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Volum 09 Numarul 2, 2003

81 Editorial

The contents of the present issue of the revue reflects the multiple interests of the members of the society towards both fundamental and clinical research.

The paper of Joana Brie presents extensively tile technique and the applications of the flow-cytometry as a means for studying the tumor kinetics, by evaluating the kinetic properties of cell populations. This technique can be applied in translational research to evaluate the posttreatment distribution of clonogenic cells that man- age to survive after radiotherapy or chemotherapy. Prof. Cornelio D. Olinici, in his rewiew Viral Carcino- genesis, discusses the principal cathegories of oncoviruses, witll an insight on their molecular implications in human malignant tumors. The paper by Romanta Lup~a, Telling bad news to cancer patients”, taboo or necessity, represents a wellcome change of subject, from the abstract science to the social-human dimension of oncology. Together with an analysis of the psihologic reactions generated by this subject, a practical guide for tile clinical oncologist is presented, in order to improve communication skills for the practising physician.

Claudia Burz retrospectively analyses the experience of a french center (University Hospital „Charles Nicolle”, Rouen, France) in the treatment of gastric cancer, presenting on a limited number of patients the toxicity and efficacy of the association of radio-chemotherapy for this disease. Sequential treatment with epirubicin, cyclophosphamide, surgery and docetaxel proved to be effective (in terms of pathologic response and survival) in a retrospective article by Daniela Grecea, for breast cancer patients stage II and III. Claudia Ordeanu presents the experience of the „I. Kiricuta” Institute regarding late complications in endocavitary brachiterapy in uterine cervix carcinoma, comparatively anaysing two lots of patients treated with two different techniques, and shows no difference in late complications for the methods used. The results of the association between radiotherapy and temozolomide in the treatment of high grade glioma are evaluated in a multicentric studx repol1ed by Dana Cernea, which demonstrates high efficacy for the combination, with an acceptable toxicity. Soft tissue sarcomas represent the subject of the critical analysis performed by Valentin Cernea on the data of the patients witll this pathology treated in the „I. Kiricuta” Institute between 1996 and 1999. He identifies in multivariate analysis a number of predictive factors for distant reccurence: histologic high grade, positive mar- gins and age over 50 years. Nicolae Todor gives an affirmative answer to the question Could be the disease free survival higher than the overall survival?, showing the main causes that can lead to this fenomenon. In the section News in Oncology, several scientific events that took place in the first part of 2003 are discussed. Luciana Neamţiu presents an ENCR (European Network of Cancer Registries) course dedicated to statistic analysis, organised in January 2003 in Lyon, France. Alexandru Eniu rewiews the latest results in the treatment of breast cancer presented at the 8th International Conference „Primary Therapy of Breast Cancer” held in March 2003 in St. Gallen, Switzerland. The proceedings of the Francophone conference on digestive tumors held in Paris, France, 2003, are analysed by Claudia Burz. Also in Paris, in April 2003, the Conference of the European Research Organisation on Genital Infection and Neoplasia (EUROGIN) took place, whose conclusions, making the subject of the International Charta, are presented by Ofelia Şuteu.

  1. Eniu

83 Flowcytometry: Investigating Tool for the Assessment of Tumor Kinetics

Ioana Brie

UMPh “Iuliu Haţieganu”, Cluj-Napoca

The study of cell kinetics has been facilitated by the use of flow cytometry to determine cellular DNA content, a method which has the advantages of speed and automation. The technique allows isolation of cell populations containing different amounts of DNA, separation of cells according to expression of specific proteins or sorting of cells on the basis of two or more criteria. Information about cell size may be obtained from analysis of scattered light. Flowcytometry can be used to estimate cell-cycle phase distribution, growth fraction and kinetic properties of cell populations, to study the proliferative rate of an unperturbed cell population, to identify the S phase arrest following a genotoxic insult, to estimate Tpot and Ts from a single biopsy of a human

tumor. Proliferating and non-proliferating cells can be distinguished by flowcytometry. Expression of proliferation-associated

antigens by human cancer cells may provide useful information about prognosis. This method can also be used after radio or chemotherapy to provide information about the cell cycle distribution of clonogenic cells that survive such treatment.

