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Volum 01, Numarul 2, 1995

Quantity or quality ?

The 2nd issue of our journal is certainly a quanti- tative progress: it counts 30 more pages as compared to the I st one. Good but explicable: among the Roma- nian scientific publications, so far, there has been no one specially dedicated to radiotherapy.

Beginning with this issue, we very much value the collaboration of Professors J. P. LeBourgois, J. B. Dubois, F. Eschewege, Dr.J. Bourhis – all high rank personalities of the French radiotherapy and who ac- cepted to be part of the Editorial Council – as well as Dr.D. White, an outstanding physicist head, of the „Clinical Science Foundation” of London.

Regarding the content, there are various contribu- tions ranging from molecular biology aspects to clini- cal studies, which reflect the personal experience of the authors. The article signed by N. Ghilezan is the fIrst part of an exhaustive study assigned to molecular biology of cancer and cancerolenesisb tl1e following chapters will appeal’ in the 3n and 4t issues of our journal. Clearly and graphically stated, it represents a real „dissertation” of wide interest for thecancer spe- cialists of today and particularly for those coming tommorrow.

Adela Bara and colab. have investigated the caro- tens inhibitor action on the protein synthesis, within an experimental pattern (Ehrlich ascites). The results exhibit their possible inhibitor role, which is related to the clinical experience of chemoprevention trials with retinoids, particularly in aero-digestive tract can- cers.

It is not accidentaly that in two other articles is discussed the problem of the advanced cancers, con- sidering their high frequency in our country. The current outlooks in III A/B stage breast cancer treat- ment and biology have been exposed by Cristina Vitoc, \\-.ho points out their late diagnosing, rather than their increasing aggressiveness. The neoadjuvant che- motherapy, as we1\ as the local treatment compulsor- iness are – at present – accepted by commun consent, though there is still controversy regarding the treat- ment sequentiality. Among the studied cases, the over- a1\ survival was 66% for the III A stage and 45% for the III B respectively, with a 15% local failure rate. The therapeutic outlooks have also been presented. The results of the radio-chemotherapy treatment have been analysed by Viorica Nagy and colab., upon a group of 139 women with cervix cancer hospitalized in the Cluj Oncological Institute. The radiotherapy and concurrent cisplatin chemotherapy offered im- proved results especially with extensive lesions ( >4 cm and/or III B stage).

Two articles are dedicated to head & neck cancers. Considering a group of 51 patients of the G. Roussy Institute, M. Ghilezan and colab. laid sn”ess on the treatment and natural history characteris~ics of old people with cancers of the larynx. The overall 5 years survival was 38% as compared to the 68% corrected survivalo The authors stated that t11e classical fraction radiotherapy with 70 Gy dose is an efficient therapeu- tic alternative for this patients. The efficacy of the BEC neoadjuvant chemotherapy for undifferentiated carcinoma of nasopharyngeal type are presented by T. Ciuleanu, and colab. in a study upon 31 parients with UCNT, who reveived BEC chemotherapy protocol, followed by radiotherapy. The BEC therapy is very active, but the long-term results are to be evaluated within randomized prospective trials.

Clinical observations have been brought up by a group from JOCN regarding the patients treated ac- cording to aggressive patterns of chemotherapy, to which have been added haematopoietic growth fac- tors. They have exposed theoretical and practical as- pects of this modern method of increasing effective- ness and safety of cytostatic treatments.

Quantity or quality? It’s up to the readers – whose observations and suggestions we are waiting for – to give the right answer to such a question. We do trust having reached the quality desideratum too. For the ,merest „risk”, at the end of Journal, there is a „reader s guide”, covering all the ” exigencies” any article is supposed to fulfill in order to be published, as well as the ‘peer review” system which will function begin- ning with the next issue. Far from being a „restrictive” mechanism, this will help authors and readers to a better understanding of their own performances, so that the qualitative level of OUIo Journal could develop. It is sure that quality is not possible without a bit of „quantity”, therefore our commun effort must be the best solution.

Editor in chief V. Cernea

Molecular mechanisms of cancerogenesis and tumor progression

Part I-

  1. Ghilezan UMF „I. Haţieganu” Cluj-Napoca, Department of Oncology and Radiotherapy

 

The progress in cellular biology from the last years made possible to unravell many aspects of the molecular mechanisms of cancerogenesis and tumor progression as well the molecular basis of the response to chemotherapy or radiotherapy. Many of these achievements have already practical applications as the identification of the susceptibility to cancer, the diagnosis at the molecular level, staging, the monitoring of the subclinical residual disease or developing new treatments. The objective of this review is to present the main aspects of the cancer biology which will transform in a very near future, the practice of oncology.

The part I of this review describes the general notions on the structure and function of the genes, the fundamentals of the proliferation and differentiation processes. Further, growth factors, receptors and signal transduction are described. The mechanisms of the cell cycle, DNA repair and apoptosis are also presented.

