Introduction: As the number of minimally invasive technologies increases in the field of thoracic surgery, so have the number of learning curve analyses performed for these innovations. Variation in learning curve methodology makes between-study comparisons and evidence syntheses difficult. Furthermore, poorly described and reported learning curve analyses make the results difficult to apply to different clinical settings. The objective of this systematic review is to characterize the variability in the methods used to construct and describe learning curves, with the goal of identifying shortcomings and potential areas for improvement in this line of research. Methods: A search of Ovid Medline, Ovid Embase, EBSCO CINAHL, and Web of Science was performed. Studies of learning curves of anatomical lung resection operations in adult patients published in the English language were eligible for inclusion. Two reviewers independently assessed studies for eligibility, and extracted relevant data. Results: The search yielded 56 articles eligible for inclusion in the present review. A variety of methods were used to construct the learning curve, with chronological grouping of cases being the most commonly used technique in 22 (39.29%) studies, followed by the cumulative sum method, employed in 21 (37.50%) studies. A total of 15 unique metrics were used for learning curve analyses; operative time was the most common metric, used in 39 (69.64%) studies. A large proportion of studies failed to provide details on learning curve parameters such as competency thresholds, surgeon’s prior experience, case complexity, and learning curve definition. Considerable heterogeneity was found in the methods and reporting standards of learning curve evaluations in minimally invasive thoracic surgery. Conflicts of Interest: None. Funding Source: Boris Family Centre for Robotic Surgery. / Thesis / Master of Science (MSc)

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24508号 / 医博第4950号 / 新制||医||1064(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 平井 豊博, 教授 武藤 学, 教授 中島 貴子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24879号 / 医博第5013号 / 新制||医||1068(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 後藤 慎平, 教授 渡邊 直樹, 教授 平井 豊博 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

京都大学 / 新制・課程博士 / 博士(人間健康科学) / 甲第23826号 / 人健博第97号 / 新制||人健||7(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 精山 明敏, 教授 椎名 毅, 教授 平井 豊博 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

Background: The standard of care for mediastinal staging during endobronchial ultrasound (EBUS) is Systematic Sampling (SS) where a minimum of 3 lymph node (LN) stations are biopsied, even if they appear normal on imaging. When LNs appear normal on PET and CT, the Canada Lymph Node Score can also identify if they appear normal on EBUS. For these Triple Normal LNs, the pretest probability of malignancy is < 6%, and routine biopsy may not be required. This preliminary study introduced Selective Targeted Sampling (STS), which omits biopsy of Triple Normal LNs and compared it firsthand to SS. Methods: A prospective, feasibility RCT was conducted to determine whether the progression of a definitive trial was warranted. Primary outcomes and their progression criterium were recruitment rate (70% acceptable minimum); procedure length (no overlap between sampling methods’ 95%CIs); and missed nodal metastasis (overlap between sampling methods’ diagnostic accuracy 95%CIs and crossing of the null for the percent difference in diagnosis). cN0-N1 NSCLC patients undergoing EBUS were randomized to the STS or SS arm. Patients in the STS arm were then crossed over to the SS arm to receive standard of care. Wilson’s CI method and McNemar’s test of paired proportions were used for statistical comparison. Surgical pathology was the reference standard. Results: Thirty-eight patients met the eligibility criteria, and all were recruited (100%; 95%CI: 90.82 to 100.00%). The median procedure lengths, in minutes, for STS and SS were 3.07 (95%CI: 2.33 to 5.52) and 19.07 (95%CI: 15.34 to 20.05) respectively. STS had a diagnostic accuracy of 100% (95%CI: 74.65% to 100.00%), whereas SS was 93.75% (95%CI: 67.71% to 99.67%) with the inclusion of inconclusive results. Percent difference in diagnosis between sampling method was 5.35% (95%CI: -0.54% to 11.25%). Conclusion: With the progression criteria successfully met, a subsequent multicentered, non-inferiority crossover trial comparing STS to SS is warranted. / Thesis / Master of Science (MSc) / Before deciding on treatment for patients with lung cancer, a critical step in the investigations is finding out whether the lymph nodes in the chest contain cancer. This is best done with a needle that biopsies those lymph nodes through the walls of the airway, known as endobronchial ultrasound transbronchial needle aspiration. Guidelines require that every lymph node in the chest be biopsied through a process called Systematic Sampling. However, new research has suggested that some lymph nodes may not need a biopsy. These lymph nodes are ones with a very low chance of cancer, based on their imaging tests. In this study, Selective Targeted Sampling was introduced whereby lymph nodes that appeared normal were not initially biopsied. The study followed a feasibility design, which proved sufficient patient interest, adequate safety and possible benefits in pursuing a larger trial comparing Selective Targeted Sampling to Systematic Sampling.

