31. Treatment outcomes and relative dose intensity of chemotherapy in patients with advanced Hodgkin lymphomaSamo Rožman, Barbara Jezeršek Novaković, Nina Ružić Gorenjec, Srdjan Novaković, 2022, izvirni znanstveni članek Povzetek: The present retrospective study was undertaken to investigate the association of relative dose intensity (RDI) with the outcome of patients with advanced stage Hodgkin lymphoma (HL) receiving ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP regimens (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). A total of 114 patients with HL treated between 2004 and 2013 were enrolled for evaluation. The association of variables with overall survival (OS) and progression-free survival (PFS) was analysed using univariate and multivariate Cox proportional hazards models. The median age of patients was 39 years, and the majority were male and had stage IV disease. A total of 54 patients received ABVD and 60 received BEACOPP chemotherapy with 24 and four deaths, respectively. Patients in the BEACOPP group were significantly younger with lower Charlson comorbidity index (CCI) and better performance status in comparison with the ABVD group, making the comparison of groups not possible. In the ABVD group, RDI was not significantly associated with OS (P=0.590) or PFS (P=0.354) in a multivariate model where age was controlled. The low number of events prevented this analysis in the BEACOPP group. The age of patients was strongly associated with both OS and PFS; all statistically significant predictors for OS and PFS from univariate analyses (chemotherapy regimen, CCI, RDI, performance status) lost their effect in multivariate analyses where age was controlled. Based on these observations, it was concluded that RDI was not associated with OS or PFS after age is controlled, neither in all patients combined nor in the ABVD group.
Ključne besede: Hodgkin lymphoma, chemotherapy, outcome, primary treatment
Objavljeno v DiRROS: 23.09.2022; Ogledov: 519; Prenosov: 159
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32. Trends and timing of risk-reducing mastectomy uptake in unaffected BRCA1 and BRCA2 carriers in SloveniaTaja Ložar, Janez Žgajnar, Andraž Perhavec, Ana Blatnik, Srdjan Novaković, Mateja Krajc, 2021, izvirni znanstveni članek Povzetek: Objectives. Risk-reducing mastectomy (RRM) is one of key prevention strategies in female carriers of germline BRCA pathogenic/likely pathogenic variants (PV/LPV). We retrospectively investigated the rate, timing and longitudinal trends of bilateral RRM uptake and the incidence and types of cancers among unaffected BRCA carriers who underwent genetic counseling at the Institute of Oncology Ljubljana in Slovenia. Materials and Methods. Female BRCA carriers without personal history of cancer were included in the study. Clinical data on PV/LPV type, date of RRM, type of reconstructive procedure, occult carcinoma and histopathology results was collected and analyzed. Results. Of the 346 unaffected BRCA carriers (median age 43 years, 70% BRCA1, 30% BRCA2, median follow-up 46 months) who underwent genetic testing between October 1999 and December 2019, 25.1% had a RRM (range 35-50 years, median age at surgery 38 years). A significant difference in time to prophylactic surgery between women undergoing RRM only vs. women undergoing RRM combined with risk-reducing salpingo-oophorectomy was observed (22.6 vs 8.7 months, p=0.0009). We observed an upward trend in the annual uptake in line with the previously observed Angelina Jolie effect. In 5.7% of cases, occult breast cancer was detected. No women developed breast cancer after RRM. Women who did not opt for surgical prevention developed BRCA1/2-related cancers (9.3%). Conclusion. The uptake of RRM among unaffected BRCA carriers is 25.1% and is similar to our neighboring countries. No women developed breast cancer after RRM while women who did not opt for surgical prevention developed BRCA1/2 related cancers in 9.3% of cases. The reported data may provide meaningful aid for carriers when deciding on an optimal prevention strategy.
Ključne besede: risk-reducing mastectomy, breast cancer, BRCA
Objavljeno v DiRROS: 21.09.2022; Ogledov: 428; Prenosov: 145
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33. New approach for detection of normal alternative splicing events and aberrant spliceogenic transcripts with long-range PCR and deep RNA sequencingVita Šetrajčič Dragoš, Vida Stegel, Ana Blatnik, Gašper Klančar, Mateja Krajc, Srdjan Novaković, 2021, izvirni znanstveni članek Povzetek: RNA sequencing is a promising technique for detecting normal and aberrant RNA isoforms. Here, we present a new single-gene, straightforward 1-day hands-on protocol for detection of splicing alterations with deep RNA sequencing from blood. We have validated our method%s accuracy by detecting previously published normal splicing isoforms of STK11 gene. Additionally, the same technique was used to provide the first comprehensive catalogue of naturally occurring alternative splicing events of the NBN gene in blood. Furthermore, we demonstrate that our approach can be used for detection of splicing impairment caused by genetic variants. Therefore, we were able to reclassify three variants of uncertain significance: NBN:c.584G>A, STK11:c.863-5_863-3delCTC and STK11:c.615G>A. Due to the simplicity of our approach, it can be incorporated into any molecular diagnostics laboratory for determination of variant%s impact on splicing.
