1. Post-radiation xerostomia therapy with allogeneic mesenchymal stromal stem cells in patients with head and neck cancer : study protocol for phase I clinical trialPrimož Strojan, Gaber Plavc, Marko Kokalj, Goran Mitrović, Olga Blatnik, Luka Ležaič, Aljaž Sočan, Aljoša Bavec, Nataša Tešić, Katrina Pretnar-Hartman, Urban Švajger, 2023, original scientific article Abstract: Background: Xerostomia is a common side effect of radiotherapy in patients with head and neck tumors that negatively affects quality of life. There is no known effective standard treatment for xerostomia. Here, we present the study protocol used to evaluate the safety and preliminary efficacy of allogeneic mesenchymal stromal stem cells (MSCs) derived from umbilical cord tissue. Methods: Ten oropharyngeal cancer patients with post-radiation xerostomia and no evidence of disease recurrence 2 or more years after (chemo)irradiation (intervention group) and 10 healthy volunteers (control group) will be enrolled in this nonrandomized, open-label, phase I exploratory study. MSCs from umbilical cord tissue will be inserted under ultrasound guidance into both parotid glands and both submandibular glands of the patients. Toxicity of the procedure will be assessed according to CTCAE v5.0 criteria at days 0, 1, 5, 28, and 120. Efficacy will be assessed by measuring salivary flow and analyzing its composition, scintigraphic evaluation of MSC grafting, retention, and migration, and questionnaires measuring subjective xerostomia and quality of life. In addition, the radiological, functional, and morphological characteristics of the salivary tissue will be assessed before, at 4 weeks, and at 4 months after the procedure. In the control group subjects, only salivary flow rate and salivary composition will be determined. Discussion: The use of allogeneic MSCs from umbilical cord tissue represents an innovative approach for the treatment of xerostomia after radiation. Due to the noninvasive collection procedure, flexibility of cryobanking, and biological advantages, xerostomia therapy using allogeneic MSCs from umbilical cord tissue may have an advantage over other similar therapies.
Keywords: oropharyngeal cancer, xerostomia, mesenchymal stromal stem cells
Published in DiRROS: 26.07.2024; Views: 421; Downloads: 188
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2. Combining radiotherapy and immunotherapy in definitive treatment of head and neck squamous cell carcinoma : review of current clinical trialsGaber Plavc, Primož Strojan, 2020, review article Abstract: Head and neck squamous cell carcinoma (HNSCC) presents as locally advanced disease in a majority of patients and is prone to relapse despite aggressive treatment. Since immune checkpoint inhibitors (ICI) have shown clinically significant efficacy in patients with recurrent/metastatic HNSCC (R/M HNSCC), a plethora of trials are investigating their role in earlier stages of disease. At the same time, preclinical data showed the synergistic role of concurrently administered radiotherapy and ICIs (immunoradiotherapy) and explained several mechanisms behind it. Therefore, this approach is prospectively tested in a neoadjuvant, definitive, or adjuvant setting in non-R/M HNSCC patients. Due to the intricate relationship between host, immunotherapy, chemotherapy, and radiotherapy, each of these approaches has its advantages and disadvantages. In this narrative review we present the biological background of immunoradiotherapy, as well as a rationale for, and possible flaws of, each treatment approach, and provide readers with a critical summary of completed and ongoing trials. Conclusions. While immunotherapy with ICIs has already become a standard part of treatment in patients with R/M HNSCC, its efficacy in a non-R/M HNSCC setting is still the subject of extensive clinical testing. Irradiation can overcome some of the cancer%s immune evasive manoeuvres and can lead to a synergistic effect with ICIs, with possible additional benefits of concurrent platinum-based chemotherapy. However, the efficacy of this combination is not robust and details in trial design and treatment delivery seem to be of unprecedented importance.
Keywords: head and neck neoplasms, immunoradiotherapy, radiotherapy, immunotherapy
Published in DiRROS: 16.07.2024; Views: 240; Downloads: 50
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3. Šola rakov glave in vratu : Onkološki inštitut Ljubljana, 1. december 20232023, not set Abstract: V zborniku je celostno predstavljena problematika rakov glave in vratu, kot jo dojemajo strokovnjaki, ki se vsakodnevno srečujejo z bolniki s temi raki. Osvetljeni so vzroki za nastanek rakov glave in vratu, incidenca, mortaliteta in sodobni epidemiološki trendi, znaki in simptomi, ki jih povzročajo, načela sodobne diagnostike in zdravljenja s posledično morbiditeto ter možnosti podporne terapije in rehabilitacije. Poseben poudarek je namenjen obravnavi teh rakov v slovenskem prostoru in nacionalnim smernicam.