The part II will approach the processes of cancerogenesis and tumor progression. In part III, they will be presented the molecular bases of the response to chemotherapy and radiotherapy and aspects for the clinical applications.

Key words: molecular biology, genes, growth factors, receptors, signal transduction, DNA repair, apoptosis

Radioterapie & Oncologie Medicală, 1995, 2:1-15

Effects of some carotenoids on proliferation and nucleotide turnover in Ehrlich ascites tumor cells

Adela Bara1, Carmen Socaciu2, G.Neamtu2

1 Oncology Institute “Prof I. Chiricuţă„, Cluj-Napoca

2University of Agricultural Sciences, Cluj-Napoca

In spite of many epidemiological studies demonstrating the preventive role of carotenoids against cancer, few and controversial data about their mechanisms at cellular level were reported. We investigated comparatively the effects of I mg p-carotene (BC), lutein (LUT) or canthaxanthin (CTX) per mouse, inoculated intraperitonealy together with a suspension (0.5 ml) of EAT cells (2 x 106 cells/ml). The tumor inhibition index (I) and the influence of carotenoids on nucleotide level and turnover were monitorized after 7 days of treatment.

A gradual inhibition of EAT proliferation and protein synthesis was obtained for CTX (27%), BC (33%) and LUT (60%)-treated mice. A similar gradual loss ofmacroergic adenine nucleotides (ATP,ADP), 5′-AMP, concomitantly with increases of 3 ‘,5’ -caMP level were observed for CTX, BC and LUT, respectively.

These data suggest that carotenoids like CTX, BC and especially LUT may have indirect inhibitory effects on EAT cell proliferation by specific modulations of adenine- and guanine-dependent pathways, which are responsible for cell decision to proliferate and differentiate.

Key words: carotenoids, Ehrlich ascites tumor cells, nucleotide turnover

Radioterapie & Oncologie Medicală, 1995.2:16-21

Present trends in locally advanced breast cancer

Cristina Vitoc

Oncological Institute „Prof. I.Chiricuţă”

The great number of women admitted in our Institute with loco-regional advanced breast cancer (LRABC) determined us to analyze the evolution of the concepts, treatments and results, focusing on the new trends. LRABC disease, included in clinical stage III-a and III-b, has a long natural history, being rather a late diagnosis than an aggressive disease. Local treatments-surgery and radiation alone or associated obtain the local control only for a short time. Further evolution with rapid onset of distant metastasis underlines the need of a systemic therapy. The multidisciplinary treatment has been accepted now as standard therapy in LRABC. Our results with this approach are: 48% 5-year disease-free survival for patients with stage tIt-a and 36% for patients with stage III-b, 66% 5-year overall survival for patients with stage III-a and 45% for patients with stage tIt-b and a local recurrence rate of 15%. Although the consensus on the necessity of the neoadjuvant chemotherapy with antracyclines and on the local treatment is established, controversies about manner, type and timing of their association and about indications in non-responsive cases, still persist. New therapy alternatives are discussed.

Key words: loco-regional advanced breast cancer, multidisciplinary treatment, prognostic, results.

Radioterapie & Oncologie Medicală, 1995, 2:22-35

Radiotherapy alone for advanced cancer of the larynx in the elderly: a series of 51 patients treated at Institute G. Roussy

  1. Ghilezan, F. Eschwege, P. Wibault, B. Luboinski, G. Mamelle

Dept. des Radiations et I-st Dept. de Chirurgie cervico-faciale, Institute Gustave Roussy, 94800 Villejuif, France

Purpose: to evaluate the results of radiotherapy for advanced cancer of the larynx in the elderly, at Institute G. Roussy between 197R to 19R4.

Materials and methods: 51 patients, mean age of70 yrs, with T3 and T4 cancer of the larynx, who refused surgery (14 %) had medical contraindications (73 %) or too extended for surgery (14 %), were irradiated with cobalt at 70 Gy/larynx, 50 Gy/NO and 65 Gy/N+ over 7 wks, 5 fr/wk. The treatment was well tolerated with minimal incidents. Result~: the overall 3 and 5 yr~ survival wa.~ 46 and 3R per cent, but the corrected survival (by exclu.~ion of the non-oncological deaths) 81 and 62 %, with conservation of the larynx in over 80 % of the patients. The causes of death were: local recurrence (54 %), intercurrent illnesses (21 %), a 2nd primary tumor (12 %), distant metastases (6 %) and other causes (suicide, traffic accidents, etc = 15 %). The main prognostic factor was age: < 65 yrs, the 3 and 5 yrs survivals were 75 and 54 % against> 65 yrs with 2R % (P=0,01).

