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Volum 06 Numarul 3, 2000

CONTENTS

Proceeding of the 4th Biennial Breast Cancer Symposium: Locally Advanced and Metastatic Breast Cancer, May 4-6, 2000, Oradea, Felix Spa, Romania

216 Editorial

The Biennial Breast Cancer Symposium that has reached its 41h edition, is the main subject of this issue of our Journal. The theme of the Symposium, The Locally Advanced and Metastatic Breast Cancer, is still, unfortunately, a very actual topic considering the larger number of patients and the need to reach a consensus on therapeutic standards as performant as possible in.these days of limited resources provided by the new financing system of health care in Romania.

The great numbers of participants with a massive and active attendance of young people in training, the presence of some outstanding specialists from abroad, a larger area of representation from different centers or the diversity of topics, are argu- ments that suggest the viability of this meeting that became indeed traditional. Let’s hope that our Society will continue this trend in quality of our next meetings!

The Journal, under a more elaborated form, is presenting the main papers delivered during the Symposium, completed as well, with other contributions, according to the initial 4 sections: Epidemiology and Natural History, Trends in the Manage- ment, Therapy of Locally Advanced and Metastatic Breast Cancer and Palliative Care & Conununity Support.

The epidemiology of breast cancer in Romania is presented by V. Pacurar, whose Territorial Cancer Registry for Bihor county becomes more and more a very valuable source of information that attracts new collaborators as is the Arad centre. Cristina Vitoc treats the natural history of the advanced breast cancer with much authority, through a statistic followed for more , than 10 years, which still remain a solitary fact in our professional literature. The imagistic investigations, especially mammography and breast echography, have been well and richly illustrated by Edina Szabo, a resourceful representative of Oradea.

The therapeutic developments have been approached under two main aspects: the rationale of the therapeutic decision as how to be adapted to the personal risk factors and according to the logical objectives that should be reached (N. Ghilezan) and how to optimize the chemotherapy by implementing the new concepts as dose dense therapy in clinical practice (Dana Grecea).

All the four papers dedicated to the Therapy… section, are remarkable through an original and valuable contribution of their authors. D. Rosner and Alexandra Flowers (Rochester. USA) put again in question the value of chemotherapy in the treatment of CNS metastases: the long natural history of breast cancer justifies in many cases these treatments which could improve significantly the quality of life. R. Tanasescu presents the prototype of a hyperthermia machine, developed as ajoint venture between the Institute of Oncology and the Technical University from Cluj, with the support of a grant from de Acad- emy of Medical Sciences. The first clinical results are very encouraging and we enjoy having this opportunity to signal this very successful and original result of Romanian oncology.

The other two papers are signed by orthopedist as they are discussing the surgical treatment of bone metastases (V. Thrdean and D. Lucaciu et all. respectively – Cluj), field again, at it start in Romania. This is also 0 positive signal from the part of our colleagues. the orthopedists, who offer us a very efficacious treatment of the so frequent and invalidating skeletal complica- ~ tions of the breast cancer and looking to further extend this cooperation. we wish them success and good luck!

In the last section. a study is enclosed on the influence of stress in the onset of anxiety and depression at the breast cancer patients and also a research project for developing a team approach in the total care of the patients with cancer. Both papers represent the contribution of a group of psychologists from the University of Timisoara, lead by Anca Munteanu and Diana Pamfil.

Finally, the papers dedicated to the Biannual Breast Cancer Symposium from May 2000, close up with a health economy study of the diagnosis, treatment and palliative care in breast cancer, from a group, belonging again to Oradea Centre (Delia Ruţă Mureşan et all).

A case report of an unusual breast colagenous spherulosis is presented by (Voichita Suciu et all.) as well the 2nd part of the ASCO 2000 meeting by T. E. Ciuleanu, under the specifically headings of the Journal. A new heading is also introduced with the present issue, dedicated to an overview of the literature, sustained by the fellows in training in the Institute of Oncology Cluj.

We hope that our readers will appreciate also this issue of our Journal that through the approaching some new fields for our country, the diversity of specialties and the number of collaborators, would be an example and an invitation for many other impending and valuable contributions.

  1. Ghilezan

217 Epidemiological Aspects of Breast Cancer

  1. Păcurar

Dept. of Oncology, University of Medicine and Pharmacy, Oradea

Breast cancer is increasing in frequency in developed countries as well as in other European countries. In Bihor and Arad counties (according to published data) breast cancer takes second place after lung cancer. The high frequency of advanced stages at diagnosis is worse prognosis factor for breast cancer patients: owing to the high frequency breast cancer is a genuine public health problem. The knowledge of the epidemiological factors is important for primary prevention of breast cancer. The increasing of the rate of cases diagnosed in early stages through education, continuous training of the physicians and mammography screening are efficient tools of breast cancer control. Cancer registries and follow up of breast cancer patients are important for efficient strive against breast cancer.