Published in DiRROS: 06.12.2023; Views: 552; Downloads: 261
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4. Radioterapija raka glave in vratuGaber Plavc, 2022, published professional conference contribution Abstract: Radioterapija je eden treh stebrov zdravljenja rakov glave in vratu. Začetki segajo v konec 19. stoletja, vsa dosedanja spoznanja pa danes omogočajo uspešno zdravljenje ob sprejemljivi toksičnosti. S sodobnimi obsevalnimi tehnikami lahko pri sluzničnih karcinomih glave in vratu v zgodnjih stadijih dosežemo popolno lokalno kontrolo bolezni, medtem ko je pri lokoregionalni bolezni obsevanje pogosto edino zdravljenje, ki prinaša možnost ozdravitve. V prihodnosti lahko ob tehničnem napredku, kot sta uporaba adaptivnega pristopa k obsevanju in uporaba visokoenergijskih delcev z ugodnejšimi fizikalnimi lastnostmi, ter predvsem ob napredku v razumevanju mehanizmov občutljivosti na obsevanje pričakujemo nadaljnje pomembne korake k izboljšanju uspehov radioterapije ob nespremenjeni ali celo zmanjšani toksičnosti.
Keywords: rak glave in vratu, radioterapija, onkološko zdravljenje
Published in DiRROS: 06.01.2023; Views: 900; Downloads: 210
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6. Oligometastatski rakIvica Ratoša, Karmen Stanič, Tanja Ovčariček, Ajra Šečerov Ermenc, Janka Čarman, Blaž Grošelj, Staša Jelerčič, Peter Korošec, Manja Šešek, Marko Kokalj, Gaber Plavc, Miha Oražem, Helena Barbara Zobec Logar, 2022, review article Abstract: Oligometastatska bolezen (OMB) predstavlja vmesno stanje med lokalno napredovalo boleznijo in obsežnejšo metastatsko boleznijo. Zaenkrat ne poznamo specifičnih biomarkerjev, ki bi nam pomagali opredeliti bolnike z majhnim bremenom bolezni, zato diagnoza OMB temelji na slikovni diagnostiki. V zadnjih letih narašča zanimanje za optimizacijo zdravljenja OMB predvsem zaradi obetavnih rezultatov dodatka lokalnega k obstoječemu sistemskemu zdravljenju. S takšnim načinom zdravljenja se je prvič pokazala možnost doseganja dolgotrajnih zazdravitev ali redko celo ozdravitev teh bolnikov. Razlikovanje posameznih vrst OMB in njihovo enotno poimenovanje je pomembno zlasti v kliničnih raziskavah, saj nam omogoča medsebojno primerjavo rezultatov različnih raziskav.
Keywords: klasifikacija, oligometastatska bolezen, sistemsko zdravljenje, onkologija
Published in DiRROS: 06.12.2022; Views: 877; Downloads: 239
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7. Neuroendocrine carcinoma of the larynx and pharynx : a clinical and histopathological studyPrimož Strojan, Robert Šifrer, Alfio Ferlito, Cvetka Grašič-Kuhar, Boštjan Lanišnik, Gaber Plavc, Nina Zidar, 2021, original scientific article Abstract: Neuroendocrine carcinomas (NECs) of the head and neck are rare and the experience scanty. The Cancer Registry of Slovenia database was used to identify cases of laryngeal and pharyngeal NECs diagnosed between 1995%2020. Biopsies were analyzed for the expression of standard neuroendocrine markers (synaptophysin, chromogranin, CD56), INSM1, Ki-67, p16, and PD-L1 (using the combined positive score, CPS). In situ hybridization for human papillomavirus (HPV) and Epstein%Barr virus (EBV) was performed. Twenty patients (larynx, 12; pharynx, 8) were identified. One tumor was well differentiated (WD), five were moderately differentiated (MD), and 14 were poorly differentiated (PD). Disease control was achieved solely by surgery in 4/4 MD/PD T1-2N0-1 tumors. Eight patients died of the disease, seven of which were due to distant metastases. All three traditional markers were positive in 11/17 NECs and the INSM1 marker in all 20 tumors. Two of fourteen p16-positive tumors were HPV-positive, but all three nasopharyngeal NECs were EBV-negative. Three tumors had CPSs % 1. In conclusion, INSM1 was confirmed to be a reliable marker of neuroendocrine differentiation. Except in WD and early-stage MD/PD tumors, aggressive multimodal therapy is needed; the optimal systemic therapy remains to be determined. p16, HPV, and EBV seem to bear no prognostic information.
