Immune RECIST criteria and symptomatic pseudoprogression in non-small cell lung cancer patients treated with immunotherapy

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.Nenavadni odzivi med zdravljenjem z imunoterapijo so nov izziv v vsakdanji onkološki praksi. Sprejeta so bila nova merila za oceno odziva na imunoterapijo, t.i. kriteriji iRECIST. Po teh kriterijih poslabšanje stanja zmogljivosti bolnika, pri katerem ugotavljamo pseudoprogres, predstavlja resnično napredovanje maligne bolezni. Metode. Opravili smo sistematični pregled literature z uporabo več elektronskih podatkovnih baz z naslednjimi iskalnimi kriteriji: simptomatski pseudoprogres, atipični odziv, imunoterapija in pljučni rak. Rezultati. V literaturi smo našli pet poročil o sedmih bolnikih z rakom pljuč, ki so jih zdravili z imunoterapijo in so izpolnjevali merila za vključitev v analizo. V članku smo predstavili tudi izkušnjo bolnice s pseudoprogresom po le enem odmerku imunoterapije, ki smo jo zdravili na Onkološkem inštitutu v Ljubljani. Zaključki. Po pregledu literature in na podlagi našega primera ugotavljamo, da kriteriji iRECIST za odgovor na imunoterapijo pri nekaterih bolnikih z nedrobnoceličnim rakom pljuč ne zadoščajo za razlikovanje pravega napredovanja rakave bolezni od pseudoprogresa. Nujno potrebujemo natančnejše metode za ocenjevanje odgovora na zdravljenje z imunoterapijo

Challenges in the Treatment of Oligometastatic Non-small Cell Lung Cancer

Since 1995, when the concept of oligometastatic non-small cell lung cancer was first described, no high-level evidence has been introduced for management of those patients subset. Data from retrospective reports and analysis and from every-day clinical practice revealed that some of the non-small cell lung cancer patients with a few metastases could benefit significantly with local radical treatment approach of primary and metastatic lesions. Recent advances in modern local treatment approaches with minimally invasive surgery and stereotactic radiotherapy, as well as introduction of immunotherapy, open new field of interest for personalized treatment of limited metastatic non-small cell lung cancer. In this report, we are summarizing limited data of case reports, retrospective studies and few randomized studies of patients with oligometastatic non-small cell lung cancer and discuss challenges of treatment in the era of molecular targeted therapy and immunotherapy

Pljučni rak - nacionalni problem

Breme pljučnega raka v Sloveniji v zadnjem desetletju ostaja nacionalni problem. Incidenčna stopnja se je pri moških sicer ustalila v zadnjih nekaj desetletjih, podatki pri ženskah pa kažejo na strm porast incidence v zadnjem desetletju, saj vsako leto zboli za skoraj 6 % več žensk. Kar dobra polovica bolnikov s pljučnim rakom ima ob diagnozi razsejan pljučni rak, ki ga kljub sodobnim načinom zdravljenja ne moremo pozdraviti. Po umrljivosti je pljučni rak pri moških in pri ženskah na prvem mestu. Vsako peto smrt zaradi raka pripišemo pljučnemu raku. Petletno preživetje bolnikov, zbolelih v obdobju 2015–2019, je bilo 19,5 %, bolnic pa 26,4 %. Izzivi v prihodnosti so v zgodnejšem odrivanju pljučnega raka. Raziskave so pokazale, da lahko presejanje pljučnega raka zniža umrljivost za 20 %, saj omogoča odkrivanje zgodnjih oblik raka. V presejalni program pljučnega raka morajo biti vključeni učinkoviti programi za opuščanje kajenja, prav tako pa je potrebno intenzivirati aktivnosti primarne preventive

Zdravilo durvalumab za zdravljenje raka pljuč

Zdravnik vam je predpisal zdravilo durvalumab, ker imate neoperabilen nedrobnocelični rak pljuč. Zdravilo se uporablja potem, ko ste uspešno zaključili zdravljenje z obsevanjem in s kemoterapijo, saj je dokazano, da zdravljenje z zdravilom durvalumab ugodno vpliva na izid bolezni

