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.

Evidence of low-dose hyper-radiosensitivity in normal cells of cervix cancer patients?

The aim of the present study was to examine the low-dose radiation response of human normal cells using the micronucleus assay. Skin fibroblasts and keratinocytes derived from 40 cervix cancer patients were studied. After in vitro gamma irradiation with single doses ranging from 0.05 to 4 Gy, the fraction of binucleated cells with micronuclei was assessed. For each patient, the Linear-Quadratic (LQ) model and the Induced-Repair (IR) model were fitted over the whole data set (0.05-4 Gy). In conclusion, the present study showed some evidence of low-dose hypersensitivity in the fibroblasts of two patients and in the keratinocytes of four of the forty patients studied.

[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%.

The efficiency of treatment in patients with uterine-confined endometrial cancer.

AIM: To present our experience regarding the efficiency of treatment in patients with uterine-confined endometrial cancer. PATIENTS AND METHODS: 775 patients with uterine-confined endometrial cancer (UCEC) were treated between July 1985 and June 2000 in the Krakow Branch of Sklodowska Memorial Institute. RESULTS: Among the 775 patients, 5-year disease-free survival was observed in 82.8% patients; 96% patients with low risk of disease recurrence, 93.6% patients with intermediate risk and 78.3% patients with high risk survived five years with no evidence of disease. In the group with a high-risk disease recurrence rate, 5-year disease-free survival was statistically higher among patients treated with adjuvant brachytherapy plus external beam radiotherapy (EBRT) in comparison to patients treated with adjuvant brachytherapy (BRT) alone (82.4% vs 72.1%). CONCLUSIONS: The recommended treatment in patients with high and moderate differentiation of UCEC with FIGO Stage IA is surgery alone. Surgery with adjuvant EBRT in the group of patients with intermediate risk of cancer recurrence allows over 90% of patients to be cured. In the group of patients with a high risk of disease recurrence adjuvant BRT with EBRT is statistically more efficient in comparison to BRT alone.

Are stromal fibroblasts from cervical tumors suitable to predict normal tissue radiation reaction?

We examined the effect of gamma-irradiation (4 Gy) alone or combined with estrogen (17beta-estradiol 15 microM) treatment on the radiation response of stromal fibroblasts from cervical tumors. The fibroblasts were derived from tumors of 9 younger (<50 years) and 9 older (>50 years) cervical cancer patients. A normal fibroblast GSH+/+ cell strain was used as a reference cell. The end-points examined 2 days after irradiation were cell cycle distribution and apoptosis as measured of the cellular response to gamma-radiation. The response of examined fibroblast groups to gamma-rays alone was comparable but apoptotic death was more marked in fibroblasts derived from the younger patients with TNM 1+2 tumors than from the older ones. There was a considerable estrogen effect on the response to gamma-rays that differed between stromal fibroblasts from the examined age groups and was dependent on the tumor stage. In particular, we found a marked decrease in the number of apoptotic cells and debris after estrogen + irradiation, as compared to irradiation alone, only in younger patients and TNM 1+2 tumors. These results indicate that the response of stromal fibroblasts to gamma-rays to a considerable extent depends on donors age and tumor stage. Since stromal fibroblasts have been used for prediction of normal tissue late effects in patients treated with radiotherapy, we conclude that they may not be an adequate model for this purpose.

A ratio of apoptosis to mitosis, proliferation pattern and prediction of radiotherapy response in cervical carcinoma.

The prognostic significance of apoptotic (AI) and mitotic (MI) indices, and the ratio of these parameters (AI/MI), MIB-1 labeling index (MIB-1LI) and proliferation pattern was studied in 130 (FIGO stage IB-IIIB) squamous cervical cancer patients before radiotherapy. Also the influence of the patients age and tumors pathological features (stage, grade, degree of keratinization) and DNA ploidy on the biological parameters were analysed. AI and MI were assessed on histological sections stained with hematoxylin and eosin, and the MIB-1LI on specimens stained with rabbit anti-human Ki-67 antibody (DAKO Ltd). Sections stained with MIB-1 antibody were used for assessment of the tumor proliferation pattern. The median age of the patients was 55 years (29-80). The median values for MIB-1LI, AI, MI, AI/MI, were: 52.3%, 1.1%, 1.5, and 0.9, respectively. In the univariate analysis median values for cut-off points were used for MIB-1LI, and AI, however, for other parameters significant cut-off points have been chosen. For MI it was 2.6 and for the AI/MI ratio 0.7. The median time of follow-up was 29 months, with a range of 2-145 months. The univariate analysis showed that tumor stage (p=0.7009), grade (p=0.6660) and AI (p=0.9378) had negligible influence on patients survival. However, MI >2.6 (p=0.0442), AI/MI