Keywords: electrochemotherapy, head and neck cancer, neuroendocrinic carcinoma
Published in DiRROS: 07.09.2022; Views: 805; Downloads: 357
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9. Priporočila za obravnavo bolnikov z rakom glave in vratu v SlovenijiPrimož Strojan, Aleksandar Aničin, Jelena Azarija, Saba Battelino, Bogdan Čizmarevič, Vojislav Didanovič, Tadej Dovšak, Marta Dremelj, Aleš Fidler, Matic Glavan, Cvetka Grašič-Kuhar, Aleš Grošelj, Andrej Kansky, Katarina Barbara Karner, Marko Kokalj, Matic Koren, Jana Krapež, Hojka Kuralt, Boštjan Lanišnik, Primož Levart, Jure Orel, Jošt Pavčič, Gaber Plavc, Luka Prodnik, Peter Pukl, Robert Šifrer, Matija Švagan, Jure Urbančič, Branko Zakotnik, Nina Zidar, Barbara Žumer, 2021, professional article Abstract: Priporočila za obravnavo rakov glave in vratu (RGV) v Sloveniji sledijo priporočilom in usmeritvam, povzetim v publikaciji neprofitne mreže 30 vodilnih severnoameriških inštitucij za obravnavo raka, National Comprehensive Cancer Network,1 in hkrati upoštevajo obstoječe zmožnosti slovenskega zdravstvenega sistema. Smernice predstavljajo poenoteno mnenje vseh štirih najpomembnejših deležnikov na področju obravnave rakov glave in vratu v državi: Klinike za otorinolaringologijo in cervikofacialno kirurgijo, Kliničnega oddelka za maksilofacialno in oralno kirurgijo ter Stomatološke klinike UKC Ljubljana, Klinike za otorinolaringologijo, cervikalno in maksilofacialno kirurgijo UKC Maribor ter Onkološkega inštituta Ljubljana
Keywords: rak glave in vratu, zdravljenje, onkolško zdravljenje
Published in DiRROS: 11.06.2021; Views: 2015; Downloads: 450
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10. Imunoterapija pri ploščatoceličnem karcinomu glave in vratu - izkušnje iz SlovenijeGaber Plavc, Primož Strojan, Jelena Azarija, Cvetka Grašič-Kuhar, 2021, original scientific article Abstract: Izhodišča: Imunoterapija z zaviralcem imunskih kontrolnih točk nivolumabom, zaviralnim protitelesom proti proteinu programirane celične smrti 1 (PD-1), je za bolnike z neozdravljivo ponovitvijo bolezni ali sistemskimi zasevki ploščatoceličnega karcinoma glave in vratu (P/Z PKGV), pri katerih je bolezen neobčutljiva na preparate platine, pomembna nova možnost zdravljenja. V primerjavi s citostatiki pomembno podaljša njihovo preživetje.
Metode: Opravljena je bila retrospektivna analiza zdravljenja z nivolumabom pri slovenskih bolnikih s P/Z PKGV, ki so prejeli prvi odmerek nivolumaba do marca 2020. Zbiranje podatkov je bilo končano septembra 2020. Uporabljene so bile opisne statistične metode in test log-rank.
Rezultati: V raziskavo je bilo vključenih 27 bolnikov. Srednji čas sledenja od prve aplikacije nivolumaba do konca opazovanja je bil 7,4 meseca, relativno šestmesečno celokupno preživetje pa 59- odstotno (95-odstotni interval zaupanja pri 41–78 %). Odgovor na zdravljenje je bil pri 85 % bolnikov ocenjen s kliničnim pregledom in rentgenskim slikanjem prsnega koša, pri čemer je bil pri 41 % kot najboljši odgovor ugotovljen delen odgovor na zdravljenje. Imunsko pogojeni neželeni dogodki so se pojavili pri 30 % bolnikov, pri čemer so bili vsi gradusa ≤ 2. En bolnik je bil sočasno z nivolumabom tudi obsevan.
Zaključek: Glede na zbrane podatke se je tudi v slovenski populaciji bolnikov s P/Z PKGV zdravljenje z nivolumabom izkazalo za varno. Zaradi kratkega časa sledenja ugotovljene učinkovitosti ni mogoče primerjati z rezultati tujih raziskav. S pričakovano odobritvijo pembrolizumaba bodo zaviralci imunskih kontrolnih točk tudi v Sloveniji dobili mesto v prvem redu zdravljenja P/Z PKGV.
Keywords: rak glave in vratu, imunoterapija, nivolumab
Published in DiRROS: 10.06.2021; Views: 1788; Downloads: 418
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