1. Influence of concurrent capecitabine based chemoradiotherapy with bevacizumab on the survival rate, late toxicity and health-related quality of life in locally advanced rectal cancer : a prospective phase II CRAB trialVaneja Velenik, Vesna Zadnik, Mirko Omejc, Jan Grosek, Mojca Tuta, 2020, izvirni znanstveni članek Povzetek: Few studies reported early results on efficacy, toxicity of combined modality treatment for locally advanced rectal cancer (LARC) by adding bevacizumab to preoperative chemoradiotherapy, but long-term data on survival, and late complications are lacking. Further, none of the studies reported on the assessment of quality of life (QOL). Patients and methods. After more than 5 years of follow-up, we updated the results of our previous phase II trial in 61 patients with LARC treated with neoadjuvant capecitabine, radiotherapy and bevacizumab (CRAB study) before surgery and adjuvant chemotherapy. Secondary endpoints of updated analysis were local control (LC), disease free (DFS) and overall survival (OS), late toxicity and longitudinal health related QOL (before starting the treatment and one year after the treatment) with questionnaire EORTC QLQ-C30 and EORTC QLQ-CR38. Results. Median follow-up was 67 months. During the follow-up period, 16 patients (26.7%) died. The 5-year OS, DFS and LC rate were 72.2%, 70% and 92.4%. Patients with pathological positive nodes or pathological T3%4 tumors had significantly worse survival than patients with pathological negative nodes or T0%2 tumors. Nine patients (14.8%) developed grade % 3 late complications of combined modality treatment, first event 12 months and last 87 months after operation (median time 48 months). Based on EORTC QLQ-C30 scores one year after treatment there were no significant changes in global QOL and three symptoms (pain, insomnia and diarrhea), but physical and social functioning significantly decreased. Based on QLQ-CR38 scores body image scores significantly increase, problems with weight loss significantly decrease, but sexual dysfunction in men and chemotherapy side effects significantly increase. Conclusions. Patients with LARC and high risk factors, such as positive pathological lymph nodes and high pathological T stage, deserve more aggressive treatment in the light of improving long-term survival results. Patients after multimodality treatment should be given greater attention to the regulation of individual aspects of quality of life and the occurrence of late side effects.
Ključne besede: rectal cancer, bevacizumab, preoperative chemoradiotherapy
Objavljeno v DiRROS: 15.07.2024; Ogledov: 108; Prenosov: 34
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2. Nuclear magnetic resonance metabolic fingerprint of bevacizumab in mutant IDH1 glioma cellsTanja Mesti, Nadia Bouchemal, Claire Banissi, Mohamed N. Triba, Carole Marbeuf-Gueye, Maja Čemažar, Laurence Le Moyec, Antoine F. Carpentier, Philippe Savarin, Janja Ocvirk, 2018, izvirni znanstveni članek Povzetek: Malignant gliomas are rapidly growing tumours that extensively invade the brain and have bad prognosis. Our study was performed to assess the metabolic effects of bevacizumab on the glioma cells carrying the IDH1 mutation, a mutation, associated with better prognosis and treatment outcome. Bevacizumab is known to inhibit tumour growth by neutralizing the biological activity of vascular endothelial growth factor (VEGF). However, the direct effects of bevacizumab on tumour cells metabolism remain poorly known. Materials and methods The immunoassay and MTT assay were used to assess the concentration of secreted VEGF and cell viability after bevacizumab exposure. Metabolomic studies on cells were performed using high resolution magic angle spinning spectroscopy (HRMAS). Results mIDH1-U87 cells secreted VEGF (13 ng/mL). Regardless, bevacizumab had no cytotoxic effect, even after a 72h exposure and with doses as high as 1 mg/mL. Yet, HRMAS analysis showed a significant effect of bevacizumab (0.1 mg/mL) on the metabolic phenotype of mIDH1-U87 cells with elevation of 2-hydroxyglutarate and changes in glutamine group metabolites (alanine, glutamate, glycine) and lipids (polyunsaturated fatty acids [PUFA], glycerophosphocholine, and phosphocholine). Conclusions In mIDH1-U87 cells, changes in glutamine group metabolites and lipids were identified as metabolic markers of bevacizumab treatment. These data support the possibility of a functional tricarboxylic acid cycle that runs in reductive manner, as a probable mechanism of action of bevacizumab in IDH1 mutated gliomas and propose a new target pathway for effective treatment of malignant gliomas.
