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Volum 15 Numarul 1, 2009

5 EDITORIAL

Alexandru Eniu

7 Raport privitor la situaţia actuală a laboratoarelor de radioterapie din România, planul na­ţional pentru radioterapie 2008-2010 / Report regarding the present state of radiotherapy labo­ratories in Romania, national program for radiotherapy 2008-2010

Valentin Cernea, Viorica Nagy, Alexandru Irimie, Mircea Savu, Alexandru Chiş, Ion Chereji

25 The PSA Dynamics Analysis According to Different Therapeutic Methods for Localized Prostate Cancer. The PSA Bounce Phenomenon

Laura Rebegea Paraschiv1, Rodica Anghel2, Mihaela Dumitru1

1Saint Andrew Apostol The Emergency Clinical Hospital, Galaţi; 2Prof. Dr. Al. Trestioreanu Cancer Institute Bucharest

PSA dynamics after brachytherapy is different in comparison with PSA changes after radical prostatectomy or after external beam radiother­apy. The aim of the present paper is to present the biochemical failure terms, the limits of the existing definitions, the description of the PSA bounce phenomenon and the occurrence moment of this phenomenon, the relationship between PSA bounce and disease free survival.At the same time the most important studies in literature are reviewed. The majority of the present studies point out that PSA bounce does not rep­resent a predictive factor for treatment failure, but an anxiety cause for patients who perform permanent implant.

Key words: PSA dynamics, PSA bounce, biochemical failure.

29 HER2 Testing in Breast Cancer Using Immunohistochemical Analysis and Chromogenic In Situ Hybridization: The Ion Chiricuţă Cancer Institute Experience

Luminiţa Leluţiu1, Rareş Buiga1, Liliana Resiga1, Alexandru Eniu1 , Nicolae Ghilezan2, Corneliu D. Olinici2

1 Ion Chiricuţă Cancer Institute, Cluj-Napoca, Romania 2Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, Romania

Background: Testing of HER2 status in breast cancer has become very important to patient care following the approval of transtuzumab (Herceptin) as the first therapy to target the HER2 oncoprotein. Many clinical trials have used immu­nohistochemistry (IHC) to test for HER2 overexpression in order to select patients for therapy. Fluorescence in situ hy­bridization (FISH) and chromogenic in situ hybridization (CISH), tests for gene amplification, are more sensitive than IHC .Weak overexpressors on IHC testing are not gene amplified on FISH or CISH analysis and may be considered false-positives results which raises the question of how best to test for HER2. Patients and methods: The authors com­pared the specificity, simplicity of a procedure and method standardization, the simplicity of evaluation for the results for each method (immunohistochemistry and chromogenic in situ hybridization). 1255 cases of invasive breast carci­noma from surgically excised tumors and core needle biopsies were included in the study. The first step was the deter­mination the HER2 status by immunohistochemistry. The cases with moderate (2+) and strong (3+) overexpression of HER2 protein were chosen for determining HER2 amplification by CISH. Results: False-positive results are a signifi­cant problem when IHC is exclusively used to test for HER2 overexpression. The false-positives results are confined to the group 2+ positive and do not respond to targeted therapy. Concordance between IHC and CISH is high when immu­nostaining is interpreted as either negative or strongly positive. Many studies have suggested that CISH may better pre­dict response to anti-HER2 therapy rather than IHC. Although IHC is less technically demanding it is more expensive than CISH. Conclusions: As a first step, IHC analysis of HER2 status in breast cancer is a useful predictor of response to therapy with Herceptin when it is strongly positive. In some cases IHC positive overexpressors are false-positives in CISH tests. Thus, screening of breast cancer with IHC and then confirmation 2+ positives IHC results by CISH is an ef­fective evolving strategy for testing HER2 as a predictor of response to targeted therapy.

Key words: Laryngeal Cancer, Lymph Node Involvement, Postoperative Radiotherapy.

36 Operable Breast Cancer: 10 Years Results Ion Chiricuţă Cancer Institute Cluj-Napoca, 1995-1996 cohorts

Cristina Vitoc1, Nicolae Ghilezan1,2, Nicolae Todor1, Radu Tănăsescu1 , Dana Grecea1, Alexandru Eniu1, Carmen Lisencu1, Alin Rancea1,2, Dumitru Mureşan1, Mihaela Galatâr1

1I. Chiricuţă Cancer Institute Cluj-Napoca; 2Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca

Objective: to evaluate the therapeutic results for operable breast cancer, cohorts 1995 – 1996, in order to have a starting point for a further analysis of the progress of treatment delivered in the Cancer Institute Cluj-Napoca, Romania. Patients and methods: 368 pa­tients (pts.) with operable breast cancer treated by clinical standards in 1995-1996 were analyzed retrospectively in relation to the clinical, pathological and therapeutic characteristics. For all the patients, the initial therapy had been surgery (radical mastectomy, conservative) followed by an adjuvant treatment according to the standards of that period in Romania (radiotherapy, chemotherapy, hormone therapy or no treatment). The main clinical & therapeutic characteristics: median age: 49 years (limits 24-84); premeno­pausal 195, postmenopausal 173; clinical stage = 0: 2; I: 41; II a: 81; II b: 129; III a: 15. Surgery: radical mastectomy: 249; conserva­tive treatment: 117 + 2 cases with cTx (occult breast cancer, no breast surgery). Radiotherapy, when indicated: 40Gy/20 fr. 26 days for chest wall, axilla and/or supraclavicular area post mastectomy (249 pts), and 50 Gy, 25 fr., 32 days for breast volume after con­servative treatments (119 pts.). Chemotherapy: anthracycline regimens (AC, EC: 128), CMF (29 pts.), other (5 pts.). Hormonal ther­apy (tamoxifen only, ovarian ablation) (210 pts.). Results: Uni- and multivariate analysis to identify the prognostic factors was com­pleted in March 2007 by calculating 10 year overall survival. At 10 years follow-up (median 134 months, maximum 152 months), 108 deaths had been registered (78 by breast cancer and 30 other causes) with 71% (260/368) overall 10 year survival and 79% dis-ease-free survival (290/368).The main single cause of failures were distant metastases (68/78 – 87%), followed by loco-regional re­currences (28/78 – 36%). The prognosis was significantly correlated only to clinical stage and pathological status of axillary LN (by uni- and multivariate analysis). Discussion & conclusions: The different treatment modalities and their combinations presented, re­flects the pattern of care in the years 1996 -1996 at the Cancer Institute Cluj. The main goal of the study was to set up a reference value to be used for further evaluation of subsequent results, as new concepts and new treatment developments are being integrated in the process of care for breast cancer patients.

Key words: Operable breast cancer, Adjuvant treatment, Failures.

45 Triple Negative Breast Cancer at the Ion Chiricuţă Cancer Institute Cluj-Napoca: Clinical Outcomes, Predictive and Prognoses Factors

Cristina Furtoş, Bogdan Gozman, Gabriela Morar Bolba, Alexandru Eniu

Ion Chiricuţă Cancer Institute, Cluj-Napoca, Department of Breast Tumors

Background: Breast cancer is a heterogeneous disease with different biologic characteristics and clinical behaviors. Numerous recent publications have analyzed the clinical characteristics of “triple negative” breast cancer that does not express estrogen (ER), proges­terone (PR) and Her2 receptors. In general, 80-90% of the triple negative cases will be “basal-like” tumors. The goal of our study is to present the descriptive analysis of a cohort of triple negative patients at the “Ion Chiricuţă” Institute of Oncology, Cluj-Napoca (IOCN). Methods: 89 patients with triple negative breast cancer who were treated from April 2004 to December 2007 were evalu­ated. Determination for ER, PR and Her2 was made through IHC and were stratified by clinical characteristics and disease evolution. Results: Median age was 48.4 years range 28 to 77; 6.8% were <35 years of age; 56 were premenopausal. Stage of the patients who relapsed, 10 pts (72%) developed distant metastases, 2 patients developed local and systemic recurrence, and 2 patients developed an isolated local recurrence. Out of the patients that recurred, 28.6% developed cerebral metastases; distribution at presentation was as follows: I 4 pts(4.49%) , IIA 20 pts (22.47%), IIB 32 pts(35.95%), IIIA 17 pts(19.10%), IIIB 13 pts(14.60%) and IIIC 3 pts(3.37%). Tumor size T1 in 33.37% of pts, T2 in 51.57% of pts and T3 in 2.2% of pts. The histology was invasive ductal carcinoma in 88.8% cases and medullar in 10 (11.2%) cases. Histological 55% were grade III. 53 patients (59.5%) were treated with neoadjuvant CT, 13 of which had a pCR, 37 had a pPR, and 2 had pSD. In our patient population, 43% had breast-conserving surgery and 38.2% of pts had node-positive disease. After surgery, eighty percent of patients had anthracycline-based, and 22.5% had anthracycline and tax­ane-based adjuvant chemotherapy, while 17% of pts had CM low-dose adjuvant CT for 1 year. 53.60% had adjuvant radiotherapy. After 16 months, mean follow-up, 14 patients recurred (15.8%) and 6 patients (6.7 %) died. Conclusions: The results of this analysis show that triple negative BC is a distinct subtype, with special characteristics: younger age at diagnosis, larger tumors, higher grade, high percentage of systemic recurrences in this group of patients. The small number of patients in our study did not allow identifica­tion of predictive and prognostic factors. Longer follow-up and an increase of our sample is required to allow further analysis.