Stereotaktična radioterapija telesa pri bolnikih s pljučnim rakom

Stereotactic body radiation therapy (SBRT) is used for treatment of early stage lung cancer for patients without lymph node involvement. The standard treatment option for early disease is surgical resection; however, this type of treatment might be too risky due to age, co-morbidities and an impaired lung function. Traditionally, the three-dimensional conformal radiotherapy (3D CRT), radiofrequency ablation or symptomatic palliative treatment have been used for these patients in the past, but significantly worse local control of disease and survival rates were achieved compared to surgery. The SBRT technique offers patients with lung cancer treatment results comparable to surgery and a lower risk of impaired lung function compared to the standard 3D CRT. Due to a lower number of fractions, the whole treatment is shorter and more convenient for the patient. This enables patients a better treatment outcome and an increased quality of life; and therefore it has become part of the global guidelines for treatment of inoperable lung cancer in the early stages of the disease and for those who refuse surgery.Stereotaktična radioterapija telesa (SBRT) bolnikov s pljučnim rakom je metoda zdravljenja bolnikov v zgodnjem stadiju bolezni, ki nimajo prizadetih regionalnih bezgavk. Standardno so ti bolniki zdravljeni z operacijo, ki pa je lahko preveč tvegana zaradi starosti, spremljajočih bolezni ali slabe pljučne funkcije. V teh primerih smo bolnikom nudili druge načine zdravljenja, kot so tridimenzionalno konformno obsevanje, radiofrekvenčna ablacija ali pa le podporna terapija. S temi pristopi je bila kontrola rakave bolezni in preživetje bolnikov občutno slabše kot z operacijo. Obsevanje s tehniko SBRT pa bolnikom ponuja primerljive rezultate zdravljenja kot operacija ob manjšem tveganju za poslabšanje pljučne funkcije kot standardno obsevanje. Zaradi manjšega števila obsevanj je zdravljenje krajše in bolnikom bolj prijazno. Vse to bolnikom omogoča boljši izid zdravljenja in boljšo kakovost življenja ter je zato že postalo del svetovnih smernic za zdravljenje neoperabilnega raka pljuč v zgodnjem stadiju bolezni in tistih, ki operacijo odklonijo

Stereotactic body radiation therapy (SBRT) in patients with lung cancer

Stereotaktična radioterapija telesa (SBRT) bolnikov s pljučnim rakom je metoda zdravljenja bolnikov v zgodnjem stadiju bolezni, ki nimajo prizadetih regionalnih bezgavk. Standardno so ti bolniki zdravljeni z operacijo, ki pa je lahko preveč tvegana zaradi starosti, spremljajočih bolezni ali slabe pljučne funkcije. V teh primerih smo bolnikom nudili druge načine zdravljenja, kot so tridimenzionalno konformno obsevanje, radiofrekvenčna ablacija ali pa le podporna terapija. S temi pristopi je bila kontrola rakave bolezni in preživetje bolnikov občutno slabše kot z operacijo. Obsevanje s tehniko SBRT pa bolnikom ponuja primerljive rezultate zdravljenja kot operacija ob manjšem tveganju za poslabšanje pljučne funkcije kot standardno obsevanje. Zaradi manjšega števila obsevanj je zdravljenje krajše in bolnikom bolj prijazno. Vse to bolnikom omogoča boljši izid zdravljenja in boljšo kakovost življenja ter je zato že postalo del svetovnih smernic za zdravljenje neoperabilnega raka pljuč v zgodnjem stadiju bolezni in tistih, ki operacijo odklonijo.Stereotactic body radiation therapy (SBRT) is used for treatment of early stage lung cancer for patients without lymph node involvement. The standard treatment option for early disease is surgical resectionhowever, this type of treatment might be too risky due to age, co-morbidities and an impaired lung function. Traditionally, the three-dimensional conformal radiotherapy (3D CRT), radiofrequency ablation or symptomatic palliative treatment have been used for these patients in the past, but significantly worse local control of disease and survival rates were achieved compared to surgery. The SBRT technique offers patients with lung cancer treatment results comparable to surgery and a lower risk of impaired lung function compared to the standard 3D CRT. Due to a lower number of fractions, the whole treatment is shorter and more convenient for the patient. This enables patients a better treatment outcome and an increased quality of lifeand therefore it has become part of the global guidelines for treatment of inoperable lung cancer in the early stages of the disease and for those who refuse surgery

