Title Extended molecular testing of consecutive tumor specimen and subsequent treatment
Title (croatian) Prošireno molekularno testiranje uzastopnog uzorka tumora i zaključci za buduće terapije
Author Finja Marie Schwenkenbecher
Mentor Christof Lamberti (mentor)
Committee member Johannes Brachmann (predsjednik povjerenstva)
Committee member Sigrun Renate Merger (član povjerenstva)
Committee member Walter Ludwig Strohmaier (član povjerenstva)
Granter University of Split School of Medicine Split
Defense date and country 2022-09-07, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Clinical Medical Sciences Oncology
Abstract Objectives: The purpose of this study is to confirm, whether detailed genetic testing of
patients with advanced tumor stage provides the basis for new molecular targeted therapies
and to determine, if detailed genetic testing extends treatment options and improves the
outcome. In addition, the frequency of molecular alterations and their level of evidence were
determined in an unselected group of patients. Furthermore, we investigated the frequency of
targetable genomic aberrations and the proportion of patients actually treated with targeted
therapy.
Materials and Methods: 54 patients who received detailed genetic testing in the year 2020
to detect possible pathogenic mutations were included in this study. All of them were
diagnosed with cancer and treated at the oncologic ambulatory health care center in Coburg.
In total, 58 detailed genetic tests were performed using the Oncomine Comprehensive v3
panels or the Oncomine Focus panels. Electronic medical records were reviewed for the
patient characteristics and Evidence Level classification was used to help interpreting somatic
variants and evaluate their diagnostic, prognostic and therapeutic implications.
Results: Most (70%) of the patients with different cancer types exhibit a targetable genetic
alteration but only 14.8% of the patients eligible for targeted therapy received a targeted
therapy. The majority (70.4%) of patients, regardless of whether they received targeted
therapy or not, deceased between the time the test was performed in 2020 and the time the
data was collected. Also, there was no significant difference between the patients receiving
targeted therapy and those receiving a physician’s choice therapy regarding their death 3
months after performing the detailed genetic test.
Conclusions: Predominantly elderly patients with advanced disease and multiple prior
therapies received detailed genetic testing. Even though a substantial number of unselected
incurable cancer patients exhibit targetable genetic alterations and are eligible for targeted
therapy only a few of the patients actually receive it. This is attributed to difficult drug
development targeting genomic aberrations, high costs of clinical trials and available drugs as
well as limited access of patients to clinical trials. Also a high mortality of the patients was
observed regardless of whether they received targeted therapy or not.
Abstract (croatian) Ciljevi: Svrha ove studije je potvrditi da li je detaljno genetsko testiranje bolesnika s
uznapredovalim stadijem tumora temelj za nove molekularno ciljane terapije. Uz to se
ispituje, proširuje li detaljno genetsko testiranje mogućnosti liječenja, te poboljšava li ishod
terapije. Štoviše, utvrđena je učestalost molekularnih promjena i njihova razina dokaza u
neselektiranoj skupini pacijenata. Nadalje, istražili smo učestalost ciljanih genomskih
aberacija i udio pacijenata liječenih ciljanom terapijom.
Materijali i metode: Uključeno je 54 pacijenata koji su 2020. godine primili detaljno
genetsko testiranje za otkrivanje mogućih patogenih mutacija. Svima je dijagnosticiran rak i
liječeni su u onkološkom ambulantnom zdravstvenom centru u Coburgu. Ukupno je
provedeno 58 detaljnih genetskih testova koriščenjem panela Oncomine Comprehensive v3
ili panela Oncomine Focus. Pregledani su digitalni medicinski zapisi pacijenata iz kojih su
izvađeni karakteristične podatke. Procjena razine dokaza je rađena kako bi se protumačile
somatske varijante i procjenile njihove dijagnostičke, prognostičke i terapijske implikacije.
Rezultati: Većina (70%) pacijenata s različitim tipovima raka pokazuje genetsku promjenu
pogodno za ciljanu terapiju, ali samo 14,8% pacijenata koji su kvalificirani za ciljanu terapiju
primilo je ciljana terapiju. Većina (70,4%) pacijenata, neovisno o tome jesu li primali ciljanu
terapiju ili ne, preminula je između vremena provedenog testa 2020. godine i trenutka
prikupljanja podataka. Također, nije bilo značajne razlike između pacijenata koji su primali
ciljanu terapiju i pacijenata koji su primali terapiju po izboru liječnika, u pogledu na smrtnost
3 mjeseca nakon genetskog testa.
Zaključci: Pretežno stariji pacijenti u naprednom stadiju bolesti i više prethodnim terapijama
primili su detaljno genetsko testiranje. Iako značajan broj neizlječivih pacijenata pokazuje
genetske promjene koje se mogu liječiti ciljanom terapijom, samo manjina pacijenata zapravo
i prima ciljanu terapiju. Ova činjenica se može pripisivati teškom razvoju lijekova usmjerena
na genomske aberacije, visokim troškovima kliničkih ispitivanja i dostupnih lijekova. Uz to,
otežavajuči dolazi i ograničeni pristup pacijentima kliničkim ispitivanjima. Također je
primijećena visoka smrtnost pacijenata bez obzira na primanje ciljane ili konvencionalne
terapije.
Keywords
Detailed genetic testing
Advanced tumor disease
Targeted therapy
Keywords (croatian)
detaljno genetsko testiranje
uznapredovala tumorska bolest
ciljana terapija
Language english
URN:NBN urn:nbn:hr:171:706220
Study programme Title: Medical Studies in English Study programme type: university Study level: integrated undergraduate and graduate Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
Type of resource Text
File origin Born digital
Access conditions Open access
Terms of use
Repository MEFST Repository
Created on 2022-09-08 13:03:00