[ES] El cáncer de pulmón no microcítico (CPNM) representa un 80% de los casos de cáncer de pulmón, siendo uno de los tipos de cáncer más frecuentes y mortales. El tratamiento con inmunoterapia ha mejorado significativamente el pronóstico de los pacientes en las últimas décadas. No obstante, no todos los pacientes responden al tratamiento, por lo que se necesitan nuevos biomarcadores para predecir qué pacientes se podrían beneficiar de la inmunoterapia. El principal objetivo de esta tesis es obtener nuevos biomarcadores no invasivos para pacientes de CPNM avanzado tratados con inmunoterapia. Se incluyeron 52 pacientes de CPNM en estadios avanzados tratados con anti-PD1 o anti-PD1 en combinación con quimioterapia (anti-PD1+CT) en primera línea. Se analizaron biomarcadores no invasivos en muestras de sangre periférica, obtenidas antes del tratamiento y en la primera evaluación de respuesta. Los biomarcadores analizados en este estudio fueron: i) parámetros hematológicos e inmunológicos, ii) expresión de genes inmunoreguladores en células mononucleares de sangre periférica (PBMCs), iii) repertorio de TCR-ß y iv) genotipo de HLA. También se analizaron 13 controles sanos, y se observó que los pacientes con CPNM presentaron menores niveles de expresión de genes relacionados con las células T. Además, los pacientes con CPNM tenían menor número de clones de TCR-ß. Se analizó el valor predictivo y pronóstico de los potenciales biomarcadores independientemente en pacientes tratados con anti-PD1 o anti-PD+CT. Se encontraron biomarcadores con valor pronóstico, bien en las muestras basales o en las muestras tomadas en la primera evaluación de respuesta. Al utilizar muestras no invasivas, también se pudo estudiar la dinámica de los biomarcadores a lo largo del tratamiento, observando que algunos cambios ocurrían de manera diferencial en pacientes respondedores o dependiendo del tratamiento. La integración de los datos de las variables analizadas ha resultado en una propuesta de un modelo multivariante capaz de predecir qué pacientes tendrán mejor pronóstico, en el subgrupo de pacientes tratados con anti-PD1. Además, se crearon dos inmunogramas no invasivos incluyendo los ratios de los biomarcadores entre muestras tomadas antes y durante el tratamiento. Estos modelos se realizaron específicamente para cada tipo de tratamiento, y podrían ser útiles para monitorizar la respuesta durante el tratamiento. Este estudio resalta el papel de la biopsia líquida como una herramienta no invasiva para analizar biomarcadores de forma integral que permiten caracterizar y monitorizar el estatus inmune en pacientes con CPNM tratados con inmunoterapia o quimioinmunoterapia. / [CA] El càncer de pulmó no microcític (CPNM) representa un 80% dels casos de càncer de pulmó, i és un dels tipus de càncer més freqüents i mortals. El tractament amb immunoteràpia ha millorat significativament el pronòstic dels pacients en les últimes dècades. Malgrat això, no tots el pacients responen, per la qual cosa es necessiten nous biomarcadors per predir què pacients es beneficiaran del tractament amb immunoteràpia. El principal objectiu d'aquesta tesi és obtindre nous biomarcadors no invasius per a pacients de CPNM avançat tractats amb immunoteràpia. Es van incloure 52 pacients de CPNM en estadis avançats tractats amb anti-PD1 o anti-PD1 en combinació amb quimioteràpia (anti-PD1+CT) en primera línia. Es van analitzar biomarcadors no invasius a partir de mostres de sang perifèrica, que es van obtindre abans del tractament i en la primera avaluació de resposta. Els potencials biomarcadors analitzats en aquest estudi van ser: i) paràmetres hematològics i immunològics, ii) expressió de gens immunoreguladors en cèl·lules mononuclears de sang perifèrica (PBMCs), iii) repertori de TCR-ß i iv) genotip d'HLA. També es van analitzar 13 controls sans, i es va observar que els pacients amb CPNM presentaven menors nivells d'expressió de gens relacionats amb les cèl·lules T. A més, els pacients amb CPNM tenien menor riquesa de repertori de TCR-ß. S'han analitzat el valor predictiu i pronòstic dels potencials biomarcadors independentment en pacients tractats amb anti-PD1 o anti-PD1+CT. S'han trobat biomarcadors amb valor pronòstic, bé en les mostres basals o en les mostres preses en la primera avaluació de resposta. Com s'han utilitzat mostres no invasives, també s'ha pogut analitzar la dinàmica dels biomarcadores al llarg del tractament, i s'han observat canvis específics de pacients responedors o del tipus de tractament. La integració de les variables analitzades ha resultat en una proposta d'un model multivariant capaç de predir quins pacients amb CPNM tindran millor pronòstic, en el subgrup de pacients tractats amb anti-PD1. També s'han fet dos immunograms no invasius incloent els ràtios dels biomarcadors entre mostres preses abans i durant el tractament. Aquests models son específics per a cada tipus de tractament, i podrien ser útils per a monitorar la resposta durant el tractament. Aquest estudi ressalta el paper de la biòpsia líquida com una eina no invasiva per a analitzar biomarcadors de forma integral que permeten caracteritzar i monitorar l'estatus immune en pacients amb CPNM tractats amb immunoteràpia o quimioimmunoteràpia. / [EN] Non-Small Cell Lung Cancer (NSCLC) represents 80% of lung cancer cases, being one of the most frequent and death causing cancers. Recently developed treatments with immunotherapy have improved patient prognosis. However, a significant number of patients do not respond to treatment, thus there is an urgent need for biomarkers to predict which patients will benefit from immunotherapy. The main objective of this thesis was to obtain novel non-invasive biomarkers for advanced-stage NSCLC patients treated with immunotherapy. This study included 52 advanced-stage NSCLC patients treated with Anti-PD1 or Anti-PD1 in combination with chemotherapy (Anti-PD1+CT) in the first line setting. Non-invasive biomarkers were analysed using peripheral blood samples, which were obtained before first cycle and at first response assessment. The potential biomarkers analysed in this study were: i) haematological and immunological parameters, ii) immune-related gene expression analysed on Peripheral Blood Mononuclear Cells (PBMCs), iii) TCR-ß repertoire, and iv) HLA genotype. 