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Volum 12 Numarul 2, 2006

89 Editorial

This issue of our journal presents some of the papers presented to the XV-th Congress of the Romanian Society for Radiation Oncology witch was held in Cluj-Napoca on September 22-24, 2005 and also general papers, case presentations and the European recommendations for training and quality control in radiation oncology.

„Quality of life- side effects evaluation criteria in oncology” is a paper presented by Prof. Dr. Viorica Nagy. This study included 300 patients with cervical cancer randomly assigned in one of two arms of the protocol: cisplatin 5 days every 21 days and cisplatin weekly administered concomitant with radiotherapy. The patients’ quality of life from the two arms of the protocol was measured using the European Organization for Research and treatment of Cancer Quality of Life Questionnaire at randomization and in the 3- rd and 5-th week of radio chemotherapy.

In „ Toxicity and study of failures in the treatment of locally advanced nasopharyngeal carcinoma” Dr. Elisabeta Ciuleanu and col asses the therapeutic failures in the nasopharyngeal carcinoma treated by chemotherapy followed by radiotherapy or by radiotherapy alone and the study of the toxicity of treatment. The most frequent causes of failures were locoregional and local and the toxicity of combined treatment was moderate without toxic death.

„The management of toxicity in concurrent radio chemotherapy for gastric tumors” is a paper signed by Dr. Anca Mihailov and col. This is a retrospectiv study which included 30 patients with gastric cancer treated with postoperative radio chemotherapy. The toxicity was acceptable and the cost of treatment moderate, consistent reasons for their large scale acceptance. The authors emphasize the fact that recent studies will probably lead to important modifications of the therapeutic standard for this type of cancer.

The study of Dr. Iolanda Sicoe and col, titled „Prognostic value of pathologic complete response in operated locally advanced cervical carcinoma” emphasize the prognostic value of pathologic complete response in patients treated with radiotherapy or radiotherapy plus chemotherapy and surgery. They concluded that this is an important prognostic factor for local control and survival in patients with locally advanced disease.

Dr. Ovidiu Veresezan and col. present a case of a 4 years old child diagnosed with a PNET tumor of the right forearm and treated by per operative interstitial brachytherapy.

In „Imaging strategies in brain tumors” Dr. Vasile Popita and col. emphasize the importance of computed tomography and magnetic resonance imaging examinations in the diagnostic of brain tumors and the possible correlations between imaging aspects and histologic type.

Cotirla Ion from the Georgetown University, SUA, in „Novel cancer drug targets – STAT proteins” presents a class of latent cytoplasmic proteins that participate in gene expression control after cellular contact with various extracellular stimuli and their possible therapeutic perspectives.

„Therapeutic failure in endometrial cancer treated at I. Chiricuta Cancer Institute from 1999 to 2001” by Dr. Claudia Ordeanu asses that the main cause of failure after surgery was local recurrence. The presence of unfavorable prognostic factors such as lymphatic invasion, the differentiation degree, or the invasion of the vascular space are indications for postoperative radiotherapy in stage I and II patients with endometrial cancer.

„Cisplatin peripheral neurotoxicity in chemo naive patients” is a paper signed by Dr. Vasile Tibre . The study presents the incidence of the peripheral neuropathy induced by different chemotherapeutic protocols with cisplatin in chemo naive patients treated for different type of cancer. The presence of peripheral neurotoxicity might represent the dose- limiting side effect of treatment thus impairing patients’ quality of life and the effectiveness of treatment.

Prof. Dr. Leon Danaila and col. presents in „ Cerebral metastases with long latency” the history of 6 patients with different primary tumors and cerebral metastases developed after 5   to 18 years from treatment. The significance of the primary tumor histology, angiogenesis and immune mechanisms in the pathogenesis of CNS metastases are also discussed.

„Pancreatic non-Hodgkin lymphoma in an AIDS patient” is a very interesting case presentation of Dr. R. Zamfir and colleagues. The possible association between these two diseases seems to be unfavorable for the prognostic of these patients.

