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Volum 13 Numarul 4, 2007

279 Acreditare CMR

281 Prof. G. Simu – In Memoriam

285 EDITORIAL G. Kacsó

287 Mitigating Toxicity Associated with the Treatment for Head and Neck Cancers

Voichiţa Bar Ad1 , Ş. Both, PhD1

1Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA

As combined-modality treatment has become the standard of care for locally or regionally advanced head and neck cancers, concomitant chemoradiotherapy is widely used. The prevalence of treatment related toxicity has been increased. Intensity modulated radiation therapy leads to a lower incidence of short term and long term sequelae. Radiation protectors may ameliorate toxicity. Amifostine was shown to reduce xerostomia in patients treated with single modality radiation therapy in the definitive or postoperative setting, when administered before radiation. However, to date, no large randomized trials showing the same effect for amifostine in the concomitant chemoradiotherapy setting are available. Other compounds, such as keratinocyte growth factor or Seikaly- Jha surgical procedure for submandibular gland transfer, remain investigational at this time. As research continues to optimize delivery of concurrent chemoradiation, targeted therapies have begun to emerge from the broadening knowledge of cancer biology. These agents hold the promise of more effective therapy with less toxicity.

Key words: Head and neck cancers, Chemoradiation, Decreasing acute and late toxicity.

Radioterapie & Oncologie Medicală, 2007, 4:287-290

291 Adjuvant or Neoadjuvant Treatment for Pancreatic Adenocarcinoma?

Anca Mihailov1, Alina Simona Muntean2, R. Dima3

1University Hospital Cluj-Napoca; 2“Prof. I. Kiricuta” Cancer Center Cluj-Napoca; 3University of Oradea, the 2nd Surgical Clinic

Pancreatic cancer represents one of the most aggressive malignancies, with a five year survival rate below 5% if all stages are combined. Its treatment represents an important interdisciplinary challenge. At diagnosis, surgery with curative intent possible in only about 10 -20% of patients.The benefit of preoperative treatment with radiotherapy or chemotherapy remains a matter of debate. Conventional fractionated radiation regimens with total doses of 45-50 Gy and small volume boost radiation have found the greatest acceptance; up to now, 5Fluorouracil has been considered the standard agent for concurrent chemoradiotherapy, still the newer compound Gemcitabine is challenging this position. On the other hand, the results of large randomised studies have shown that adjuvant chemotherapy should be the basis of standard care following resection for pancreatic cancer. Further studies are needed in order to define the best chemotherapy protocol, given the encouraging development of novel agents in metastatic setting. What we probably need is a well designed, standardized protocol of radiochemotherapy to be employed in further trials and, maybe, trials comparing neoadjuvant therapy to adjuvant therapy in order to truly define the role of neoadjuvant therapy in the treatment of pancreatic cancer.

Key words: Pancreatic cancer, Adjuvant, Neoadjuvant, Radiochemotherapy, Chemotherapy.

Radioterapie & Oncologie Medical@, 2007, 4:291-299

300 Therapeutic Indications in Testicular Tumors with Germinal Cell “Low Risk” Stage I

  1. Căinap1, G. Kacsó2

“Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, “Prof. I. Kiricuta” Cancer Center Cluj-Napoca: 1Dept. of Medical Oncology; 2Dept. of Brachytherapy

In the late 2-3 decades the incidence of testicular cancer is raising. Most of these patients are diagnosed in an early stage. For the clinician to treat a curable disease pose more problems, because he must put in balance the potential harm done with the actual treatments. In the following article the authors make a review of the literature, underlying the advantages or disadvantages of different type of treatment and the remaining questions to be asked in the nearest future.

Key words: Testicular cancer, Chemotherapy, Radiotherapy, Surveillance.

