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Volum 11 Numarul 2, 2005

81 Editorial

I hope that these issues will raise your interest and maybe open your appetite for writing a paper dealing with our Journal specific topics.

The first general paper of C.D. Olinici continues part one exposed in the previous number concerningthe cell cycle abnormalities implied in cancerogenesis.

Liliana Resiga et al. present the actual classification of endometrial pre-malignant lesions and theirtherapeutic management.

An original study belongs to Ioana Brie et al.: on a small series they demonstrate that tumor cell in vitro radiosensitivity measured by comet assay can accurately predict the clinical response to radiotherapy for patients with stage IIB-III squamous cervix carcinoma.

  1. Todor and Ioana Brie presents theirs original „home made” flexible software for automatic analysis of comet assay, concluding on a 25% enhancement in accuracy comparing to visual assessement.

Similarly, O. Bãlãcescu et al. conclude that on an ovarian cell tumor model in vivo and in vitro we may be able by microarray technique to identify the “gene signature” predicting resistance to Cisplatin.

Claudia Ordeanu et al. performed a retrospective study on 474 patients with cervical carcinoma identifying the causes for delayed diagnosis and providing practical solutions.

The negative prognostic impact of anemia is clearly demonstrated by Viorica Nagy et al. on 347 women stage IIB- III cervix squamous carcinoma, treated by RT+/- Cisplatin +/- Surgery, with 11% absolute benefit in 3 years survival if Hb is higher then 11g/dl. Alina Muntean is doing the review of the literature on the same topic, emphasizing the current guidelines for correcting anemia before radiotherapy.

Dana Cernea et al. perform a retrospective analysis of the rare primitive spinal tumors, underlying the radiotherapy technical peculiarities.

Oral Etoposide as second or third line chemotherapy can be an alternative for platinum refractory/resistant ovarian cancers as proved by Adela Vãcar et al. on 25 such patients, stage III-IV (RR=16%, TTP= 4 months, median SV= 7.4 months, 14.8 % G3-4 hematological toxicity).

  1. Rãdulescu et al. sign the case report on a malignant lung hemangioma, a rare histological finding, needing an aggressive surgical approach whenever is possible.

I wish you a pleasant summer holiday and we are waiting you in our pages, as authors, in autumn.

Gabriel Kacsó

83 Cell Cycle. Implications in Oncology. Part II

  1. D. Olinici1, 2

1UMPh „Iuliu Haţieganu” Cluj-Napoca , Dept. of Pathology

2Cancer Institute „Prof. I. Chiricuţã”, Cluj-Napoca

Proliferation is a fundamental biological process for tissue growth and homeostasis. An initial step in malignant transformation is represented by the unregulation of cell division. Recent advances in the understanding of the mechanisms which govern the cell cycle are likely to provide information pertinent to the prediction of clinical behavior and might open new avenues for the treatment of cancer.

Key words: Cell Cycle, Control, Clinical Implications

Radioterapie & Oncologie Medicalã, 2005, 2:83-89

90 Precursor Lesions of Endometrial Carcinoma

Liliana Resiga1, Milena Duma1, A. Şerban2,3, C.D. Olinici1,3

1 Cancer Institute „Prof. I. Chiricuþã” Cluj-Napoca;

2Adults Clinical Hospital of Cluj-Napoca;

3Dept. of Pathology, U.M.Ph. „Iuliu Haţieganu” Cluj-Napoca

Endometrial carcinoma is the most common invasive cancer ot the female genital tract. Clinicopathological, immunohistochemical and molecular genetic studies have provided additional data to allow for the development of a dualist model of endometrial carcinogenesis. Atypical hyperplasia is recognized as the precursor for the endometrioid type of endometrial carcinoma and endometrial intraepithelial carcinoma (EIC) as the precursor for the endometrial serous carcinoma. The following article summarizes current knowledge about the relationship of these precursor lesions to the various forms of endometrial carcinoma, its therapeutic impact.

Key words: Endometrial carcinoma, Hyperplasia, Precursor, EIC.

Radioterapie & Oncologie Medicalã, 2005, 2:90-95

96 Relationship Between Tumor Cells’ in vitro Radiosensitivity Measured by Comet Assay and Clinical Response to Radiotherapy of Cervix Carcinomas

Ioana Brie, Maria Perde, Piroska Virág, Eva Fischer, Olga Soriţãu, I.D.Postescu,

Viorica Nagy, O. Coza, Iolanda Sicoe, N. Todor, V. Cernea, N. Ghilezan

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

Introduction: Intrinsic cellular radiosensitivity (RS) is a genetic factor involved in the inter-individual variability of the response to radiotherapy (RT). Comet assay (CA) might be a reliable assay to be used in the prediction of clinical RS. Purpose: The aim of our study is to correlate the in vitro RS of tumor cells with the clinical response after curative RT. Methods: Twelve patients with loco-regionally advanced cervix carcinoma were included so far. Tumor cells obtained by biopsy were irradiated in vitro and analysed by CA. For each tumor the degree of DNA lesions was scored before, immediately after and at two hours after irradiation. Tumor response was clinically assessed at the end of the treatment. In vitro parameters of RS were correlated with the clinical results. Results: Three biological parameters were evaluated: the background level, the magnitude of induction by irradiation and the repair of the radioinduced lesions. Clinical responses at the end of RT correlated with I and R. Conclusions: The extent of comet formation, as determined by CA, reflect cervix cancer cell RS. The measures of R are significantly correlated with clinical outcome. CA appears to be a good predictive measure of cervix tumor cell RS and a promising tool for the prediction of the clinical response to RT.

