Darjana Jovanovic

High dose chemotherapy with stem cell support in the treatment of testicular cancer.

Testicular germ cell cancer (TGCC) is rare form of malignant disease that occurs mostly in young man between age 15 and 40. The worldwide incidence of TGCC is 1.5 per 100000 man with the highest rates in North Europe. After discovery of cisplatin cure rates of TGCC are very favorable between 90%-95% and unlike most solid tumors, cure rate for metastatic TGCC is around 80%. Metastatic TGCC is usually treated with 3-4 cycles of bleomycin, etoposide, cisplatinum chemotherapy with or without retroperitoneal surgery and cure rates with this approach are between 41% in poor risk group and 92% in good risk group of patients. Cure rates are lower in relapsed and refractory patients and many of them will die from the disease if not cured with first line chemotherapy. High dose chemotherapy (HDCT) approach was used for the first time during the 1980s. Progress in hematology allowed the possibility to keep autologous haematopoietic stem cells alive ex-vivo at very low temperatures and use them to repopulate the bone marrow after sub-lethal dose of intesive myeloablative chemotherapy. Despite the fact that there is no positive randomized study to prove HDCT concept, cure rates in relapsed TGCC are higher after high dose therapy then in historical controls in studies with conventional treatment. Here we review clinical studies in HDCT for TGCC, possibilities of mobilising sufficient number of stem cells and future directions in the treatment of this disease.

Male breast cancer in the era of modern therapies: Serbian single centre experience report.

To the Editor: Male breast cancer is a rare disease, accounting for less than 1% of total malignant diseases and less than 1% of all breast cancer cases (1). Inspired by the Ruddy and Winer’s article published in Annals of Oncology (2), we analyzed our group of patients treated at the Oncology Institute of Vojvodina from 2006 to 2010. We analyzed the medical records of 44 patients managed at our Institute. The median follow-up was 50 months (25–83). Diagnosis was established after radical mastectomy in case of 72% of studied patients; the rest of patients underwent less radical surgery or biopsy in case with primary metastatic disease. Adjuvant radioand chemotherapy were administered according to standard protocols (3). The Kaplan–Meier estimator and Mann–Whitney U-test were used for statistical analyses. In our group, 34% of patients had T1 disease, while 50%, 3%, and 13% had T2, T3, and T4, respectively. Lymph node status was—N0 32%, N1 32%; also, N3 and N4 both by 18%. Seventeen patients (39%) had stage IV disease in the time of diagnosis while stage I, II, and III was found in 9%, 41%, and 11%, respectively. Hormone receptor positive disease in our group of male patients was diagnosed in 78% of patients, while three patients (10%) had HER2 positive disease from 32 patients with known HER2 status. Grade two was the most often determined (62%), while G1 and G3 disease was diagnosed in 21% and 17% of patients. In the time of diagnosis, 27 patients had no metastases and 21 of them were treated with adjuvant chemotherapy. FAC protocol (5-flurouracil, doxorubicin, and cyclophosphamide) was applied in case of 81% of patients; combination of AC protocol (doxorubicin and cyclophosphamide) and taxanes was administered in two patients (10%), and CMF (cyclophosphamide, methotrexate, and 5-flurouracil) was also applied in two patients. Tamoxifen was given to all patients with positive estrogen receptors. After disease progression, the patients were mostly treated with taxane therapy and/or capecitabine. None of the patient was given trastuzumab therapy. Primary metastatic disease was found in 17 studied patients and 14 (82%) of them were given FAC therapy and followed with tamoxifen in case of hormone positive disease; two patients were treated with taxanes initially, and one patient was treated with hormonal therapy only. The median of progression free survival (PFS) in the analyzed group of patients was 29 months, and median overall survival (OS) was 40 months. Fouryear PFS was 28% and OS was 43%. In addition, we analyzed survival based on clinical and histopathologic parameters. The univariate analysis showed that tumor size and number of involved lymph nodes in axilla had no significant impact to 4-year PFS and OS. Patients with stage III and stage IV disease had shorter 4-year PFS (5% versus 64%, p = 0.0006) and OS (19% versus 70%, p = 0.0044), mainly on the account of 17 patients with primary metastatic disease. Four-year survival of the patients with metastases was 17% with the median time to progression of 11 months and median time for overall survival of 35 months. These data speak in favor of the efficacy of larger number of therapies administered in metastatic stage of disease. Hormone receptor status did not influence PFS and OS. None of the patients with HER2 positive or grade 3 disease survived more than 3 years, but we didn’t find statistical significance because of the small number of studied patients. Patients with primary metastatic disease had more often tumors of ≥5 cm (p = 0.03) and ≥4 positive ipsilateral axillary lymph nodes (p = 0.01). In contrast to the majority of studies that have been analyzed by Ruddy and Winer (2) our study was a report of the 44 patients who were treated after the year 2005, with more recent standards in adjuvant treatment and with more drugs to treat metastatic Address correspondence and reprint requests to: Lazar Popovic, MD, TA, Clinic for medical Oncology, Oncology Institute of Vojvodina, Put dr Goldmana 4, Sremska Kamenica 21204, Serbia, or e-mail: lazar.popovic@ yahoo.com

Paratesticular rhabdomyosarcoma of a young adult

Sarcomas represent large and diverse group of malignant tumours, originating from mesenchymal cells. Nearly 15% of all childhood tumours and about 1% of all tumours in adults are sarcomas [1]. The incidence of adult soft tissue sarcomas in Europe is 5/100,000 [2]. Rhabdomyosarcoma accounts for 4.6% of all soft tissue sarcomas and it is the most common paediatric sarcoma, while it is extremely rare in adults [3].

Concurrent Chronic Lymphocytic Leukemia and Merkel Cell Carcinoma in Primary Skin Tumor and Metastatic Lymph Node

Association between chronic lymphocytic leukemia and other malignancies has been known for a long time. This epidemiological phenomenon is explained by immunosuppression caused by disease itself or by the applied therapy. Merkel cell carcinoma is a rare malignant tumor of the skin of neuroendocrine origin diagnosed almost exclusively in immunocompromised host. We presented an unique case of coexisting infiltration of chronic lymphocytic leukemia cells within primary cutaneous Merkel cell carcinoma and metastatic lymph node in young HIV-negative female patient.