Key words: Flowcytometry, proliferation, markers.

Radioterapie & Oncologie Medicală, 2003, 2:83-87

88 Viral Carcinogenesis

  1. D. Olinicil,2

1Deparment of Pathology, UMPh” Iuliu Halieganu „,

2Cancer Institute” I. Kiricuta” Cluj-Napoca

Although the role of viruses in human carcinogenesis is likely to be limited, investigations in this domain allowed important discoveries like reverse transcriptase, recombinant DNA technology, messenger RNA splicing, oncogenes and tumor suppressor genes. In this paper we discuss the main categories of viruses involved in human oncogenesis, their molecular biology and implications in various neoplasms.

Key words: viruses, molecular biology, human neoplasia.

Radioterapie & On cologie Medicala, 2003, 2:88-97

98 Telling Bad News to Cancer Patients is Taboo or Necessity

Romanta Lupşa

UMPh Tg. Mureş Department of Oncology

Telling the truth about the diagnosis and prognosis to cancer patients is necessary for getting informed consent to start anti-cancer treatment or palliative care. In Romania to tell the truth to the patient is a taboo subject or an orphan child that nobody would want to adopt neither GP nor specialists. There are no arguments for hiding the truth in the name of protection or letting the patients die „happily” in their ignorance. The patients have the right to know the truth and the doctors have the responsibility to inform them of this fact. In this article there are: motivation for telling the truth; who, when and how should communicate. Also, there are the six steps of communication, the reactions of the patients when they become aware of their diagnosis. Good doctor-patient communication is based on trust, reducing uncertainty, prevention of unrealistic hope. In the XXI-sty century cancer patients have the absolute right (ethically, morally and legally) to know the truth about their illness and to give informed consent regarding their treatment knowing the benefits and harm of this treatment.

Key words: informed consent, cancer, telling bad news.

Radioterapie & Oncologie Medicala, 2003, 2:98-101

102 Radio-chimiotherapy dans cancers gastrique

Etude retrospective sur une serie des patients traites entre 1994-2001 au

Centre Hospitalier Universitaire „Charles Nicolle” Centre „Henri Becquerel „,

Rouen, France

Claudia Burz, B.Paillot, P.Michel, S.H.Seng, C.Hamidou

Centre Hospitalier Universitaire Rouen

Le but de l’étude est l’évaluation de l’expérience du Centre Hospitalier Universitare (CHU) – Centre Henri Becquerel (CHB) Rouen concernant l’efficacité et la tolérance d’un traitement par radio-chimiothérapie pour adénocarcinome gastrique, en situation adjuvante ou palliative. Seize patients ont été opérés pour un cancer gastrique; 8 patients ont beneficiés d’un traitement adjuvant et 8 patients, sans traitement adjuvant, ont été traités pour une reprise évolutive de la maladie (moyen 11 mois plus tard). Le traitement préconisé: 6 cures de chimiotherapie type Cisplatin-Fluorouracil (PF) associées à la radiothérapie. La dose de radiothérapie: 45-55Gy sur le lit tumoral et la région cèliaque en cas de traitement adjuvant et 50- 65 Gy sur le lit de la récidive en cas de traitement palliatif. La chimiothérapie etait a base de platine: Cisplatine (COOP): 100 mg/m2 jour (J)1, 5FU: 1000 mg/m2 J1-J5; une réduction de 25% a été faite pour les cures associées à laradiotherapie. La toxicité la plus importante etait au niveau digestif; selon le nombre de cycles reçus la toxicité la plus importante a été observée au 3-éme et 4-eme cure de chimiothérapie. Les facteurs pronostique de toxicité grade 3 retrouvés ont été: le sexe masculin et la dose de radiothérapie. En cas de traitement adjuvant, la survie sans recidive a été 19 mois et la survie à 3 ans de 50 %; pour les patients qui ont eu un traitement palliatif, la symptomatologie s’est ameliorée pendant le traitement chez 5 patients, la survie sans progression a été de 4 mois et la median de survie de 6 mois. L’incidence et la sévérité des toxicités aiguës sont importantes; les études ultérieures doivent trouver la meilleure association afin d’améliorer la survie ainsi qu’une toxicité acceptable.

