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Volum 16 Numarul 3, 2010

113 Editorial

Ioana Carmen Brie

114 Modern Radiotherapy for Prostate Cancer: a Literature Review

Răzvan Gălălae, MD, PhD

Senior Scientist/Consultant, Paul Scherrer Institute, Center for Proton Therapy, Villigen, Switzerland
& Associate Professor and Lecturer, Medical Faculty, Christian-Albrecht’s-University of Kiel, Germany

Background: Prostate cancer is the most common malignancy in men in developed countries. However, significant geographical differences e.g. between Western/Central and Eastern Europe remain evident. Although modern radiotherapy randomized trials with meaningful follow up (beyond ten years) on prostate cancer are still generally lacking, several different important questions have been addressed and can be evidence – based answered. Material and Methods: Literature reports which potentially could make an important contribution to everyday clinical practice were evaluated and discussed. Specific questions were analyzed: local dose escalation using modern photon beam external radiotherapy (XB-RT), methodological influence on survival endpoints and the importance of hypofractionation, value of dose escalation in relation to risk stratification of prostate cancer, role of interstitial brachytherapy in the context of dose escalation and hypofractionation, and the problem of the “moving target volume” in modern radiotherapy of prostate cancer. Results: Three randomized phase III trials, including the MD Anderson Cancer Center US- experience, a large Dutch multicenter trial and MRC RT01 (UK), indicate that the benefit achieved by local dose escalation (ad 74 to 78 Gy) in terms of superior biochemical tumor control by approximately 10% has been accompanied by increases especially in grade ≥ 2 rectal late toxicity in >10%. Two of the trials evidenced no outcome benefit in low-risk population, while one trial demonstrated superiority of higher doses in all treated patients including those with low-risk disease. None of the studies could show a significant difference in overall survival. In addition, one of the phase III trials and several prospective cohort studies demonstrated a decreased risk of distant metastases by higher local doses and thus better local tumor control. The role of interstitial brachytherapy is explained in detail and the potential hazards of the “moving target problem” as well. Two randomized phase III trials using High Dose Rate (HDR) brachytherapy boost (Hoskin et al. 2007, and Sathya et al. 2003) showed superiority versus conventional XB-RT alone. Radiobiological implications were discussed as well. In this context, toxicity in modern brachytherapy is generally lower. Conclusions: Results are very significant in terms of consequences on everyday clinical practice. Interstitial brachytherapy was shown to apply safely and reliably the highest achieved biochemical equivalent doses and solve best and most complete the “moving target problem”. Local dose escalation was proved beneficial for higher-risk prostate cancer by both conformal external photon beam radiotherapy (XB-RT), and the HDR brachytherapy boost in terms of biochemical control versus conventional XB-RT alone. However, dose escalation by external beam RT seems to be associated with more (especially rectal) and more severe side effects.

Key words: Prostate Cancer, Radiotherapy, Dose Escalation.

123 Correlation Between Type 2 Diabetes and Malignant TumorsNew Possibilities in the Complex Therapy of Cancers?!

Bánhegyi RJ1, Rus-Gal PO1, Nagy AK1, Martyin T2, Varga R3, Pikó B1

Pándy Kálmán County Hospital: 1County Centre of Oncology, 2Department of Infectious Diseases (Hepatology and Immunology), 31st Department of Internal Medicine, Gyula

Nowadays the lack of exercise and improper feeding are the main characteristics of modern life style. This favors not only formation of type 2 diabetes or cardio-vascular diseases, but also increaseas the incidence and prevalence of malignant tumors. Today there are many epidemiologic trials that demonstrate the connection between type 2 diabetes and development of several malignomas. The explanation should be searched in common paths of pathologic processes. One of them is hyperinsulinsulinemia, which accompanies insulin resistence. A hyperinsulinemic state leads to increased glucose uptake in the highly insuline sensitive tumor cells and this supports tumor growth. This makes type 2 diabetes a metabolic condition favoring tumor formation. Thus, we can imagine using oral insulin sensitizers in cancer therapy. Currently several international trials are testing the anti-tumor activity of metformin and thiazolidinediones (TZD). Besides, encouraging results were obtained when using anti-IGF-R antibodies in treatment of tumors. A common therapy of diabetes and tumor may lead to new possibilities in treatment of malignant diseases. By doing this, we can weaken the tumor and strenghten the body, enabling it to fight against cancer.

