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Volum 11 Numarul 1, 2005

3 Editorial

The subject of the first article signed by Corneliu D. Olinici is cell cycle and his implication in oncology. The author emphasis the importance of recent progress in the understanding of mechanisms witch governs the cell cycle and their possible implication in new strategies of cancer treatment.

Ioana Brie and Valentin Cernea are the authors of an interesting paper about the importance of epidemio­logical requirements for the studies of radiosensitivity. The goal of in vitro radiosensitivity research is to develop specific and rapid assays that can detect patients at for severe complications to radiotherapy.

The investigation of CER 1 involvement in ovarian cancer is the subject of a research signed by Luminiþa Leluþiu and col. Examining tissue from patients with ovarian carcinoma they suggest that it may be an associa­tion between CER1 deletions and higher grade and serous type of ovarian carcinoma.

The benefit of combined treatment: neoadjuvant chemotherapy plus radiotherapy versus radiotherapy alone is evaluated by Elisabeta Ciuleanu and col. The results were similar in terms of response rate, 5 years survival or disease free survival but neoadjuvant chemotherapy could probably compensate the poor quality of radio­therapy in terms of total dose or total treatment time.

„Permanent Iodine 125 brachytherapy as curative option for organ confined prostate cancer – toxicity and short term biochemical outcome” is the title of the paper signed by G. Kacsó and coworkers. For selected patients, Iodine 125 interstitial brachytherapy offers comparable results to radical prostatectomy with accept­able urinary morbidity and less rectal toxicity and sexual dysfunction.

Quality assurance and quality control in radiotherapy are important parameters for any modern radiotherapy centre. The goal of the article signed by Daniela Martin and coworkers was to describe the first steps of QA and QC programmes for equipment and treatment planning process in Radiotherapy Department of „Prof. Dr. Ion Chiricuþã” Cancer Institute.

Nicolae Todor and Rareş Buiga using a simulation program in Visual Basic for Excel investigate the graph of the data for a binary variable. The imunohystochimic evaluation of galectin-3 on a set of ovarian tumors is the practical example.

„Breast Carcinoma with Signet-Ring Cell” is the subject of a case report by C.D. Olinici and coworkers The paper report a breast tumor showing two different histological appearances: a signet ring cell carcinoma with invasive and with in situ patterns and a classical ductal invasive and in situ carcinoma. The signet-ring cell carcinoma of the breast is a very rare tumor.

The „New achievements of radio-chemotherapy in standard treatments in oncology” was the subject of a round table discussion organized by U.M.F „Iuliu Haþieganu” Cluj and Viorica Nagy briefly presents the papers.

American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) proposed a global core curriculum in medical oncology. Viorica Nagy exposes the recommendations of these two professional societies.

We wish you to enjoy the reading of this issue of our journal.

Dana Cernea

5 Cell Cycle. Implications in Oncology. Part I

  1. D. Olinici1, 2

1UMPh „Iuliu Haţieganu” Cluj-Napoca, Dept. of Pathology 2Cancer Institute „Prof. I. Chiricuţă”, 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 Medicală, 2005, 1:5-12

13 Translational Research in Radiotherapy: ImportantEpidemiological Requirements for the Studies on Radiosensitivity

Ioana Brie1 ,V. Cernea1,2

1 Cancer Institute „I. Chiricuţă” Cluj-Napoca, 2U. M. Ph. „Iuliu Haţieganu” Cluj-Napoca

The goal of in vitro radiosensitivity (RS) research is to develop specific and rapid assays that can detect patients at risk for severe complications to radiotherapy. The predictive value of an in vitro assay is assessed by correlating „in vitro RS” with „clinical RS”. This requires appropriate epidemiological study designs, because the failure to prove the usefullness of such an assay may be due not solely to the assay itself but also to the choice of study methodology. The present paper presents the epidemiologic requirements specific for the good studies on RS and recommendations for future research.

Key words: Radiosensitivity, Radiotherapy, Normal tissues, Side effects, Epidemiology.

Radioterapie & Oncologie Medicală, 2005, 1:13-18

19 Analysis of CER1 (3p21.3) in Ovarian Carcino ma UsingFluorescence In Situ Hybridization. Part II.

Luminiţa Leluţiu1, S. Imreh2, C. D. Olinici1,3, N. Ghilezan1 ,3

1Cancer Institute „Prof. I. Chiricuţă”, Cluj-Napoca, 2Karolinska Institutet, Microbiology and Tumor Biology Center, Stockholm, Sweden, 3UMPh „Iuliu Haţieganu”, Cluj-Napoca

The aim of this study was to investigate CER1 involvement in ovarian cancer. We extracted nuclei from the paraffin embedded ovarian cancer tissue samples, selected and tested bacterophage P1-derived artificial chromosome (PAC) probes for CER1, developed optimal FISH probe for CER1 detection and optimized the FISH protocol for paraffin embedded material. Examining tissue from 13 ovarian carcinoma cases with CER1 and centromere specific probes, we detected CER1 deletions in 10 cases.We suggest that it may be association between CER1 deletions and higher grade, serous type of ovarian carcinoma.

