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Volum 14 Numarul 4, 2008

193 EDITORIAL

Anton Cucuianu

195 Operable Gastric Cancer Treatment – Where are We and What is the Future?

Călin Căinap1,2, Gabriel Kacsó1,2, Alina Marti3, Anca Hodorog2

1Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca; 2Ion Chiricuta Cancer Center Cluj-Napoca, Romania; 3Service d’Oncologie, Centre Hospitalier, Auxerre, France

Gastric cancer remains one of the most deadly cancers, the majority of the patients die in the following year. Gastric cancer is a very challenging malignancy given that it presents late, has complex pathogeneses mechanisms with multiple carcinogenic processes im­plicated, and is only moderately sensitive to chemotherapy and radiation. Few changes have occurred in the last century concerning the etiology of gastric cancer, but it is the only cancer whose incidence has really diminished. The standard treatment is multidisci­plinary: surgery, radiotherapy and chemotherapy, which each in its own way, improves the chance of survival of the patient. The arti­cle tries to emphasize the controversies, underlying the actual standard treatment.

Key words: Gastric Cancer, Treatment, Surgery, Radiotherapy, Chemotherapy.

199 Osteoblast Differentiation and Immunocytochemical Characterization of Human Mesenchymal Stem Cells

Ciprian Tomuleasa1,2, Olga Soriţău1, Vasile Foriş1,2, Valentin Lung-Illes2 , Ioana Brie1,2, Piroska Virág1, Eva Fischer-Fodor1, Maria Perde-Schrepler, Corina Tatomir1, Ion Dan Postescu1, Gabriela Cherecheş1, Doina Piciu1

1Ion Chiricuta Cancer Center Cluj-Napoca, Romania, Radiobiology of Department2Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca

Background: Mesenchymal stem cells are non-hematopoietic cells with self-renewal potential that can differentiate into a variety of cell types, such as osteoblasts, adipocytes or neuronal cells. These cells possess multilineage differentiation potential due to certain cellular transcription factors, like the proteic homeodomaine Nanog, the transcription factor Oct 3/4 and it’s cofactor SOX 2. Once these factors are stimulated, differentiation is inhibited. Aim: The aim of the current study is to differentiate human mesenchymal stem cells into mineralized osteoblasts and to investigate the expression of stage-specific antigens. Material and Methods: Mesen­chymal stem cells were isolated from human bone marrow and cultured in osteogenic medium. Using monoclonal antibodies we characterized these adult stem cells by identifying their specific surface markers SSEA- 4, CD 29, CD105, Oct 3/4, Nanog and SOX

  1. We evaluated the specific markers of the mineralized osteoblasts (differentiated from bone marrow stem cells) using immunohis­tology protocols for Osteopontin and Osteonectin. Results: Respecting the immunocytochemical staining protocols used, the results are positive for SSEA-4, CD 29, CD 105 and Oct ¾. We obtained weak positivity for both Nanog and SOX 2. The monospecific an­tibody technique of Anti-Alkaline Phosphatase FITC staining also demonstrated the presence of this specific isoenzyme. Conclusion: The isolation of human stem cells offers the promise of a remarkable array of novel therapeutics but it is vitally important that every aspect of the biology of a stem cell should be well known before we move on to a clinical setting.

Key words: Mesenchymal Stem Cells, Osteoblast Differentiation, Stage Specific Markers, Immunocytochemistry.

206 Predictive Value of HER Status for Pathological Response to Antracycline Based Neoadjuvant Chemotherapy in Hormone Receptor Negative Breast Cancer

Renata Zahu, Sandu Istrate, Radu Tănăsescu, Carmen Popa, Nicolae Todor

Ion Chiricuta Cancer Center, Dept. of Breast Tumors, Cluj-Napoca, Romania

Purpose: To evaluate the pathological complete response rate to neoadjuvant anthracycline based chemotherapy in hormone-receptor nega­tive breast cancer and to establish the Her2 status’s significance for this response. Materials and methods: Sixty-two patients’ medical re­cords were analyzed, who presented with locally advanced breast cancer and received a minimum of four cycles of primary chemotherapy with AC or EC regimen followed by breast conserving or total surgery. The pathological complete response was defined as no carcinoma in breast and axillary nodes. Results: The median age was 48 years old. Twenty six patients were Her2 3+/ER-/PR-, and thirty six patients were triple negative (HER2 -/ER-/PR-). Pathological complete response was 16%, 8% among HER2 overexpressing patients and 22% in basal-like subtype. Conclusion: There wasn’t any significant statistical difference between the two groups regarding complete pathological re­sponse rate to anthracyclines based chemotherapy. Although other studies have shown that the overexpression of HER2 gene is associated with a worse prognosis but a good pathological response to the anthracyclines based chemotherapy regimens, our data do not suggest that HER2 status might have an influence in hormone receptor negative patients.

