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Volum 16 Numarul 2, 2010

The 20th Congress of the Romanian Society for Radiotherapy and Medical Oncology A Continuous Challenge: The Gynecologic Cancers (updated program)

55 Editorial

Gabriel Kacsó

56 Colorectal Cancer Stem Cells

Ciprian Tomuleasa1, Sergiu Şuşman2, Olga Soriţău1, Dan Rus-Ciucă2, Gabriel Kacsó2,3, Rareş Buigă4, Alexandru Irimie2,5

Ion Chiricuţa Institute of Oncology, Departments of 1Immunology, 3Radiotherapy, 4Pathology and 5Surgery, Cluj Napoca, România;

2 Iuliu Haţieganu University of Medicine and Pharmacy, Cluj Napoca, România.

Although the treatment of colorectal cancer has seen considerable progress during the past few years, the mortality associated with this type of tumor remains high. This article presents existing methods of treatment, focusing on the new treatments made possible by the advances in the field of normal and tumor stem cells. Starting from the normal architecture of the colon and the properties of the cells identified in it, we sought to present a few notions concerning these cells which have a direct relevance for both pathology and treatment. The manner in which they divide – symmetrically or asymmetrically – as well as the molecules which control their circulation through the body are just a few examples which are likely to influence the treatment of colorectal cancer in the future.

Key words: Cancer, Stem Cells, Colorectal.

64 Retrospective Analysis of the Angiogenesis in Brain Tumors: Clinical and Patho-biological Aspects

Liana Vereşezan1,2, Ovidiu Vereşezan3, Annie Laquerriere1,2, François Proust2,4, Corneliu Olinici5

1Rouen University Hospital Pathology Department, 2The University of Rouen Medical School, 3Henri Becquerel Cancer Centre, Rouen, France – Radiotherapy Department, 4Rouen University Hospital Neurosurgical Department, 5 „Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca

Introduction: The proliferation of solid tumors is dependent on the process of tumor neoangiogenesis. The dependence of gliomas on neoangiogenesis is supported by vascular hyperplasia, by vascular endothelial proliferation and by the necrosis associated with high-grade gliomas. Objectives: We discuss the experience of the Rouen University Hospital (France) in using imunohistochemistry for quantifying the vascularisation of gliomas and correlations with clinical evolution. Materials and methods: The clinical evolution of 69 patients who were treated between 2004 and 2007 at the Rouen University Hospital was retrospectively analysed. For all these patients VEGF, VEGFR, and EGFR antibodies, Ki67 index and p53 protein were studied by immunohistochemical methods. The clinical variables that were examined were: gender, age of diagnosis, imaging appearance, type of resection, histological grade, time to progression and overall survival. Results: With a median follow-up of 16 months, time to progression was 12 months and median survival was as high as 16 months. The VEGF expression was non-characteristic (either for normal endothelial cells or for tumor cells), and consequently non-contributory. The VEGFR expression was specific for the endothelial cells (either for normal endothelial cells or neoformation vessels). The EGFR expression was observed only for oligodendroglial cells, and also non-contributory in assessing neovascularisation. The Ki67 index was significantly correlated with the degree of differentiation, with histology and with lesion prognosis. The level of the p53 protein was predictive for high grade glioma relapses of initially well differentiated tumors. Conclusions: Current knowledge does not allow identification of molecular markers that reliably assess neovascularization, an essential step in evaluating the early response to experimental antiangiogenesis therapy.

Key words: Brain Gliomas, Angiogenesis, Molecular Markers.

69 Magnetic Resonance Angiography for NeuroVascular Bundle Dosimetry after Prostate Brachytherapy

Paola Mangili1, Gianpiero Cardone2, Andrei Fodor3, Luciano Nava4, Andrea Losa4, Barbara Longobardi1, Riccardo Calandrino1, Giorgio Guazzoni4, Giuseppe Balconi2, Nadia Di Muzio3

1Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy; 2 Department of Radiology, San Raffaele Turro H, Milan, Italy; 3 Department of Radiotherapy, San Raffaele Scientific Institute, Milan, Italy; 4 Department of Urology, San Raffaele Turro H, Milan, Italy.