13 healthy subjects were also included in this study. NSCLC patients presented lower T cell related gene expression levels than controls. Furthermore, cancer patients had a lower number of unique TCR-ß clones. We have assessed the predictive and prognostic value of the analysed variables independently on patients treated with anti-PD1 or anti-PD1+CT. We found prognostic biomarkers that could be useful to identify patients who benefit from treatment. Since we used non-invasive samples, we also observed differences in immune-related biomarkers at first response assessment in patients responding to treatment. In addition, biomarker dynamics were useful to identify changes occurring throughout treatment. The integration of data from the analysed variables has resulted in a proposal of a multivariate model capable of predicting patients with improved outcomes to treatment with anti PD1 therapy. Moreover, we have developed two non-invasive inmunograms including the ratios of on- and pre-treatment samples, which could be useful to monitor patients throughout treatment. Altogether, this study highlights the role of non-invasive biomarkers to characterize and monitor immune status in NSCLC patients treated with immunotherapy or chemoimmunotherapy. / This Thesis was supported by the following grants: Fundación Científica Asociación Española Contra el Cáncer. PRDVA18015MORE; Centro de Investigación Biomédica en Red Cáncer. Project B16/12/00350 e Instituto de Salud Carlos III: PI18/00266 / Moreno Manuel, A. (2024). Non-Invasive Immunogram. A Multidimensional Approach to Characterize and Monitor Immune Status in Non-Small Cell Lung Cancer [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/204490

Είναι ευρέως αποδεκτό και καλά τεκμηριωμένο ότι ο υποδοχέας του επιδερμικού αυξητικού παράγοντα (epidermal growth factor receptor, EGFR) ελέγχει σημαντικές λειτουργίες των καρκινικών κυττάρων, όπως τον πολλαπλασιασμό και την απόπτωση, αλλά και διαδικασίες όπου συμμετέχουν περισσότεροι του ενός τύποι κυττάρων, όπως τη διήθηση και την αγγειογένεση. Μεταξύ των τύπων καρκίνου, στην ανάπτυξη των οποίων συμμετέχει ο EGFR, είναι και ο μη μικροκυτταρικός καρκίνος του πνεύμονα (ΜΜΚΠ). Πολύ πρόσφατα δεδομένα δείχνουν ότι ένα άλλο μόριο που εμπλέκεται στην ανάπτυξη του καρκίνου του πνεύμονα είναι το Notch. Ο ρόλος του είναι περίπλοκος και διττός: Έχει προταθεί ότι το Notch επάγει την ανάπτυξη του ΜΜΚΠ και αναστέλλει την ανάπτυξη του μικροκυτταρικού καρκίνου του πνεύμονα (ΜΚΠ). Επιπλέον, έχει βρεθεί ότι το μονοπάτι μεταγωγής σήματος του Notch επηρεάζει, αλλά και επηρεάζεται από άλλα μόρια. Στην παρούσα μεταπτυχιακή εργασία διερευνήθηκε ο ρόλος του EGFR και του Notch στην ανάπτυξη κυττάρων ΜΜΚΠ χρησιμοποιώντας τον προσδέτη του EGFR, EGF και τον αναστολέα της γ-σεκρετάσης DAPT. Για τη διεξαγωγή των πειραμάτων χρησιμοποιήθηκαν οι ανθρώπινες καρκινικές κυτταρικές σειρές ΜΜΚΠ Η23, Α549, Η661 και ΗCC827. Οι κυτταρικές σειρές Η23, Α549 και Η661 εκφράζουν τον αγρίου τύπου (wild type, wt) EGFR και η κυτταρική σειρά HCC827 εκφράζει EGFR που φέρει τη μετάλλαξη (mutation) (DE746- A750). Αρχικά με ανάλυση κατά western μελετήθηκε το προφίλ των κυττάρων ως προς τα επίπεδα έκφρασης του ενδοκυττάριου τμήματος του Notch (Notch Intracellular Domain, NICD). Βρέθηκε ότι τα κύτταρα Η23 εκφράζουν τα υψηλότερα επίπεδα Notch ICD, τα κύτταρα Η661 και HCC827 μέτρια επίπεδα και τα κύτταρα Α549 τα χαμηλότερα. Στη συνέχεια με τη μέθοδο του ΜΤΤ έγινε έλεγχος του DAPT στον πολλαπλασιασμό των κυττάρων και βρέθηκε ότι τα κύτταρα Η661 είχαν τη μεγαλύτερη αναστολή, παρόμοια συμπεριφορά έδειξαν και τα Α549. Τα κύτταρα Η23 εμφάνισαν μικρότερη ανταπόκριση σε σχέση με τα Η661 ενώ τα κύτταρα HCC827 εμφανίστηκαν ανθεκτικά στο DAPT. Η ανασταλτική δράση του DAPT στα κύτταρα Η661 