This isssue of our Journal continues to publish the full text of the contribution presented at the 3rd. Balkanic Oncology Congress, which took place in Poiana BrAşov, Romania, 10-14 september 2000. Some of the reports from the „Lung, Head and Neck Cancer” Section are published as well as other ones.
Cancer is a leading cause of death allover the world. This imposes a stronger focus on epidemiological research in order to identify etiological factors and to elaborale preventive programs. The papers by Ofelia ~uteu et al. and by Emilia Mihut are focused on the role of potential risk factors for the general population and for children so as: smoking, alcohol, nutrition factors, infectious agents and other cancerigen substances. Control programs of the factors could decrease with 1/3 the cancer morbidity. The 3rd paper from epidemiological field signed by Ioana Radulescu et al. show the incidence, prevalance and mortality for lung, breast, rect and colon, head and neck, and cervix cancer in Cluj county during 1990-1999.
In the last few years promising anticancer therapies with new mechanisms of action have been developed based on the better understanding of the cancer biology. Adriana Poruţiu discusses such a subject in her article „Gene Therapy in malignant melanoma”.
New progress done in lung cancer therapy does’t improve significanty the five years survival. There is clearly a need for more efforts to understand the biology of lung cancer, to improve the diagnosis and to find new therapeutical strategies. Svetlana Encică reports the OMS clasification of lung cancer 1999, and Anca Mihailov et al. present the results of the combination Vinorelbine-Cisplatin in the study of the 2nd phase, on 22 pacients with loco-regionally advanced lung cancer treated in Oncological Institute Cluj.
The effort of the staff of the Oncological Intitute Cluj to improve cancer therapy is well known. This is also reflected in the next five articles. So, V. Cernea et al. report the experience of this Institute in hyperfractionated radiotherapy in cancer of de larinx. The authors emphasise that the hyperfraction radiotherapy is more efective than standard radiotherapy. G. Kacso et al. presents the results of the radiotherapy alone in a retrospective study on 335 pacients with larynx carcinoma Tl-4, NO- 2, treated between 1985- 1995 at the Cancer Institute Cluj. The results of this study are comparable with others reported in the literature. Concomitent chemoradiotherapy for advanced head and neck carcinoma in Oncological Institute Cluj and at the Center Henri Becquerel, Rouen, Franta are shown by A. Udrea et al. In the experience of both Institutes the results are better in concomitent chemoradiotherapy vs the secvential treatment. Finally, the authors stress on the need for further research for developement of new drugs to improve the control of head and neck cancer. Elisabeta Ciuleanu et al. suggest a possible answer to this question and analyse the results ofTaxol-5FU- LV as 2nd line chemotherapy on 28 pacients with refractary nazo-pharingeal carcinoma and show that this combination is marginaly active.
We welcome the contribution of the group from 3rd Pediatric Clinic who presents their experience regarding abdominal tumors in children. Anca Bojan and L. Petrov from Haernatology Deparment Of The Oncological Institute Cluj, propose a practical prognostic score for multiple mieloma based only on creatinine level and haemoglobine.
In Case Reports, A. Moga from University Hospital Sibiu, Oncological Department, hopefully is breaking the ice: the first clinical observation from new collaborating centres.
We appreciate all new contributions to our journal. Review of literature and CME end this issue.
Ofelia Şuteu1, N. Ghilezan2,3
lDepartment of Epidemiology,
2Department of Oncology, UMPh. „I. Hatieganu” Cluj Napoca
3Institute of Oncology”Prof I. Chiricuţă” Cluj Napoca
The final contribution of Epidemiology, in the last half of the present century, to the discovery of the causes of the neoplasm disease by identifying numerous environmental factors (including life style elements) responsible for the apparition of the cancer and the estimation of the number of the annual deaths by cancer, attributed to each factor, have allowed the outline and the implementation of the main efficient prophylactic approaches with their application on the population.
Smoking, wich represents 30% of the total causes of cancer in industrialized countries, together with other important etiological factors, including alcohol, alimentary factors, infectious agents, carcinogen substances in the social and professional environment outline the approach for the primary prophylaxis, avoiding the contact with the known carcinogen factors wich could decline the cancer cases with one third in the industrialized countries.