Key words: CER1, PACs and centromere probes, FISH, Ovarian Cancer

Radioterapie & Oncologie Medicalã, 2005, 1:19-28

29 Neoadjuvant Chemotherapy Plus Radiotherapy versus Radiotherapy Alone and the Quality of Radiation Therapy in the Treatment of Locally Advanced Nasopharyngeal Carcinoma

Elisabeta Ciuleanu1, T. E. Ciuleanu1,2, N. Todor1, N. Ghilezan1,2

1Cancer Institute „Prof. Dr. I.. Chiricuţă” Cluj-Napoca; 2U. M. Ph. „Iuliu Haţieganu” Cluj-Napoca

Background: To asses, în a retrospectiv study, if trere is a long term benefit of adding neoadjuvant chemotherapy (CT) to standard radiotherapy (RT) for the primary treatment of locoregionally advanced nasopharyngeal carcinoma (NPC) patients (pts), taking also into account the quality of the RT: optimal (ORT) or poor quality (PRT), în terms of a lower total dose or prolonged overall treatment time. Material and methods: Between 1/1990-12/1995, 185 locoregionally advanced NPC patients (pts) entered the study. Combined CT+RT consisted în 3 cycles of neoadjuvant BEC (Bleomicyn, Epirubicin, Cisplatin) or EC (Epirubicin, Cisplatin) followed by standard RT (70Gy/ 7 wks), versus the same RT alone. Results: 175 pts. were evaluable for long term follow-up, 81 pts had CT+RT and 94 RT alone. Response rate (RR) at the end of the primary treatment was similar for CT+RT vs RT (89% vs 85%, p=.46). RR în the CT+RT arm was not influenced by ORT vs PRT (92% vs 81%, p=.35) but was different în the RT arm (ORT vs PRT: 92% vs 68%, p < .01). Survival (S) was not significantly influenced by the addition of neoadjuvant CT vs RT alone (5 years S: 53% vs 44%, p=.16). Five -years S în the CT+RT arm was not influenced by ORT vs PRT ( 52% vs 56%, p=.81), but radiation quality decisively influenced S în RT arm (ORT vs PRT: 56% vs 14%, p<.01). Disease free survival (DFS) was similar for CT +RT vs RT alone (5 years DFS 44% vs 40%, p=.3). DFS în the CT+RT arm was not influenced by radiation quality (ORT vs PRT:45% vs 42%, p=.74) unlike the DFS în the RT arm (ORT vs PRT: 50% vs 19%, p<.01).Freedom from local relapse (FLR) was not different among CT+RT vs RT ( 5y FLR 62% vs 56%, p=.98). FLR în the CT +RT arm was the same for ORT vs PRT (63% vs 59%, p=.98), but difference was significant în the RT alone arm (ORT vs PRT: 67% vs 30%, p<.01). Conclusions: Neoadjuvant CT+RT and RT alone results were similar în terms of RR, 5 years S, DFS, FLR. în the RT alone arm, a poor quality RT gave significantly worse results for all these endpoints. în the combined modality arm, neoadjuvant CT efficiently compensated for the poor quality RT.

Key words: Nasopharingeal carcinoma, Neoadjuvant chemotherapy.

Radioterapie & Oncologie Medicală, 2005, 1:29-37

38 Permanent Iodine 125 Brachytherapy as Curative Option for Organ Confined Prostate Cancer – Toxicity and Short Term Biochemical Outcome

  1. Kacsó1, J. M. Hannoun-Levi2, S. Marcié 2, P.Y Marcy2 ,
  2. Quintens3 , J. Amiel3, J. P. Gerard 2

1 „Ion Chiricuţă” Cancer Institute, Radiation Oncology Department, Cluj, Romania; 2 Centre „Antoine Lacassagne”, Radiation Oncology Department, Nice, France; 3 Hopital Pasteur, Urology Department, Nice, France