Mots clés: cancer gastrique, traitement adjuvant, chimiotherapie, radiotherapie.

Radioterapie & Oncologie Medica/ă, 2003, 2:102-107

108 Sequential Treatment with Epirubicin, Cyclophosphamide (EC) and Docetaxel (DOC) in Stage II and III Breast Cancer

Dana Grecea1, Gh. Iacob2, N. Ghilezan1,3

1Cancer Institute „I. Kiricuta”;

2Urological and Renal1ransplantion Institute;\

3UMPh „I.Hatieganu” Cluj-Napoca

Purpose: A retrospective nonrandomized study to evaluate the efficacy of sequential administration of epirubicin plus cyclophosphamide (EC) followed by surgery and docetaxel (DOC). Patients and methods: Between 07/1995 and 0 1/200 I, 74 patients with untreated breast cancer stage II and III received epirubicin (E) 100 mg/m2 given in 30 minutes followed by cyclophosphamide (C) 600 mg/m2 (q3w). After four cycles of neoadjuvant chemotherapy, the patients were evaluated for response and conservative, 15 patients (17.57%), or definitive surgery 59 patients (82.43%) was done. After surgery, the patients received four cycles of docetaxel (DOC) 100 mg/m1 (I hour, q3w). The median age was 46 (24-66) years, with 51 (690/0) premenopausal and 23 (31%) postmenopausal patients. Results: The pathological response was pT lower to 2 cm: 39 patients; pT 2-5 cm: 35 patients; pN+ 1-3: 8 patients pN+ = 4 and more than 4: 66 patients. Overall survival at 60 month was 51.77% and DFS was 56.72% at36 month. For patients with pN+ 1-3, at 5 years DFS was 69.44%, and for those with pN+ =4 and more than 4, DFS was 43.72%. Overall survival at 5 years follow-up was 75.25 for patients with pN+ 1-3, and 54.3% for those with pN+ = 4 more than 4. Conclusions: These preliminary results suggest the efficacy and safety of the neoadjuvant sequential chemotherapy in breast cancer stage II and III treatment. This regimen appears very active in terms of DFS and overall survival, in correlation with the pathological response.

Key words: breast cancer, sequential chemotherapy, relapse.

Radioterapie & Oncologie Medicală, 2003, 2:108-115

116 A Study of Late Complications in the Endocavitary Brachytherapy in Uterine Cervix Carcinoma

The Experience of the „I. Kiricuta” Cancer Institute Cluj with Medium Dose Radiotherapy in the 1999-2000 Period

Claudia Ordeanu1, O. Coza1,2, S. Gavrişl, Daniela Suciu1

1Cancer Institute „I. Chiricuţă”;

2UMPh „Iuliu Hatieganu” Cluj-Napoca

Purpose: the aim of the treatment of the cervical cancer is to obtain local control with minimal late complications. This study analize the late toxicity in patients treated for cervical cancer with two types of endocavitary brachytherapy: ring-type vaginal applicator (RA) or with vaginal colpostats (VC). Material and method: 57 patients were included: 29 were treated with the ring applicator and a second group (28 patients) by vaginal ovoids. The late complications were evaluated by the franco-itlalian glossary. Results: the global bladder toxicity was 7% (4 patients): 2 G1 treated with VC and in the two patients treated by the ring applicator the toxicity was 1 G3 + 1 G4. A single rectal late complication (G2) appeared with the ring-type applicator. For the vagina 7% (4 patients) presented late reactions, all of them treated with vaginal colpostats (three G1 and one G2). Conclusions: concerning the late toxicity the two types of vaginal applicators are comparable.

Key words: cervical cancer, brachytherapy, late toxicity.

