Variation of vascular density within and between tumors of the uterine cervix and its predictive value for radiotherapy.

Vascular density in different regions of a number of uterine cervix carcinomas was determined by morphometric analysis of stained histologic sections. Variance analysis indicated a larger inter- than intra-tumoral inhomogeneity of the vasculature, suggesting a certain individual vascularization pattern in these tumors. As indicated by a retrospective study of archival biopsies, this pattern has a predictive value in regard to the efficacy of radiotherapy.

Flow cytometric analysis of primary cervical and vulvar carcinomas and their metastases.

In a series of 25 patients with cervical carcinoma and 35 patients with vulvar carcinoma, clinically classified (FIGO) as Stage I and Ib, respectively, DNA ploidy and S-phase cell fraction were estimated in paraffin-embedded samples of the primary tumors and their metastases by means of flow cytometry (FCM). The two groups of patients were selected cases in whom lymph nodes removed at radical operation were histopathologically verified as metastatic ones. Prevailing part of primary tumors of both anatomic sites had diploid DNA content and low S-phase fraction.

Vascular density in carcinoma of the uterine cervix and its predictive value for radiotherapy.

The vascular density (VD) in stage-III tumors of the uterine cervix was determined by morphometric analysis of histologic, Masson-trichrome stained sections prepared from biopsies. In a retrospective study, VD was found to be related to results of radiotherapy, larger VD being associated with prolonged survival, in agreement with similar observations made earlier with stage-IB and -IIA tumors of the cervix. In a complementary study the variation of VD within tumors was investigated in relation to the variation between tumors using surgically removed cervical carcinomas in stage IB.

Prognostic significance of vascular density and a malignancy grading in radiation treated uterine cervix carcinoma.

In a retrospective study of 95 patients with squamous cell carcinoma of the uterine cervix (Stage IB, IIA, III) treated by radiation only, pretreatment biopsy material was used for assessment of the prognostic value of histopathological multifactorial malignancy grading and a morphometric estimation of vascular density in stroma. By comparison of the two systems, vascular density has been proved superior to malignancy grading with respect to prognostic value.

[Tumor vascularity: its possible prognostic and therapeutic value].

Three studies have been conducted in order to find out a correlation between the degree of tumor vascularization and local recurrences or the survival of patients after radiotherapy. The results have been reviewed. They show a better effect of radiotherapy in tumors with dense capillary vascularization than in tumors with poor vascularization.

Tumor vascularization, hypoxia, staging of tumors and radiocurability.

Retrospective, morphometric analysis of histological preparations from cervical cancers indicate that the stromal component of the neoplastic tissue is richer in vascular elements in the cases in which the patients have a prolonged survival after radiotherapy. The finding supports earlier observations which indicate a relationship between intercapillary distance and radiocurability of cervical cancers. The routine determination of a vascularity index V, denoting the grade of vascular density in the neoplastic tissue, is suggested as a complementary parameter for the classification of tumours.

A morphometric study of vascularization in uterine cervix cancers.

The stromal, parenchymal, and vascular cellular constituents were identified and their relative proportion determined in biopsy specimens derived from untreated uterine cervix carcinomas. In the stroma of the tumors that eventually responded well to radiation treatment resulting in a prolonged survival of the patients, the proportion of vascular cells was increased in comparison to the cases that were associated with a poor patient survival. The observations were interpreted in terms of the radiobiological oxygen effect reflecting the radiosensitivity variation of cells in tumor areas vascularized to varying extent.

Irradiation scheme using three daily fractions in the radiation therapy of pharyngeal and oral carcinomas.

A group of 34 patients were treated by irradiation using 3 daily fractions of 1 Gy each at 4 h intervals. The overall TD in all of the patients was 60 Gy administered within 26 days. The irradiation was carried out by telecurietherapy utilizing 60Co.

Prognostic significance of lymphocytic infiltration in radiation-treated uterine cervix carcinoma.

In a retrospective series of 45 patients with uterine cervix carcinoma Stage Ib and IIa who had been treated by radiation, biopsy material obtained prior to treatment was reevaluated for the presence of lymphocytic infiltration. The analysis based on 5 degrees of the intensity of stromal reaction has shown that the presence of lymphocytic infiltration, the intensity of which was significantly related to the proportion of blood vessels in stroma, was connected with a favorable outcome of treatment. The results suggest that vascular density being the determinant factor in oxygenation of the cancer tissue and its radiotherapeutic control may also play an important role in the immunological reaction against the tumor.

Dynamic dose-fractionation combined with oxygen breathing at ambient pressure and high-dose metronidazole in head and neck, and uterine cervix cancer.

The paper summarizes the results of dynamic dose-fractionation combined with oxygen breathing at ambient pressure and metronidazole in head and neck, and uterine cervix cancer. The patients were given high oral doses of metronidazole (5-6 g/m2) three hours before dose fractions (4.5 Gy for two days) initiating the radiation treatment series.