Finally, we present in „oncological news” the new Romanian legislation regarding the use of opioids with analgesic purpose; some data form the „European multidisciplinary colorectal cancer congress, Berlin, Germany, February 12-14 2006 and the European recommendations for training and quality assurance in radiotherapy.

Dana Cernea

91 Imaging Strategies in Brain Tumors

  1. Popiţa1, I. Turoş2, C. Căpuşan2, S. Nemeş3

1“Prof. I.Kiricuta” Cancer Institute, Dept. of Radiology & Medical Imagery;

2AsRo Medica Cluj-Napoca;

3Baia Mare County Hospital, Dept. of Radiology

It has become generally recognized that magnetic resonance imaging (MRI) is the imaging study of choice in the evaluation of intracerebral tumors. Practically, cost and availability are always important issues, so at virtually all medical centers, computed tomography (CT) still remains the primary choice in the search for these lesions. Knowing the type and agresivity of the tumor before treatment, is extremely important and can be done by assesement of the structural components of the tumor. CT and MRI provides more informations about tumor’s tissue characterization.

Key words: Detection, Localisation, Characterisation.

Radioterapie & Oncologie Medicală, 2006, 2:91-102

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103 Quality of Life – Side Effects Evaluation Criteria in Oncology

Viorica Nagy1,2, N.Ghilezan1,2, N.Todor2, O.Coza1,2, Claudia Ordeanu2

1UMPh “Iuliu Haţieganu”;

2„I. Kiricuta” Cancer Institute, Cluj-Napoca

Background: Recording and reporting the morbidity of cancer treatment is an important issue, which can be approached in various ways. Quality of life (QL) is one of the different methods for measuring side effects from cancer and its therapy. QL covers the subjective perceptions of the positive and negative aspects of cancer patient’s symptoms, including physical, emotional, social, cognitive functions and, importantly, disease symptoms and side effects of treatment. QL is accepted as a possible way to collect more meaningful data about patient’s subjective experiences on cancer therapy. In Institute of Oncology Cluj-Napoca, in 2003 a randomised trial was initiated, which compares two cisplatin-based radio-chemotherapy regimens in locally advanced cervical cancer, one of the aims being the quality of life evaluation. Patients and methods: Between March 2003-November 2004, this study included 300 patients with cervical cancer stage IIB (143), IIIA

(101) and IIIB (56). The patients were randomly assigned in one of the two arms of the protocol: (A) cisplatin 20 mg/m2 x 5 days, every 21 days (149 patients) and (B) cisplatin 40 mg/m2/weekly (151 patients), administered concomitant with the radiotherapy.After 46 Gy on the pelvis patients with good response were operated (radical hysterectomy with pelvis lymphadenectomy) and the others continued radio-chemotherapy until 64 Gy. The patients’ QL from the two arms of the protocol was measured using the European Organization for Research and treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C 30, v.3.0) at randomisation and in the 3rd and 5th week of radio-chemotherapy. Results: The compliance at baseline was 94%, in the 3rd week 91% and in the 5th week 78%. In arm (A) a significant improvement of global health status (p<0.001) and a decrease in pain (p<0.01) were observed, while in arm (B) fatigue increased (p=0.01) and role functioning diminished (p=0.05). In both treatment arms depression and feel tensing (emotional functioning) (p<0.01 and p=0.05)), nausea and vomiting (p<0.01), and diareea intensifed (p<0.01). Conclusions: Concomitant radio-chemotherapy with cisplatin=20 mg/ m2x 5 days, every 3 weeks offers improved quality of life for patients with cervical cancer. Information from QL may help to decide about the relative effectiveness of cancer treatment, enhance patients’ decision making by providing them with data regarding the side-effects of such treatment, improve the quality of cancer care.

Keywords: Quality of life, Cervical cancer, Radio-chemotherapy.