Imunoterapija prvič tudi za zdravljenje lokalno napredovalega nedrobnoceličnega pljučnega raka

During the last fifteen years, we have witnessed rapid development in the field of the lung cancer treatment, which remains cancer with the highest morbidity and mortality worldwide. Most patients with metastatic disease are treated with chemotherapy, targeted treatment is appropriate for less than 20% of patients with non-small cell lung cancer (NSCLC). In 2010, we were impressed by the results of research from the field of immunotherapy. Tumor cells must be recognized as foreign in order to be removed by the immune system. However, tumor cells have developed various mechanisms to escape immune control, one of which is the release of immune inhibitory molecules such as the ligand programmed cell death (PD-L1), which is the principal mediator of immunosuppressive action. Medicinal products which are currently used to treat metastatic NSCLC are monoclonal antibodies against PD-L1 or PD-1. By binding to PD-L1 or its PD-1 receptor on immune cells, they prevent the immunosuppressive effect and enable the activated T lymphocytes to function successfully. In Slovenia, two medicinal products with the described mode of action are registered, nivolumab and pembrolizumab. At the ESMO 2017 Congress, the results of PACIFIC study showing benefit with immunotherapy treatment also in locally advanced patients with NSCLC were presented. Patients had received durvalumab or placebo after standard treatment with chemoradiotherapy. In the group treated with durvalumab, the progression-free survival was significantly longer. The synergistic effect of irradiation, a widely recognized method of local treatment, in combination with immunotherapy, blurs the boundaries between the systemic and local treatment of cancer, as has been shown by numerous pre-clinical studies. Future research will provide answers which method of combining immunotherapy and irradiation is most appropriate.V zadnjih petnajstih letih smo priča hitremu razvoju na področju zdravljenja pljučnega raka, ki ostaja v svetovnem merilu še vedno rak z najvišjo obolevnostjo in umrljivostjo. Večina bolnikov z metastatsko boleznijo se zdravi s kemoterapijo (KT), tarčno zdravljenje je primerno za manj kot 20% bolnikov z nedrobnoceličnim pljučnim rakom (NDPR). V letu 2010 so nas navdušili rezultati raziskav na področju imunoterapije. Tumorske celice morajo biti prepoznane kot tuje telesu, da jih imunski sistem lahko odstrani. Vendar so tumorske celice razvile različne mehanizme za izmikanje imunskemu nadzoru, eden od teh je tudi sproščanje imunskih zaviralnih molekul kot je ligand programirane celične smrti (PD-L1), ki je glavni mediator imunosupresivnega delovanja. Zdravila, ki se trenutno uporabljajo za zdravljenje metastatskega NDPR, so monoklonska protitelesa proti PD-L1 ali PD-1. Z vezavo na PD-L1 ali njegov receptor PD-1 na imunskih celicah preprečijo imunosupresiven učinek in omogočijo uspešno delovanje aktiviranih T limfocitov. V Sloveniji sta registrirani dve zdravili z opisanim načinom delovanja, nivolumab in pembrolizumab. Na kongresu ESMO 2017 pa so bili predstavljeni rezultati raziskave PACIFIK, ki opisujejo dobrobit zdravljenja z imunoterapijo tudi pri lokalno napredovalih bolnikih z NDPR. Bolniki so po standardnem zdravljenju s kemoradioterapijo prejemali durvalumab ali placebo. V skupini, zdravljeni z durvalumabom, je bil čas brez napredovanja bolezni značilno daljši. Sinergistično delovanje obsevanja, ki je splošno priznan način lokalnega zdravljenja, v kombinaciji z imunoterapijo briše meje med sistemskim in lokalnim načinom zdravljenja raka, kar so pokazale tudi številne predklinične raziskave. Bodoče raziskave bodo podale odgovore, kateri način kombiniranja imunoterapije in obsevanja je najbolj primeren