συνοδεύτηκε με επαγωγή της απόπτωσης η οποία προσδιορίστηκε με τη μέθοδο αννεξίνης V καθώς και με επαγωγή της αυτοφαγίας η οποία ανιχνεύτηκε κάνοντας ανάλυση κατά western για τα πρωτεϊνικά επίπεδα της beclin-1. Περαιτέρω τα κύτταρα ενεργοποιήθηκαν με EGF και εν συνεχεία προστέθηκε DAPT. Παρατηρήθηκε ότι στα κύτταρα Η23 η προσθήκη του EGF δεν επέτρεψε να δράσει ανασταλτικά το DAPT ενώ στα Η661 εν μέρει ο EGF αντέστρεψε την ανασταλτική δράση του DAPT. Επιλέγοντας τις κυτταρικές σειρές Η23 και Η661, μελετήθηκε η δράση του DAPT και του EGF στα επίπεδα του Notch ICD. Παρατηρήθηκε ότι στα κύτταρα Η23, το DAPT μείωσε με χρονοεξαρτώμενο τρόπο τα πρωτεϊνικά επίπεδα του Notch ICD μέχρι και 6 ώρες μετά την προσθήκη του στα κύτταρα ενώ 24 ώρες μετά το φαινόμενο αντιστράφηκε. Η προσθήκη του EGF δεν επηρέασε τα επίπεδα του Notch ICD σε καμία από τις χρονικές στιγμές που μελετήθηκαν. Στα Η661 κύτταρα το DAPT προκάλεσε χρονοεξαρτώμενη μείωση των επιπέδων Notch ICD η οποία διήρκησε μέχρι και 24 ώρες μετά τη προσθήκη του DAPT. Ο EGF όπως και προηγουμένως δεν επηρέασε τα επίπεδα του Notch ICD. Παρατηρώντας ότι στα Η661 το DAPT ασκεί δράση με μεγαλύτερη διάρκεια σε σχέση με τα κύτταρα Η23, τα κύτταρα Η661 ενεργοποιήθηκαν με EGF και στη συνέχεια προστέθηκε το DAPT προκειμένου να δούμε τη δράση του συνδυασμού στα επίπεδα του Notch ICD. Βρέθηκε ότι ο EGF αντέστρεψε την μείωση των Notch ICD επιπέδων που προκαλεί μόνο του το DAPT. Τα αποτελέσματα αναδεικνύουν ότι τα μονοπάτια του EGFR και του Notch, συνηγορούν προς την ίδια κατεύθυνση για τη μείωση του όγκου και αυτό υποδηλώνει έναν ελκυστικό δρόμο συνδυαστικών προσεγγίσεων για τη θεραπεία του ΜΜΚΠ, που μπορεί να ενισχύσει τη δράση των ανασταλτικών παραγόντων του EGFR σε όγκους. Συμπερασματικά, θα μπορούσαμε να υποθέσουμε ότι στο ΜΜΚΠ: α) τα δύο μονοπάτια EGFR και Notch συνεπικουρούν για την ανάπτυξη του όγκου, β) η αναστολή του Notch είναι πιο αποτελεσματική σε κύτταρα με ενδιάμεσα επίπεδα ενεργού Notch 1, προκαλώντας τόσο απόπτωση όσο και αυτοφαγία, και γ) η μετάλλαξη του EGFR προσφέρει αντίσταση στη δράση αναστολέα της γ-σεκρετάσης. / It is widely accepted and well established that the epidermal growth factor receptor (EGFR) controls important processes of tumor cells, such as proliferation and apoptosis, but also processes involving more than one type of cells such as invasion and angiogenesis. It has been found that the EGFR has an important role in the development of several types of cancer including non-small cell lung cancer (NSCLC). Very recent data indicate that another molecule, which is involved in the development of lung cancer, is Notch. Its role is complicated and is under investigation. It is suspected that Notch has a growth promoting function in NSCLC, whereas exerts an inhibitory effect in small cell lung cancer (SCLC). Furthermore it has been found that the signaling pathway of Notch can affect/ can be affected by other molecules. This thesis investigated the role of EGFR and Notch in cell growth of NSCLC cells using the ligand of EGFR, EGF and gamma-secretase inhibitor, DAPT. To conduct the experiments the human NSCLC cell lines H23, A549, H661 and HCC827 were used. The cell lines H23, A549 and H661 express the wild type (wt) EGFR and the cell line HCC827 expresses EGFR bearing the mutation (mt) DE746-A750. Initially, we studied the profile of NSCLC cells regarding the