Ključne besede: RNA sequencing, DNA variant, splicing
Objavljeno v DiRROS: 21.09.2022; Ogledov: 438; Prenosov: 245
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34. BAP1-defficient breast cancer in a patient with BAP1 cancer syndromeAna Blatnik, Domen Ribnikar, Vita Šetrajčič Dragoš, Srdjan Novaković, Vida Stegel, Biljana Grčar-Kuzmanov, Nina Boc, Barbara Perić, Petra Škerl, Gašper Klančar, Mateja Krajc, 2022, izvirni znanstveni članek Povzetek: BAP1 cancer syndrome is a rare and highly penetrant hereditary cancer predisposition. Uveal melanoma, mesothelioma, renal cell carcinoma (RCC) and cutaneous melanoma are considered BAP1 cancer syndrome core cancers, whereas association with breast cancer has previously been suggested but not confirmed so far. In view of BAP1 immunomodulatory functions, BAP1 alterations could prove useful as possible biomarkers of response to immunotherapy in patients with BAP1-associated cancers. We present a case of a patient with BAP1 cancer syndrome who developed a metastatic breast cancer with loss of BAP1 demonstrated on immunohistochemistry. She carried a germline BAP1 likely pathogenic variant (c.898_899delAG p.(Arg300Glyfs*6)). In addition, tumor tissue sequencing identified a concurrent somatic variant in BAP1 (partial deletion of exon 12) and a low tumor mutational burden. As her triple negative tumor was shown to be PD-L1 positive, the patient was treated with combination of atezolizumab and nab-paclitaxel. She had a complete and sustained response to immunotherapy even after discontinuation of nab-paclitaxel. This case strengthens the evidence for including breast cancer in the BAP1 cancer syndrome tumor spectrum with implications for future cancer prevention programs. It also indicates immune checkpoint inhibitors might prove to be an effective treatment for BAP1-deficient breast cancer.
Ključne besede: BAP1, breast cancer, hereditary cancer syndromes, immunotherapy
Objavljeno v DiRROS: 19.09.2022; Ogledov: 446; Prenosov: 179
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35. Smernice za zdravljenje bolnikov z rakom požiralnika in ezofagogastričnega stika (EGS)Franc Anderluh, Marko Boc, Goran Gačevski, Gorana Gašljević, Samo Horvat, Nežka Hribernik, Marija Ignjatović, Ana Jeromen, Jera Jeruc, Peter Korošec, Tanja Mesti, Srdjan Novaković, Irena Oblak, Janja Ocvirk, Martina Reberšek, Nada Rotovnik-Kozjek, Matevž Srpčič, Ajra Šečerov Ermenc, Borut Štabuc, Vaneja Velenik, Neva Volk, Vesna Zadnik, 2022, slovar, enciklopedija, leksikon, priročnik, atlas, zemljevid Ključne besede: rak požiralnika, rak ezofagogastritičnega stika, smernice, zdravljenje
Objavljeno v DiRROS: 07.09.2022; Ogledov: 676; Prenosov: 261
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36. Identification of spliceogenic variants beyond canonical GT-AG splice sites in hereditary cancer genesVita Šetrajčič Dragoš, Ksenija Strojnik, Gašper Klančar, Petra Škerl, Vida Stegel, Ana Blatnik, Marta Banjac, Mateja Krajc, Srdjan Novaković, 2022, izvirni znanstveni članek Povzetek: Pathogenic/likely pathogenic variants in susceptibility genes that interrupt RNA splicing are a well-documented mechanism of hereditary cancer syndromes development. However, if RNA studies are not performed, most of the variants beyond the canonical GT-AG splice site are characterized as variants of uncertain significance (VUS). To decrease the VUS burden, we have bioinformatically evaluated all novel VUS detected in 732 consecutive patients tested in the routine genetic counseling process. Twelve VUS that were predicted to cause splicing defects were selected for mRNA analysis. Here, we report a functional characterization of 12 variants located beyond the first two intronic nucleotides using RNAseq in APC, ATM, FH, LZTR1, MSH6, PALB2, RAD51C, and TP53 genes. Based on the analysis of mRNA, we have successfully reclassified 50% of investigated variants. 25% of variants were downgraded to likely benign, whereas 25% were upgraded to likely pathogenic leading to improved clinical management of the patient and the family members.
