Tumorska kaheksija kao predskazatelj kemoterapijske toksičnosti i vremena do tumorske progresije u bolesnika s proširenim karcinomom pluća [Cancer cachexia as a predictor of chemotherapy toxicity and time-to-tumor progression in patients with advanced non-small cell lung cancer]

Srdić, Dražena (2017) Tumorska kaheksija kao predskazatelj kemoterapijske toksičnosti i vremena do tumorske progresije u bolesnika s proširenim karcinomom pluća [Cancer cachexia as a predictor of chemotherapy toxicity and time-to-tumor progression in patients with advanced non-small cell lung cancer]. PhD thesis, Sveučilište u Zagrebu.

[img] PDF
Download (1MB)

Abstract

Background. Cancer cachexia and sarcopenia are frequently observed in cancer patients and associated with poor survival. The majority of studies of cancer cachexia and sarcopenia have been done in patients with solid tumors of different origin, and there are currently no good predictors of the benefit of chemotherapy or factors that predict survival in advanced cancer. The purpose of our prospective study was to evaluate prevalence of cachexia and sarcopenia using international consensus definition and criteria for diagnosis in patients with diagnosed advanced non-small cell lung cancer (NSCLC) stage IIIB and IV and their relation to chemotherapy toxicity and survival prediction. A secondary aim was to compare several biochemical and haematological markers (CRP, IL-6, protein and albumin) with time to tumor progression in order to assess prognostic value or to guide a treatment. Patients and Methods. Between December 2013 and April 2015, the prospective cohort study of one hundred Caucasian patients with advanced NSCLC stage IIIB or IV, who were referred consecutively to Department for Respiratory Diseases “Jordanovac” was evaluated. Anthropometric measurements and biochemical / haematological data (CRP, albumin, protein, IL-6, haemoglobin) together with body composition measurements (total muscle cross sectional area, lumbar skeletal muscle index) were obtained for each patient before starting with platinum-doublet therapy. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured by computerized tomography, and sarcopenia was defined using a previously published cut-off point. Toxicity was assessed after cycle 1 of treatment and time-to-tumor progression was determined prospectively. Results. One hundred patients with advanced lung cancer were recruited: 67 were male, median age was 64 years. The median time to disease progression was 187 days. The prevalence of cachexia and sarcopenia in study cohort was 69 %, and 47 %, respectively. CRP, IL-6 and albumin concentration in cachectic, compared to non-cachectic patients demonstrated statistically significant difference (p = 0,020, p = 0,040, p = 0,003). Cachexia and sarcopenia were not found to be predictors of chemotoxicity nor time to tumor progression. On the contrary, albumin concentration with established cut-off point of 37.5 g/L was clearly proved as the predictive factor of both chemotoxicity (OR (95% CI) = 0.85; p < 0.001) and survival (HR (95% CI) = 0,55). Conclusion. Albumin level has shown to be more important predictive marker of chemotherapy toxicity and survival than cachexia and sarcopenia. This approach in clinical settings can be used to guide the choice of oncologic treatment.

Abstract in Croatian

Uvod. Tumorska kaheksija i sarkopenija često se javljaju u bolesnika oboljelih od karcinoma i povezani su s lošim ishodom. Većina ispitivanja tumorske kaheksije i sarkopenije učinjena je kod pacijenata sa solidnim tumorima različitog podrijetla te trenutno ne postoje definirani predskazatelji koristi diferentnog onkološkog liječenja citostaticima ili preživljenja u pacijenata koji boluju od uznapedovalog karcinoma. Hipoteza. Glavna hipoteza. Kaheksija i sarkopenija u bolesnika s proširenim ne-mikrocelularnim karcinomom pluća uzrokuju slabiji odgovor na onkološku terapiju, uz veću toksičnost kemoterapije i kraće vrijeme do progresije bolesti, a time i kraće preživljenje u odnosu na skupinu bolesnika koji nisu kahektični i/ili sarkopenični. Pomoćne hipoteze. Bolesnici kod kojih je izmjerena niža razina albumina prije započetog onkološkog liječenja imaju veću mogućnost razvitka kemoterapijske toksičnosti i kraće vrijeme do progresije bolesti. Povišeni biokemijski parametri upale – CRP i IL-6 su češće prisutni u bolesnika s kaheksijom i sarkopenijom. Ispitanici i metode. Prospektivno istraživanje provedeno je od prosinca 2013. godine do travnja 2015. godine. U studijsku kohortu uključeno je 100 bolesnika (bijelaca) oboljelih od uznapredovalog ne-mikrocelularnog karcinoma pluća stadija IIIB i IV koji su se javili u Kliniku za plućne bolesti Jordanovac, u Zavod za tumore pluća i sredoprsja. Prikupljeni su i izračunati antropometrijski, biokemijski i hematološki parametri (CRP, albumini, proteini, IL-6, hemoglobin) te analiza tjelesnog sastava (ukupna mišića površina, indeks mišićne površine) kod svakog pacijenta prije započinjanja dvojnog kemoterapijskog protokola s platinom. CT-om je mjerena površina mišića na razini L3, a sarkopenija je definirana koristeći prethodno evaluirane granične vrijednosti. Kemoterapijska toksičnost je evaluirana nakon apliciranog prvog ciklusa kemoterapije, a vrijeme do tumorske progresije je izraženo u danima od dana aplikacije kemoterapeutika do dana kada je verificirana radiološka progresija bolesti. Rezultati. Od 100 pacijenata uključenih u istraživanje, 67 su bili muškarci, medijan starosti 64 godine. Medijan vremena do tumorske progresije bolesti iznosio je 187 dana. Prevalencija kaheksije i sarkopenije u studijskoj kohorti iznosila je 69% i 47%. CRP, IL-6 i razina albumina u kahektičkih i nekahektičkih bolesnika je bila statistički značajno različita (p = 0,020, p = 0,040, p = 0,003). Kaheksija i sarkopenija nisu se pokazali predskazateljima kemoterapijske toksičnosti niti vremena do tumorske progresije. Suprotno tome, razina albumina s utvrđenom graničnom vrijednosti od 37,5 g/L pokazala se kao predskazateljem kemoterapijske toksičnosti (OR (95% CI) = 0,85; p < 0,001) i preživljenja (HR (95% CI) = 0,55). Zaključak. Razina albumina prepoznata je kao predskazatelj kemoterapijske toksičnosti i preživljenja. Kaheksija odnosno sarkopenija ovdje nisu prepoznate kao predskazatelji, vjerojatno zbog visoke prevalencije u studijskoj kohorti (69 %, odnosno 47 %). Ovakve spoznaje se u klinici mogu koristiti za individualiziranje onkološke terapije.

Item Type: Thesis (PhD)
Mentors:
Mentor
Samaržija, Miroslav
Departments: Izvan medicinskog fakulteta
Depositing User: Anja Majstorović
University: Sveučilište u Zagrebu
Institution: Medicinski fakultet
Number of Pages: 74
Status: Unpublished
Creators:
CreatorsEmail
Srdić, DraženaUNSPECIFIED
Date: 28 February 2017
Date Deposited: 17 Jan 2019 12:29
Last Modified: 17 Jan 2019 12:29
Subjects: /
Related URLs:
    URI: http://medlib.mef.hr/id/eprint/3059

    Actions (login required)

    View Item View Item

    Downloads

    Downloads per month over past year