[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.

Prognostic significance of pretherapeutic and therapeutic factors in patients with advanced cancer of the uterine cervix treated with radical radiotherapy alone.

The prognostic importance of various pretherapeutic and therapeutic factors was analysed in a group of 413 cervical cancer patients with stage IIB (183 pts) and IIIB (230 pts) treated with radical radiotherapy, which consisted of external irradiation and intracavitary brachytherapy. Univariate analysis of pretherapeutic factors revealed the prognostic significance of patient age, history of abortion, stage, haemoglobin and hematocrit levels. Five-year overall survival rate in stage IIB patients was 51%, in stage IIIB 40% and the respective rates for local control at each stage were 61%, and 46%. Univariate analysis of therapeutic factors showed that survival and local control rates increased with the dose, but a significant difference was found only in the case of a paracentral (point A) dose. In a multivariate analysis only patient age, abortions, and clinical stage appeared to have a significant and independent impact on survival. Linear regression analysis results indicated that prolongation of treatment time between 33 and 108 days caused a loss of local control of 0.36% per day.

[Adenoid cystic carcinoma of the breast. Analysis of 7 patients]. / Rak gruczolowo-torbielowaty gruczolu sutkowego. Analiza 7 chorych.

A retrospective analysis of 7 patients with adenoid cystic carcinoma of the breast operated at Center of Oncology in Kraków is presented. Ten years without evidence of disease survived 6 (85.7%) patients. One patient only, with poorly differentiated carcinoma, presented axillary metastases and died of metastases to the lungs and hepar.

Whole abdominal external beam radiation in the treatment of primary carcinoma of the fallopian tube.

Thirty-two patients with adenocarcinoma of the fallopian tube, treated between 1975 and 1990, were studied. Thirteen patients had stage I disease, 9 stage II, and 10 stage III. All patients underwent bilateral salpingo-oophorectomy, total abdominal hysterectomy, and subcolic omentectomy. All patients received postoperative primary whole abdominal external beam radiotherapy. Seventeen patients (53.1%) of the treated group survived NED for at least 5 years. Survival was 76.9% for stage I, 55.6% for stage II, and 20% for stage III. In the Cox multivariate analysis, two variables were independently related to survival: stage of disease and size of residual disease after surgery. Postoperative teleradiotherapy was totally ineffective in gross residual (>2 cm in diameter) disease (0% 5-year NED survivors) and not effective enough in small residual disease (<2 cm in diameter) (33% 5-year NED survivors). Despite postoperative whole abdominal external beam radiotherapy, 3 patients with microscopic, 4 with small, and 4 with gross residual disease did fail within the peritoneal cavity.

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.

[Primary fallopian tube carcinoma. Analysis of 32 cases]. / Pierwotny rak jajowodu. Analiza 32 przypadków.

A retrospective analysis of 32 patients with primary fallopian tube carcinoma treated at Center of Oncology in Kraków is presented. In all cases therapy consisted of primary total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by adjunctive radiotherapy. Five year without evidence of disease survived 53.1% of the patients. Stage of disease was the only prognostic factor: survival at 5 years was 76.9% for stage Io, 55.6% for stage IIo, and 20% for stage III.

[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.

Primary invasive vaginal carcinoma treated with radiotherapy: analysis of prognostic factors.