Key words: Tumor cells, Cervix carcinoma, In vitro radiosensitivity, Radiotherapy.

Radioterapie & Oncologie Medicalã, 2005, 2:96-105

106 Algorithm for the Appreciation of DNA Lesions by Comet Assay

  1. Todor, Ioana Brie

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

The images obtained by comet assay can be evaluated by visual or computerized analysis. Until now we performed only the visual analysis, since we have none of the commercially available specific softwares. Giving the facts that such specific softwares are very expensive and that there is no clear standardization of the evaluation parameters, we tried to ellaborate an open, flexible soft solution, which is able to potentially cover any further conceptual evolution of comets’ classifying parameters. The paper presents this solution and the endpoints proposed to be followed for now on.

Key words: Comet assay, Image analysis, Specific software.

Radioterapie & Oncologie Medicalã, 2005, 2:106-1110

111 Applications of the Functional Genomic in Ovarian Cancer.

Microarray Reaction

  1. Bãlãcescu1, Ioana Neagoe1, Audrey Kauffmann2, V. Lazãr2, N. Ghilezan1

1 Cancer Institute „Prof. I. Chiricuþã”, Cluj-Napoca ;

2 Gustave Roussy Institute, Villejuif, France

Functional Genomic, using microarray technique, can provide multiple informations about the simultaneous expression of thousands of genes or even for all human genome. The cellular profile as a consequence of gene expression can determine the phenotype, cellular functionality as well as the response to cytostatic drugs. Transcriptomic studies can characterize very precise by the cellular status at a moment. Ovarian cancer present the worst prognostic among gynecological malignancies, as the majority of cases are diagnosed at an advanced stage. Using the microarray method in cancer research, specially in ovarian carcinoma, represents a real progress in evaluation of tumor progression and cellular response to drugs treatment.

Key words: Functional Genomic, Transcriptomic, Microarray, Ovarian cancer.

Radioterapie & Oncologie Medicalã, 2005, 2:111-115

116 Reasons fot a Late Diagnosis and Treatment for Cervix Cancer : The Experience of Cancer Institute Cluj-Napoca

Claudia Ordeanu1, Viorica Nagy1,2, N. Ghilezan1

1 Cancer Institute “Prof. I. Chiricuþã”, Cluj-Napoca;

2 UMPh “Iuliu Haþieganu” Cluj-Napoca

The cervix cancer in Romania is the second cause of death due to neoplasia in women, mainly through advanced stages at presentation. Looking for an explanation for this late diagnosis & therapy, we have analysed the characteristics of the patients’ accrual in the Cancer Institute Cluj during the years 1999 and 2000. The resulting data point to a low efficiency of the screening programs and a poor management at the population level (lack of specific information about the risk factors) but also in the involvement of the different categories of professionals (family physician, specialists, nurses, social workers).

Key words: Cervix Cancer, Late Diagnosis.

Radioterapie & Oncologie Medicalã, 2005, 2:116-120

121 Prognostic Value of Pretreatment Hemoglobin Level in Locally Advanced Cervical Cancer

Viorica Nagy1,2, Claudia Ordeanu2, O.Coza1,2, N.Todor2, E.Szakács2, N.Ghilezan1,2

1 U.M.Ph. „Iuliu Haþieganu”; 2 Cancer Institute „Prof. I. Chiricuþã”, Cluj-Napoca

Anemia is frecvently observed in patients with cervical cancer. This study investigates the impact of pretreatment hemoglobin (Hb) level on prognosis and results in locally advenced cervical cancer. Between March 1999 and March 2001 in this randomized study of the Cancer Institute Cluj there were included 347 patients with stage IIB (132), IIIA (131) and IIIB (84) cervical cancer. The study had 2 arms: radiotherapy and concomitant radio-chemotherapy with cisplatin. After 46 Gy on the pelvis, patients with good response were operated (radical hysterectomy with pelvic lymphadenectomy) and the others continue radio-chemotherapy until 64 Gy/pelvis. The Hb level was measured preterapeutically: 96 patients (28%) had the Hb < 11 g/dL and 251 patients had > 11 g/dL. The 3 yearsurvival rate of patients who had low Hb level was 75%, in comparison with 86% in the patients with pretreatment Hb level > 11 g/ dL (p=0.02). Anemia (Hb < 11 g/dL) was significantly correlated with the stage (17% in stage IIB, 28% in IIIA and 44% in IIIB) and the tumour volume (20% for tumours < 4 cm and 36% for tumours > 4 cm). The relapse was more frequent in patients with anemia, in comparison with those who had normal pretreatment Hb level. In conclusion, the pretreatment Hb level is an important prognostic factor in determining the efficacy of radiotherapy/radiochemotherapy in cervical cancer. Raising the pretreatment Hb level may have a beneficial impact on the response to radiotherapy.