protein levels of Notch intracellular domain (Notch ICD) using western blot analysis. It was found that H23 cells express the higher levels Notch ICD, H661 and HCC827 cells express intermediate levels and A549 cells express the lowest levels of Notch ICD. The next step was the evaluation of DAPT effect in cell proliferation using the MTT assay. We found that DAPT caused the greatest inhibition to H661 and A549 cells. DAPT was less effective to H23 cells while had no effect to HCC827 cells. The inhibitory effect of DAPT in H661 cells was in line with the induction of apoptosis and autophagy, as was detected using annexin V assay and western blot analysis for beclin-1, respectively. Furthermore, cells were stimulated with EGF and subsequently DAPT was added. We found that the stimulatory effect of EGF was not reversed by DAPT in H23 cells. However a partial reverse of EGF stimulation was observed in H661 cells. The next step was to study the effect of DAPT and EGF at Notch ICD protein levels, in H23 and H661 cells. We found that DAPT reduced the protein levels of Notch ICD in H23 cells, with a time-dependent manner, up to 6 hours after DAPT addition and this effect reversed 24 hour later. The addition of EGF did not affect the levels of Notch ICD at any time point tested. In H661 cells, DAPT caused a time-dependent reduction of Notch ICD protein levels up to 24 hours after DAPT addition to cells. EGF as previously, did not affect the levels of Notch ICD in these cells. Since DAPT was more effective to H661 cells, these cells stimulated with EGF and then DAPT was added in order to study the effect of the combination at the levels of Notch ICD. We found that EGF reversed the decrease of Notch ICD protein levels caused by DAPT alone. These results indicate that the pathways of EGFR and Notch might act with a synergistic fashion and this could be an attractive approach for the treatment of NSCLC. Summarizing our results, we might assume that in NSCLC: a) both pathways of EGFR and Notch exert a significant role in tumor growth, b) the inhibition of Notch is more effective in cells with intermediate levels of activated Notch 1, causing both apoptosis and autophagy, and c) the EGFR mutation confers resistance to the effect of γ- secretase inhibitor.

<p>Hemioterapija koja se koristi za lečenje karcinoma utiče i na kardiovaskularni sistem. Ciljevi&nbsp; istraživanja&nbsp; su: u tvrditi uticaj kardiotoksičnosti&nbsp; na&nbsp; reživljavanje&nbsp; bolesnika&nbsp; sa uznapredovalim stadijumom NSCLC; utvrditi učestalost pojave kardiotoksičnosti kod bolesnika koji su lečeni hemioterapijom prve linije (gemcitabin/cisplatin i paclitaxel/carboplatin) sa i bez prethodnih kardiovaskularnih oboljenja i utvrditi učestalost pojave kardiotoksičnosti u toku primene protokola docetaxel/cisplatin kao hemioterapije druge linije, u odnosu na primenu protokola gemcitabin/ cisplatin i paclitaxel/carboplatin, kao terapije prve linije. Istraživanjem je obuhvaćeno 270 bolesnika sa citolo&scaron;ki ili patohistolo&scaron;ki dokazanim NSCLC kliničkog stadiju ma III i IV.