Between 1965 and 1988, 125 patients with primary invasive vaginal carcinoma were treated with radiation therapy at the Center of Oncology in Kraków. Twenty-two superficial stage I patients received radium or cesium intracavitary radiation alone. The remaining 11 patients with stage I disease whose lesions were either large or thick and 77 patients with stages II and III were treated with a combination of external irradiation followed by intracavitary brachytherapy. Fifteen patients with stage IVA received external irradiation only. Five-year NED survival was achieved in 42.4% of patients. In the Cox multivariate analysis three variable were independently related to beneficial survival: grade G1 + G2, stage I + II, and age below 60 years. Of 66 patients who died of vaginal cancer, locoregional failure was found in 51 (77.3%), locoregional and distant in 5 (7.6%), and distant only in 10 (15.1%) patients. Late radiation morbidity occurred in 16 (12.8%) patients.

[Teratoma of the ovary. Analysis of prognostic factors]. / Potworniaki jajnika. Analiza czynników rokowniczych.

Forty-one patients with teratoma of the ovary were operated in the Center of Oncology in Kraków. The five-year disease-free survival for all patients was 68.3%. The histological grading appear to be an important prognostic factor. The five-year disease-free survival for patients with grade 0 was 100%, grade I--80%, grade II and III--14.3%.

[Homogeneous dysgerminoma of the ovary. Analysis of 25 cases]. / Homogenne rozrodczaki jajnika. Analiza 25 przypadków.

Between 1972 and 1985, 25 patients with ovarian pure dysgerminoma were treated in the Center of Oncology in Cracow. In twenty-two (88%) patients total abdominal hysterectomy with bilateral salpingo-oophorectomy and postoperative radiotherapy was undertaken. Unilateral salpingo-oophorectomy alone was undertaken in 3 patients in stage IA. The five-year disease-free survival for all patients was 84%, for patients in stage IA degrees -- 100% (11/11), I degree -- 94.4% (17/18), II degrees and III degrees -- 57.1% (4/7).

[Breast cancer in women under the age of 35]. / Rak sutka u kobiet do 35 roku zycia.

A retrospective analysis of a group of 102 women younger than 36 years is reported. All patients were treated initially only surgically by Halsted or Patey mastectomy. Disease-free 10-year survival was noted in 39.2% of the patients. The effectiveness of the treatment proved to be the same in the group of women under and over the age 35. For all patients with breast cancer, despite their age, identical prognostic factors were observed.

External beam radiotherapy in the management of ovarian carcinoma.

Between 1970 and 1983, 345 patients with ovarian cancer clinical stage I, II, and III were irradiated postoperatively. Five-year NED survival was achieved in 41.7% of patients. The most important prognostic factors were histological grade and clinical stage of cancer. Postoperative external beam radiotherapy appeared to be highly efficient for the patients with microscopic residual disease, giving 70% 5-year survival, and moderately efficient for patients with small, i.e. < or = 3 cm in diameter residual disease, giving 40% 5-year survival. The optimal technique of irradiation appeared to be the irradiation given to the entire abdominal cavity with additional irradiation coned down to the pelvis. External beam radiotherapy was ineffective in patients with gross residual disease, i.e. > 3 cm in diameter, and useless as palliative treatment given to patients with inoperable cancer of the ovary.

Adjuvant progestagen therapy improves survival in patients with endometrial cancer after hysterectomy. Results of one-institutional prospective clinical trial.

A prospective study was conducted to determine the effectiveness of adjuvant hormonotherapy in endometrial cancer after surgery. Two hundred and five patients were randomly assigned to adjuvant progestagen treatment or were given no additional therapy. The follow-up was 5-years. We concluded that there was evidence of gain from adjuvant progestagen therapy in postoperative endometrial cancer. The group of patients who received progestagens had significantly longer survival than the control group without hormonotherapy (Logrank test; P < 0.001).

[Prognostic factors in patients with ovarian cancer]. / Czynniki rokownicze u chorych na raka jajnika.

350 patients with ovarian cancer were operated and irradiated postoperatively in the Center of Oncology in Kraków. 5-year survival with no recurrence was 41.7% (I.--77.3%, II.--44.1%, III.--7.7%). Stage, histological grade and residual volume tumor appears to be an important prognostic factors.