Prognostic factors in patients with carcinoma of the vulva--our own experience and literature review.

AIM OF THE STUDY: The objective was the analysis of prognostic factors and treatment outcomes of 104 patients with vulvar cancer, treated between 1990 and 2003 in the Center of Oncology, Maria Sklodowska-Curie Memorial Institute, Cracow, Poland. MATERIAL AND METHODS: The median age of patients was 67. Advanced disease (TNM III and IVA) was found in 54 (51.9%) patients and grade 2 and 2 in 50 (48.1%). Inguinal lymph nodes were clinically uni- or bilaterally involved in 40.4% of patients. Fifty-seven (54.8%) patients underwent radical vulvectomy with bilateral inguinal lymphadenectomy and 47 (45.2%) radical vulvectomy only. Cancer differentiation was well in 38 (36.2%) of patients, moderate in 38 (36.2%) and poor in 28 (36.6%). Adjuvant radiotherapy was applied in 30 (28.8%) cases. RESULTS: Five-year overall survival rate was observed in 44.4% of patients. Depending on TNM grade, 5-year OS rates were 61.4% for grade 1, 54.9% for grade 2, 40.1% for grade 3 and 13.3% for IVA. In patients aged < 70, 5-year OS rate was 54.7% compared to 30.5% for those > or = 70. Among patients with G1 cancer differentiation 64.4% survived five years, with G2 39.1% and with G3 24.9%, respectively. CONCLUSION: Univariate analysis revealed a statistically significant, unfavorable impact of age > or = 70, with G3 cancer differentiation, clinically confirmed inguinal lymph node involvement and TNM classification stage on 5-year overall survival. Cox multivariate analysis demonstrated that independent prognostic factors for 5-year survival were the age of the patient, clinical status of inguinal lymph nodes and TNM classification grade.

Significance of hypoxia in uterine cervical cancer. Multicentre study.

PURPOSE: The aim of the study was to evaluate hypoxia markers (VEGF, GLUT-1, and HIF-1alpha) in cervical cancer tissue depending on staging (FIGO) and grading. We also analyzed the adverse effects of radiotherapy according to expression levels of hypoxic markers in the studied tissue. MATERIAL AND METHODS: Expression of hypoxia-inducible factor-1alpha (HIF-1alpha), glucose transporter 1 (GLUT-1) and vascular endothelial growth factor (VEGF, also known as proangiogenic factor) were estimated in biopsy or surgical specimens from 106 patients diagnosed with uterine cervical cancer. Immunohistochemical methods with EbVision+ complex using monoclonal antibodies anti-VEGF and anti-HIF-1alpha and polyclonal antibody anti-GLUT-1 were applied. RESULTS AND CONCLUSIONS: Hypoxia features measured by percentage of cells undergoing reaction with antibodies anti-HIF-1alpha, anti-GLUT-1 and anti-VEGF were similar in all clinical stages; however the biggest hypoxia features were shown in low differentiated cancers G2 and G3. The 5-year survival for FIGO Stage III patients was shorter in cases with a high expression of hypoxic markers. We observed adverse effects in 45.3% of patients, which occurred more often in patients with higher expression of the studied factors. The presence of hypoxic cells is established as one of the most important factors affecting resistance against tumor radiotherapy and patient prognosis.

[Follow-up of 70 patients with advanced ovarian cancer after negative second-look laparotomy]. / Abstention thérapeutique dans les cancers ovariens avancés après laparotomie de second look négative.

OBJECTIVES: To analyze the results of treatment of 70 patients with stage III and IV ovarian cancer after second look laparotomy with negative findings and to identify causes of failure and prognostic factors. MATERIALS AND METHODS: Between 1985 and 1998, seventy patients with ovarian cancer stage III and IV were treated with surgery and at least six courses of chemotherapy with cisplatin doxarubicin and cyclophosphamide. Then a second look laparotomy was performed. RESULTS: The actuarial survival rate without evidence of disease was 50% at 5 years. Locoregional failure was observed in 31 patients (88%) and distant metastases in 9, but they were the sole reason for unsuccessful treatment in only 4 (12%). Adverse prognostic factors were: grade 3 differentiation, primary stage IIIC and IV, and residual infiltration exceeding 2 cm after first laparotomy. CONCLUSION: Our results are comparable with reports in the literature. The actuarial survival rate without evidence of disease at 5 years in patients with advanced ovarian cancer after second look negative laparotomy is 50%.

Biologically effective doses in radiotherapy of cervical carcinoma*.

Presented study evaluates biologically effective dose (BED) in patients receiving low-medium dose-rate (LDR/MDR) brachytherapy (BRT) plus external beam radiotherapy (XRT) based on tumor cell proliferation values in cancer of the cervix patients. This study includes 229 patients treated entirely by radiotherapy at the Centre Oncology in Krakow. Doses to Point A were estimated for total treatment for each brachytherapy insertion. BED3 were calculated for reference points in the rectum. The linear quadratic equation was used to calculate BED, which is proportional to log cell kill, and the normalized total dose (NTD), that is, equivalent to a 2 Gy fraction schedule. In BEDs 10 calculation overall treatment time for each patient. Tumor proliferation rate was based on Bromodeoxyuridine labeling index (BrdUrdLI) assessed on biopsy material before beginning the radiotherapy. Total BED at those points was summed for each patient. The medium overall treatment time was 90 days (range 30--210). The mean calculated total BED for point A for tumour and "early reactions" was equal to 104.0 Gy10 and 229.0 Gy3 for the rectum, equivalent to NTD=86.6 Gy and 137.4 Gy in 2 Gy fractions, respectively. Kaplan-Meier analysis revealed that age >50 years, higher than mean BRBEDs and totBEDs doses, gaps in treatments shorter than 40 days and disease free survival (DFS) was significant prognostic factor for overall survival. In the multivariate Cox anaysis age >50 years, BRBED10 >77 Gy and gaps ?40 days appeared to be significant for overall survival. None of the examined parameters was significant for tumor control. However, patients age and shorter gaps in the treatment were predictive for DFS.