Key words: Breast Cancer, HER2, Hormone Receptor, Chemotherapy, Pathologic Response.

211 Capecitabine (Xeloda) Efficacy, Safety and Clinical Benefit in Patients with Relapsed Metastatic Breast Cancer after Treatment with Anthracyclines and Taxans

Dana Grecea 1, Carmen Vasiliniuc 1, Roxana Draghici 1, Luciana Neamţiu 1, Alin C. Rancea 1,2, Liliana Resiga 1, Dan I. Postescu 1, Viorica Nagy 1,2, Nicolae Ghilezan 1,2

1 Ion Chiricuta Cancer Center Cluj Napoca,Romania; 2 Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, Romania

Background: Capecitabine is a rationally designed oral, tumor- activated fluoropyrimidine carbamate with high activity in metastatic breast cancer. The present study was designed to further evaluate the efficacy and safety of capecitabine in patients with metastatic breast cancer previously treated with antracyclines and taxans- containing regimens (either paclitaxel or docetaxel). In addition to re­sponse rates and survival times, patients’ preference for oral therapy and QoL were increasingly important considerations in MBC. Patients and methods: 35 patients with documented metastatic breast cancer progressing after neoadjuvant or adjuvant antracycline and taxane- containing chemotherapy treated between July 2002 and January 2006 were included. The treatment schedule consisted of 3-weeks cycles of oral capecitabine 1250mg/m2, twice a day, for 14 days followed by a 7-day rest period. The patients were evalu­ated for response and toxicity after a total of 210 cycles of chemotherapy. Results: Baseline characteristics of the patients were: me­dian age 52 years (range 33-73), median ECOG PS 1 (range 0-2) and adequate bone marrow, renal and hepatic functions. The median number of metastatic sites was 2 (range 1-5).The stabilization of the disease (SD) was obtained for 9 patients (25.7%) with an overall response of 34 %, in 10 patients (28.5%) was achieved a partial response (PR) and in other two patients (5.7 %) a complete response (CR). The median time to progression was 6.6 months and the median overall survival was 10.4 months, with a significant advantage for the responding patients. For patients achieving a CR or PR, the median survival was 18 months, for those with SD 9 months and for the patients with PD 4.5 months. Capecitabine was generally well- tolerated: most treatment- related adverse events were grade 1 or 2 in intensity; a grade 3 treatment- related adverse events occurred and included the hand-foot syndrome (11%), diarrhea (7%), vomiting (5%), and nausea (6%). There were no treatment-related deaths. The patients who received Xeloda had a significant and sustained improvement in the global health status, pain intensity and analgesic consumption. Conclusions: This study confirms that capecitabine achieves a high tumor control rate in heavily pretreated patients with metastatic breast cancer. The patients who re­ceived Xeloda had a significant improvement in global health status. Due to its favorable safety profile and convenient oral admini­stration, capecitabine can be given as an outpatient therapy. Based on consistently high efficacy and good tolerability capecitabine should be considered as the reference treatment in this setting.

Key words: Xeloda, metastatic breast cancer.

217 A Phase II Study of Weekly versus 3 Weeks Docetaxel in Patients with Metastatic Breast Cancer

Corina Idu1, Daniela Grecea1, Carmen Vasiliniuc1, Luciana Neamţiu2

Ion Chiricuţă Cancer Center Cluj-Napoca, Romania: 1Dept. of Breast Tumors; 2Dept. of Epidemiology

The purpose of this study is to evaluate the activity of weekly vs 3 weeks Docetaxel in patients with metastatic breast cancer in the Oncology Institute of Cluj Napoca. Sixty women were included in our study. All patients were histologically confirmed metastatic breast cancer. Patients received either docetaxel 35 mg/m2 weekly or docetaxel 100 mg/m2 on day 1 every three weeks. Overall re­sponse rate was 39.5% in weekly regimen vs 59.2% in three weeks docetaxel group. Complete response was observed at 3 patients in our study. In 3 weeks docetaxel group, partial response was observed at 15 patients vs 10 patients in the weekly group. Time to pro­gression was 7 months in the 3 weeks group and 8 months in the weekly regimen. In our study the 3 weeks regimen was proved to have better results than weekly docetaxel.

Key words: Docetaxel, Metastatic Breast Cancer, Study.