Key words: risk factors, cancer, prevention.
Radioterapie & Oncologie Medicală, 2001, 2:123-129
Emilia Mihuţ, Ştefania Neamţu
Institute of Oncology ,”Prof I. Chiricuţă”, Cluj-Napoca
Non-Hodgkin’s lymphomas represent a group of malignant neoplasms, which is increasing for the last decades. Since 1970s, the incidence rate of non-Hodgkin’s lymphomas in adults and teenagers between 15-19 years has increased by almost 60% and ranges from 3-4% per year. The incidence rate in children under 15 years of age was not significantly change. Important advances in the knowledge of histopathology and new diagnostic tools, as well as the improvement of the registered data and ageing of the population, only partially explain this increase. Two viruses were identified as possible etiologic agents for non-Hodgkin’s lymphoma: the Epstein-Barr virus (EBV) and HTL V -I. Congenital and acquired immunodeficiencies could also represent predisposing factors. Finally, epidemiological studies indicate that environmental factors may play an important role in the etiology of non-Hodgkin lymphomas.
Key words: non-Hodgkin’s lymphoma, epidemiology, EBV, immunosuppression, environmental factors, children
Radioterapie & Oncologie Medicală, 2001, 2: 130-137
Ioana Rădulescu1, Larisa Ciule2, N. Todor3
1Diagnosis and Treatment Center Cluj
2Clinic of Radiology Cluj
3Institute of Oncology „Prof I. Chiricuţă „, Cluj-Napoca
The incidence of cancer in our district is continuously rising. The highest incidence had the lung cancer, followed by breast cancer, gastric, colorectal, lung -head and neck, and cervical cancer. Lung cancer had the highest incidence in males, followed by gastric, lung,head and neck, colorectal and prostate cancer, Breast cancer had the highest incidence in females followed by cervical, colorectal, gastric, lung and ovarian cancer. Lung cancer generated the highest mortality, followed by gastric, colorectal, breast and lung, head and neck cancer. Breast cancer had the highest prevalence, followed y lung, head and neck, cervical, colorectal, uterine and urinary bladder cancer.
Key words: cancer, incidence, prevalence, mortality.
Radioterapie & Oncologie Medicaăi, 2001, 2: 138-145
Institute of Oncology “Prof I. Chiricuţă” Cluj-Napoca
Early reports of spontaneous remissions of growing melanomas were the first suggestions that melanomas were potentially immunogenic tumors. Studies of human antibody responses to autologous melanomas also supported this belief, and they provided an immunologic basis to explain the spontaneous remissions. Several genes that code for melanoma-associated antigens have been identified and cloned. Tumor immunotherapy using gene-modified melanoma vaccines, therefore, is a rational strategy, but progress in understanding the mechanisms of immune activation and the nature of tumor T-cell interactions is necessary.
The scope for clinical benefit from gene therapy is enormous, limited only by the poor performance of currently available vector systems.
Key words: malignant melanoma, gene therapy, immunotherapy, vaccin
Radioterapie & Oncologie Medicală, 2001, 2: 146-153
Heart Institute, Dept af Pathalagy, Cluj-Napoca
Lung cancer classification remains a topic to be talked over. The last references on lung cancer provided by the World Health Organisation are based on worked out criteria in light microscopy in order to be used by the pathologysts in every lab, including those with less performant equipments. There are changes of the previous classification; for example, large cell carcinoma subtypes are admitted, as well as basaloid carcinoma and lymphoepithelioma- like carcinoma; this classification contains a new group of lung carcinoma: pleomorphic with sarcomatoid and sarcomatous elements. The aim of this paper is to give more details on same new aspects related to the lung cancer including premalignant changes resorting to the WHO 1999 classification as well as to the latest data in the field.
Key words: lung, 1999 WHO classification.