Radioterapie & Oncologie Medicală, 2006, 2:103-109

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110 Toxicity and Study of Failures în the Treatment of Locally Advanced Nasopharyngeal Carcinoma

Elisabeta Ciuleanu1, T.E. Ciuleanu1,2, N. Todor1, N. Ghilezan1,2

1Cancer Institute „Prof. I. Chiricu]@”;

2UMPh „Iuliu Ha]ieganu” Cluj-Napoca

Background: To asses, în a retrospective study, the therapeutic failures în the nasopharyngeal carcinoma (NPC) treated by chemotherapy (CT) followed by radiotherapy (RT) or by RT alone, also the study of the toxicity of treatment. Patients and methods: Between January/ 1990-December/1995, 185 locaregionally advanced NPC patients (pts) entered în the study. Combined CT+RT consisted în 3 cycles of neoadjuvant BEC (Bleomicin, Epirubicin, Cisplatin) or EC (Epirubicin, Cisplatin) followed by standard RT versus the same RT alone. Results: There were 33% female, 67% male of 185 pts.; 82% of them had a undifferentiated cc. (WHO 3), 18% pts. had a nonkeratinizing carcinoma (WHO 2); 96% of pts.were în stage IV and only 4% of pts. were în stage III (UICC-1992). Only 175 pts. were evaluable for treatment failures and also for RT treatment toxicity, because 10 pts. refused the RT treatment. When we made de statistical study, 65 pts.(37%) were alive with CR, 3 (2%) alive with PR, 91 pts. (52%) were with failures, of whom 82 died. The reason of failures were 21 T+, 7N+, 19M+, 28TN+, 2TM+, 7NM+, 7TNM+. Chemotherapy toxicity was moderate. Hematological toxicity: gr. III-IV leucocytes toxicity occur at 5%, gr. III-IV neutropenia at 6,5% and gr.III-IV anemia at 7%, of cycles. The toxicity at 2 month after the end of the RT treatment, consist în xerostomia at 54% of cases, gr.l RTOG – 83%, gr.ll.-17%. Late toxicity consist also în xerostomia at 34% of pts. gr. l RTOG – 88%. Conclusions: The causes of failures were: locoregional at 31%, local 23%, distant metastasis 21%, locoregional and distant metastasis 18%, only regional at 8%, of cases. Chemotherapy and radiotheray toxicity were moderate without toxic death.

Key words: Nasopharyngeal carcinoma, Toxicity, Failures.

Radioterapie & Oncologie Medicală, 2006, 2:110-114

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115 The Management of Toxicity in Concurrent Radiochemotherapy for Gastric Tumors

Anca Mihailov1, Alina Munteanu2, G. Kacso2,3, F. Mureşan1 ,

  1. Oniu1, Mircea Cazacu1,3

1University Hospital, 4th Surgical Clinic;

2„Prof. I Kiricuta” Cancer Institute Cluj-Napoca;

3UMPh „I. Haţieganu” Cluj-Napoca

A retrospective study was done which included 30 patients with gastric and rectal cancer respectively treated with postoperative radiochemotherapy between May 2000 and December 2002. The toxicity of the treatment was acceptable in the group of gastric cancer patients, with grade 3 toxicities noted as follows: hematologic 12%, gastrointestinal 34%, asthenia 34%, 3 discontinuations due to toxic effects but no toxic deaths. In the rectal cancer group the global toxicity was moderate, predominantly digestive and hematological. The toxicity profile of both protocols and their moderate cost are consistent reasons for their large scale acceptance. Still, we have to emphasize the fact that recent studies will probably lead to important modifications of the therapeutic standard in both types of cancer.

Key words: Gastric cancers, Rectal cancers, Radiochemotherapy, Toxicities.