Key words: Conformal Radiation Therapy, Prostate Cancer, Toxicity Triple Negative Breast Cancer, Clinical Outcomes.

51 Male Breast Cancer – The Ion Chiricuţă Cancer Institute Experience Cluj-Napoca 1996-2007*

Ioana Puşcaş1, Nicolae Todor1, Nicolae Ghilezan2

1Ion Chiricuţă Cancer Institute Cluj-Napoca; 2 Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca

Male breast cancer is a rare disease representing about 1% of all breast cancers and less than 1% of all cancers in men.The goals of the cur­rent retrospective study are to analyse the incidence, the clinical and histopathological data, the treatment and survival rates of males with breast carcinoma registered in Cancer Institute Cluj, in the period 1996-2007. In this period of time, 74 patients have been registered repre­senting 0,8% from the total amount of breast cancer cases seen in the Institute. The median age: 62 years (range: 34 -82 years); median fol­low-up 40,4 months. Clinical stages: I = 4.7 %; II = 32.8%; III = 57.8% and IV = 4,7%. The 5 year overall survival rate was 72% (CI: 56% – 84%). The treatment followed the same guidelines as those for female breast cancer, for that period. Tumor size and nodal involvment are the most important prognostic factors in male breast cancer.

Key words: Male breast cancer, Prognostic factors, Survival.

56 Prognostic Factors in 118 Patients with Newly Diagnosed Primary High Grade Gliomas

Dana Cernea1, Renata Zahu1, Teodora Flonta1, Iolanda Hossu1, Victor Bogdan1 , Ştefan Florian2, Magda Petrescu3, Nicolae Todor1

1Ion Chiricuţă Cancer Institute Cluj-Napoca; 2 Neurosurgery Department, County Hospital Cluj-Napoca; 3Pathology Department, County Hospital, Cluj Napoca, Romania

Background: High grade gliomas have a poor prognosis with a median survival of 9-36 months. We analyzed the prognostic factors which can predict the outcome of these patients. Material and Methods: One hundred eighty patients (118) treated between 2005­2007 with high grade gliomas were retrospectively analyzed: 91 patients (77%) with glioblastoma multiforme (GBM), 27 patients (23%) with anaplastic astrocytoma (AA); patients between 20 and 81 years old with a median of 55 years; 66 (56%) males and 52 females (44%). All patients had received postoperative radiotherapy: conventional fractionation (1.8 – 2 Gy/ fraction) with curative intent (total dose 60 Gy) in 93 patients (79%), and with modified fractionation in 25 patients (45 Gy in 15 fractions). Chemotherapy with Temozolomide according to Stupp protocol was administrated in 40 patients and another type of chemotherapy in 34 patients. 44 patients had received no chemotherapy. We analyzed age, gender, neurological performance status (NPS), histology, type of sur­gery, radiotherapy, chemotherapy as possible prognostic factors and the correlation of these factors with survival. Results: Overall survival was 60% at 1 year and 25% at 2 years. Prolongation of survival was significantly associated with good NPS, patients’ age less than 50 years, postoperative radiotherapy and chemotherapy. Conclusions: Surgery followed by concomitant radiochemotherapy with Temozolomide should be considered for all patients. The most important adverse prognostic factors in patients with malignant gliomas are advanced age, poor neurological status, unresectable tumor, histological features of glioblastoma. There are ongoing ef­forts to identify additional prognostic factors (biologic and genetic alterations) which could be important in making decisions about optimal therapy.

Key words: Prognostic factors, Glioblastoma multiforme, Anaplastic astrocytoma, Radiotherapy, Chemotherapy, Survival.

63 UICC World Cancer Congress: World Cancer Declaration 2008, August 27-31, 2008, Geneva, Switzerland

   Viorica Magdalena Nagy

65 31st Annual San Antonio Breast Cancer Symposium (SABCS) December 10-14, 2008, San Antonio, Texas, USA

Larisa Ciule

72 Important International Cancer Conferences and ESTRO Teaching Courses 2009

76 Active members of the Romanian Society for Radiotherapy and Medical Oncology 2009

77 Guidance for Authors on the Preparation and Submission of Manuscripts