Radioterapie & Oncologie Medicală, 2001. 2: 154-157
Anca Mihailovl, T. E.Ciuleanu1,2, N. Todor1, R. Curca1, Dana Iancu1, Natalia Taju1, Cristina Cebotaru1, Ioana Rădulescu1, Cristina Neacşu1, AI. Eniu1, C. Căinapl, E. Banu1, Helene Homokosl, N. Ghilezan1,2
11nstitute of Oncology „Prof I. Chiricuţă”, Cluj-Napoca
2U.M Ph. ,”I. Haţieganu „, Cluj-Napoca
Vinorelbine is considered the most active Vinka alkaloid in NSCLC, and its association with Cisplatin is still considered the most cost/effective protocol in many institutions. Purpose: To assess, in a phase II trial, the results obtained in locoregionally advanced (stage III B) NSCLC patients with VP combination, delivered in an outpatient setting. Methods: From VIU1999 to V /2000,23 previously untreated patients received VP (Vinorelbine 25 mg/m2, days 1, 8, 15 and Cisplatin 100 mg/m2 day 1 with saline hyperhidration) q3wks. The patients had 3 cycles followed by radiotherapy (RT) at 60 Gy; if indicated. Patients with pleural effusions or necrotic tumor had no RT and continued VP up to 6 cycles (less if progressive disease). Results: Males 83%, age 60 (47-72), WHO PS 1 in 17,2 in 4,3 in 2 patients; histology: large cells 12, squamous 7, adenocarcinoma 4. Toxicity: 58 cycles were given, with no toxic death but 1 withdrawal due to persistent grade 2 nephrotoxicity. Toxicity was mild overall. Grade 3-4 neutropenia occurred in 6 cycles. Grade 3 nausea/vomiting occurred in 1 patient. Activity: at the time of the analysis, 21 were evaluable for response, and 9 patients had an objective response (OR) to CT (=43%, CI [9%-65%]), 2 complet responses (CRs), 7 partial responses (PRs). Survival (S): median S is 8.3 months, with a projected 47% one-year survival. As of June 2000, 18 patients were alive and 5 have died by disease progression (2 locoregional failure, 3 locoregional failure and distant metastases). Conclusion: The combination of Vinorelbine and Cisplatin proved active in advanced NSCLC patients and was safely delivered in an outpatient setting, with manageable toxicity.
Key words: NSCLC, Vinorelbine.
Radioterapie & Oncologie Medicală, 2001, 2:158-162
1U.M.Ph. „I. Haţieganu”, Cluj-Napoca
2Institute of Oncology” Prof I. Chiricula „, Department of Radiotherapy, Cluj-Napoca
Objectives: Analysing the results and the optimal time dose ratio for hyperfractionated radiotherapy vs standard radiotherapy in cancer of the larynx.
Material and Methods: between 1987 and 1993, 106 patients with T3 and T4larynx squamous cell carcinoma entered in a prospective non-randomised study comparing standard 2 Gy/day, lOGy/week (ST -group B), vs. hyperfractionated 2 x 1,2 Gy/day, 12 Gy/week (HF-group A) radiotherapy. Total doses administered were: 70-72 Gy and 74-84 Gy for standard and hyperfractionated schedules respectively.
Results: 5 years actuarial survival: 68% for T4 in group A (HF) and 28% in group B (ST), for T3: 75% in group A and 73% in group B. Local failure was the most frequent (45% of failures) followed by loco-regional failures (12%). A logistic regression was performed for some fractionation parameters. Total dose (TD), overall treatment time (OTT) and the dose int~nsity, were found to be significant (p= 0.02) for local control at 3 years. Biologicaly effective dose (BED) based on LQ model was calculated for booth HF and STD radiotherapy schedules. The average value of BED 10 was 88.76 Gy forHF and 86.2 for STD radiotherapy (p=0.04). For BED 3 the average values are: 108. 38 forHF and 112, 53 for STD (p=0.15).
Conclusions: Hyperfractionated radiotherapy is a valid therapeutic option for the advanced laryngeal cancer. Significant survival differences were for T4 tumours but not for T3. TD, OTT and dose intensity are therapeutic factors with significant prognostic value. BED values suggest that HF is biologically more effective as STD radiotherapy, but the toxicity is almost the same.