Objective: With prostate brachytherapy (PB) the erectile function preservation rate is high, but a gradual decline occurs during the follow-up. The role of radiation dose to the Neurovascular Bundles (NVBs) in brachytherapy-related impotence is controversial, because of localisation difficulties. We investigated whether the use of Magnetic Resonance Angiography (MRA) improves the ability to localize NVBs with precision and to evaluate the administered dose to these structures. Materials and Methods: 10 patients, treated with prostate brachytherapy in monotherapy for cT1-T2 prostate cancer, underwent both conventional morphologic and angiographic MR examination after implantation. A “radiographic localization” of the NVBs was compared with the MRA localization while the NVBs dosimetry based on morphologic MR images was compared with that based on fused transverse T1w, T2w and MRA images. Results: MRA 2D-TOF sequence performed with the endorectal coil allowed an accurate evaluation of NVBs. The real locations of the bundles with respect of the prostate gland were found patient dependent. The differences between radiographic and MRA localization of NVBs were up to 3.3 cm (mean 0.6 cm). The NVBs doses evaluated on MRA images were found different from those derived from “radiographic localization” up to 189%. Conclusion: Conventional MR imaging cannot adequately visualize NVBs leading to unreliable dosimetric results. This study demonstrated that merging morphologic and angiographic MR images can lead to an accurate dosimetry of the NVBs.

Key words: Magnetic Resonance Angiography, Prostate Brachytherapy, NeuroVascular Bundle imaging, Potency.

75 Pilot Study using Gabapentin for Hot Flashes in Early Menopause Induced by Breast Cancer Treatment

Ciule Dorina-Larisa1, Nicolae Todor2

1County Emergency Hospital Cluj-Napoca, Romania,

2Ion Chiricuţă Institute of Oncology, Cluj-Napoca, Romania

Purpose: To consider whether treatment with Gabapentin may be effective in reducing hot flash frequency, severity and duration, and, at the same time evaluate the safety and tolerability profile. Patients and Methods: This is a pilot nonrandomized study which included 48 young breast cancer patients (45 years old or younger) in early menopause because of oncological treatment. We assessed the efficacy of Gabapentin in the treatment of moderate to severe hot flashes. Participants received Gabapentin titrated to 900 mg/day in three divided doses for 8 weeks and were followed up for 12 weeks. The patients recorded frequency, severity and duration of hot flashes on a 1-week, self-report hot flash diary before the start of the study and during weeks 4, 8 of treatment and after another 4 weeks, when the study was finished. Results: The median age of the patients was 40 years (range, 23-45). Data were available on 48 participants at 4 weeks, and 42 at 8 and 12 weeks. The percentage decreases in hot flash severity score between baseline and weeks 4, 8 and 12, respectively were: 54%, 61% and 15%; the hot flash frequency: 38%, 44% and 10%, and hot flash duration: 35%, 44% and 9%. The differences were statistically significant. The most frequent adverse events were: dizziness, somnolence, fatigue and nausea. Conclusion: Gabapentin is an effective non-hormonal treatment in the control of hot flashes at a dose of 900mg/day, in terms of frequency, severity and duration. This drug should be considered for treatment of hot flashes in young women with cancer therapy-induced early menopause.

Key words: Breast Cancer, Early Menopause, Gabapentin, Vasomotor Symptoms.

85 Defying the Hayflick Limit- Spontaneous Immortalization of HepCSC-1 Hepatic Cancer Stem Cell Line

Ciprian Tomuleasa1,2, Dan Rus-Ciucă2, Olga Soriţău1, Daniela Todea3, Bogdan Pintea4, Teodora Pop2,4, Ofelia Mosteanu2,4, Sergiu Susman2, Alexandru Irimie2,5

Departments of 1Cancer Immunology, 3Pathology and 5Surgery of Ion Chiricuţă Institute of Oncology, Cluj-Napoca;

