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Volum 14 Numarul 2, 2008

69 Curs postuniversitar

– Strategii terapeutice contemporane în oncologie – reuniune post ASCO/ECCO/ASTRO-

– Actualitati în terapia moleculara tintita a cancerului

71 18th Annual Congress of the Romanian Society for Radiotherapy and Medical Oncology and ESMO Course (Second announcement)

76 Editorial

Ioana Brie

77 The Sentinel Node Navigation Radiotherapy (SNNRT)

Ion-Christian Kiricuta, Bernd Schicker, Uwe Goetz

Institute of Radiation Oncology, St. Vincenz-Hospital, Limburg, Germany

The sentinel node concept (SNC) and the sentinel node procedure (SNP) is crucial to understand the relationship of the primary tumor to its re­gional lymphatics. The adjuvant radiotherapy to lymphatic basins indicated by the SNP could avoid a systematic lymphadenectomy in sentinel node positive patients. We will present here the concept of sentinel node navigation radiotherapy. Also we shall present data on the selection of lympatic areas to be included in the clinical target volume (CTV) in head and neck, breast, apparently localized prostate cancer and Merkell Cell carcinoma patients based on the pattern of lymphatic spread indicated by the SNP. Conformal irradiation techniques for adjuvant radio­therapy of the head and neck, axillary and internal mammary chain (IMC), inguinal and pelvic lymphatic areas are presented. Basic data on the lymphatic drainage and involvement of different lymph nodes for head and neck, breast, and prostate cancer as well as Merkel Cell carcinoma patients based on the SNP were used. For treatment planning and CTV delineation the individual location of lymph nodes in axial CT slices was used. The data obtained using the SNP changed the criteria of selection of different lymphatic basins to be included in the CTV in a sig­nificant manner. The data provided by the study performed at the The Netherlands Cancer Institute in Amsterdam on breast cancer patients by Estourgie applying the SNP, made necessary a change in the treatment strategy in 29% of the cases investigated. In Merkel Cell carcinoma pa­tients the SNP is the only available method to describe the individual lymphatic basin and to adapt the optimal treatment strategy. The conven­tional irradiation techniques for lymphatic areas in the axilla, IMC, groin and pelvis actually in use are not adequate and have side effects. At our institution new conformal irradiation techniques for lymphatic areas or basins have been developed and are presented here. The concept of the sentinel node navigation radiotherapy and the individual selection of lymphatic areas to be included in the CTV based on the SNP were presented. Sparing of organs at risk and homogenous dose coverage of the CTV using the proposed irradiation techniques is possible.

Key words: Sentinel Node Concept, Lymphatic Basins, Head and Neck Cancer, Breast Cancer, Merkell Cell Carcinoma.

84 Epidemiology of Genitourinary Cancers in Romania, 1985-2005

Ofelia Şuteu1,2, Patricia Şuteu2, Florian Nicula1, Daniela Coza1

1Ion Chiricuţă Cancer Center Cluj-Napoca, Dept. of Epidemiology; 2Iuliu Haţieganu University of Medicine and Pharmacie, Cluj-Napoca

Objective: The aim of the study was to examine the incidence and mortality rates and time trends for genitourinary (GU) cancers in Romania, during the period 1985-2005. Methods: The crude, age-specific and directly age-standardized incidence and mortality rates for GU cancers in Romania were calculated. Time trend of the incidence and mortality was assessed by the percent change between 1985 and 2005. Results: Although in Romania, incidence and mortality rates of GU cancers are lower than in western countries, there was a general increase in the incidence and mortality during the registered period. For urological cancers, the increase concerned both sexes, though incidence and mortality rates in women remained significantly lower than in men. The most important rise in in­cidence was registered by kidney cancers (by 142% in men, p<0.05 and 102% in women, p<0.05), followed by testis (101%, p<0.05) and prostate cancer (69.6%, p<0.05). There is a “shift to the left” trend of the incidence in the occurrence of cases towards the younger age groups, especially for kidney and bladder in female and testis, prostate and bladder cancers in men. Mortality rose on average by 15% for testicular, prostate (p<0.05) and bladder cancers and by 1.92% for bladder cancer in women. Conclusions: Our data support that the application of available knowledge on prevention, diagnosis and treatment of these cancers could define a strat­egy to reduce during the following years the impact of the ascending course of incidence and mortality through GU cancers in Ro­mania.

Key words: Urogenital Cancers, Incidence, Mortality, Trends.