Key words: hyperfractionation. larynx cancer. BED, therapeutic ratio.
Radioterapie & Oncologie Medicală, 2001, 2: 163-167
1 Institute of Oncology „Prof I. Chiricuţă„, Cluj-Napoca
2U.M Ph. „I. Haţieganu”, Cluj-Napoca
Purpose: evaluate survival, pattern of failure and toxicity after radiotherapy alone for larynx carcinoma in a single institution retrospective analyses, with long follow-up, in order to improve our policy of tratrnent.
Materials & methods: between 1985 to 1995, at the Cancer Institute Cluj, 335 patients with larynx squamous carcinoma, TI-4, NO-2 were irradiated with curative intent as first and sole treatment, with dose ranging from 45 to 84 Gy in standard (SF) or hyperfractionation (HF) regimens.
Results: with a median follow-up of29 months, local control and five year survival were 91 and 82 % for Tl, 76 and 57 % for T2, 44 and 35 % for T3, 31 and 28 % for T4 (p< 0.001),83 % of a” patients being No. The pattern of failure was: 10cal~L) 25 %, regional (R) 1%, LR6%, distant metastases (M) 3 % andLR+M 1%. Spinallymphnode recurrences (out of field) were exceptional (0,5 %). A dose-effect analyses identified the optimal doses for maximal local control with minimal side effects: 56Gy/SF forTI, 66Gy/SF forT2, 70 Gy/SF forT3-4. HF did not improve the LC or SV in any ofT categories, but these has to be taken with caution due to serious biasis of a retrospective study.
Conclusions: For Tl-2 RT alone obtaines good local control and survival with excelent function and cosmesis. Doses of 56 Gy/SF seem the most appropiate for true Tl lesions, 66Gy/SF for T2, and 70 Gy/SF for T3-4. There is useless to extend the radiation field to the spinal chain in No cases. Our analyses confirm the prognostic value of stage (T &N), origin site (glottic better than supraglottic better than subglottic), age (better for younger than 65 years old) and infirm the prognostic significance of gender, anterior commissure or preepiglottic space involvement. Five year survival and local control were comparable to those repported in the litterature.
Key words: larynx carcinoma, radiotherapy, pattern of failure.
Radioterapie & Oncologie Medicală, 2001, 2:168-175
1Institute of Oncology „Prof I. Chiricuţă”, Cluj-Napoca
2U.M.Ph. „I. Haţieganu „, Cluj-Napoca
One hundred twenty eight patients with squamous cell carcinoma of the head and neck had a chemoradiotherapy in our institution between 1988-1995. Ninety percent were stage IV, 34% with an oropharynx primary, 26% larynx, 25% an oral cavity and 15% a hypopharynx primary.
Methods: a concomitant schedule combining 70Gy/7weeks with Cisplatynum (DDP) 100mg/sm (19%), DDP 100 mg/ ~ sm+5 Fluorouracil (5 FU) 600 -1000mg/sm (11 %) or Carboplatinum (CBDCA) 400 mg/sm (9%), every 21-28 days was used for 40% of the patients. Three to four cycles of induction chemotherapy (DDP 100mg/sm + FU 600-1000 mg/sm, every 21-28 days) followed by irradiation at 70Gy/7weeks for 41% of the patients. Seven patients had sequential or concomitant chemoradiotherapy with other drugs. Fifteen percent of the patients did not had the irradiation after the induction chemotherapy.
Results: The main toxicity was mucositis grade 2-3 RTOG for 90% in the concomitant arm and 57% in the sequential arm. Nausea and vomiting was important, 36% grade 2-3 WHO in the sequential arm and 22% in the concomitant arm. Objective response rates were significantly higher with the concomitant treatment than with the sequential modality (p<0.05). Univariate analysis showed that the performance status was a prognostic factor for response to induction chemotherapy, with significantly differences between those with a Zubrod 1 and those with 2,3 Zubrod performance status p< 0.02). From the 128 patients the oropharynx primaries and the non-keratinizing oropharynx tumors had a significantly better objective response rate (p<0.03 and respectively p<0.01) than others. ProgressIon free survival (Kaplan-Meier) at 5 years was 68% and overall survival (Kaplan Meier) was 31 % at 5 years.