Radioterapie & Oncologie Medicală, 2006, 2:115-120

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121 Prognostic Value of Pathologic Complete Response in Operated Locally Advanced Cervical Carcinoma

Iolanda Sicoe1, Claudia Ordeanu1, O. Coza1,2, S. Gavriş1, A. Rancea1,2, Al. Trăilă1 ,

  1. Todor1, Viorica Nagy1,2

1“Prof. I. Kiricuta” Cancer Institute , Cluj-Napoca;

2U.M.Ph. “Iuliu Ha]ieganu”, Cluj-Napoca

Purpose: To evaluate the efficacy of radio+/- chemotherapy, the analyses of therapeutic failure and survival in accordance with pathologic sterilization in operated locally advanced cervical carcinoma, after radio±chemotherapy. Methods and Patients: Between March 1999-July 2002, at the “ Prof. Ion Kiricuta“ Cancer Institute, Cluj-Napoca, a randomized trial included 282 patients with locally advanced cervical carcinoma which received radiotherapy or radiochemotherapy, followed by surgery. 196 patients were stage IIB (69,5%), 74 were stage IIIA (26,25%) and 12 patients were stage IIIB (4,25%). The A arm of the protocol included patients treated by radiotherapy. In B arm, patients received radiotherapy plus cisplatin as radiosensitizer.At 4-6 weeks from the end of radiotherapy the Wertheim lymphadenocolpohisterectomy was performed. Results: Pathologic sterilization was obtained at 179 patients from 282 (63%) which received concomitant radiochemotherapy. The rate of complete responses (CR) was significantly greater in radiochemotherapy (RT+CT) arm (72%) versus radiotherapy arm (55%) (p=0.02). The 3-year survival rate (SV3) is significantly superior in patients with pathologic sterilization after RT+CT: 87% versus 69% (p<0.01). Treatment failures are less for the patients with sterile sample (8%) versus those with residual disease (23%), (p<0.01). The size of residual cervical tumor after RT+/- CT was proved as a prognostic factor for pathologic response. This was reflected in pathologic sterilization: 74% vs 65%, in SV3: 83% vs 73% and in the rate of treatment failure: 12% vs 21% for tumor < 3 cm and > 3 cm, respectively. Conclusion: Pathologic complete response in patients treated with RT+/- CT and surgery is a significant prognostic factor for local control and survival in locally advanced cervical carcinoma. Regarding the therapeutic options, the important rate of pathologic sterilization in these cases could conduct to exclusive radiochemotherapy for patients with favorable tumor response or to association with surgery for the rest.

Key words: Cervical carcinoma, Radiochemotherapy, Prognostic factor.

Radioterapie & Oncologie Medicală, 2006, 2:121-126

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127 Interstitial Brachytherapy in Soft Tissue Sarcomas. Technical Aspects in Children

  1. Vereşezan1, G. Kacsó1,2, Ştefania Neamţu1, C. Ciuce2,3

1“Prof. I. Kiricuta” Cancer Institute Cluj-Napoca;

2“Iuliu-Haţieganu” U.M.Ph. Cluj-Napoca;

3County Clinical Hospital Cluj-Napoca, 1st Surgical Clinic

We present the case of a 4 years old child who was diagnosed at the age of 1 year and 10 months with peripheral primitive neuroectodermal tumor (pPNET) localized to the right forearm and treated by perioperative interstitial brachytherapy at the second local recurrence. The local control achieved by adding interstitial brachytherapy to the surgery indicate this method as a therapeutic approach in the local treatment of pediatric tumors for which external radiotherapy is unadvisable because of severe functional complications.

Key words: Interstitial brachytherapy, Peripheral primitive neuroectodermal tumor.

Radioterapie & Oncologie Medicală, 2006, 2:127-130

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131 Novel Cancer Drug Targets – STAT Proteins

I. Cotârlă

Georgetown University, Lombardi Cancer Center, NW Washinghton DC, USA

STATs (Signal Transducers andActivators of Transcription (STATs) are a class of latent cytoplasmic proteins that participate in gene expression control after cellular contact with various extracellular stimuli. Seven mammalian members (from Stat 1 to 6 with 2 subtypes for STAT5) have been identified and their corresponding genes are located on chromosomes 2, 12 and 17. STATs’ activation are involved in control of several critical cellular functions as proliferation, survival, differentiation, development, apoptosis, immune response and lactation. Their involvement was also demonstrated in cancerogenesis and tumor progression so they are valuable target for therapeutic intervention. Blocking the STAT-signaling pathway is possible by using neutralizing antibodies (C225), selective inhibitors of tyrosine and seine kinases or physiological specific protein inhibitors. These new approaches are discussed in detail and the therapeutic perspectives are presented.