&nbsp; Dobijeni su rezultati koji ukazuju da je preživljavanje bolesnika u III i IV stadijumu NSCLC koji su imali pojavu kardiotoksičnosti tokom hemioterapije prve i druge linije kraće u odnosu na bolesnike bez pojave kardiotoksičnosti, sa statističkom značajno&scaron;ću nakon prvog, drugog, četvrtog ciklusa hemioterapije i nakon &scaron;est meseci (p=0.004, p=0.020, p=0.030 i p&lt;0.0005. respektivno). Kardiotoksičnost kod bolesnika u III i IV stadijumu NSCLC koji su primali hemioterapiju prve linije prema protokolu gemcitabin/cisplatin se če&scaron;će javila ukoliko su imali prethodne kardiovaskularne bolesti, ali statistička značajnost nije utvrđena. Kardiotoksičnost kod bolesnika u III i IV stadijumu NSCLC koji su primali hemioterapiju prve linije prema protokolu paclita xel/carboplatin se če&scaron;će javila ukoliko su imali prethodne kardiovaskularne bolesti, a statistička značajnost utvrđena prilikom prvog kontrolnog pregleda kod bolesnika u III stadijumu (p=0.037). Kod bolesnika u III i IV stadijumu NSCLC koji su primali hemioterapiju prve linije prema protokolima gemcitabin/cisplatin paclitaxel / carboplatin kardiotoksičnost se če&scaron;će javila ukoliko su imali prethodna kardiovaskularna oboljenja, ali je statistička značajnost ustanovljena samo pri prvom kontrolnom pregledu , (p=0.022). Kod bolesnika koji su primali hemioterapiju druge linije kardiotoksičnost značajno če&scaron;će javila u toku prvog ciklusa hemioterapije (p=0.049) u odnosu&nbsp; na&nbsp; bolesnike&nbsp; koji&nbsp; su&nbsp; primali hemioterapiju&nbsp; prve&nbsp; linije.&nbsp; Kod bolesnika koji su imali prethodne kardiovaskularne bolesti u toku druge linije hemioterapije kardiotoksičnost se statistički značajno če&scaron;će javila u odnosu na prvu liniju hemioterapije u toku četvrtog ciklusa hemioterapije (p=0.020). Uspostavljanje ravnoteže između efektivnosti hemioterapije i rizika od o&scaron;tećenja kardiovaskularnog sistema zahteva blisku saradnju onkologa i kardiologa , sa ciljem kreiranja individualne terapije za svakog bolesnika.</p> / <p>Lung&nbsp; cancer&nbsp; chemotherapy&nbsp; affects&nbsp; the&nbsp; cardiovascular&nbsp; system&nbsp; as&nbsp; well. The research&nbsp; objectives&nbsp; were&nbsp; to&nbsp; establish:&nbsp; the&nbsp; effects&nbsp; of&nbsp; cardiotoxicity&nbsp; on&nbsp; the survival of advanced NSCLC patients;&nbsp; the frequency of cardiotoxicity in the patients&nbsp; treated&nbsp; with&nbsp; the&nbsp; first - line&nbsp; chemotherapy&nbsp; (gemcitabine/cisplatin&nbsp; and paclitaxel/carboplatin),&nbsp;&nbsp; with&nbsp;&nbsp; or&nbsp;&nbsp; without&nbsp;&nbsp; the&nbsp;&nbsp; history&nbsp;&nbsp; of&nbsp;&nbsp; cardiovascular comorbidities, and the frequency of cardiotoxicity registered in the course of the&nbsp; second - line&nbsp; chemotherapy&nbsp; with docetaxel/cisplatin,&nbsp; as&nbsp; compared&nbsp; to&nbsp; the first - line chemotherapy&nbsp; with gemcitabine/cisplatin and paclitaxel/carboplatin.&nbsp;&nbsp;&nbsp; The&nbsp;&nbsp;&nbsp; investigation&nbsp;&nbsp;&nbsp; included&nbsp;&nbsp;&nbsp; 270&nbsp;&nbsp;&nbsp; patients&nbsp;&nbsp;&nbsp; with citologically&nbsp; or histopathologically&nbsp; confirmed&nbsp; NSCLC&nbsp; at&nbsp; the&nbsp; clinical&nbsp; stages III&nbsp; and&nbsp; IV. The&nbsp; obtained&nbsp; research&nbsp; results&nbsp; suggest&nbsp; the&nbsp; patients&nbsp; with&nbsp; stage&nbsp; III and IV NSCLC who developed&nbsp; cardiotoxicity in the course of&nbsp; the first &ndash; and second - line&nbsp;&nbsp; chemotherapy&nbsp;&nbsp; had&nbsp;&nbsp; a&nbsp;&nbsp; shorter&nbsp;&nbsp; survival&nbsp;&nbsp; than&nbsp;&nbsp; those&nbsp;&nbsp; without