221 Phyllodes Tumors and Primary Breast Sarcomas. The experience of “Ion Chiricuţă” Cancer Center, Cluj, between 1998-2006

Zsolt Fekete, Daniela Martin, Cristina Vitoc, Valentin Cernea, Dan Eniu, Alin C. Rancea, Mihaela Galatâr, Nicolae Todor, Viorica Nagy

Ion Chiricuta Cancer Center Cluj-Napoca, Romania

Introduction: The proper treatment of phyllodes tumors and breast sarcomas is still a matter of debate, since they are rare and there is a lack of randomized trials. Objective: To identify the clinical and pathological risk factors associated with poor outcome (local relapse, metastasis) and to point out the optimal treatment for different prognostic groups. Materials and methods: 52 patients with phyllodes tumors and pri­mary breast sarcomas were treated with curative intent between 1st Jan. 1998 and 31st Dec. 2006. 36 patients underwent total mastectomy, 16 lumpectomy; 17 patients with radical surgery or lumpectomy received adjuvant radiotherapy and 11 chemotherapy. Results: With a median follow-up of 48 months the overall survival at 5 years was 83% and the disease free survival at 5 years was 67%. The primary tumor control was achieved in 39 patients (75%). 6 patients experienced local relapse, but 4 were salvaged by local resection. 3 patients had both local re­lapse and visceral metastases. One patient had lymph node involvement and visceral metastases, and only 3 developed visceral metastases alone. Univariate analysis of prognostic factors in relation to the local-relapse free survival showed a tendency for increased survival for pa­tients less than 50 years of age, patients with total mastectomy and patients who received adjuvant radiotherapy. The differences were not statistically significant. Conclusions: Primary disease control was achieved in 75% of cases. The main goal of the treatment remains local control. There was a 23% increase in local-relapse free survival by mastectomy versus lumpectomy and a 25% increase when adjuvant radio­therapy was used. The optimal combination treatment for primary breast sarcomas needs to be defined in prospective randomized studies.

Key words: Phyllodes tumors, Breast sarcomas, Treatment .

227 Unusual Massive Craniospinal Metastasis of a Treated Medulloblastoma

Emilia Mihuţ1, Dana Cernea2 , Ştefania Neamţu1, Rodica Cosnarovici1, Vasile Popiţa3 , Iolanda Hosu2, Victor Bogdan2

Ion Chiricuta Cancer Center, Cluj-Napoca, Romania: 1Dept. of Paediatric Oncology; 2Dept of Radiation Oncology; 3Dept. of Radiology

A case of an 11year old boy with medulloblastoma of posterior fossa is presented. After initial surgery, the patient was irradiated using the ecranio-spinal technique and received chemotherapy. After almost 2 years, he presented cranio-spinal massive recurrence. After chemother­apy, he presents now complete clinical and imagistic response.

Key words: Medulloblastoma, Radiotherapy, Chemotherapy, Craniospinal metastasis.

232 Incidental Diagnosis of a Sigmoid Tumour on PET-CT in a Thyroid Cancer Patient. A Case Report

Cosmin Lisencu1, Ioana Puşcaş2, Doina Piciu3

Ion Chiricuta Cancer Center Cluj-Napoca: 1Surgery Department; 2Radiotherapy Department; 3Nuclear Medicine Department

Thyroid cancer is a relatively uncommon malignancy, more frequent in women than in men (2.5 to 1). The association between thyroid and colon cancer is very rare, more often being found in some hereditary syndromes as Cowden’s disease or familial adenomatous polyposis coli. We present a case of a 54-year-old patient with thyroid cancer, who had a positron-emission tomography for his residual thyroid disease. The surprise finding was a sigmoid tumour, confirmed by colonoscopy and further surgery.

Key words: Thyroid cancer, PET-CT, sigmoid cancer.

237 Malignant Chondroid Syringoma – Case Report and Review of the Literature

Ileana Matei1, Felicia Constantina2, Gabriel Matei2

Dr. Constantin Opriş Emergency County Hospital Baia Mare, 1Department of Pathology, 2Department of Radiation Oncology

Malignant chondroid syringoma is an extremely rare variety of sweat gland carcinoma and case reports have been relatively few. In this pa­per, we report the case of a 54-year-old female diagnosed with malignant chondroid syringoma that appeared on the left buttock and slowly grew up in about 20 years. From a histological point of view, the tumour consists of both epithelial and mesenchymal-like components (chondromyxoid stroma, even with ossification). Given the location, the size of the tumour, and the histological findings, the tumour was classified as a malignant chondroid syringoma. This report discusses the clinical and pathological features, behaviour and treatment, includ­ing surgical excision and postoperative radiotherapy.

Key words: Malignant chondroid syringoma, Skin lesion, Radiotherapy.

241 Contents of Journal of the Romanian Society for Radiotherapy and Medical Oncology, Vol. XIV, 2008

245 Index of Themes 2008

248 Index of Authors 2008

250 Guidance for Authors