Možnosti deintenzifikacije zdravljenja HPV pozitivnih ploščatoceličnih karcinomov orofarinksa
Treatment deintensification strategies in HPV-associated oropharyngeal squamous cell carcinoma

Keywords: oropharyngeal cancer, human papillomavirus, HPV, treatment deintensification, head and neck cancer

Abstract

Do nedavnega sta bila poglavitna dejavnika tveganja za nastanek ploščatoceličnega karcinoma orofarinksa kajenje in prekomerno uživanje alkohola. Prognoza teh bolnikov je praviloma slaba, zaradi česar je zdravljenje intenzivno in multimodalno, kar edino nudi možnost ozdravitve, a hkrati povzroča resne neželene učinke. V zadnjih letih pa opažamo naraščanje incidence karcinoma orofarinksa, natančneje nebnic in jezične tonzile, pri bolnikih, ki so mlajši od tipičnih bolnikov s tem rakom in niso podvrženi škodljivim razvadam. Pri njih je povzročitelj karcinoma visokorizični podtip človeškega virusa papiloma (HPV). Ti bolniki v primerjavi s prvimi bolje odgovorijo na nekirurško zdravljenje in imajo pomembno daljše preživetje. Obenem to pomeni, da so ti bolniki agresivnega zdravljenja deležni v zgodnejšem življenjskem obdobju in morajo s posledicami tega živeti bistveno dlje. Zato se upravičeno poraja vprašanje, ali morda teh bolnikov s HPV povezanim rakom orofarinksa ne zdravimo pretirano agresivno. Predlaganih je bilo več načinov za zmanjšanje intenzivnosti zdravljenja, znani pa so tudi že prvi rezultati raziskav. Ti potrjujejo, da je način deintenzifikacije zdravljenja s kombinacijo sočasnega obsevanja in cetuximaba, ki je nadomestil cisplatin oz. karboplatin, neuspešen. Bolj obetavni so zgodnji rezultati kliničnih raziskav, ki vključujejo bodisi manj invazivno kirurgijo ali zmanjšanje odmerka radioterapije, z ali brez predhodne izbire bolnikov, primernih za deintenzifikacijo, z uvodno kemoterapijo. Mnoge raziskave so še v teku in morda bodo izsledki že kmalu spremenili paradigmo zdravljenja v tej skupini bolnikov. Do takrat pa ostaja zdravljenje karcinomov orofarinksa enako za vse bolnike, ne glede na etiologijo njihove bolezni.


Abstract (Eng)

Until recently, the major risk factors for development of oropharyngeal squamous cell carcinoma were smoking and alcohol consumption. Prognosis of these patients is poor, thus intensive and often multimodal approach to treatment is warranted if cure is to be hoped for. However, side effects of such treatment are serious. In recent years, there is a steep increase of oropharyngeal cancer, most notably of base of tongue and tonsils, in younger patients who are not heavy smokers or drinkers. In these patients the culprit is infection with high-risk human papillomavirus (HPV). Albeit the response to non-surgical treatment and prognosis are much better in these patients compared to those with non-HPV mediated oropharyngeal cancer, these patients are treated aggressively earlier in their life and will have to live with side effects of such treatment for considerably longer. The legitimate question arises whether we are treating these patients too aggressively. Several strategies to treatment deintensification were proposed and the first results are already available. These confirm that substituting platinum based concomitant chemotherapy in the setting of radical chemoradiotherapy with concomitant cetuximab is equally toxic yet less effective. More promising are the early results of clinical studies utilizing transoral surgical approaches and de-escalation of radiotherapy dose with or without induction chemotherapy used for selection of patients suitable for treatment deintensification. We are still awaiting results of several such studies that could influence the treatment paradigm of these patients. Until then, the treatment of patients with oropharyngeal cancer remains the same regardless of HPV status.

Published
2019-12-06
How to Cite
Plavc, G., & Strojan, P. (2019). Treatment deintensification strategies in HPV-associated oropharyngeal squamous cell carcinoma. Onkologija : A Medical-Scientific Journal, 23(2), 8-20. https://doi.org/10.25670/oi2019-010on
Section
Review Article
Page
8-20