[Results of a randomized prospective trial comparing postoperative abdominopelvic radiotherapy with postoperative chemotherapy in early ovarian cancer]. / Résultats d'un essai prospectif randomisé comparant une radiothérapie abdominopelvienne postopératoire et une chimiothérapie postopératoire dans les cancers de l'ovaire précoces.

PURPOSE: In a prospective randomized trial, our aim was to evaluate and compare the tolerance and efficacy of postoperative radiotherapy and chemotherapy in the treatment of early ovarian cancer. MATERIAL AND METHODS: Between 1990 and 1996, 150 patients with ovarian cancer stage IA, IB grades G2-3, and all patients classified IC and IIA, who did not have evidence of residual disease after surgery, were randomized to two treatment branches: radiotherapy or chemotherapy (CH). In the radiotherapy branch (76 patients), a whole abdomen irradiation of 30 Gy in 24 fractions over 5 weeks, with a pelvic boost to 50 Gy, was delivered. In the chemotherapy branch (74 patients), there were six series of polychemotherapy separated with 3-weeks interval. In each series patients received association of cisplatin (50 mg/m2, d1), adriamycin (50 mg/m2, d1) and cyclophosphamide (500 mg/m2, d1). RESULTS: The tolerance of the treatment was good and comparable in both groups. In the radiotherapy branch, three late grade G3 intestinal complications were observed (three bowel obstructions, which required surgery in two cases). The actuarial survival rate without evidence of disease was 81% at 5 years for both groups. In our series we found that histological grade had the strongest influence on survival prognosis; it was the only significant factor in a multivariate analysis. Patients with grade G3 tumors had the worst survival. CONCLUSION: These data suggest that efficacy of postoperative radiotherapy and chemotherapy administered to our patients with early ovarian cancer gave approximately identical results.

Pure immature teratoma of the ovary: analysis of 22 cases.

Between 1970 and 1991, 22 patients with pure immature teratoma were treated at the Center of Oncology in Krakow. Sixteen (72.7%) patients had stage I, four (18.2%) stage II, and two (9.1%) stage III of disease, nine (40.9%) patients had grade 1, 11 (50%) grade 2, and two (9.1%) grade 3 tumors. Eight stage Ia, grade 1 patients were treated with surgery only, the remaining 14 (63.6%) received postoperative chemotherapy. Five-year NED (no evidence of disease) survival was achieved in 81.8% of patients. Out of 16 stage I patients, 15 (93.8%) survived 5-year NED, out of six stage II and III, three (50%) patients only survived this period. We cured all grade 1 patients, and 81.8% (9/11) grade 2; two grade 3 patients died because of tumors. We also cured all six stage Ia patients, treated with unilateral salpingo-oophorectomy (with or without chemotherapy), and all eight stage Ia grade 1 patients treated with surgery only.

[Cervix neoplasms in women younger than 36 years of age]. / Rak szyjki macicy u kobiet ponizej 36 roku zycia.

Between 1970 and 1986, 252 women under 36 years of age with cervical carcinoma were treated in the Center of Oncology in Cracow. The five-year disease-free survival for all patients was 52.8%. In the multivariate analysis tumor stage IIB and III and the age under 30 years were adverse prognostic factors.

Argyrophilic nucleolar organizer regions, bromodeoxyuridine labelling index and DNA ploidy in squamous cell carcinoma of the uterine cervix.

There is increasing evidence that rapidly proliferating tumours, i.e. those with a high bromodeoxyuridine labelling index (BrdUrdLI), could benefit from an accelerated course of radiotherapy. Also, DNA ploidy may be a prognostic factor in term of patients survival. Thus, measurements of cell kinetics and DNA ploidy might become part of routine characterization of tumours before treatment. It is supposed, that a simple and cheap argyrophilic nucleolar organizer regions (AgNOR) test reflects the proliferative status of the tumour and correlates with BrdUrdLI. The BrdUrdLI, AgNOR test and DNA ploidy were assessed in 49 squamous cell carcinoma (SCC) of the cervix (stage II B-III B) and 5 normal epithelium. The number of NORs per cell nucleus, the mean AgNOR particle area and the total AgNOR area per cell were evaluated. Significant differences in the proliferative rate were found within the examined groups of tumours assessed by the BrdUrdLI and AgNOR test. The mean BrdUrdLI values were significantly lower in normal than in carcinomatous cells, while for AgNOR values this was true for stage III B only. The mean number of AgNORs and total AgNOR area per cell were not significantly higher at stage III B than at stage II B, respectively. A high DNA aneuploidy was found in the examined tumours: 78% in stage II B and 77% in stage III B of disease. The results of proliferative markers were not significantly different in diploid than in aneuploid tumours. A significant correlation (p < 0.0001) was found between the mean AgNOR values and BrdUrdLI, however the correlation coefficient was poor (r = 0.50). This was due to different fragments of the same tumours used in these tests. Therefore these techniques might be used as independent methods reflecting the proliferative rate of the tumour.