Key words: Cervical cancer, Hemoglobin, Anemia, Prognostic factor.

Radioterapie & Oncologie Medicalã, 2005, 2:121-125

126 Postoperative Radiotherapy in Spinal Cord Glioma – A Retrospective Study

Dana Cernea1, Andra Fizeşan1, V. Bogdan1, Magda Petrescu2, V. Popiþpţa1

1 Cancer Institute „Prof. I. Chiricuþã”, Cluj-Napoca;

2 County Clinic Hospital Cluj, Dept. of Pathology

Purpose: to describe the outcome of patients with spinal cord glioma treated with surgery and radiation therapy.

Methods and patients: Eight patients with spinal cord glioma were treated in Cancer Institute of Cluj between 1997 and 2004. There were 5 female and 3 male patients ranging from 15 to 64 years of age with a median age of 46 years. There were 3 ependymomas, 2 astrocytomas and 3 oligodendroastrocytomas. Surgery was subtotal resection în all patients. All patients received radiation therapy: 4 patients with a total dose of 45-50 Gy (1.8-2 Gy per fraction) and 3 patients with 30 Gy în 10 fractions and 20 Gy în 5 fractions because of their altered neurological status. One patient received chemotherapy after the completion of radiation therapy.

Results: Three patients have died because of local evolution of their disease after an interval between 10 months and 41 months after surgery. Five patients are alive and the length of survival is between 12 months and 96 months from the first treatment.

Conclusion: The treatment of spinal cord glioma is surgery followed by radiation therapy. Local failure is the main cause of death. Irradiation doses of 45 to 54 Gy with 1.8-2 Gy per fraction are usually used to treat spinal cord tumors.

Key words: Spinal cord glioma, Radiation therapy, Spinal cord myelopathy.

Radioterapie & Oncologie Medicalã, 2005, 2:126-129

130 Etoposide (Vepesid) Per Oral in Recurrent Ovarian Carcinoma

Adela Vãcar, Smaranda Vãcar, N. Todor

Cancer Institue „Prof. I. Chiricţã”, Dept. of Clinical Oncology, Cluj-Napoca

Ovarian carcinom represents the 6th cause of neoplastic death in women. Most cases develop recurrences after the first line of chemotherapy. Purpose: assesment of efficiency and toxicity profile of Vepeside (VP16, Etoposide) in recurrent ovarian carcinoma. Patients and method: The retrospective study includes 25 cases of recurrent ovarian cancer trated with VP16 po in Cancer Institute Cluj from 01.1997 to 12.2001. Patients received at least one prior chemotherapeutic treatment based on platinum compounds.VP16 po (100mg/m2/day, d1-5 every, 21days) was continued until disease progression, adverse effects prohibited further therapy or they accomplished 6 courses. Results and conclusions: 25 cases of advanced and metastatic ovarian carcinoma were included in this study: stage (st) III 19cases, st IV 6 cases. Median age was 51 years. A total of 71 courses of chemotherapy were administered, with a median of 2.8 courses. 3 complete response, 1 partial response and 6 stationary occurred. Hematologic toxicity was generaly moderated, with only 4 cases of severe toxicity. There were no treatment related deaths. VP16 po has a moderate activity for treatment of recurrent epithelial ovarian cancer, with severe toxicity recorded only in a few cases.

Key words: Vepeside 16 po, Recurrent ovarian cancer.

Radioterapie & Oncologie Medicalã, 2005, 2:130-134

135 Malignant Pulmonary Haemangiopericytoma – a Rare Lung Tumor

  1. Rãdulescu1,3, C. Duncea1,3, T.E. Ciuleanu2,3, Letiþia Rãdulescu2

15th Medical Clinic;

2Cancer Institute“Prof. I. Chiricuţã”, Cluj-Napoca ;

3U.M.Ph. “Iuliu Hţieganu” Cluj-Napoca

Although rare, lung hemangiopericytoma in adults is similar to hemangiopericytomas with other localizations (soft tissues). It can be asymptomatic and occur as a single pulmonary nodule on the chest X rays, or as multiple tumors with extension to the adjacent tissues. Although generally benign, curable after radical surgery, it may also have a malignant clinical course with dissemination in both lungs, infiltration of vital organs (heart, pulmonary artery, etc.), and even pulmonary metastases. The treatment of choice is surgical resection. Certain histologic features may indicate a malignant potential. The clinical course of the patients is variable, some being cured after surgery, other presenting relapses and necessitating a second intervention, and also radio – and chemotherapy. We report a case of lung hemangiopericytoma , with an aggressive, fatal clinical course, and discuss radiologic and pathologic correlations.

Key words: Hemangiopericytoma, Lung tumor, Pulmonary radiological examination.

Radioterapie & Oncologie Medicalã, 2005, 2:135-137

138 REVIEW OF LITERATURE

140 BOOK REVIEWS

143 GUIDELINES FOR AUTHORS