Oxygen tension and prediction of the radiation response. Polarographic study in human breast cancer.

Serial polarographic measurement of the tissue oxygen tension (pO2) was made in the course of fractionated irradiation (preoperative or sole treatment) of advanced breast cancer in 24 patients. In responsive tumors increase in pO2 appeared sooner before expressive tumor size reduction became noticeable. Repeated recording of unchanged pO2 values has proved to be a good prognostic indicator of local failure.

Vascularization and radiocurability in cancer of the uterine cervix. A retrospective study.

The proportion of vascular elements in relation to the parenchymal and stromal components was determined by morphometric analysis of the histologic preparations from biopsies of uterine cervix cancers. In all cases, the material was obtained from tumors in Stages Ib and IIa before any therapy was initiated. In the 23 cases in which radiation treatment of the lesions resulted in a survival longer than 5 years, the proportion of blood vessels in the neoplastic tissue was found to be larger, and especially the stromal components were richer in vascular elements than in the 22 cases in which survival was shorter than 5 years.

Radiation-induced changes in cell proliferation kinetics in uterine cervix cancer.

In vitro double labeling autoradiography for measuring the labeling index, duration of S phase and potential doubling time has been used to assess the effect of a single and fractionated test dose of irradiation in uterine cervix cancer applied in 21 patients. Tumor-labeling index fell significantly in those tumors which had a high labeling index before irradiation, and these cases were found later to exhibit a good radiation response. Duration of S phase which ranged between 9 and 27 hours prior to irradiation was increased.

Changes in blood flow of growing experimental tumor determined by the clearance of 133Xe.

133Xe clearance method has been employed for measurement of the blood flow in 6C3HED lymphosarcoma implanted in flank of C3H mice. In small tumors (9-day old) the mean rate of blood flow was 9.4 +/- 5.

Cytokinetic analysis at various ages of an ascites tumor after radiation.

A cytokinetic analysis has been made of 5-day and of 10-day old murine 6C3HED ascites lymphosarcoma (Gardner) by using a growth curve, percentage of labeled mitoses curves, and continuous labeling curves. The doubling time increased from 36 h in the proliferative phase of growth to 252h in the stationary phase. The slowing down of the growth rate was due to prolongation of the cell cycle time, with greatest extension in G1 and increased cell loss.

Cell proliferation kinetics and nuclear morphology in endometrial cancer under progesteron treatment.

Cell proliferation kinetics by using the double labeling with 3HTdR--14CTdR, and nuclear morphology were studied in 20 patients with endometrial cancer who were given progesteron as a preliminary therapeutic measure. Results of these studies indicate that we have to face the fact that in all histological types of endometrial cancer considerable variations in the amount of tumor cells undergoing secretory conversion occur due to the primary heterogeneity of the tumor cell population.

Results of dynamic dose-fractionation combined with breathing oxygen in comparison to conventional treatment in head and neck and uterine cervix cancer.

A dynamic dose-fractionation regime combined with breathing oxygen at ambient pressure was introduced in the treatment of head- and neck cancer, and uterine cervix cancer. The efficacy of the method was analyzed in relation to the results obtained by treating comparable cases with conventional fractionation regime. Final evaluation of the method will have to await the accumulation of further experience during a prolonged observation period.

The effect of repeated dose of x-irradiation on the progress of HeLa cells through the cell cycle.

In contradistinction to the increased fraction of HeLa S 3 cells in S phase after irradiation by a single dose in a range of 25--200 R, cultures irradiated by a second dose at time of morphologic restitution of mitotic activity exhibited decreased fraction of cells in S phase. The interpretation is that passage from G1 to S was reduced due to disturbances in subsystems which have not been fully repaired.

Preliminary analysis of failures in the radiotherapy of uterine cervix cancer with a dynamic dose-fractionation in combination with breathing oxygen at ambient pressure.

Complementary to a previous preliminary analysis of the results obtained in treating head and neck tumors, this paper summarizes observations in testing uterine cervix cancers with a dynamic dose-fractionation regime using Cobalt 60 radiation in combination with oxygen breathing at ambient pressure. A total of 30 cases in different stages are reviewed which had no treatment prior to radiotherapy. In agreement with previous observations, normal tissue reactions were decreased in comparison to those seen after conventional dose-fractionation.

The effect of anemia on the radiotherapy results of the uterine cervix cancer.

Relationship between hemoglobin level and survival and/or recurrence rate was studied in radiation treated group of postmenopausal women with uterine cervix carcinoma. The data suggest that anemia alters unfavorably the effectiveness of radiotherapy. A possible explanation of the lowered control rate is that due to deficiency of tissue oxygenation by reduced oxygen carriage proportion of hypoxic cells increases and impairs the radiosensitivity.