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.

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.

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. Irrespective of the DNA content and low proliferative activity the early stage carcinomas behaved aggressively as indicated by the presence of metastases, the DNA content of which corresponded in most of the cases with that of primary tumor. It appears that prediction of the tumor growth based only on cytogenetic and cytokinetic parameters may be connected with difficulties.

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. The study made on this tumor model has shown that serial polarographic pO2 determinations with suitable electrodes causing minimal trauma and providing consistent and reproductive data about changes in tumor microcirculation and oxygenation, may enlarge the scale of indicators of the radiation response.

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.

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. Twenty-eight patients had the tumor in the oropharynx, 1 in the hypopharynx, 1 in the oro- and hypopharynx and 4 in the oral cavity. There was a prevalence of advanced clinical stages. At present 25 of the patients are living, 21 of them without clinical symptoms of the disease. The skin reacted to irradiation only with a slight erythema and hyperpigmentation. Irradiation reactions in the oropharyngeal and oral mucosa were grave and were accompanied by significant subjective complaints. No post-irradiation complications were observed.

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. It was concluded that vascular density at least in cervical cancers of the stages studied can be a diagnostic parameter of a prognostic value as well as of a therapeutic usefulness.

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.

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.

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 +/- 5.0 ml/100g/min. but with progressing growth of tumors the rate of blood flow significantly decreased. In large tumors (14-day old) the mean rate of the blood flow was only 5.4 +/- 2.8. Our results demonstrate that this type of tumor, similarly as most of transplanted tumors are not well perfused and, that there is an inverse relationhip between the blood flow and the tumor size.

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.

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

Treatment failures were analysed in 43 head and neck cancer patients treated with a dynamic dose-fractionation in combination with breathing oxygen at ambient pressure. Infiltrative T3-4 lesions with necrosis showed poorer results than exophytic and necrosis-free infiltrative lesions. Possible differences in the oxygenation of the different types of lesion were considered to explain the results.

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. Exophytic type of tumors with relatively good vascularization appears to react better to the treatment then less vascularized endophytic tumors. For the evaluation of the possible role of the dynamic fractionation in these results collection of further data is needed.

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. Encouraging results obtained so far suggest that the new treatment can be accepted as a possible improved routine in the therapy of some cancer sites.

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. After successive daily irradiation with 2 X 1 Gy in 8 hours interval (without metronidazole) to the tumor dose 29 Gy, 5-day radiation free interval was inserted and then the identical treatment series was repeated to the total dose 60 Gy. Nausea and vomiting were the principal toxic symptoms which were rather severe in gynecological patients. The benefit of metronidazole combination was studied in comparison with a group of patients given dynamic dose-fractionation with breathing of oxygen only. Preliminary analysis of the data suggests that the combination with radiosensitizer has not produced an increase in the curability of cancer in these particular sites.

Variations in sensitivity of synchronized Chinese hamster cells to oxic and anoxic X-ray exposures.

V-79 Chinese hamster cells in monolayer cultures on glass surfaces were synchronized by treatment with hydroxyurea and exposed at different times thereafter to X-rays in the air or in oxygen-free argon. Survival determinations indicated that the oxygen enhancement ratio OER as expressed by the ratio of the respective D0 values varied over a narrow range in the different phases of the cell cycle. These changes resulted from cyclic alterations in both aerobic and anaerobic D0 values, and perhaps in n values.

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. The measurement of the kinetic parameters made immediately after irradiation with a whole-body single dose of 3 Gy (300 rad) showed an increase in duration of the cell cycle in the 5-day-old tumor, while in the 10-day-old tumor the cell cycle time was decreased due to reduce length in the G1 phase.