Conclusions: a classic irradiation with 70 Gy over 7 wks is an efficacious indication for elderly patients with advanced cancer of the larynx for whom more aggresive treatments with the loss of the organ, are not justified due to the high frequency of non-oncological deaths.

Key words: radiotherapy, advanced larynx cancer, elderly

Radioterapie & Oncologie Medicală, 1995, 2:36-40

Concurrent Radio.chemoterapy in Advanced Cervical Carcinoma

Viorica Nagy1,2, N. Ghilezan1,2, N. Todor2

1 UMF Cluj-Napoca

20ncologicallnstitute „Prof l.Chiricuţă”

Purgose: to improve the efficacy of radiotherapy for advanced cervix carcinoma by intensifying external irradiation with a „boost in field’ associated with or not with cisplatinwn as radiosensitizer.

Methods and materials: During January 1988 through December 1993 a prospective nonrandomized study was carried on at Institutul Oncologic Cluj, 2nd Radiotherapy Dept., on 139 patients with advanced stages of cervix carcinoma. The protocol consist in delivering with the classical „box” technique for cobalt, 55 Gy on the whole pelvis over 5 weeks supplemented with 2 Gy pendular irradiation weekly on the cervix-vagina axis. A DDP chemotherapy was associated (20 mg/mp x 5 days) every 21 days. The compliance to protocol was excelent with minimal toxicity.

Results.: The increasing volume & stages were associated with poor results but the main prognostic factor was the local response at 55 Gy/ 5 weeks: the operable patients had 94% local control and 93% 3 yrs survival vs 54 and 64% for inoperable cases. The more advanced lesions or stages, responded better to radio-chemotherapy than to irradiation alone.

Conclusions: concomitant radio-chemotherapy improve significantly the local control and survival for advanced cervix carcinoma comparative with irradiation alone.

Key words: cervix carcinoma, advanced stages, radio-chemotherapy

Radioterapie & Oncologie Medicală, 1995, 2:41-51

BEC neoadjuvant chemotherapy for undifferentiated carcinoma of nasopharyngeal type

T.E. Ciuleanu, N. Ghilezan, Elisabeta Ciuleanu, V. Cernea, N. Todor, A. Udrea, L. Vâţă, Simona Stein

Oncological Institute „Prof. l. Chiricuţă”

Thirty-five locoregionally advanced undifferentiated carcinoma of nasopharyngeal type (UCNT) patients received 3 courses of neoadjuvant BEC chemotherapy (Bleomycin 15mg dl push+ 12mg/m2 c.i. dl-5, Epirubicin 70mg/m2 dl, CDDP 100mg/m2 dl) followed by RT (64-70Gy/ 7wks). Activity: 33/35pts (94 %), had an objective response to chemotherapy, with 14/35 CR (=40 %). The CR rate was not influenced by the Tor N category (N3 vs N2: 31 % vs 47%, CR, p=ns). There were no toxic deaths. After completion of radiotherapy, 24/32 evaluable pts (75%) obtained CR. Median follow-up: 20 mths (3+,40+). Two-years survival: 80% for chemotherapy CR vs 54 % in the other pts (p=0.15). There were no significatlt differences in survival in respect with sex, age, performance status, Tor N categories. As of March 94, 18pts (51 %) wereCR (3+ ,40+mths), 5PR and 12 have failed: 2 were initially refractory, and 10 chemotherapy responders relapsed after a median of 15 mths (6;26). Patterns offailure: 2pts T+, 5pts T+N+, Ipt T+N+M+, 4pts M+. Conclusions: a).Our results confirm BEC as a highly active regimen for UCNT. b). The benefit in terms of survival needs to be defined within prospective randomised trials.

Keywords: nasopharyngeal, neoadjuvant BEC chemotherapy, radiotherapy

Radioterapie & Onclogie Medicală, 1995, 2: 52-58

The role of haematopoietic growth factors in chemotherapy of solid tumors: biological and clinical aspects

  1. Ghilezan1, A. Udrea2, T.E. Ciuleanu1

1UMF Cluj, Department of Oncology & Radiotherapy

2Oncological Institute „Prof. I.Chiricutd”

The use of haematopoietic growth factors avoid the haematological complications and afford the intensification of chemotherapy. The usual doses of 5-1 0 mgikg given subcutaneously, have a good therapeutic efficacy (shortening the period of neutropenia, less infectious complications) and very few side effects. Due to the specific activity of haematopoietic factors presently available (GM-CSF, G-CSF) only on the myeloid line, thrombocytopenia becomes the main toxicity. Based on the experience gained in the 2nd Radiotherapy Dept. of the Oncological Institute Cluj, the relevant theoretical and practical a.”pects of this new modality to improve the efficacy and safety of chemotherapy are presented.

Keywords: haematopoietic growth factors, hematology, chemotherapy, neutropenia

Radioterapie & Oncologie Medicala, 1995, 2: 58-64