Key words: Type 2 diabetes, Tumor’s insulin resistence, Metformin, Anti-IGF-R monoclonal antibodies, Complex metabolic control.

132 Head and Neck Cancers in Children Treated with Radiochemotherapy at the “Ion Chiricuta” Institute of Oncology

Renata Zahu1, Dana Cernea1, Stefania Neamtu1, Emilia Mihut1, Rodica Cosnarovici1, Victor Bogdan1, Nicolae Todor1, Vasile Popita1, Tiberiu Guttman1

1 “Prof. Dr. Ion Chiricuta” Institute of Oncology, Cluj Napoca

Background: Only very limited data are available in the Romanian medical literature on the incidence and treatment of head and neck cancers in children. Our aim was to retrospectively analyze the clinical features and results of treatment in 25 children treated at our institution for head and neck malignancy. Material and methods: We performed a retrospective case review of children under the age of 18 years with histologic proven head and neck cancer, treated between 1998-2008 with radiochemotherapy. Data regarding demographic characteristics, disease site and histology, treatment details were collected from the medical records of the patients. Results: The most common site of disease was the nasopharynx (13 children had undifferentiated carcinoma of the nasopharynx), followed by parapharyngeal space, tonsillar fossa, mandible, skull base and paranasal sinuses. The most common histology was undifferentiated carcinoma, followed by rhabdmyosarcoma and lymphoma. Progression free survival for nasopharyngeal carcinoma, treated by induction chemotherapy and radiotherapy was 74% at 2 years. Conclusion: Radiotherapy plays an important role in the treatment of head and neck cancers in children and should be applied in centers with experience in the pediatric age group.

Key words: Head and neck cancer, Children, Histology, Chemotherapy, Radiotherapy.

136 Surgical and Oncological Outcomes in Large Kidney Tumors’ Treatment: One Single Center Experience

Feciche Bogdan, Crisan Nicolae, Mihaly Zoltan, Ona Victor, Bungardean Catalina*, Cebotaru Cristina**, Coman Ioan

Urological Department, Clinical Municipal Hospital, Cluj-Napoca:
* Pathology Department, Clinical Municipal Hospital, Cluj-Napoca; ** Oncological Institute Cluj-Napoca

Introduction: Loco-regional advanced kidney cancers are a challenge for urologist. Aim of the study: We evaluate the outcome of nephrectomies performed for large kidney cancers: T3a with more than 7 cm of tumor diameter, T3b, T4, T3/4 N+, T3/4 M+. Patients and Methods: From July 2002 to October 2009, 47 patients (21 female and 26 male; mean age 57 years, ranging from 28 to 74) were included in a study of large kidney tumors. These 47 patients were selected from 213 consecutive renal cell carcinomas operated in our hospital during this period. The approach used in all cases was a thoraco-abdominal incision with the abdominal component as the first or a bi-subcostal transperitoneal approach only. Results: The median follow-up was 34.6 months. Twenty-seven patients (55.31%) are now tumor-free, 9 (19.14%) are alive but with a disease-progression status while 11 patients died with a median overall survival of 14.5 months. Conclusions: Despite technical challenge and significant postoperative morbidity, we achieved by radical surgery 55 % disease free survival at three years for loco-regionally advanced kidney cancer.

Key words: Kidney, Tumor, Thrombus, Surgery.

140 CpG Island Promoter of Igr-1r is Partial Methylated in Non Small Cell Lung Cancer

Roxana Ola1,2, Ioana Berindan Neagoe2,3, Ovidiu Balacescu2, Marilena Motoc4,
Ali Mougsen5, Anica Dricu5,6

1Babes-Bolyai University, Faculty of Biology and Geology, Department of Experimental Biology, Cluj-Napoca;
2Institute „Ion Chiricuta”,
Department of Functional Genomics and Experimental Pathology, Cluj-Napoca;
University of Medicine and Pharmacy „Iuliu Hatieganu”, Department of Immunology, Cluj-Napoca, Romania;
University of Medicine and Pharmacy “Victor Babeş”, Department of Biochemistry, Timişoara, Romania;
5Karolinska Institute, Cancer Center Karolinska, Stockholm, Sweden;
University of Medicine and Pharmacy Craiova, Department of Biochemistry, Romania;