Key words: breast cancer, epidemiology, cancer registries.

Radioterapie & Oncologie Medicaăl, 2000, 3:217-222

223 Natural History of the Loco-Regional Advanced and Metastatic Breast Cancer

Cristina Vitoc

Cancer Institute „Prof I. Chiricuţă” Cluj-Napoca

In the introduction part are presented low incidence of the local advanced breast cancer (LABC) and the metastatic breast cancer (MBC) in the developed country vs. developing country. In spite of recent progress of adjuvant treatment, it maintains a high risk of the metastatic recurrence in all stades of the breast cancer. The data of Institutional Register of Cancer in the Cancer Institute „I,Chiricuţă” Cluj-Napoca, on 1999, present the high percent 80%, with advanced breast cancer which is in our medical care. These aspects justify the theme of our symposium and it is a challenge for the medical Rumanian oncological world. Further on, there are presented cancerogenesis multistadial theory of the breast cancer, the main characteristics of the natural history of the LABC and MBC with some data including the diagnosis, the preterapeutical workup, the aims of the treatment with type of the approach and following-up. This presentation is the clinical viewpoint of the goal to open the way to next discussions.

Key words: local advanced breast cancer, metastatic breast cancer, incidence, natural history, diagnosis, work-up, treatment, following-up.

Radioterapie & Oncologie Medicală, 2000, 3:223-228

236 Therapeutic Objectives and Strategies in Advanced Breast Cancer

  1. Ghilezan1,2, Cristina Vitoc2

1U.M.Ph. „I. Haţieganu „,

2Cancer Institute „Prof I. Chiricuţă” Cluj-Napoca

The advanced breast cancer comprises many clinical situations as locally advanced, relapses (local recurrences and distant relapses) and metastatic disease. Their common characteristics are the gravity of prognosis and the need to tailor the treatment according to the individual risk factors. With the exception of locally advanced breast cancer that could benefit significantly from an aggressive multidisciplinary approach based on an anthracycline neoadjuvant chemotherapy followed by surgery and radiotherapy, for all other clinical situation, the main objective of the treatment is to improve the quality of life and the prevention of complications, and less the survival. Practical reccomendations are presented for treatment as well the problems to be solved in the future and the trends in therapeutic developments.

Key words: advanced breast cancer, risk factors, treatment.

Radioterapie & Oncologie Medicală, 2000, 3:236-243

244 Dose Dense: New Developments in Breast Cancer Treatment

Dana Grecea

Cancer Institute „Prof I. Chiricuţă” Cluj-Napoca

Optimal management of cancer today requires a thorough and continous updated understanding of cancer cell kinetics’ and biochemistry. It should be understand the way cancer grows and how the growth is perturbed by chemotherapy as it plays an important role in breast cancer treatment. The present concept is simultaneous combination chemotherapy. For many years the dose level (mg/m2) was the only way to increase the intensity of therapy, because the other variable, the interval between doses could not be manipulated. It is a well estabilished fact of pharmacology that for many drugs and ~ many tumors, the escalation of dose increases the number of cancer cells killed. Simultaneous chemotherapy combinations have proven to be more effective than mono chemotherapy. The best combination regimens provide all drugs in adequate dosage. Sequential and alternating schedueling are two approaches to overcoming this problem of dose level. Sequential schedules are more dense for each agents. The latest and most succesful application of this chemotherapy in breast cancer involves the use of Taxanes.

Key words: breast cancer, dose intensity, dose dense, sequential sheduling.

Radioterapie & Oncologie Medicală, 2000, 3:244-249

250 Management of Brain Metastases from Breast Carcinoma with Systemic Chemotherapy: Current Status of Therapy

  1. Rosner1, Alexandra Flowers2

1Dpt. of Gynecology and Obstetrics, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NZ USA

2Department of Neurology, Hartford Hospital and the University of Connecticut School of Medicine, Hartford, CT, USA

