25.2 months (95% CI 18.9 to 31.6), p = 0.005. The median PFS of all patients was 16.4 months (95% CI 13.0 to 19.9). PFS of patients with PD-L1 expression was 10.1 months (95% CI 0.1 to 20.4) and in patients with negative or unknown PD-L1 status was 17.9 months (95% CI 14.2 to 21.7), p = 0.003. Conclusions 10-year overall survival of stage III NSCLC patients after CCRT is 11.2%. PFS and OS differ with regard to PD-L1 status and are significantly shorter for patients with PD-L1 expression. New treatment with check-point inhibitors combined with RT therefore seems reasonable strategy to improve these results.
Keywords: NSCLC, non-small cell lung cancer, locally advanced, immunotherapy, chemoradiotherapy
Published in DiRROS: 10.06.2024; Views: 91; Downloads: 60
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7. Intercalated chemotherapy and erlotinib for advanced NSCLC : high proportion of complete remissions and prolonged progression-free survival among patients with EGFR activating mutationsMatjaž Zwitter, Karmen Stanič, Mirjana Rajer, Izidor Kern, Martina Vrankar, Natalija Edelbaher, Viljem Kovač, 2014, original scientific article Abstract: Background. Pharmaco-dynamic separation of cytotoxic and targeted drugs might avoid their mutual antagonistic effect in the treatment of advanced non-small cell lung cancer (NSCLC). Patients and methods. Eligible patients were treatment-naive with stage IIIB or IV NSCLC. In addition, inclusion was limited to never-smokers or light smokers or, after 2010, to patients with activating epidermal growth-factor receptor (EGFR) mutations. Treatment started with 3-weekly cycles of gemcitabine and cisplatin on days 1, 2 and 4 and erlotinib on days 5 to 15. After 4 to 6 cycles, patients continued with erlotinib maintenance. Results. Fifty-three patients were recruited into the trial: 24 prior to 2010 (of whom 9 were later found to be positive for EGFR mutations), and 29 EGFR mutation-positive patients recruited later. Unfavourable prognostic factors included stage IV disease (51 patients - 96%), performance status 2%3 (11 patients - 21%) and brain metastases (15 patients - 28%). Grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. The 15 EGFR negative patients had 33% objective response rate, median progression-free survival (PFS) 6.0 months and median survival 7.6 months. Among 38 EGFR positive patients, complete response (CR) or partial response (PR) were seen in 16 (42.1%) and 17 (44.7%) cases, respectively. PET-CT scanning was performed in 30 patients and confirmed CR and PR in 16 (53.3%) and 9 (30.0%) cases, respectively. Median PFS for EGFR mutated patients was 21.2 months and median survival was 32.5 months. Conclusions. While patients with EGFR negative tumors do not benefit from addition of erlotinib, the intercalated schedule appears most promising for those with EGFR activating mutations.
Keywords: non-small cell lung cancer, EGFR activating mutations, gemicitabine, erlotinib
Published in DiRROS: 11.04.2024; Views: 268; Downloads: 86
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8. Induction gemcitabine in standard dose or prolonged low-dose with cisplatin followed by concurrent radiochemotherapy in locally advanced non-small cell lung cancer : a randomized phase II clinical trialMartina Vrankar, Matjaž Zwitter, Tanja Bavčar-Vodovnik, Ana Milič, Viljem Kovač, 2014, original scientific article Abstract: The optimal combination of chemotherapy with radiation therapy for treatment locally advanced non-small cell lung cancer (NSCLC) remains an open issue. This randomized phase II study compared gemcitabine in two different schedules and cisplatin - as induction chemotherapy, followed by radiation therapy concurrent with cisplatin and etoposid. Patients and methods. Eligible patients had microscopically confirmed inoperable non-metastatic non-small cell lung cancer; fulfilled the standard criteria for platin-based chemotherapy; and signed informed consent. Patients were treated with 3 cycles of induction chemotherapy with gemcitabine and cisplatin. Two different aplications of gemcitabine were compared: patients in arm A received gemcitabine at 1250 mg/m2 in a standard half hour i.v. infusion on days 1 and 8; patients in arm B received gemcitabine at 250 mg/m2 in prolonged 6-hours i.v. infusion on days 1 and 8. In both arms, cisplatin 75 mg/m2 on day 2 was administered. All patients continued treatment with radiation therapy with 60-66 Gy concurrent with cisplatin 50 mg/m2 on days 1, 8, 29 and 36 and etoposid 50 mg/m2 on days 1-5 and 29-33. The primary endpoint was response rate (RR) after induction chemotherapy; secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). Results. From September 2005 to November 2010, 106 patients were recruited to this