Radioterapie & Oncologie Medicală, 2003, 2:116-120

121 Temozolomide in Treatment of High Grade Gliomas

Dana Cernea1, A. Udrea1, D. Filip2, Ileana Pop3, A. Moga4, R. Curcă5, L. Miron6

1Cancer Institute I. Kiricuta” Cluj;

2County Hospital Baia Mare, Dept. of Oncology;

3County Hospital Zalau, Dept. of Oncology;

4County Hospital Sibiu, Dept. of Oncology;

5County Hospital Alba, Dept. of Oncology;

6University Hospital” Sf Spiridon” Iasi, Dept. of Oncology

Purpose: to present the results obtained in treatment of primary high grade gliomas with postoperative radiotherapy and chemotherapy with Temozlomide, the toxicity and the compliance to treatment. Material and methods: We treated 17 patients, 9 with glioblastoma multiforme, 5 with anaplastic astrocytoma, 2 with oligoastrocitoma and 1 patient with oligodendroglioma. The standard treatment was surgery followed by radiotherapy. Temozolomide (75 mg/sqm/d x 7 d/wk) was administered concomitant with conventional radiotherapy followed by Temozolomide monotherapy (200 mg/sqm / d x 5 days, every 28 days) in five patients. Adjuvant Temozolomide (200 mg/sqm/d x 5 days, every 28 days) after three weeks from the complation of radiotherapy was administered to twelve patients. Results: Concomitant radiation plus Temozolomide was followed by 3 complete responses, 1 partial respons, and 1 stable disease. For patients with adjuvant Temozolomide we obtained 3 complete responses, 7 stable disease, and 2 patients with progressive disease. Median survival was 16 months for patients with concomitent treatment, and 8,5 months for patients with adjuvant treatment. The toxicitie was moderate. Conclusion: Combined treatment with radiotherapy and Temozolomide, concomitent or adjuvant, is feasible with acceptable toxicities and good compliance. This protocol may prolong the disease free interval and possible the survival of patients with high grade gliomas.

Key words: Temozolomide, radiotherapy, glioblastoma multiforme, anaplastic astrocytoma.

Radioterapie & Oncologie Medicală, 2003. 2:121-124

125 Soft tissue Sarcomas: Treatment Results and Prognostic Factors. Experience of”I. Kiricuta” Cancer Institute Between 1996-1999

  1. V. Cernea1,3, Daniela Martin3, D. Eniu2,3, A. Udrea3, Adriana Porutiu3, Mihaela Galatar3, N. Todor3

1UMPhIuliu Haţieganu” Cluj- Napoca, Dept. of Oncology-Radioterapy

2UMPhIuliu Haţieganu” Cluj- Napoca, Dept. of Oncological Surgery

3Cancer Institute I. Chiricuta” Cluj-Napoca

Purpose: To investigate the results as well as the prognostic factors for localized soft tissue sarcomas (STS). Materials and methods: Retrospective study which includes 65 patients of III treated between 1996-1999 at Institute of Oncology Cluj. Treatment of the primary consisted of surgery followed by postoperative radiotherapy. Patients with high grade tumors have adjuvant chemotherapy based on antracyclines and in some cases on Ifosfamide. Results: Survival at 3 years was 59%. Local control was achieved for 67% of patients. High grade tumors, deep stated, 12, positive resection margins and local recurrence are factors negative affecting survival. Multivariate analysis shows a high risk for metastasis for high grade tumors, age above 50 years and positive margins. Conclusions: STS are a heterogeneous group of tumors with variable clinical behavior for witch the first treatment is to be correctly done in specialized centers. Identifying prognostic factors is mandatory for the choice of appropriate treatment.

Key words: sarcomas, radiotherapy, porognostic factors.

Radioterapie & Oncologie Medicală, 2003, 2:125-129

130 Could Be Disease Free Survival Higher then Overall Survival?

  1. Todor

Cancer Institute „I. Kiricuta” Cluj-Napoca

Based on some imaginary examples, the main causes which can lead us to the situation when disease free survival is higher then overall survival, are presented.

Key words: Kaplan-Meier method, disease free survival.

Radioterapie & Oncologie Medicală, 2003, 2:130-132

133 ENCR Statistical Analysis Course on Time Trends, January 14-17,2003, Lyon, France

Luciana Neamtiu

134 Primary Therapy of Early Breast Cancer. The 8th International Conference, March 12-15,2003, St. Gallen, Switzerland

Al. Eniu

138 Advances in Digestive Cancer. The 27th Conference of Digestive Pathology, March 29-April3, 2003, Paris, France

Claudia Burz

141 The Conference of the European Research Organisation on Genital Infection and Neoplasia (EUROGIN), April 13-16, 2003, Paris, France

Ofelia Şuteu