cardiotoxicity,&nbsp; with&nbsp; the&nbsp; statistical&nbsp; significance&nbsp; registered&nbsp; after&nbsp; the&nbsp; first, second,&nbsp; and&nbsp; fourth&nbsp; chemotherapy&nbsp; course,&nbsp; as&nbsp; well&nbsp; as&nbsp; six&nbsp; months&nbsp;&nbsp;&nbsp; later (p=0.004,&nbsp; p=0.020,&nbsp; p=0.030&nbsp; and&nbsp; p&lt;0.0005&nbsp; respectively). Stage&nbsp; III&nbsp; and&nbsp; IV NSCLC&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; patients&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; receiving&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; the&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; first - line&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; chemotherapy&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; with gemcitabine/cisplatin developed cardiotoxicity more frequently if they had a former history of cardiovascular diseases, but with no statistical significance registered. Stage&nbsp; III and IV NSCLC patients on the&nbsp; first - line&nbsp; chemotherapy protocol&nbsp;&nbsp;&nbsp; with&nbsp;&nbsp;&nbsp; paclitaxel/carboplatin&nbsp;&nbsp;&nbsp; developed&nbsp;&nbsp;&nbsp; cardiotoxicity&nbsp;&nbsp;&nbsp; more frequently&nbsp; if&nbsp; they&nbsp; had&nbsp; a&nbsp; former&nbsp; history&nbsp; of&nbsp; cardiovascular&nbsp; diseases,&nbsp; and&nbsp; the&nbsp; statistical significance was registered at the first control examination in stage III&nbsp; NSCLC&nbsp; patients&nbsp; (p=0.037).&nbsp; Stage III&nbsp; and&nbsp; IV&nbsp; NSCLC&nbsp; patients&nbsp; receiving the&nbsp;&nbsp; first-line&nbsp;&nbsp; chemotherapy&nbsp;&nbsp; protocols&nbsp;&nbsp; with&nbsp;&nbsp; gemcitabine/cisplatin&nbsp;&nbsp; and paclitaxel/carboplatin&nbsp; developed&nbsp; cardiotoxicity&nbsp; more&nbsp; frequently&nbsp; if&nbsp; they&nbsp; had former cardiovascular diseases, but the statistical significance was registered at&nbsp;&nbsp; the&nbsp;&nbsp; first&nbsp;&nbsp; control&nbsp;&nbsp; examination&nbsp;&nbsp; only, one&nbsp;&nbsp; month&nbsp;&nbsp; after&nbsp;&nbsp; chemotherapy application (p=0.022). The&nbsp; patients receiving the&nbsp; second - line&nbsp; chemotherapy developed&nbsp; cardiotoxicity&nbsp; much&nbsp; more&nbsp; often&nbsp; during&nbsp; the&nbsp; first&nbsp; chemotherapy course (p=0.049),&nbsp;&nbsp; as&nbsp;&nbsp; compared&nbsp;&nbsp; to&nbsp;&nbsp; the&nbsp;&nbsp; patiens&nbsp;&nbsp; receiving&nbsp;&nbsp; the&nbsp;&nbsp; first - line chemotherapy.&nbsp; Among&nbsp; the&nbsp; patients&nbsp; with&nbsp; a&nbsp; former&nbsp; history&nbsp; of&nbsp; cardiovascular diseases,&nbsp;&nbsp;&nbsp; those&nbsp;&nbsp;&nbsp; receiving&nbsp;&nbsp;&nbsp; the&nbsp;&nbsp;&nbsp; second &ndash; line&nbsp;&nbsp;&nbsp; chemotherapy&nbsp;&nbsp;&nbsp; developed cardiotoxicity&nbsp; during&nbsp; the&nbsp; fourth&nbsp; chemotherapy&nbsp; course&nbsp; significanly&nbsp; more freequently&nbsp;&nbsp; than&nbsp;&nbsp; the&nbsp;&nbsp; patients&nbsp;&nbsp; on&nbsp;&nbsp; the&nbsp;&nbsp; same&nbsp;&nbsp; course&nbsp;&nbsp; of&nbsp;&nbsp; the&nbsp;&nbsp; first-line chemotherapy&nbsp; (p=0.020). To&nbsp; achieve&nbsp; the&nbsp; balance&nbsp; between&nbsp; chemotherapy efficacy&nbsp; and&nbsp; the&nbsp; risk&nbsp; of&nbsp; the&nbsp; cardiovascular&nbsp; system&nbsp; damage&nbsp; requires&nbsp; a&nbsp; close cooperation of an oncologist and a cardiologist, aimed at designing a unique, individual therapy for each patient.</p>