Ključne besede: symptomatic pseudoprogression, atypical response, immunotherapy, lung cancer, idh1 mutation, malignant glioma, bevacizumab, metabolic fingerprint
Objavljeno v DiRROS: 11.06.2024; Ogledov: 116; Prenosov: 54
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3. Bevacizumab plus chemotherapy in elderly patients with previously untreated metastatic colorectal cancer : single center experienceJanja Ocvirk, Maja Ebert Moltara, Tanja Mesti, Marko Boc, Martina Reberšek, Neva Volk, Jernej Benedik, Zvezdana Hlebanja, 2016, izvirni znanstveni članek Povzetek: Metastatic colorectal cancer (mCRC) is mainly a disease of elderly, however, geriatric population is underrepresented in clinical trials. Patient registries represent a tool to assess and follow treatment outcomes in this patient population. The aim of the study was with the help of the patients% register to determine the safety and efficacy of bevacizumab plus chemotherapy in elderly patients who had previously untreated metastatic colorectal cancer. Patients and methods. The registry of patients with mCRC was designed to prospectively evaluate the safety and efficacy of bevacizumab-containing chemotherapy as well as selection of patients in routine clinical practice. Patient baseline clinical characteristics, pre-specified bevacizumab-related adverse events, and efficacy data were collected, evaluated and compared according to the age categories. Results. Between January 2008 and December 2010, 210 patients with mCRC (median age 63, male 61.4%) started bevacizumab-containing therapy in the 1st line setting. Majority of the 210 patients received irinotecan-based chemotherapy (68%) as 1st line treatment and 105 patients (50%) received bevacizumab maintenance therapy. Elderly (% 70 years) patients presented 22.9% of all patients and they had worse performance status (PS 1/2, 62.4%) than patients in < 70 years group (PS 1/2, 35.8%). Difference in disease control rate was mainly due to inability to assess response in elderly group (64.6% in elderly and 77.8% in < 70 years group, p = 0.066). The median progression free survival was 10.2 (95% CI, 6.7%16.2) and 11.3 (95% CI, 10.2%12.6) months in elderly and < 70 years group, respectively (p = 0.58). The median overall survival was 18.5 (95% CI, 12.4%28.9) and 27.4 (95% CI, 22.7%31.9) months for elderly and < 70 years group, respectively (p = 0.03). Three-year survival rate was 26% and 37.6% in elderly vs. < 70 years group (p = 0.03). Overall rates of bevacizumab-related adverse events were similar in both groups: proteinuria 21/22 %, hypertension 25/19 %, haemorrhage 2/4 % and thromboembolic events 10/6 %, for elderly and < 70 years group, respectively. Conclusions. In routine clinical practice, the combination of bevacizumab and chemotherapy is effective and welltolerated regimen in elderly patients with metastatic colorectal cancer.
Ključne besede: metastatic colorectal cancer, bevacizumab, chemotherapy, elderly
Objavljeno v DiRROS: 30.04.2024; Ogledov: 331; Prenosov: 102
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4. Bevacizumab and irinotecan in recurrent malignant glioma, a single institution experienceTanja Mesti, Maja Ebert Moltara, Marko Boc, Martina Reberšek, Janja Ocvirk, 2015, izvirni znanstveni članek Povzetek: Treatment options of recurrent malignant gliomas are very limited and with a poor survival benefit. The results from phase II trials suggest that the combination of bevacizumab and irinotecan is beneficial. Patients and methods. The medical documentation of 19 adult patients with recurrent malignant gliomas was retrospectively reviewed. All patients received bevacizumab (10 mg/kg) and irinotecan (340 mg/m2 or 125 mg/m2) every two weeks. Patient clinical characteristics, drug toxicities, response rate, progression free survival (PFS) and overall survival (OS) were evaluated. Results. Between August 2008 and November 2011, 19 patients with recurrent malignant gliomas (median age 44.7, male 73.7%, WHO performance status 0%2) were treated with bevacizumab/irinotecan regimen. Thirteen patients had glioblastoma, 5 anaplastic astrocytoma and 1 anaplastic oligoastrocytoma. With exception of one patient, all patients had initially a standard therapy with primary resection followed by postoperative chemoradiotherapy. Radiological response was confirmed after 3 months in 9 patients (1 complete response, 8 partial responses), seven patients had stable disease and three patients have progressed. The median PFS was 6.8 months (95% confidence interval [CI]: 5.3-8.3) with six-month PFS rate 52.6%. The median OS was 7.7 months (95% CI: 6.6-8.7), while six-month and twelve-month survival rates were 68.4% and 31.6%, respectively. There were 16 cases of hematopoietic toxicity grade (G) 1-2. Non-hematopoietic toxicity was present in 14 cases, all G1-2, except for one patient with proteinuria G3. No grade 4 toxicities, no thromboembolic event and no intracranial hemorrhage were observed. Conclusions. In recurrent malignant gliomas combination of bevacizumab and irinotecan might be an active regimen with acceptable toxicity.