In conclusion, concomitant chemoradiotherapy had a significantly better objective response rate than the sequential treatment, but the toxicity was greater with the concurrent treatment. There were no differences in progression free survival or overall survival at 5 years according to treatment modality.
Key words: head & neck carcinoma, chemotherapy, radiotherapy, chemoradiotherapy.
Radioterapie & Oncologie Medicală, 2001, 2:176-183 1
1 Institute of Oncology „Prof I. Chiricuţă„, Cluj-Napoca
2 „H. Becquerel” Centre, Rouen Cedex, France
3University Hospital, Rouen Cedex, France
Purpose: review of the CHB experience in concurrent radio-chemotherapy for advanced locoregionally head and neck squamous cell carcinoma.
Patients and Methods: between 1990 and 1996, forty patients presenting an advanced loco-regionally head and neck carcinoma have been treated with a concurrent radio-chemotherapy at the CHB. Radiation protocols were as follows: Jifractionated split course – 22 patients -55% and conventional – 18 patients – 45% to a total dose of 66-70Gy. The :hemotherapy consisted of2 to 4 courses, at 21-28 days, of Cis plat in (20mg/m2 day 1- day 5) or Carboplatin (aria under curve [AUC5]- 2 patients) and infusional5 -Fluorouracil (750 mg/m2 day 1- day 5) for the majority of patients- 34 (85%).
Results: five toxic deaths have been registered (7.5%). Thirty one patients (77.5%) experienced (World Health Organisation
WHO] grade 3-4 mucositis, as the main toxicity. The complete response rates were 55% for the primary and 51 % for the
cervical nodes.. The progression free survival (Kaplan-Meier) at 2 and 4 years were 37.5% (95% confidence interval [ Cl] [7% to 57%) and 25% respectively (95% CI 0.5% to 49%). Overall survival rate (Kaplan-Meier) at 2 and 4 years were 12% (95% CI 17% to 47%) and of 22.9% respectively (95% CI 7.7% to 38.1 %). Performance status (Karnofski index) lias the only significant prognostic factor in univariate analysis for the overall 2 years survival.
Conclusions: the incidence and severity of the acute and late toxicities were important. Careful follow-up of the patients including use of the simptomatic adapted measures is mandatory. Concurrent radio-chemotherapy is a therapeutic option for loco-regionally advanced head and neck cancer, but the optimal combination of radio and chemotherapy still has to be defined.
Keywords: Head and Neck Carcinoma, Chemotherapy, Radiotherapy, Radio-chemotherapy.
Radioterapie & Oncologie Medicală, 2001, 2:184-191
Elisabeta Ciuleanul, T. E Ciuleanul,2, N. Todor1, Marişca Marian1, M. Mureşan1, Carmen Lisencul, A. Fodor, N. Ghilezanl,2
1 Institute of Oncology „Prof I. Chiricuţă„, Cluj-Napoca
2U.M.Ph. „I. Haţieganu” Cluj-Napoca
Purpose: Some recent reports found Taxol in combination with platinum or anthracyclines as an effective drug for relapsed nasopharyngeal carcinomas. The aim of this phase II study is to evaluate the efficacy of Taxol + 5 Fluorouracil + Leucovorin combination (” TFL „) as 2nd line chemotherapy (CT) for refractory/ relapsed nasopharyngeal carcinoma (NPC) patients.
Methods: From 9/1998 to 1/2000,24 NPC patients (initially refractory to 1st line CT or relapsed), 17 with loco regional disease, 1 with distant metastases, 6 both loco regional + metastatic, received up to 6 courses ofTFL: P 175 mg/m2 in 3 hours, day 1, L 30 mg/m2 in 20 min followed by F 600 mg/m2 in 2 hours, day 1 to 5, every 21 days.