The management of brain metastases (BM) from breast carcinoma (BC) is an often challenging experience for both treating physicians and patients. Radiation therapy is the standard treatment, while chemotherapy is still regarded as an experimental modality. The rationale for designing the present prospective pilot study using systemic chemotherapy alone to treat BM from BC was based on the fact that most patients have multiple BM in the presence of widespread disease. A total of 126 patients with BM from BC were treated with systemic chemotherapy alone as primary modality, with regimens similar to those used for systemic cancer. Sixty- six of 126 patients (53%) had an objective response. There were 16 (13%) complete responders (CR), 50 (40%) partial responders (PR), 13 (11 %) with stable disease (S), and 47 (37%) non- responders (NR). The responses for BM were similar to extracranial metastases. Median duration of remission was 10 months (mo) (range 6- 72 mo) for CR, 8 mo (2- 30 mo) for PR, and 3.5 mo (2- 15 mo) for S patients. The median survival from initiation of chemotherapy was 18 mo for CR (6-78 mo), 10 mo for PR (3-62 mo), and 6 mo for S (3- 18 mo), in contrast with 2.4 mo (1- 5 mo) for NR. In our experience prior chemotherapy for primary disease or extracranial metastases did not preclude further responses of BM to non- cross-resistant regimens, invalidating the concept of the brain as pharmacological sanctuary. The neurologic responses were similar in both groups: 52 % (32 of 62) in patients who received prior chemotherapy, and 53% (34 of 64) in patients with no prior chemotherapy. Systemic chemotherapy also controlled relapse of BM with a success rate of 40% (18 of 45 patients). The advantage of systemic chemotherapy was reflected in survival, by controlling simultaneously intra- and extracranial metastases. About 40 % of responders survived longer than 12 mo, and 20% were alive at 18 mo. Our findings suggest that systemic chemotherapy is an effective approach in the management of BM in chemosensitive disease such as BC, and should be considered as part of multimodality therapy as the most promising strategy in prolonging survival.

Key words: brain metastases, breast carcinoma, systemic chemotherapy, management.

Radioterapie & Oncoiogie Medicală 2000, 3:250-263

264 Hyperthermia: Preliminary Experience at the Cancer Institute Cluj-Napoca

  1. Tănăsescu

Cancer Institute „Prof I. Chiricuţă”, U. M Ph. „I. Haţieganu” Cluj-Napoca

The therapeutically effects of the tumor’s exposure at a heat over 40 Celsius degrees are known since the Antiquity. The biologic mechanisms of action of the hyperthennia have became to be scientifically studied in the 60 of our century, some of them remaining to be elucidated in the future. There are two main modalities ofhyperthennia application, superficial and deep, based especially on radio frequency waves. In the whole world, Japan is the country where these treatment methods have suffered the most spectacular progress, it represents also the world number one manufacturer of modem deep heating devices. Hyperthermia is used as well as single option and in association with standard oncologic methods of treatment, radio and chemotherapy. In the palliative cancer treatment, hyperthemia represents an attractive solution for the patients almost treated, regarding to the impressive ratio of objective response (up to 80%) and also to the minimal adverse reactions. Currently, at the Cancer Institute we dispose of an antitumor hyperthennia installation for superficial sites, based on a microwave emission system (magnetron at 2450Mhz). The device has a cooling module with pennanent circulating silicon oil in order to refresh the target volume and has the possibility of monitoring the heat distribution using 4 microtennocouples. The command system is based on an original soft created at the Technical University in Cluj- Napoca and applied on a Pentium PC. The tests we made on the tissue-equivalent phantom in order to detennine the distribution of the heat in the target volume were very promising. At this moment, a working protocol is established and in the shortest time, the hyperthennia installation will be able to be used in breast cancer superficial recurrences.

Key words: hypertennia, microwaves, palliative treatment.

Radioterapie & Oncologie Medicala. 2000, 3:264-266

267 Surgical Treatment of Metastatic Bone Lesions

  1. Turdean

Orthopaedic Dept., University District Hospital, Surgical Clinic No.1., Cluj-Napoca