Ključne besede: hereditary cancer, RNA sequencing, spliceogenic
Objavljeno v DiRROS: 07.09.2022; Ogledov: 463; Prenosov: 238
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37. Real-world data on detection of germline and somatic pathogenic/likely pathogenic variants in BRCA1/2 and other susceptibility genes in ovarian cancer patients using next generation sequencingVida Stegel, Ana Blatnik, Erik Škof, Vita Šetrajčič Dragoš, Mateja Krajc, Brigita Gregorčič, Petra Škerl, Ksenija Strojnik, Gašper Klančar, Marta Banjac, Janez Žgajnar, Maja Ravnik-Oblak, Srdjan Novaković, 2022, izvirni znanstveni članek Povzetek: Detection of germline and somatic pathogenic/likely pathogenic variants (PV/LPV) in BRCA genes is at the moment a prerequisite for use of PARP inhibitors in different treatment settings of different tumors. The aim of our study was to determine the most appropriate testing workflow in epithelial ovarian cancer (EOC) patients using germline and tumor genotyping of BRCA and other hereditary breast and/or ovarian cancer (HBOC) susceptibility genes. Consecutive patients with advanced non-mucinous EOC, who responded to platinum-based chemotherapy, were included in the study. DNA extracted from blood and FFPE tumor tissue were genotyped using NGS panels TruSightCancer/Hereditary and TruSight Tumor 170. Among 170 EOC patients, 21.8% had BRCA germline or somatic PV/LPV, and additionally 6.4% had PV/LPV in other HBOC genes. Sensitivity of tumor genotyping for detection of germline PV/LPV was 96.2% for BRCA genes and 93.3% for HBOC genes. With germline genotyping-only strategy, 58.8% of HBOC PV/LPV and 68.4% of BRCA PV/LPV were detected. By tumor genotyping-only strategy, 96.1% of HBOC PV/LPV and 97.4% of BRCA PV/LPV were detected. Genotyping of tumor first, followed by germline genotyping seems to be a reasonable approach for detection of PV/LPV in breast and/or ovarian cancer susceptibility genes in non-mucinous EOC patients.
Ključne besede: BRCA, ovarian cancer, tumor genotyping, HBOC
Objavljeno v DiRROS: 06.09.2022; Ogledov: 503; Prenosov: 274
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38. Priporočila za obravnavo bolnikov z rakom debelega črevesa in danke2020, slovar, enciklopedija, leksikon, priročnik, atlas, zemljevid Ključne besede: rak debelega črevesa, rak danke, bolniki, zdravljenje
Objavljeno v DiRROS: 18.03.2022; Ogledov: 788; Prenosov: 428
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39. Prednostno genetsko testiranje na zarodne mutacije pri bolnikih z metastatskim rakom prostate/pankreasa/dojk, ki potrebujejo izvid za zdravljenje raka s PARP inhibitorjiKsenija Strojnik, Ana Blatnik, Marta Banjac, Simona Hotujec, Natalija Klopčič, Janja Ocvirk, Srdjan Novaković, Mateja Krajc, 2021, slovar, enciklopedija, leksikon, priročnik, atlas, zemljevid Ključne besede: genetika, rak prostate, genetsko testiranje, klinične poti
Objavljeno v DiRROS: 16.03.2022; Ogledov: 652; Prenosov: 356
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40. Klinična pot genetske obravnave bolnic z epitelijskim nemucinoznim rakom jajčnikov/jajcevodov/primarnim peritonealnim seroznim karcinomomErik Škof, Ksenija Strojnik, Marta Banjac, Ana Blatnik, Vida Stegel, Natalija Klopčič, Simona Hotujec, Srdjan Novaković, Mateja Krajc, 2021, slovar, enciklopedija, leksikon, priročnik, atlas, zemljevid Ključne besede: rak jajčnikov, genetika, zdravljenje, klinične poti
Objavljeno v DiRROS: 16.03.2022; Ogledov: 674; Prenosov: 337
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