study. No statistically signifficant differences were found in RR after induction chemotherapy between the two arms (48.1% and 57.4%, p = 0.34). Toxicity profile was comparable and mild with grade 3/4 neutropenia as primary toxicity in both arms. One patient in arm B suffered from acute peripheral ischemia grade 4 and an amputation of lower limb was needed. With a median follow-up of 69.3 months, progression-free survival and median survival in arm A were 15.7 and 24.8 months compared to 18.9 and 28.6 months in arm B. The figures for 1- and 3-year overall survival were 73.1% and 30.8% in arm A, and 81.5 % and 44.4% in arm B, respectively. Conclusions. Among the two cisplatin-based doublets of induction chemotherapy for inoperable NSCLC, both schedules of gemcitabine have a comparable toxicity profile. Figures for RR, PFS and OS are among the best reported in current literature. While there is a trend towards better efficacy of the treament with prolonged infusion of gemcitabine, the difference between the two arms did not reach statistical significance
Keywords: induction chemotherapy, non-small cell lung cancer, radiation therapy, randomized clinical trial
Published in DiRROS: 11.04.2024; Views: 439; Downloads: 319
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9. Priporočila za obravnavo bolnikov s pljučnim rakomMartina Vrankar, Nina Boc, Izidor Kern, Aleš Rozman, Karmen Stanič, Tomaž Štupnik, Mojca Unk, Maja Ebert Moltara, Vesna Zadnik, Katja Adamič, Jernej Benedik, Marko Bitenc, Jasna But-Hadžić, Anton Crnjac, Marina Čakš, Dominik Časar, Eva Ćirić, Tanja Čufer, Ana Demšar, Rok Devjak, Goran Gačevski, Marta Globočnik Kukovica, Kristina Gornik-Kramberger, Maja Ivanetič Pantar, Marija Ivanović, Urška Janžič, Staša Jelerčič, Veronika Kloboves-Prevodnik, Mile Kovačević, Luka Ležaič, Mateja Marc-Malovrh, Katja Mohorčič, Loredana Mrak, Igor Požek, Nina Turnšek, Bogdan Vidmar, Dušanka Vidovič, Gregor Vlačić, Ana Lina Vodušek, Rok Zbačnik, Ivana Žagar, 2023, professional article Abstract: Leta 2019 so bila objavljena Priporočila za obravnavo bolnikov s pljučnim rakom, ki so v slovenski prostor vnesla prepotrebno poenotenje diagnostike in zdravljenja z namenom izboljšanja preživetja bolnikov s pljučnim rakom. Posodobitev Priporočil tri leta po izidu izvirnika prinaša največ novosti v poglavju o sistemskem zdravljenju bolnikov s pljučnim rakom. To kaže na izjemen napredek na področju razumevanja onkogeneze in biologije pljučnega raka ter s tem razvoja novih zdravil. Breme pljučnega raka ostaja veliko, saj je pljučni rak pri nas in v svetu še vedno najpogostejši vzrok smrti zaradi raka. Za vsako peto smrt zaradi raka je odgovoren pljučni rak. Skoraj tretjina bolnikov s pljučnim rakom ne prejme specifičnega onkološkega zdravljenja, bodisi zaradi slabega stanja zmogljivosti, spremljajočih bolezni ali obsega bolezni. Polovica bolnikov ima ob diagnozi razsejano bolezen, zaradi česar izboljšanje preživetja z malimi koraki sledi napredku v zdravljenju bolnikov s pljučnim rakom. Ti podatki nas opominjajo, da se bomo morali za velike premike v obravnavi bolnikov s pljučnim rakom lotiti drugačnih pristopov. Kot najbolj obetavno se ponuja zgodnje odkrivanje bolezni, ko so možnosti ozdravitve pljučnega raka najboljše. Zapisana Priporočila so usmeritev za obravnavo bolnikov s pljučnim rakom. Le s sodobnim multidisciplinarnim pristopom obravnave lahko bolniku ponudimo zdravljenje, ki mu omogoča najboljši izhod prognostično neugodne bolezni.
Keywords: pljučni rak, priporočila
Published in DiRROS: 27.07.2023; Views: 594; Downloads: 234
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10. Fizikalni modeli imunoterapije in radioterapijeDamijan Valentinuzzi, Martina Vrankar, Katja Uršič Valentinuzzi, Mojca Unk, Olga Gordeeva, Alen Hadžić, Gregor Serša, Maja Čemažar, Robert Jeraj, 2023, published scientific conference contribution Abstract: V prispevku bomo predstavili rezultate fizikalnih modelov imunoterapije, ki smo jih razvili v programski skupini Medicinska fizika na Fakulteti za matematiko in fiziko Univerze v Ljubljani. Glavni cilj raziskav je bila prepoznava bioloških značilnosti tumorjev, od katerih je odvisen odziv na zdravljenje s protitelesi receptorja programirane celične smrti l (angl. anti-programmed-death-1 (anti-PD-1)). Posebno pozornost smo namenili meritvam modelskih parametrov ter preverbi rezultatov modeliranja, kar je eden izmed predpogojev za uspešno translacijo modeliranja v rutinsko predklinično in klinično prakso. Predstavili bomo tudi načrte za prihodnost, tj. modeliranje kombinacije anti-PD-1 in radioterapije.
Keywords: imunoterapija, radioterapija, medicinska fizika, tumorji
Published in DiRROS: 16.06.2023; Views: 501; Downloads: 138
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