Radioterapie & Oncologie Medicală, 2007, 4:300-304

305 New Developments in Molecular-Based Treatments for Malignant Gliomas

  1. Ghilezan

„Prof. I. Kiricuta” Cancer Institute, Cluj-Napoca

Background: Malignant gliomas are the most frequent histological type of the CNS tumors seen in adults, characterized by a very poor prognosis due to a rapid evolution and resistance to classical treatments. Recent advances in molecular and cell biology are translated in clinical practice by targeting the key pathogenic mechanisms of glioblastomas. Methods: A review of the main journals from the last five years have been performed and a download from the NCI Clinical trials data bank on molecularly targeted therapies for gliomas. Results: Gliomas express many characteristic histological features as extensive invasion, endothelial proliferation, necrosis, markedly anaplastic cells, intense mitotic activity, atypical mitosis and reduced apoptosis. At the molecular level several abnormalities have been identified as overexpression of oncogenes like epidermal growth factor receptor (EGFR), mutations of tumor suppressor genes as phosphatase and tensin homolog (PTEN) and p53. These alterations point to abnormalities in cell pathways involved in cell signaling and cell proliferation and consequently many new drugs and molecules have been developed to target key components of these mechanisms. The first results and pitfalls of phase II and III trials with these new compounds are presented with emphasis on tyrosine kinase and PI3K/Akt pathway inhibitors, angiogenesis inhibition, integrin antagonists and targeting glioma stem cells. As the molecular pathogenesis of gliomas is not linked to a single genetic defect or biologic mechanism, probably there are several possible targets for which different agents would be needed. The methodology for introducing in clinical practice of these new molecules is not yet clear because the doses are likely to be determined by biological end points and not by the maximum tolerated dose. Conclusions: The new molecular targeted therapies have already entered in phase II and III trials and demonstrate a real potential to improve clinical results, more often in combination with radiation and cytotoxic agents.

Key words: Glicomas, Biological therapies.

Radioterapie & Oncologie Medicală, 2007, 4:305-311

312 Effects of BTL-10 Laser Irradiation on Human Fibroblasts Cell Culture Proliferation

  1. Crişan1, Olga Şoriţău2, Mihaela Băciuţ1, G. Băciuţ1, R. Câmpian1, Liana Crişan1 , Ondine Lucaciu1

1“Iuliu Haţieganu” University of Medicine and Pharmacy Cluj-Napoca, Dept. of Cranio-Maxillofacial Surgery; 2 “Prof. I. Kiricuta” Cancer Institute Cluj-Napoca, Radiobiology Laboratory

Introduction: The proliferation effects of laser irradiation at the molecular and cellular levels have been shown by different studies. The aim of this study was to asses the effect of near-infrared laser light (830 nm) at the proliferation of fibroblasts cell culture. Material and methods: The cells of a human fibroblasts Hfl cell line were used. The cells were irradiated by a 830 nm semiconductor BTL-10 laser emitting an convergent beam in a continuous or pulsed mode at an energy density ranging from 2 to 64 J/ cm2. The power output was from 20 to 100 mW. The irradiated cells were incubated and their proliferation activity was assessed by the MTT assay at 24, 48 and 72 hours. Results: At 24 hours a increase in proliferation was obtained at energy density ranging from 2 to 4 J/cm2 and pulsed mode (5 Hz and 50 Hz). At 72 hours the proliferation activity was higher in the energy density ranging from 8 to 32 J/cm2 and pulsed mode (5Hz). Conclusion: It can be concluded than the laser light of the near-infrared region (830 nm) stimulates fibroblasts cell proliferation but to a varying degree according to the irradiation dose and mode.

Key words: Low-Level Laser, Fibroblast Cell Proliferation, Hfl Cell Line, MTT Assay.

Radioterapie & Oncologie Medicală, 2007, 4:312-317

318 Relationship Between Chronic Exposure to Hard Metals and Chromosomal Aberrations Evaluated by Micronuclei Assay

  1. Foriş1,2, Ioana Brie1, Maria Perde-Schrepler1, Piroşka Virág1, Eva Fischer-Fodor1 , Olga Şoriţău1, V. Cernea1,2

1 „Prof. I. Kiricuta” Cancer Institute, Radiobiology Laboratory Cluj-Napoca 2 „Iuliu Haţieganu” University of Medicine and Farmacy, Cluj-Napoca