Key words: STAT proteins, Signaling pathaways, Receptor blockade.

Radioterapie & Oncologie Medicală, 2006, 2:131-137

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138 Therapeutic Failure in Endometrial Cancer Treated at „I. Kiricuta” Cancer Institute from 1999 to 2001

Claudia Ordeanu1, S.Gavriş1, O.Coza1,3, Viorica Nagy2,3

” I. Kiricuta” Cancer Institute, Cluj-Napoca:

1Dept. of Brachiterapy;

22nd Radiotheraphy Dept. Radioterapie II;

3“Iuliu Haţieganu” UMPh, Cluj-Napoca

Introduction: The purpose of this study is to determine therapeutic failure and its main causes in endometrial cancer. Patients and method: From January 1999 to December 2001, at “Kiricuta” Cancer Institute of Cluj-Napoca 248 patients were treated for endometrial cancer. The patients’ characteristics were the following: average age was 57 (range: 36 to 79); stage distribution: stage I – 172, stage II – 48 and stage III – 28. 230 patients were treated by total hysterectomy with bilateral annexectomy; in 6 cases surgery was accompanied by pelvic lymphadenectomy. 8 patients were treated by exclusive brachytherapy. 2 patients in stage IIB, and IIIB, respectively, exclusively received RTE. 45 (26.1%) of the stage-I patients, 34 (70.8%) of the stage-II patients, and 18 (64.2%) of the stage-III patients received adjuvant radiotherapy. Results: The main cause of failure was local recurrence – 14 of the total of 30 cases (46.6%); 12 presented distance metastases, out of which 8 were hematogenic, and 4 were pelvic, inguinal, or lumbo-aortic ganglionic metastases; in 4 cases local recurrence was associated with distance metastases. 40% of the lymphatic invasive cases (p < 0.01), 32% of the G3-histologic grade cases (p < 0.01), 30% of the vascular invasive cases (p < 0.01), and 20% of the over 50% of myometrial invasive cases (p < 0.001), respectively, developed recurrence/metastases. Conclusion: The unfavorable histologic prognosis factors were lymphatic invasion, the differentiation degree, the invasion of the vascular space, and the degree of the myometrial invasion; the main cause of therapeutic failure was central recurrence. Our results support the use of adjuvant RT in stage I-II endometrial cancer patients, with high risk factors.

Key words: Endometrial cancer, Therapeutic failure, Adjuvant radiotherapy.

Radioterapie & Oncologie Medicală, 2006, 2:138-142

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143 Cisplatin Peripheral Neurotoxicity In Chemonaive Patients

  1. Ţibre1,2, R. Câmpean2, Cristina Indrei2

1“Ion Minea” Clinic for Neurology , Cluj-Napoca;