Results: There were 18 men and 6 women; median age 45 [20-59]; performance status (PS) 1 in 22 patients, 2 in 2 patients. Histology was UCNT in 12 and nonkeratinizing epidermoid carcinoma in 12 patients. Previous treatment consisted in Epirubicin and Cisplatin based neoadjuvant CT followed by radiotherapy at 70 Gy. Ten patients were initially refractory, while the remaining 14 relapsed after a median objective response (OR) of 5 [2-15] months. TFL was administered at a median of 21 days [21-35]. Eighty seven cycles were delivered, median per patient 3,5 [1-6]. Activity: 3 patients (=12,5%, CI= 0%-27%) had a partial respoIise'(PR), 3 stable disease, and 18 progressed. Toxicity was mild and there were no toxic deaths. Grade 3-4 toxicity included anaemia in 2%, leukopenia, stomatitis and vomiting in 1 % of cycles. Compliance: no patient refused treatment due to toxicity. Median follow-up was 6 months [3-15] Median survival after TFL was 7,3 months. One year actuarial survival was 48% [Cl 24%-74%]. To date, all 3 pts are maintaining their response to TFL [2+…11 +months].
Conclusion: TFL combination is marginally active as 2nd line treatment for NPC patients. Toxicity of the combination is mild and it can be safely administered in an outpatient setting.
Key words: nasopharyngeal carcinoma,Taxol, relapse, refractory.
Radioterapie & Oncologie Medicală. 2001, 2: 192-196
Anca Bojan, L. Petrov
U.M.Ph. „I. Hatieganu”, Institute of Oncology „Prof I. Chiricuta”, Cluj-Napoca
One hundred eleven patients diagnosed with multiple myeloma in the haematology departement of the Oncological Institute of Cluj-Napoca were treated with standard chemotherapy were analised in order to evaluate the prognostic value of several clinical and laboratory factors. The variables analysed were serum levels of creatinine, haemoglobin, calcium, stage, plasma cell percentage, cellular type (according to Griepp classification), age,sex and performance status. In a multivariate Cox analysis two variables were significantly and independently associated with poor survival: high serum level of creatinine and low level of haemoglobin. According this prognostic factors we are proposing a prognostic index which allowed an efficient separation of prognostic groups of patients.
Key words: multiple myeloma, survival, prognostic factors, prognostic index..
Radioterapie & Oncologie Medicală, 2001, 2:197-207
Paraschiva Cherecheş-Panţa1, Lavinia Popescul, Ştefania Neamţu2, Dana Câmpeanl, Dana Secan1, M.Nanulescu1
1U.MPh. “Iuliu Haţieganu”, Clinica Pediatrie III, Cluj-Napoca
2Institute of Oncology „Prof I. Chiricuţă”, Cluj-Napoca
The authors present the experience of a pediatric clinic regarding abdominal tumors in children and the prevalence of Wilms tumor (WT) among these type of diseases. In a period of time of 6 years, 263 cases with abdominal tumor were admited, 58.9% being renal tumors. Hydronephrosis were the most prevalent cases. Ten cases with WT were admitted, 3 cases being infants. There are presented pathological types, different stages of each case, therapeutical procedures and the clinical course of cases with WT.
Wilms Tumor represents the third cause of renal masses in children, and is the first cause of solid malignant renal tumours. The diagnosis is sugested by palpation of the abdominal mass with lombar contact, is confirmed by ultrasound, i. v. urography and CT scan and staged by pathology.
Key words: Wilms tumor, children, abdominal masses.
Radioterapie & Oncologie Medicală, 2001, 2:208-214
A.Moga1,2, Emilia Popescu2, Angela Maier1,2, Lucian Vlad1,2
1University of Sibiu „Victor Papilian„, Faculty of Medicine, Sibiu
2Dept. of Oncology, Sibiu County Hospital
The article presents the clinical observation of a 42-years old woman diagnosed with malignant thymoma stage III. The difficulties of diagnosing, the therapeutic strategy are emphasized. The patient receive three cycles of chemotherapy ADOC regimen and than radiotherapy at a dose of 60 Gy given in 30 fractions for six weeks followed by partial response. The article also contains data from published articles on the above mentioned topic.
Key word: Malignant thymoma, diagnosis, therapeutic strategy.
Radioterapie & Oncologie Medicală, 2001, 2:215-219