Influence of nutritional status on survival in patients treated for retroperitoneal sarcoma

Ramanović, Manuel (avtor), Rotovnik Kozjek, Nada (mentor), Perhavec, Andraž (komentor)

Retroperitoneal sarcomas (RPS) are rare connective tissue malignancy posing both diagnostic and therapeutic challenge in surgical oncology. The present thesis investigated the impact of body composition and immune and inflammatory-related biomarkers on oncologic and operative outcomes in patients with primary RPS underwent surgery for curative intent. In retrospective study were included total of 100 patients operated at Institute of Oncology in Ljubljana between 1999 and 2020. According to availability of preoperative computed tomography (CT) scans, study cohort was divided into 2 subgroups: one with CT scans (N = 58) and the other without. Using CT scans at the third lumbar vertebrae level, the preoperative skeletal muscle area (SMA), visceral and subcutaneous adipose tissue area (VAT and SAT), and muscle radiation attenuation (MRA) were measured. To diagnose malnutrition the Global Leadership Initiative on Malnutrition (GLIM) criteria were used, whereas low muscle mass (myopenia) was defined based on updated European Working Group on Sarcopenia in Older People criteria. Furthermore, using the maximally selected log-rank statistics, optimal cohort-specific cut-off values for body composition parameters were investigated. Fearon et al. criteria from 2011 were used to define cachexia. Myosteatosis was defined based on a BMI-adjusted MRA cut-offs. After a median follow-up period of 116 months, the estimated 5-year overall survival (OS) and local-recurrence free survival (LRFS) rates were 66.8 % and 77.6 %, respectively. Prevalence of malnutrition and cachexia was identical at 23.2 % of patients, while myopenia was detected in 33.3 %. Patients with preoperative malnutrition (log rank p = 0.035), myopenia (log rank p = 0.032) and cachexia (log rank p = 0.028) had a significantly lower 5-year OS. The skeletal muscle index and high subcutaneous adipose tissue index predicted LRFS in the univariate analysis (p = 0.052 and p = 0.039, respectively). Myosteatosis was linked to higher postoperative morbidity, but it was not correlated with OS and LRFS (p = 0.023). Lymphocyte to monocyte ratio (LMR) was the strongest inflammation-related prognostic biomarker, associated with OS (LMR ≤ 3 vs. LMR > 3, multivariate adjusted-HR 2.67, p = 0.027). Other immune and inflammation-related biomarkers did not yield sufficient evidence to be regarded as independent predictors in primary RPS. Based on research results we may conclude that preoperative body composition, nutrition disorders (malnutrition, cachexia), and nutrition related syndromes (myopenia, myosteatosis) and inflammation-related indices are important risk factors for survival and oncologic outcome in primary RPS.

• Jezik: Angleški jezik
• Ključne besede: malnutrition, sarcopenia, cancer cachexia, inflammation, nutrition, body composition, surgical oncology, retroperitoneal sarcoma
• Vrsta gradiva: Doktorsko delo/naloga
• Tipologija: 2.08 - Doktorska disertacija
• Organizacija: BF - Biotehniška fakulteta
• Založnik: [M. Ramanović]
• Leto izida: 2024
• PID: 20.500.12556/RUL-165872
• UDK: 613.24:616.006
• COBISS.SI-ID: 218892035
• Datum objave v RUL: 12.12.2024

Sekundarni jezik

• Jezik: Slovenski jezik
• Naslov: Vpliv prehranskega statusa na preživetje bolnikov, zdravljenih zaradi retroperitonealnega sarkoma

Izvleček

Retroperitonealni sarkomi (RPS) predstavljajo redko skupino malignih bolezni mehkih tkiv in predstavlja tako diagnostični kot terapevtski izziv. Pričujoča doktorska naloga je raziskala vpliv telesne sestave ter imunskih in z vnetjem povezanih biomarkerjev na onkološke in operativne izide pri bolnikih s primarnim RPS, ki so bili operirani z namenom ozdravljenja. V retrospektivno študijo je bilo vključenih skupno 100 bolnikov, operiranih na Onkološkem inštitutu v Ljubljani med letoma 1999 in 2020. Glede na razpoložljivost predoperativnih računalniških tomografov je bila študijska kohorta razdeljena v 2 podskupini: ena z CT (angl. Computer tomography, CT) slikovno diagnostiko (N = 58) in druga brez. Z uporabo računalniške analize CT-ja na nivoju tretjega ledvenega vretenca smo izmerili predoperativno površino skeletnih mišic (angl. Skeletal muscle area, SMA), površino visceralnega in podkožnega maščobnega tkiva (angl. Visceral adipose tissue area, VAT in angl. Subcutaneous adipose tissue area, SAT) ter oslabitev sevanja pri prehodu skozi mišice (angl. Muscle radiation attenuation, MRA). Za diagnosticiranje podhranjenosti so bila uporabljena merila Globalne pobude za opredelitev podhranjenosti (angl. Global leadership initiative for malnutrition, GLIM), medtem ko je bila nizka mišična masa (miopenija) opredeljena na podlagi posodobljenih meril Evropske delovne skupine za sarkopenijo pri starejših ljudeh. Z uporabo statistične metode maksimalnega log-rank testa so bile izračunane optimalne mejne vrednosti parametrov telesne sestave za to kohorto bolnikov. Kaheksija je bila opredeljena na osnovi kriterijev Fearona s sodelavci iz leta 2011. Miosteatoza je bila opredeljena na podlagi mejnih vrednosti MRA, ki so bile prilagojene ITM. Ocenjena stopnja 5-letnega celotnega preživetja (OS) in preživetja brez lokalnega recidiva (LRFS) v obdobju 116 mesecev (mediana) je bila 66.8 % oziroma 77.6 % Prevalenca podhranjenosti in kaheksije je bila enaka pri 23.2 % bolnikov, miopenija pa je bila ugotovljena pri 33.3 %. Bolniki s predoperativno podhranjenostjo (p = 0.035), miopenijo (p = 0.032) in kaheksijo (p = 0.028) so imeli značilno nižje 5-letno OS. Nizek SMI in visok indeks podkožnega maščobnega tkiva sta napovedala lokalno ponovitev LRFS v univariatni analizi (p = 0,052 oziroma p=0.039). Miosteatoza je bila povezana z večjo pooperativno obolevnostjo, vendar ni bila povezana z OS in LRFS (p=0.023). Razmerje med limfociti in monociti (angl. Lymphocyte to monocyte ratio, LMR) je bil najmočnejši z vnetjem povezan prognostični biomarker, povezan z OS (LMR ≤ 3 proti LMR > 3, multivariatno prilagojeno HR 2.67, p = 0.027). Drugi imunski in z vnetjem povezani biomarkerji niso dali zadostnih dokazov, da bi jih lahko šteli za neodvisne napovednike pri primarnem RPS. Na osnovi rezultatov raziskave tako ugotavljamo, da so predoperativna telesna sestava, motnje prehranjenosti (podhranjenost, kaheksija) in s prehranjevanjem povezani sindrom (miopenija, miosteatoza) in z vnetjem povezani indeksi pomembni dejavniki tveganja za ponovitev bolezni in preživetje pri primarnem RPS.

• Ključne besede: podhranjenost, sarkopenija, rakasta kaheksija, vnetje, prehrana, sestava telesa, onkološka kirurgija, retroperitonealni sarkom