2 Iuliu Haţieganu University of Medicine and Pharmacy, Cluj; 4 3rd Medical Clinic, Cluj-Napoca, Romania.

Background & purpose: Cancer stem cells (CSC) express high level of telomerase and proliferate unlimited, being practically immortal. We aimed to stabilize a human cultured hepatocarcinoma CSC line. Materials and Methods: Hepatocellular carcinoma-derived cancer stem cells were isolated from a partial hepatectomy of a patients with hepatocarcinoma on underlying cirrhosis and hepatitis B virus infection. Cancer stem-like cells expressed the pluripotency markers CD133, CD90, Oct 3, Nanog, GAPDH, CXCR4 or ABCG2 and were resistant to conventional chemotherapy in comparison with other cell types. Reverse-transcriptase polymerase chain was used to assess the telomerase expression. Results: Cell clones derived from human hepatocellular carcinoma stem cells were immortalized by overexpression of telomerase reverse transcriptase. The resulting cell line, HepCSC-1 (Hepatic cancer stem cell line) displayed multidrug resistance prior to immortalization and expressed the markers of hepatocyte progenitor cells albumin, a1-antitrypsin, a-fetoprotein and cytokeratin 18. HepCSC-1 cells were compared with mesenchymal stem cells isolated from the human healthy liver and with the hepatocarcinoma-derived cell line HepG2. The expression profile of telomerase levels was much more significant in comparison with all the other cell lines. Conclusion: We succeeded in generating a well characterized stable clonal human liver cancer cell line for in vitro drug testing, that we called HepCSC-1.

Key words: Hepatic Cancer, Stem Cell Line Immortalization, HepCSC-1.

89 Elastography in the Early Detection of Prostate Cancer

Călin Radu Giurgiu1, Sorin Dudea2, Ioan Coman2

1 Clinical Municipal Hospital of Cluj-Napoca, Department of Urology,

2 Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

Background & Purpose: Elastography (E) is a noninvasive ultrasound (US) method able to make the difference between tissues depending on their consistency. Our objective was to establish if E might improve early prostate cancer detection, alone or in association with others US methods (transrectal US = TRUS, Doppler US). Material & method: From March 2008 to December 2009 we analyzed 47 patients having at least one of the following malignancy suspicion criteria: PSA > 4 ng /ml, nodule(s) at digital rectal examination (DRE +) or TRUS. All the patients underwent TRUS, Doppler-US and E in the same session, followed by systematic TRUS prostate biopsies (6-12 cores) under local or general anesthesia. Histopathological findings were correlated with imagistic acquirements and clinical data. Results: The mean age of our patients was 68 years (49-74 years); the PSA ranged from 4.3 to 23 ng/ml. Seventeen patients (36.5 %) have been diagnosed with prostate cancer. E. had a sensitivity value of 70.6%, specificity 67.8%, positive predictive value of 57.14% and a negative predictive value of 79.17%, all values being superior to TRUS or Doppler US. Its diagnostic reliability was higher for patients having PSA <10 ng / ml, lower number of biopsies (6 vs. 10-12 cores), aged > 70 years and prostate volume < 55 grams. Conclusions: E. seems a reliable diagnostic method. Associated to others ultrasound methods (TRUS or/and Doppler), E might increase the diagnosis accuracy of early prostate cancer. Further study is needed to better define the role of E as a diagnostic tool in prostate cancer.

Key words: Prostate Cancer, Diagnosis, Elastography.

94 Undifferentiated Carcinoma of the Uterus

Case Presentation and Review of the Literature

Zsolt Fekete1,2, Alexandru Trăilă2, Rareş Buiga2, Viorica Nagy1,2

1 Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca;

2 Ion Chiricuta Institute of Oncology Cluj-Napoca, Romania.

Undifferentiated carcinoma is a subtype of uterine cancer with a worse prognosis than grade III endometrioid adenocarcinoma. We present a case with two synchronous uterine cancers- a small cell undifferentiated carcinoma and a mucinous adenocarcinoma.

Key words: Undifferentiated Cervix Carcinoma, Case Report.

98 Atypical Pelvic Relapse 6 Years after Radical Surgery and Adjuvant Radiotherapy for Stage IB2 Cervix Cancer

Septimiu Istrate1, Gabriel Kacsó1,2, Straciuc Oreste3, Minerva Miloiu1

1 Ion Chiricuta Institute of Oncology; 2 Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania;

3 Pozitron Diagnosztika PET/CT Oradea, Romania

We present the therapeutic solution for a 50 old woman with an IB2 FIGO stage cervical cancer presenting an atypical right massive lateral pelvic relapse 6 years after radical surgery and adjuvant radiotherapy.

Key words: Cervix Cancer, Late Recurrence, Therapy.

102 Report on the 2nd European Lung Cancer Conference (ELCC). 28 April-1 May, 2010, Geneva, Switzerland

Petronela Rusu

106 Report on the 5 ESTRO National Societies Meeting on “Radiation Oncology in Europe: Recent developments and future perspectives in patient care, research, training and legislation” 28-29 March 2010, Brussels, Belgium

Ovidiu Coza, Viorica Nagy

108 Guidance for Authors on the Preparation and Submission of Manuscripts to the Journal of Radiotherapy and Medical Oncology