The most common locations of bone metastases are: spine, pelvic ring, femur, humerus. The pain, functional impairement or neurological deficit are the frequent simptoms. The bone scan is the most sensitive methode to detect skeletal metastasis, but the CT -scan and MRI offer important detailes for surgery. The surgical treatment is paliative one, only .Its aim is to improve the life quality and not the life expectancy. The life quality is improved by preserving the walking ability, improving the general mobility, making easier the patient care. Surgery can be done in prophylactic way (to prevent a fracture of a bone containing a metastasis) or in „curative” way (to „cure” a facture of a bone containing a metastasis-pathologic fracture). As a prophylactic treatment, the intramedullary nailing of long bones, without opening the lesion side, is the best choice. In radio-chemoresistant metastasis or large metastasis,debulking of the tumor, medullary insertion of polymethylmethacrilate and fixation with nail is advised. In the spine, the prophylactic treatment consists in transpedicular segmental fexation in vertebral bodies below and above the tumour. It has be done before the colaps of vertebral body and neurological signs. The treatment of a pathological fracture in a long bones consists in marginal tumor excision according to Enneking principles and reconstruction. The reconstruction can be perfonned, either by prosthetic replacement, or by filling of bone defect with polymethymethacrylate and fixation with intramedullry nail or plate and screws. In the spine the treatment follows the same principles marginal excision of the tumor, decompression of the cord and reconstruction with bone cement and metal fixation, by anterior or posterior approache according with lesion location. Instable lesion, neurological threat.,drug resistant pain is an absolute indication, but the appearance of neurologic deficit is an emergency. The overall approach of a patient with scheletal metastases is a multidisciplinary team approach. Surgery is being ethically motivated, clinically indicated, and also cost effective. The best choice for a surgical treatment is a prophylactic one.

Key words: metastatic bone, surgical treatment.

Radioterapie & Oncologie Medicală, 2000, 3:267-273

274 Bone Metastases the Assessment of Fracture Risk and Principles of Orthopaedic Management

  1. Lucaciu, I. Hopulele, S. Hopulele, M. Picoş, S. Salcă

Ortopedical and Trauma Hospital. UMPh. „Iuliu Haţieganu” Cluj-Napoca

Skeletal metastases are very common and are associated with various complications, of which pathologic fractur~ is the most dramatic. Prophylactic fixation may alleviate invalidity and suffering associated with fracture, but the indication of prophylactic fixation needs a perfect assessment of fracture risk. This risk must be estimated on the basis of combined radiological and clinical criteria. Through adequate selection of the candidates for prophylactic fixation and a proper treatment of pathologic fractures, the quality of life in the advanced stages of neoplasms may improve significantly.

Key words: bone metastases, fracture risk, orthopaedic management.

Radioterapie & OncologieMedicală, 2000, 3:274-279

280 The Influence of Stress in the Occurence of Anxiety and Depresive Reactions in Breast Cancer

Anca Munteanu

Dept. of Psychology, West University, Timişoara

Premises: Beaming in mind the 3-dimensional character of the human being (body, mind and soul), we start from the premises that the fight against cancer may be more successful in a holistic approach. This strongly demands the inclusion of psychologists within this endeavour. The Investigated Question: The topic is part of psycho-oncology and endeavours to find the role of stress factors that accompany breast cancer in women in influencing the immunological status through generating depressive reactions, anxiety and loss of self-esteem. Methodology: A field study comprised an experimental group (50 women suffering from cancer) and a control group (50 healthy women). The applied tests: Beck Depression Scale, Cattell Anxiety Questionnaire, Self-Esteem Evaluation Questionnaire. Results: Prior to statistical interpretation significant differences between the two groups were established, regarding both depression, anxiety and self-esteem. The ill women had quantitatively and qualitatively higher degree of depression and anxiety, while self-esteem was severely impaired. Conclusions: The allopathic treatment of breast cancer asks for its completion by psychotherapy in order to strenghthen the psychological tonus of the patients. It is a compulsory condition of remission and healing.

Key words: breast cancer, stress, depression, anxiety, the diminution of immunology, psychotherapy.

Radioterapie & Oncologie Medicală, 2000, 3:280-284

285 Complex Cancer Assistance (Project Outline)

Anca Munteanu1, Diana Pamfil1,2

1Dept. of Psychology, West University, Timişoara

2Dept. of Psychology, „Tibiscus „University, Timişoara

This study resumes a major research project initiadet by the Psychology department of the mentioned faculty at the Vest University in Timisoara, intitled Complex Cancer Assistance. Based on a highly competent partnership and a wholistic outlook in cancer, it endeavours the institutionalization of psychological research, training arid complex assistance regardin the neoplazic desease. We plan the following directions of activity: the realization of research programs that will focus upon the psychological and social factors in the etiology and the therapy of cancer; the development of an informational and educational prevention network for the public concerning cancer; the foundation in Timisoara of the first national „Center of Complex Cancer Assistance”, that will ensure not only the training of national councelling specialists and psychotherpists specialized in oncology, but also direct psychological assistance. The project is enlightened by the thought that by including psychologists in the fight against cancer, this desease could become a less darker chapter in human pathology.

Key words: wholoistic approach, institutionalization of complex cancer assistance, trainig of psecialists in oncological councelling and psychotherapy, direct psychological assistance, complementary medical assistance.