Ključne besede: recurrent malignant glioma, systemic therapy, bevacizumab
Objavljeno v DiRROS: 17.04.2024; Ogledov: 267; Prenosov: 87
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5. Rak jajčnikov : česa še ne vemo? : ginekološki simpozij : Ljubljana, 2. 12. 2021 : zbornik znanstvenih prispevkov2021, zbornik strokovnih ali nerecenziranih znanstvenih prispevkov na konferenci Povzetek: Ginekološki simpozij Rak Jajčnika: Česa še ne vemo? zajema sklop predavanj, kjer so predstavljeni začetna obravnava žensk s tumorji v področju jajčnikov, nadaljnja predoperativna priprava, najradikalnejši kirurški posegi in zadnje smernice na področju sistemske terapije. Prav tako pozornost namenjamo tudi stereotaktičnemu obsevanju in imunoterapiji, ki na področju ginekoloških rakov počasi dobiva svojo veljavo in mesto.
Ključne besede: napredovali rak, mejno maligni tumorji, ekstraabdominalna kirurgija, citoredukcija, bevacizumab, polimorbidnost, stereotaktično obsevanje, imunoterapija, zborniki, elektronske knjige
Objavljeno v DiRROS: 10.03.2022; Ogledov: 881; Prenosov: 421
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6. Naše izkušnje z zdravilom bevacizumab v primarnem zdravljenju epitelijskega raka jajčnikovErik Škof, Dushan Mangaroski, 2020, izvirni znanstveni članek Povzetek: Izhodišče: Zdravilo bevacizumab uporabljamo v sklopu primarnega sistemskega zdravljenja napredovalega epitelijskega raka jajčnikov v kombinaciji s paklitakselom in karboplatinom od leta 2013.
Namen: Prikazati učinkovitost in varnost zdravljenja z bevacizumabom v redni klinični praksi v sklopu primarnega zdravljenja raka jajčnikov.
Metode: V retrospektivno analizo smo vključili bolnice z epitelijskim rakom jajčnikov, ki so se zdravile z bevacizumabom na Onkološkem inštitutu Ljubljana v obdobju od 1. 1. 2013 do 31. 12. 2016. Cilja raziskave sta bila varnost in učinkovitost (preživetje brez ponovitve bolezni, celokupno preživetje) zdravljenja z bevacizumabom. Raziskavo je odobrila etična komisija na Onkološkem inštitutu Ljubljana.
Rezultati: V opazovanem obdobju je bilo z bevacizumabom zdravljenih 111 bolnic z napredovalim epitelijskim rakom jajčnikov. Najpogostejši neželeni učinki so bili: bolečine (52 %), krvavitev (45 %), arterijska hipertenzija (44 %). Resne neželene učinke (stopnja 3/4) je imelo 12 % bolnic: venska tromboza/ embolija (3 %), proteinurija (3 %), arterijska hipertenzija (2 %), krvavitev (2 %), bolečine (1 %), fistula (1 %). Mediani čas sledenja je bil 59 mesecev. Mediano preživetje brez ponovitve bolezni je bilo 18 mesecev, mediano celokupno preživetje pa 41 mesecev.
Zaključki: Zdravljenje z bevacizumabom v redni klinični praksi je varno in učinkovito ‒ v skladu z do zdaj znanimi rezultati prospektivnih raziskav GOG 218 in ICON 7.
Ključne besede: rak jajčnikov, epitelijski rak, bevacizumab, kemoterapija
Objavljeno v DiRROS: 09.09.2020; Ogledov: 2104; Prenosov: 549
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