Purpose: prospective analysis of biochemical response, acute and late morbidity for patients with localized prostate cancer treated with ultrasound guided permanent I-125 transperineal prostate interstitial (TPI) brachytherapy (BT). Material &methods: Between June 2001 – March 2004, 52 consecutive patients with clinically localized prostate cancer were treated at „Antoine Lacassagne” Cancer Center, Nice (France) with TPI BT as sole local therapy +/- neoadjuvant hormonal treatment (NAHT). Median age was 64 years (range 54–75). The clinical stage was T1c in 17 patients (32%), T2a in 31 (60%), T2b in 3 (6%) and T2c in 1 case (2%). Median pre-treatment PSA was 7.64 ng/ml (range 2.71- 13.8 ng/ml), Gleason score < 4 vs. 5 vs. 6 vs. 7 (3+4) for 27 vs. 27 vs. 40 vs. 6% of cases. The median prostate volume was 37 cc (range 16- 60) and the prescribed dose 160 for 6 men (pre-TG43) respectively 145 Gy (TG-43) for all others. Sixteen patients (30%) received NAHT, of which 68% contained LHRH analogues. PSA relapse was defined according to ASTRO Consensus Statement but subtracting „bounce-PSA”. Acute and late toxicity were recorded using NCI CTC 2.0 and SOMA LENT criteria. The median follow-up was 14 months (6- 36 months). Results: Acute urinary toxicity (UT) at 3 months after BT was of G1 in 42% cases, 42% G2, 2% G3 and 2% G4 whereas late UT was noted as G1 in 36.5% of patients, 36.5% being G2, 9.5% G3 and 2% G4. There were no acute or late rectal toxicity (RTY) higher than G2, as only 13.5% presented G1 and 4% G2 acute RTY, respectively 15% G1 and 8% G2 late RTY. At 3 vs. 6 vs. 12 vs. 18 vs. 24 months, G3- 4 erectile dysfunction (ED) was 25 vs. 18 vs. 24 vs. 22 vs. 15%, correlated with age, NAHT and associated diabetes. Only 6% of men younger than 70 years, with no NAHT or diabetes complaint about G3-4 ED at 2 years after BT. The 2 year PSA relapse free survival was 98%. All patients were discharged 24 hours after the implant. Conclusions: for selected patients, I-125 TPI BT offers efficacy comparable to radical prostatectomy or conformal radiotherapy, with acceptable urinary morbidity, less severe rectal toxicity and sexual dysfunction, at least for the first 2 years after the implant.

Key words: Prostate cancer, Brachytherapy, Acute & late toxicity.

Radioterapie & Oncologie Medicală, 2005, 1:38-45

46 Quality Assurance and Quality Control in Radiotherapy: Importance and Technical Aspects of Departmental Level Implementation in Cancer Institute Cluj-Napoca

Daniela Martin¹, V. Cernea¹ ², A. Chiş¹, D. Dordai¹, V. Bogdan¹, Ruxandra Fizeşan¹, N. Ghilezan¹ ²

¹ Cancer Institute „Prof. Dr. I. Chiricuţă” Cluj- Napoca, ² UMPh „Iuliu Haţieganu” Cluj- Napoca

Recent developments in radiotherapy technology have created new possibilities for cure, but the superior performance of modern equipment cannot be fully exploited unless a high degree of accuracy and reability is reached, wich is only possible through quality assurance programmes. Our goal was to describe the first steps of QA and QC programmes for equipment and treatment planning process in Radiotherapy Department of ”Prof. Dr. I. Chiricuþã” Cancer Institute. This implies that both the parameters related to the patient (diagnosis, decision, indication for treatment, follow-up) and also the procedures related to the technical aspects, achievement of safe effective treatment were subjected to careful quality control. Audit of individual radiotherapy prscriptions will identify apparent planning or prescription errors that could be corrected prior to the initiation of therapy. The objectives for audit for radiotherapy treatment policy will review patients management: indication, the choice of target volume, the prescribed dose, the adequacy of target volume coverage and protection of normal structure.

Key words: Quality assurance, Quality control, Radiotherapy, Audit, Equipments, Treatment

Radioterapie & Oncologie Medicală, 2005, 1:46-53

54 Randomness in the Evaluation of a Binary Pattern

  1. Todor, R. Buiga

Cancer Institute „Prof. Dr. I. Chiricuţă” Cluj- Napoca

Using a simulation program in Visual Basic for Excel it is investigated the graph of the data for a binary variable. Galectine-3 evaluation on a set of ovarian tumors treated at Oncology Institute „Ion Chiricuþã” is the practical example. The paper shows a practical method to evaluate the correctness of data.

Key words: Percentage evaluation, Simulation, Regression, Visual Basic, Excel

Radioterapie & Oncologie Medicală, 2005, 1:54-62

59 Breast Carcinoma with Signet-Ring Cells

Case Report and Review of the Literature

C.D. Olinici1,2, Doiniţa Crişan1, Ioana L. Muntean2, Liliana Resiga2

1U.M.Ph. „Iuliu Haţieganu”Dpt. of Pathology, Cluj-Napoca, 2Cancer Institute „Prof. I. Chiricuţă”, Cluj-Napoca

Signet-ring cell carcinomas of the breast are very rare. Although their histogenesis is controversial, most cases are regarded as variants of infiltrating lobular carcinomas. This paper reports a breast tumor showing two different histologic appearances: a signet ring cell carcinoma with invasive and with in situ patterns and a classical ductal invasive and in situ carcinoma. The histological features, the immunoreactivity for estrogen and progesterone receptors and the lack of lobular changes suggest that the signet-ring cell component arose from the ductal epithelium.

Key words: Breast, Signet-ring cell carcinoma

Radioterapie & Oncologie Medicalã, 2005, 1:59-63

64 ONCOLOGICAL LIFE IN ROMANIA

66 CONTINUOUS MEDICAL EDUCATION

66 Recommendations of ASCO/ESTRO for a General Curriculum in Medical Oncology

Viorica Magdalena Nagy, T. E. Ciuleanu

74 REVIEW OF LITERATURE

76 CALENDAR OF THE INTERNATIONAL EVENTS 2005

78 GUIDELINES FOR AUTHORS