Radioterapie & Oncoiogie Medicală, 2000, 3:285-288

289 Economical Aspects of Diagnosis, Treatment and Palliative Care for Breast Cancer

Delia Ruţă Mureşan1, Edina Szabo1, V. Păcurar1,2

1University Oncological Center Oradea

2Faculty of Medicine and Pharmacy, University of Oradea

Objectives: Breast cancer is a matter of public health with important socio-economic implications. This paper tries to establish the economic impact of cancer over society by analysing „cost of illness” through the calculation cost of diagnosis (pretreatment evaluation), cost of treatment depending on clinical stage and on different treatment strategies, the cost of palliative care in preterminal stages, the cost of a mammographic screening- program in Bihor County. Material and Methods: The cost of each treatment sequence (surgery, radiotherapy, chemotherapy and hormonotherapy) was calculated having in view the expenses for: medical care, medicine and medical supply, staff salary, medical equipment, days of admission. The costs of breast cancer treatment according on the extent of disease (operable, locally advanced, metastatic or relapsed) and the integration of each treatment sequence in the complex treatment was estimated. Palliative care costs were calculated within clinic and home. The cost of a regional breast cancer-screening program in 4 variants with a screening interval of2 or 3 years was estimated. Results: The costs of the treatment with an operable beast cancer patient vary between 34,300,000-88,340,000 lei, the cost of treatment in advanced stages vary between 61,480,000- 98,600,000 lei; while the cost of a relapsed cases varies between 236,140,000-327,140,000 lei. Metastatic treatment cost vary between 233,040,000-233,500,000 lei. The cost of palliative care vary between 41,620,000-55,010,000 lei to which immeasurable costs are added. The cost of a screening- program for the female population of Bihor County between 50- 69 of age / 72,045 female inhabitants vary depending on the length of the program (2 or 3 years) between 4,297,024,000- 5,436,033,730 lei. These costs can be reduced taking into consideration an achievable 70% compliance rate. Screening detected new breast cancer cases treatment costs’ (50 new breast cancer cases/ 100,000 eligible females in the first screening tour) will reach to 5,4-8,8 milliard lei. Conclusions: although chemotherapy within primary treatment of the disease rises significantly the cost, its inclusion in the multimodality treatment must be properly done taking into account prognostic factors and the stage of disease and having in view the high cost of the disease (4 times the primary treatment) of the treatment of local or distant relapse. The high number of breast cancer cases treated in advanced stages and the palliative care implies immeasurable societal costs that must be taken into account once evaluating cost! efficiency. The introduction of a screening- program brings about higher cost during the first three years: the cost of the screening – program (4,297,024,000 -5,436,033,730 lei) + the cost of the treatment of screening detected new breast cancer cases (5,4-8,8 milliard lei), but it is hoped to reduce mortality in about 3 – 7 years.

Key words: breast cancer, diagnosis, treatment, economical aspects.

Radioterapie & Oncologie Medicală, 2000, 3:289-300

301 Breast Collagenous Spherulosis

Voichita Suciu1, Cosmina I. Fachiol2, Angela Răşinariu1, C.D. Olinici1,2

1Cancer Institute „Prof Ion Chiricuţă” Cluj-Napoca

2Department of Pathology, U.M.Ph. „Iuliu Hţieganu „ Cluj-Napoca

The authors describe a case of collagenous spherulosis discovered incidentally in a benign breast tumor. The histological, histochemical and immunohistochemical diagnosis, as well as the problems of differential diagnosis are briefly discussed.

Key words: breast, collagenous spherulosis.

Radioterapie & Oncologie Medicală, 2000, 3:301-304

305 Report on ASCO Meeting from May, 19-23, 2000, New Orleans, LA, SUA (II)

T.E. Ciuleanu

Cancer Institute „Prof I. Chiricuţă” Cluj-Napoca

The 36th annual ASCO meeting was held between May, 19 -23, 2000, in New Orleans, LA. This is a brief review of the new achievements, as reflected in the oral communications, in some tumor types such as urologic, gynecologic tumors, melanomas, sarcomas, CNS tumors and lymphomas. Our report does not cover the poster, educational and meet the professor sessions. Topics such as head and neck, lung and digestive tumors were covered in the previous issue of this journal.

Key words: ASCO, trial

Radioterapie & Oncologie Medicală, 2000, 3: 305-311

312 Brussels Statement. 2nd European Breast Cancer Conference, September 26-30, 2000

Maria Retegan Turdean

314 REVUE OF LITTERATURE 316 QUESTIONNAIRE CME

322 GUIDELINES FOR AUTHORS