Matej Bracko

Publications (48) View all

• Source

  Available from: Maja Marolt Music

  Article: Neoadjuvant capecitabine, radiotherapy, and bevacizumab (CRAB) in locally advanced rectal cancer: results of an open-label phase II study.

  Vaneja Velenik, Janja Ocvirk, Maja Music, Matej Bracko, Franc Anderluh, Irena Oblak, Ibrahim Edhemovic, Erik Brecelj, Mateja Kropivnik, Mirko Omejc
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  ABSTRACT: Preoperative capecitabine-based chemoradiation is a standard treatment for locally advanced rectal cancer (LARC). Here, we explored the safety and efficacy of the addition of bevacizumab to capecitabine and concurrent radiotherapy for LARC. Patients with MRI-confirmed stage II/III rectal cancer received bevacizumab 5 mg/kg i.v. 2 weeks prior to neoadjuvant chemoradiotherapy followed by bevacizumab 5 mg/kg on Days 1, 15 and 29, capecitabine 825 mg/m2 twice daily on Days 1-38, and concurrent radiotherapy 50.4 Gy (1.8 Gy/day, 5 days/week for 5 weeks + three 1.8 Gy/day), starting on Day 1. Total mesorectal excision was scheduled 6-8 weeks after completion of chemoradiotherapy. Tumour regression grades (TRG) were evaluated on surgical specimens according to Dworak. The primary endpoint was pathological complete response (pCR). 61 patients were enrolled (median age 60 years [range 31-80], 64% male). Twelve patients (19.7%) had T3N0 tumours, 1 patient T2N1, 19 patients (31.1%) T3N1, 2 patients (3.3%) T2N2, 22 patients (36.1%) T3N2 and 5 patients (8.2%) T4N2. Median tumour distance from the anal verge was 6 cm (range 0-11). Grade 3 adverse events included dermatitis (n = 6, 9.8%), proteinuria (n = 4, 6.5%) and leucocytopenia (n = 3, 4.9%). Radical resection was achieved in 57 patients (95%), and 42 patients (70%) underwent sphincter-preserving surgery. TRG 4 (pCR) was recorded in 8 patients (13.3%) and TRG 3 in 9 patients (15.0%). T-, N- and overall downstaging rates were 45.2%, 73.8%, and 73.8%, respectively. This study demonstrates the feasibility of preoperative chemoradiotherapy with bevacizumab and capecitabine. The observed adverse events of neoadjuvant treatment are comparable with those previously reported, but the pCR rate was lower.
  Radiation Oncology 08/2011; 6:105. · 2.32 Impact Factor
• Article: EGF61 polymorphism predicts complete pathologic response to cetuximab-based chemoradiation independent of KRAS status in locally advanced rectal cancer patients.

  Siwen Hu-Lieskovan, Daniel Vallbohmer, Wu Zhang, Dongyun Yang, Alexander Pohl, Melissa J Labonte, Peter P Grimminger, Arnulf H Hölscher, Robert Semrau, Dirk Arnold, Kathrin Dellas, Annelies Debucquoy, Karin Haustermans, Jean-Pascal H Machiels, Christine Sempoux, Claus Rödel, Matej Bracko, Vaneja Velenik, Heinz-Josef Lenz
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  ABSTRACT: Cetuximab has shown significant clinical activity in metastatic colon cancer. However, cetuximab-containing neoadjuvant chemoradiation has not been shown to improve tumor response in locally advanced rectal cancer patients in recent phase I/II trials. We evaluated functional germline polymorphisms of genes involved in epidermal growth factor receptor pathway, angiogenesis, antibody-dependent cell-mediated cytotoxicity, DNA repair, and drug metabolism, for their potential role as molecular predictors for clinical outcome in locally advanced rectal cancer patients treated with preoperative cetuximab-based chemoradiation. 130 patients (74 men and 56 women) with locally advanced rectal cancer (4 with stage II, 109 with stage III, and 15 with stage IV, 2 unknown) who were enrolled in phase I/II clinical trials treated with cetuximab-based chemoradiation in European cancer centers were included. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor samples and genotyping was done by using PCR-RFLP assays. Fisher's exact test was used to examine associations between polymorphisms and complete pathologic response (pCR) that was determined by a modified Dworak classification system (grade III vs. grade IV: complete response). Patients with the epidermal growth factor (EGF) 61 G/G genotype had pCR of 45% (5/11), compared with 21% (11/53) in patients heterozygous, and 2% (1/54) in patients homozygous for the A/A allele (P < 0.001). In addition, this association between EGF 61 G allele and pCR remained significant (P = 0.019) in the 59 patients with wild-type KRAS. This study suggested EGF A+61G polymorphism to be a predictive marker for pCR, independent of KRAS mutation status, to cetuximab-based neoadjuvant chemoradiation of patients with locally advanced rectal cancer.
  Clinical Cancer Research 06/2011; 17(15):5161-9. · 7.74 Impact Factor
• Article: Biomarkers for cetuximab-based neoadjuvant radiochemotherapy in locally advanced rectal cancer.