96 Xeloda Based Combinations for Metastatic Colorectal Carcinoma: a Phase II Study

Anca Mihailov1, Flaviu Mureşan1,2, Ovidiu Fabian1,2, Răzvan Simescu1,2, Traian Oniu1,2, Mircea Cazacu1,2

1University Hospital, 4th Surgery Clinic Cluj; 2Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca

Purpose: To evaluate the efficacy and toxicity of two Capecitabine (Xeloda) regimens, XELOX and XELIRI, in patients (pts.) with metastatic colorectal cancer, as a first line therapy. Patients and methods: Between January 2004 and January 2007, 73 patients with untreated metastatic or locoregionally advanced colorectal cancer received a XELOX or XELIRI regimen until progression, for a maximum of 6 cycles. Results: 32 patients received prior adjuvant treatment (5FU based) in both groups, 7 stage II at diagnosis and 25 stage III at diagnosis; 41 patients from both groups received no prior chemotherapy (stage IV disease before enrollment). 62 % (20 pts) patients from the XELIRI group had a WHO PS of 1, and 15 (38 %) had a PS of 2, while the distribution was different in the XELOX group: 24 patients (61 %) were given a PS of 2 and 12 (37 %) of them were given a PS of 1. A total of 68 patients com­pleted the planned 6 cycles of XELOX or XELIRI, respectively, a median of 6 cycles being administered. Both regimens proved to be active; 4 (11.11%) patients from the XELIRI group achieved a complete response, 9 (25%) a partial response, 15 (41.6%) had sta­ble disease and 8 (22%) progressed during therapy. The results were similar in the XELOX group, with 3 (8.11%) complete re­sponses, 13 (35.14%) partial responses, 14 (37.8%) patients having stable disease and 7 (18%) having disease progression during therapy. Except for one death by myocardial infarction possibly related to Capecitabine therapy, toxicity was mild, with very few grade three events. Median follow-up was 12 months, range (10-36). Median overall survival was 15.4 months (CI:12,8-18,3), and median time to disease progression was 9 months. Conclusion: Both regimens proved active in metastatic setting, with moderate tox­icity and increased compliance from patients. They seem to be a reasonable alternative for FOLFOX and FOLFIRI regimens, thus avoiding the morbidity and costs of protracted continuous 5FU infusions.

Key words: Capecitabine, Metastatic Colorectal Cancer, XELOX, XELIRI, Activity, Toxicity.

104 Concomitent Preoperative Chemoradiotherapy with Capecitabine inLocally Advanced Rectal Adenocarcinoma: a Phase II Study

Alina-Simona Muntean1, Adriana Mureşan1, Anca Mihailov2, Angela Parau3 , Lucian Lazăr1, Alin Rancea1,4, Viorica Nagy1,4, Gabriel Kacso1,4, Nicolae Ghilezan1

1Ion Chiricuta Cancer Center, Cluj-Napoca; 24th Surgery Clinic Cluj-Napoca; 33rd Medical Clinic Cluj-Napoca; 4IuliuHatieganu University of Medicine and Pharmacy Cluj-Napoca

Purpose: The aim of the study was to evaluate the efficacy and tolerance of preoperative concomitant radiotherapy Capecitabine in locally advanced rectal adenocarcinoma. Patients and methods: Twenty-two patients with locally advanced rectal adenocarcinoma (uT3 –T4 N0 or uN1-2 M0; TNM stage: IIA = 9, IIB = 2, IIIB = 9, IIIC = 2) evaluated as inoperable or potentially resectable, were included in this study at the Ion Chiricuta Cancer Center, Cluj-Napoca, between January 2007–February 2008. Capecitabine (825 mg/m2) was adminstered concomitantly with radiotherapy twice daily, at 12 hours interval. Radiotherapy was delivered using high energy photons (15MV) from a linear accelerator for the whole pelvis (primary tumor, mesorectum and lymph nodes) with a total dose (TD) = 45 Gy/25 fractions (fr.) /5 weeks followed by a boost limited to the primary tumor of 5,4 Gy (TD = 50,4 Gy/38 fr, with 1,8 Gy/fr, 5 days/week). Surgery was planned 6-8 weeks after the completion of radiochemotherapy. The pathological specimen was evaluated for primary tumor, number of examined lymph nodes and resection margins. The compliance and toxicity of the concomitant preoperative treatment, and complications after surgery were recorded. Results: All patients underwent surgery: abdomino-perineal resection was performed in 68% and low anterior resection in 32% patients. A sphincter-sparing procedure was performed in 6 of 22 patients with the distance of the lower pole of the tumor from the anal verge ≤ 5cm. The pathological response rate (pCR) was complete in 13.6%, partial (pPR) in 45% and stable disease in 40% of cases. 21 out of the 22 patients had a radical R0 and 1 only a R1 resection (positive microscopic radial margin). The grade 3 toxicity was mainly hematological (22.6%): leucope­nia in 13.6% and neutropenia in 9% patients. Nonhematologic toxicity was: proctitis in 9% and skin toxicity in 9% patients. No grade 4 toxicity was registered. Conclusions: Concomitent preoperative radiochemotherapy with Capecitabine in patients with locally advanced rectal adenocarcinoma has a strong rational support: efficacy, favorable safety profile and moderate toxicity. The oral chemotherapy i.e Capecitabine could be a convenient alternative to preoperative radiochemotherapy with 5-fluorouracil.

Key words: Capecitabine, Concomitent Radiochemotherapy, Surgery, Rectal Cancer.