Insulin-like growth factor 1 receptor (igf-1r) dysfunction is highly prevalent in patients with lung cancer. In addition, epigenetic modifications are said to be involved in the pathogenesis of lung cancer. Our aim was to study the igf-1r methylation status in non-small cell lung cancer (NSCLC) cells, and propose that igf-1r hypo-methylation may provide a basis for potential use of hyper-methylating agents for lung cancers treatment. First, we analyzed the DNA methylation patterns of igf-1r in 6 different subtypes of NSCLC and found a partial methylation profile of igf-1r oncogene in all cell lines analyzed. To determine whether increased igf-1r methylation is associated with IGF-1R down regulation and thereby inducing cell death in NSCLC, cells were treated with S-Adenosylmethionine (SAM), a hyper-methylating agent. NSCLC cell lines had different levels of sensitivity to SAM treatment. Neither igf-1r methylation status, nor IGF-1R protein expression was affected by SAM treatment, suggesting that SAM-induced cytotoxicity is independent of igf-1r methylation status in NSCLC cell lines.

Key words: Insulin like growth factor receptor 1, lung cancer, DNA methylation.

148 Early Stage Lung Cancer Diagnosis by Paraneoplastic Nephrotic Syndrome

Magdalena Crăciun1, Alina Lenghel2, Ina Maria Kacsó1,3, Gabriel Kacsó1,2

1Emergency County Hospital Cluj, Mihai Manasia Clinic of Nephrology and Dialysis;
2Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca;
3 “Prof.Dr. Ion Chiricuta” Institute of Oncology, Cluj-Napoca, Romania

Paraneoplastic glomerulopathies are rare but sometimes important manifestations of neoplastic disease. Lung cancer is one of the most frequent causes of paraneoplastic nephrotic syndrome which usually precedes the discovery of the causal tumor. We present a case in which the investigation of a paraneoplastic syndrome, helped to establish a timely diagnosis of a non-small cell lung carcinoma (NSCLC) and permitted curative treatment.

Key words: Nephrotic Syndrome, Paraneolastic, Lung cancer.

153 Metastatic Lobular Carcinoma of the Breast with Occult Primary Tumor: Three Case Reports

Harieta Garofide, Gabriela Morar-Bolba, Carmen Lisencu, Bogdan Fetica, Alexandru Eniu

“Prof.Dr. Ion Chiricuţa” Institute of Oncology, Cluj Napoca, România

Invasive lobular carcinoma of the breast represents the second most frequent type of invasive breast cancer and accounts for approximately 5%-10% of all breast malignancies. 10% of patients present metastases at the time of diagnosis and less than 1% of patients have an occult primary tumor. Lobular carcinoma of the breast is known to metastasize to unusual sites such as the gastrointestinal tract, peritoneum, and gynecologic organs. We present three cases of metastatic lobular carcinoma with an occult primary tumor and unusual metastatic sites, emphasizing the differential diagnosis difficulties. The first one is the case of a 68 year old patient who underwent splenectomy for a suspicion of a spleen lymphoma, which proved to be splenic metastases of breast lobular carcinoma; the second one is the case of a 62 year old patient diagnosed with stenotic intestinal metastasis of breast lobular carcinoma and the third patient was diagnosed with gastric and peritoneal metastasis from breast cancer, initially suspected as linitis plastica and a Krukenberg tumor. Immunohistochemical examinations were useful for establishing the appropriate diagnosis in order to decide on appropriate therapeutic options. The particularities of the cases include the unusual presentation, the relatively good prognosis for metastatic disease, and the treatment implication of the lobular histology, which is the high endocrine responsiveness.

Key words: Lobular Breast Cancer, Metastatic, Occult.

159 Report on ESTRO 29

Kacso Gabriel

Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca; “Prof.Dr. Ion Chiricuţa” Institute of Oncology, Cluj Napoca, România

From September 12 to 16, 2010, Barcelona hosted the 29th Congress of the European Society of Therapeutic Radiology and Oncology (ESTRO). Almost 5000 participants all over the World attended this prestigious meeting. Physicians (mainly radiation oncologist but also other specialties involved in cancer management), physicists, radiation technologist, industry and, of course, patients representatives shared their thoughts on how research and technology can and are improving cancer care.

This report focus only on over 50 randomized trials (RZT) presented, whether updates, preliminary (interim) data or meta-analyses. For details the reader is invited to consult the Abstract Book packed in the Volume 96, September 2010, Supplement 1 of the “Green Journal” Radiotherapy & Oncology.

Key words: ESTRO 29 Meeting, 2010, randomized trials.

165 Guidance for Authors on the Preparation and Submission of Manuscripts to the Journal of Radiotherapy and Medical Oncology