Background: Hard metals are a group of widely distributed contaminants with toxic potential, even at low levels of exposure. Concerning that there is a great number of exposed people, the establishment of a linkage between chronic exposure to low level of hard metals and chromosomal aberrations is very important. Objective: The aim of the study is to evaluate the relationship between exposure and chromosomal aberrations in a chronic exposed populations, trying to identify specific biomarkers of exposure or effect. Patients and method: The level of chromosomal aberrations is evaluated using a specific genototixicity test, cytokinesis block micronucleus assay. The study includes 156 subjects divided into two major groups: one includes exposed people from a zone contaminated with hard metal particles, the second one is the control group including non-exposed populations. Results: There is a great interindividual variability concerning the in vitro baseline and radiation induced unstable chromosomal aberrations, irrespectively of any evaluated region. In vitro irradiation with a unique dose of 2 Gy determines an important and also extremely variable induction of suplemmentary unstable aberrations. Conclusions: The high level of unstable chromosomal aberrations in exposed populations lead us to conclude that these could be used as biomarkers for both exposure and effect of this exposure to various environmental genotoxic compuonds, including hard metal particles.

Key words: Hard metals, Biomarkers, Micronuclei assay.

Radioterapie & Oncologie Medicală, 2007, 4:318-323

324 Helical Tomotherapy in the Treatment of Prostate Cancer

  1. Fodor1, N. Di Muzio1, C. Cozzarini1, C. Fiorino2, F. Alongi1, F. Fazio1,2,3,4

Scientific Institute San Raffaele Milan, Italy: 1Division of Ra diotherapy; 2Division of Physics; 3Division of Nuclear
Medicine; 4University Milano-Bicocca, Italy
TomoTherapy Hi-Art is the first intensity modulated radiotherapy- image guided radiotherapy (IMRT-IGRT) built-in machine. The helical tomotherapy (HT) differs from the precedents approaches because the treatment is delivered in a spiral fashion and the binary multi-leaf collimator (MLC) present in the gantry realizes the fluency modulation. It has an integrated MVCT (mega voltage computer tomography) imaging capability, who offers the benefit of on line volumetric imaging, so maybe the best solution of IGRT. In two consecutive prostate adenocarcinoma prospective phase I- II HT studies, first with a hypofractioned regimen of 58 Gy/20 fr for 50 patients with radical prostatectomy pT2R1 or pT3R1/R0 and second with a “boost in field” technique for 40 patients T1b-c – T2a-b, delivering 56 to 74.2 Gy/28fr for well defined low to high risk PTV-s (pelvic lymph nodes, upper 2/3 of seminal vesicles, their lower 1/3 or the prostate) we succeed to significantly decrease the acute and late gastro-intestinal toxicity, but not the genito­urinary one compared to matched 3DCRT patients, while keeping an excellent coverage of the target volumes and shortening the overall treatment time by ~ 30 %.

Key words: Prostate cancer, Helical tomotherapy, Hypofractioned radiotherapy.

Radioterapie & Oncologie Medicală, 2007, 4:324-332

333 Chronic Disseminated Intravascular Coagu lopathy Associated with Gastric Adenocarcinoma – Case Presentation

Olga Orăşan1, F. Mureşan2, N. Rednic1, M. Lencu1, Monica Cazacu2

14th Medical Clinic; 24th Surgical Clinic – “Iuliu Haţieganu” University of Medicine and Pharmacy Cluj-Napoca;

Disseminated intravascular coagulopathy (DIC) may complicate the evolution of some neoplasia: pancreas, gastrointestinal, ovary, prostate, and lung. This is the case of a 67 years old woman with a signet ring gastric adenocarcinoma complicated with DIC. The presence of the severe hemorrhagic syndrome contraindicated surgical treatment and chemotherapy. The patient deceased 3 weeks after diagnosis.

Key words: Mucosecretant adenocarcinoma, Disseminated intravascular coagulopathy.

Radioterapie & Oncologie Medicală, 2007, 4:333-336

337 Radiobiology: Molecular Mecanisms and Implications in Cancer Treatment

Ioana Brie, N. Ghilezan

340 ONCOLOGICAL LIFE IN ROMANIA

342 CONTENTS OF JOURNAL OF ROMANIAN SOCIETY OF RADIATION THERAPY AND MEDICAL ONCOLOGY, VOLUME XIII, 2007

346 TOPIC’S INDEX 2007

349 AUTHOR’S INDEX 2007

352 GUIDELINES FOR THE AUTHORS