2U. M. Ph. “I. Haţieganu” Cluj-Napoca

Introduction: Cisplatin (cis-diammine-dichloroplatinum, CDDP) is a platinum compound that blocks both replication and transcription of cellular DNA followed by apoptosis in dividing cells. CDDP was proved to be effective in a treatment of lung, ovary, urinary bladder and tests tumors. The exactly mechanism of action is not known, but in vitro it has demonstrated to block fast axonal transport with apoptosis of sensitive cells in dorsal root ganglia. Cisplatin-induced peripheral neuropathy is a sensory neuropathy mainly affecting large-diameter nerve fiber, and correlate with cumulative dose. Objective: This case-control study was done to evaluate peripheral neurotoxicity to Cisplatin (CDDP) at the onset and distance from treatment (long term toxicity) by means of Total Neuropathy Scale (TNS). Methods: The peripheral neurotoxicity was grading by means of composite score, Total Neuropathy Scale in a 19 chemonaive patient treated with Cisplatin (CDDP) for different types of cancer. Control group were defined as 47 subjects with any complaint or signs of neuropathy, with normal glicemic values in which we established normal interval of confidence for peroneal and sural nerve velocity as well as for motor and sensory nerve response. We have defined normal interval of confidence as mean ± 2SD and used lower limit of normal (LLI) for motor and sensory response amplitude as cut-off value in our TNS. Results: The most frequently gravity form of neuropathy in our study, was mild sensory neuropathy (63%), followed by moderate form (21%). In our patients group we didn’t found severe neuropathy. Cumulative symptomatic dose was varied between 200 and 600 mg/m2, with an average of 416 mg/m2. Interestingly, neurophysiological study show us not only high statistical difference in amplitude on sensory sural nerve (p<0.0002) between patient and normal group, but also statistical significance between amplitude of normals versus patients on motor peroneal nerve (p<0.02), in spite of lack of motor complains and motor signs. We hypothesized presence of subclinical motor nerve lesion due to cisplatin neurotoxicity. We have also found clinical signs of presence or progression of polyneuropathy after cessation of therapy, at a distance for month to years. Conclusion: CCDP produce a sensory clinic neuropathy and in a less degree a subclinical motor neuropathy. This is generally mild neuropathy and could last month to year after cessation of chemotherapy. Chemotherapy induced peripheral neurotoxicity has important clinical relevance because it might represent the dose-limiting side effect of the treatment, thus impairing patients’ quality of life and the effectiveness of treatment.

Key words: Cisplatin, Sensory neuropathy, Total Neuropathy Score.

Radioterapie & Oncologie Medicală, 2006, 2:143-150

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151 Cerebral Metastases with Long Latency

  1. Dănăilă, M. Rădoi, F. Ştefănescu

Prof. „V. Voiculescu” Institute for Cerebrovascular Disease, Bucharest, Dept. Of. Neurosurgery

The onset of cerebral metastases is a frequent event in the antural history of cancer and an important cause of death. This history of 6 patients with different primary tumors and cerebral metastases developed after a latent period from 5 to 18 years are presented. These cases have been selected from a total of 232 surgical interventions done in the significance of the priamry tumor histology, angiogenesis and immune mechanisms in the pathogenesis of CNS metastases are discussed.

Key words: CNS metastase.

Radioterapie & Oncologie Medicală, 2006, 2:151-157

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158 Pancreatic Non Hodgkin’s Lymphoma in anAIDS Patient. Case Report

  1. Zamfir1, Vl. Braşoveanu1, S. Erscoiu2, I. Popescu1

1Fundeni Clinical Institute, General Surgery and Liver Transplant Center, Bucharest, Romania;

2„Victor Babeş“ Institute & Tropical Diseases Clinical Hospital, Bucharest, Romania

The asociation AIDS – nonHodgkin’s lymphoma (NHL) isrecognized with increased frequency but the pancreatic extranodal localizations are exceedingly rare, reason to present thje diagnostic and therapeutic problems encountered in a clinical case. The improving of life expectancy for AIDS patients will also increase the incidence of such unusual presentations that should be dealt with, in the same manner as the NHL de novo.

Key words: AIDS, Extranodal NHL, Pancreas.

Radioterapie & Oncologie Medicală, 2006, 2:158-160

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161 The New Romanian Legislation Regarding the Use of Opioids with Analgesic Purpose

Viorica Nagy

163 European Multidisciplinary Colorectal Cancer Congres. February, 12-14, 2006, Berlin, Germany

  1. Filip

164 European Recommandations for the Specialists’Training and the Development of Radiotherapy Quality Assurance

Viorica Nagy

165 Questionnaire CME