111 Comparative Analysis of Adjuvant Treatment of Colorectal Cancer Patients Treated in Two Romanian Hospitals

Răzvan-Ovidiu Curcă

Emergency County Hospital, Alba Iulia, Department of Oncology

The paper presents a comparative and comprehensive analysis of the pattern of care of colorectal cancer patients in two hospitals in Romania, the Emergency County Hospital Alba Iulia and the Ion Chiricuţă Cancer Center in Cluj Napoca.

Key words: Colorectal Cancer, Adjuvant Treatment.

117 Bisphosphonates in Metastatic Prostate Cancer

Oana Marina1, Gabriel Kacsó1,2

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

Introduction: Metastases occur in 70-80% of patients with advanced prostate cancer and are often located in the bone. Bisphospho­nates (BP) represent an important method of their treatment. Purpose: to evaluate the efficiency and toxicity of different type of BP in terms of the incidence of skeletal events, the time to the first skeletal- related event and the incidence and severity of adverse ef­fects. Materials & methods: retrospective study of 35 stage D2 prostate cancer patients diagnosed between January 2003 and De­cember 2005, treated with BP for their bone metastases. The median age of the patients was 66 years. At least three cycles of BP were administered, half of them being with zoledronic acid. Results: skeletal events were registered in 7 (21%) patients (6% Zometa vs. 15% other bisphosphonates).The median time until the first event was 17 months (22 for Zometa vs. 15 for Aredia or Clodronate). Three patients (9%) had fractures (3% Zometa vs. 6% other BP). Spine compression caused by vertebral collapse occurred in 2 (6%) patients with a similar incidence irrespective of BP type. Palliative radiation was required in 6 (18%) patients (1/3 treated with Zo­meta, 2/3 receiving other BP) and the symptoms improved in 80% of those cases. None of the patients underwent bone surgery. Se­vere toxicity resulted in osteonecrosis of the mandible (1case) and kidney failure (1 case). The other adverse effects included arthral­gia, myalgia, temporary exacerbation of bone pain and gastrointestinal adverse reactions. Conclusions: Zoledronic acid seems to be more effective in treating bone metastases since it reduces the incidence of skeletal events and increases the time interval until the first skeletal related event, compared to Aredia or Clodronate.

Key words: Bisphosphonates, Prostate Cancer.

121 Malignant Gastric Carcinoids – Diagnostic and Classification Difficulties

Flaviu Mureşan1,2, Mircea Cazacu1,2, Anca Mihailov1, Iacob Domşa1 , Răzvan Simescu1,2

14th Surgery Clinic Cluj-Napoca; 2IuliuHaţieganu University of Medicine and Pharmacy Cluj-Napoca

Gastric malignant carcinoids are a rare category of digestive oncological pathology. Its diagnosis is difficult and very often late be­cause the lesion originates in the submucosa of the stomach wall (endoscope biopsy is often inconclusive) and also because of the unspecific clinical manifestations even with distant metastasis (absence of carcinoid syndrome). The proper therapeutic attitude in­cludes removal of the tumour (surgically or endoscopically) along with complementary chemotherapy, depending on the carcinoid type, size of the lesion and disease stage. We hereby give our personal experience with regard to the problems of diagnostic and clas­sification by the type of patients diagnosed with gastric malignant carcinoids in our survey. This paper also presents particularities of surgical and complementary treatment and of the postoperative outcome.

Key words: Gastric Malignant Carcinoids, Surgical Treatment, Chemotherapy.

126 Cytogenetic and Molecular Response after Dasatinib in Blastic Phase Chronic Myeloid Leukemia. Case Report

Delia Dima, Andrei Cucuianu, Ljubomir Petrov

Ion Chiricuta Cancer Center Cluj-Napoca

Chronic myeloid leukaemia (CML) in blastic phase carries an adverse prognosis. Small molecule tyrosine kinase inhibitors may change the outlook in these patients. We present the case of a 62 year old female who was diagnosed in March 2006 with chronic phase, Philadelphia positive CML. She was initially treated with hydroxyurea with the achievement of a complete haematological response (CHR) but in July 2006 the patient progressed to blastic phase. Imatinib was started at 400mg/d and CHR was obtained, but in November 2006, blastic phase CML relapsed. Imatinib 600mg/d was attempted but it was poorly tolerated, while having no significant effect. Subsequently, the patient was started on dasatinib 2 x 70mg daily gaining the achievement of CHR after one month. A recurrent problem was bilateral pleural effu­sion requiring evacuation and reduction of dasatinib to 100mg/d. Major cytogenetically remission was obtained in 3 months and complete cytogenetically remission (CCR) in 6 months. RQ-PCR, performed at 6 months showed a major molecular response (MMR). CCR and MMR were maintained at 18 months follow-up. This case report underscores the progress being made in recent years in the treatment of CML, even in advanced phases, due to the introduction of tyrosine kinase inhibitors.

Key words: Chronic Myeloid Leukaemia, Blastic Phase, Imatinib, Dasatinib.

129 Report on the First World Congress of Brachytherapy, Boston 2008

Claudia Ordeanu

130 Important International Cancer Conferences

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