  Peter P Grimminger, Peter Danenberg, Kathrin Dellas, Dirk Arnold, Claus Rödel, Jean-Pascal Machiels, Karin Haustermans, Annelies Debucquoy, Vaneja Velenik, Christine Sempoux, Matej Bracko, Arnulf H Hölscher, Robert Semrau, Dongyun Yang, Kathleen Danenberg, Heinz-Josef Lenz, Daniel Vallböhmer
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  ABSTRACT: Phase II trials in locally advanced rectal cancer have shown that cetuximab-based neoadjuvant radiochemotherapy is feasible but without an improvement in complete pathologic response rates. Our goal was to identify patients who would benefit from cetuximab-based neoadjuvant chemoradiation measuring gene expression levels of proteins involved in tumor growth [endothelial growth factor receptor (EGFR)], angiogenesis [VEGF, VEGF receptors 1 and 2 (VEGFR1, VEGFR2)], DNA repair [excision repair cross-complementing 1 (ERCC1)], and drug metabolism [thymidylate synthetase (TS)]. We also determined mutation status of KRAS and BRAF. This study was carried out on 130 patients with locally advanced rectal cancer who were enrolled in 4 different phase II clinical trials, using cetuximab-based chemoradiation. Tumor tissues were obtained before neoadjuvant and at surgical therapy. After microdissection, intratumoral gene expression levels and KRAS/BRAF mutation status were analyzed. A significant decrease of TS, VEGFR1, and VEGFR2 gene expression was seen following neoadjuvant therapy (P < 0.03). High pretreatment VEGF gene expression levels were associated with nonresponse (P = 0.070). KRAS mutations were found in 42% and mutant KRAS (KRAS mt) was significantly associated with pathologic nonresponse (P = 0.037). In patients with wild-type KRAS (KRAS wt), low EGFR was significantly associated with higher nonresponse and VEGF mRNA expressions were associated with complete pathologic response (P = 0.012; P = 0.06). KRAS transversion (KRAS tv) was associated with tumor regression: nonresponse was more common in patients with KRAS tv than with KRAS wt (P = 0.007). BRAF V600E mutations were not detected in any of the patients. This study suggests that pretreatment intratumoral EGFR and VEGF mRNA expression levels as well as KRAS mutation status are predictive markers of pathologic response to neoadjuvant cetuximab-based chemoradiation in locally advanced rectal cancer.
  Clinical Cancer Research 05/2011; 17(10):3469-77. · 7.74 Impact Factor
• Article: Primary bone angiosarcoma in a patient with Gaucher disease.

  Samo Zver, Matej Bracko, Dusan Andoljsek
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  ABSTRACT: Skeletal pain and the resulting skeletal complications are common in Gaucher disease. The patients therefore usually receive symptomatic treatment and only rarely undergo additional diagnostic procedures. The paper describes the case of a patient with Gaucher disease who had advancing pain in the right knee and femur, which was first attributed to the basic disease. After a pathological fracture of the painful part of the leg, it became evident that the patient suffered from primary bone angiosarcoma. From this case, we learnt that not every skeletal pain in Gaucher disease represents a skeletal manifestation of this disease. Further surgical treatment was made difficult by the thrombocyte dysfunction discovered in the patient.
  International journal of hematology 09/2010; 92(2):374-7. · 1.17 Impact Factor
• Source

  Available from: Damijan Miklavcic

  Article: Towards treatment planning and treatment of deep-seated solid tumors by electrochemotherapy.

  Damijan Miklavcic, Marko Snoj, Anze Zupanic, Bor Kos, Maja Cemazar, Mateja Kropivnik, Matej Bracko, Tjasa Pecnik, Eldar Gadzijev, Gregor Sersa
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  ABSTRACT: Electrochemotherapy treats tumors by combining specific chemotherapeutic drugs with an intracellular target and electric pulses, which increases drug uptake into the tumor cells. Electrochemotherapy has been successfully used for treatment of easily accessible superficial tumor nodules. In this paper, we present the first case of deep-seated tumor electrochemotherapy based on numerical treatment planning. The aim of our study was to treat a melanoma metastasis in the thigh of a patient. Treatment planning for electrode positioning and electrical pulse parameters was performed for two different electrode configurations: one with four and another with five long needle electrodes. During the procedure, the four electrode treatment plan was adopted and the patient was treated accordingly by electrochemotherapy with bleomycin. The response to treatment was clinically and radiographically evaluated. Due to a partial response of the treated tumor, the metastasis was surgically removed after 2 months and pathological analysis was performed. A partial response of the tumor to electrochemotherapy was obtained. Histologically, the metastasis showed partial necrosis due to electrochemotherapy, estimated to represent 40-50% of the tumor. Based on the data obtained, we re-evaluated the electrical treatment parameters in order to correlate the treatment plan with the clinical response. Electrode positions in the numerical model were updated according to the actual positions during treatment. We compared the maximum value of the measured electric current with the current predicted by the model and good agreement was obtained. Finally, tumor coverage with an electric field above the reversible threshold was recalculated and determined to be approximately 94%. Therefore, according to the calculations, a small volume of tumor cells remained viable after electrochemotherapy, and these were sufficient for tumor regrowth. In this, the first reported clinical case, deep-seated melanoma metastasis in the thigh of the patient was treated by electrochemotherapy, according to a treatment plan obtained by numerical modeling and optimization. Although only a partial response was obtained, the presented work demonstrates that treatment of deep-seated tumor nodules by electrochemotherapy is feasible and sets the ground for numerical treatment planning-based electrochemotherapy. EudraCT:2008-008290-54.
  BioMedical Engineering OnLine 02/2010; 9:10. · 1.40 Impact Factor