Influence of allogeneic blood transfusion on clinical outcome during radiotherapy for cancer of the uterine cervix

Anemia has long been reported to adversely affect the efficacy of radiation treatment in cervical cancer. On the basis of these findings, many radiation oncologists routinely use blood transfusions with the intent to maintain hemoglobin above specified levels during radiation therapy. However, allogeneic blood transfusions have been previously linked with biological and clinical phenomena correlated with immune suppression. In this study we have analyzed the effects of blood transfusion on the outcome of 130 patients with stage-IIB and -III cervical carcinomas treated with external radiation and intracavitary brachytherapy with or without concomitant platinum administration at the University of Arkansas for Medical Sciences between 1990 and 1999. With the exception of hemoglobin and hematocrit levels at the onset of treatment between the transfused and untransfused groups (p < 0.001), the distribution of age, histology, total radiation dose and duration of treatment were not significantly different between the 2 groups of stage-IIB and -III patients. Among the 45 stage-IIB patients who received blood during radiation treatment, there were 31 deaths (68.8%), compared with 14 (31.8%) among the 44 patients who did not receive blood (p > 0.05). Among the 30 stage-III patients who received blood during radiation treatment, there were 27 deaths (90%), compared with 6 (54%) among the 11 patients who did not receive blood (p > 0.11). In multivariate analysis of survival, there was a significant difference due to transfusion with a risk ratio (RR) of 2.6 (95% CI 1.6, 4.2; p < 0.001) after adjusting for no chemotherapy (RR = 2.2, 95% CI 1.4, 3.5; p < 0.001), considering all patients collectively, stage-IIB patients only (RR = 1.9, 95% CI 1.1, 3.3; p < 0.01), and stage-III patients only (RR = 3.2, 95% CI 1.2, 8.7; p < 0.02). These results suggest that routine blood transfusion of anemic cervical cancer patients does not improve outcome and may represent an independent variable predictive of diminished survival during primary radiation treatment for cervical cancer. Prospective randomized studies are strongly warranted to confirm this hypothesis.     

The prognostic implications of anaemia in the outcome of patients with early stages of uterine cervix carcinoma

 We studied the prognostic value of anaemia in the evolution of patients with early stages of uterine cervix cancer and treated with radical surgery. An observational study of 114 patients treated for cervical cancer at the ”La Fe” Maternity Hospital in Valencia (Spain) during the period 1971 to 1989. Survival analyses were carried out whereby both recurrence and mortality rates were considered. The level of haemoglobin influences the prognosis of the patients in the study presented, and explains a variation in the disease-free interval in correlation with that of tumour size. However, its influence on the survival interval proved to be somewhat less. Its predictive value is not diminished when associated with other important factors regarding the influence on patient evolution and is seen to be a protector variable against recurrence. Patients with haemoglobin levels of less than 13 gr/dl have a less favourable prognosis and this prognosis worsens still further when levels are lower than 12 gr/dl, which is more frequently the case in patients under 40 years of age and with a greater stromal invasion depth. The influence of haemoglobin levels is equally as important in its influence on prognosis and patient evolution as the volume of the tumour itself. The effect of this variable depends on both the clinical characteristics of the patients and the pathological characteristics of the tumour. Received: 17 October 2001 / Accepted: 28 December 2001     

Elevated lymphocyte ATP-ase activity in patients with cancer of the uterine cervix.

Elevated lymphocyte Adenosine Tri-Phosphatase (ATP-ase) activity was found in 23 och 28 patients with cervical uterine carcinomas of various stages. Treatment with external irradiation and radium insertion was followed by a decline in the lymphocyte ATP-ase activity in 22 patients, while the activity remained unchanged in one patient. No correlation between the tumour stage and the lymphocyte ATP-ase activity was demonstrated. In 24 patients the clinical effect of the treatment was well correlated with the decline in ATP-ase activity. It is suggested that the determination of lymphocyte ATP-ase activity could be valuable in screening for cervical carcinoma and for follow-up after radical treatment.     

Coexistence of metastatic neuroendocrine carcinoma of the uterine cervix with human immunodeficiency virus infection

Abstract. Balega J, Ulbright TM, Look KY. Coexistence of metastatic neuroendorcine carcinoma of the uterine cervix with human immunodeficiency virus infection.
Women now constitute 28% of new cases of human immunodeficiency virus (HIV) infection. Cervical cancer in HIV-infected women has a high recurrence and death rate, as well as decreased intervals to recurrence and death. Neuroendocrine carcinomas of the cervix are characterized by a high frequency of early nodal and distant metastases.
We present the first report of a neuroendocrine carcinoma of the cervix in an HIV-positive patient. A 28 year old with a 9-year history of HIV succumbed to metastatic neuroendocrine carcinoma of the cervix 5 months after diagnosis.
Given the aggressive nature of the cell type, an extended metastatic workup should be considered prior to surgery. The immune suppression present in HIV-positive patients with neuroendocrine cervical carcinoma may make such a workup particularly crucial, such that surgery is offered only to those who can be expected to benefit.     

Significance of total hysterectomy in uterine cervical cancer persistent in the uterine cervix after radiotherapy

Radiation therapy is an important means for treating advanced cases of cervical cancer. There are cases, however, in which cancer cells persist even after treatment has been completed. We in the Department of Gynecology at the Cancer Institute Hospital actively performed total hysterectomies in such patients with no distant metastases and no extension of the parametrial induration to the pelvic wall, and obtained favorable results. In the present study, the clinical stage, histological type, degree of removal of involved tissue, and relationship between the prognosis and the maximum diameter of the tumor in the extirpated uterus were examined in 28 patients with advanced cervical cancer treated during the thirty-year period from 1957 to 1986. The following results were obtained: 1. The clinical stage and histological type of the cancer prior to radiation therapy did not significantly affect the prognosis after total hysterectomy. 2. The 3-year survival rate for the patients in whom all involved tissue could be removed was 81.0 percent. In contrast, all those in whom complete removal was impossible survived less than 3 years, despite additional therapy. 3. Prognosis was better in the patients who had tumors with a maximum diameter of less than 2 cm than in those who had tumors with a maximum diameter of 2 cm or more (p less than 0.05). 4. Patients in whom all involved tissue could be removed and in whom the maximum diameter of the tumor was less than 2 cm had a good prognoses, with 88.9 percent surviving at least 3 years after surgery.     

Operative treatment of recurrent cancer of the uterine cervix after radiotherapy

During the period 1976-83, 47 women were operated on for recurrent or persistent cancer of the uterine cervix following initial radiation therapy. The operations performed were Wertheim's operation combined with dissection of the pelvic nodes, or some type of pelvic exenteration. With a 5-year survival of 31% in our material, surgical treatment of centrally located recurrences is a realistic possibility. We recommend an exenterative procedure as the operation is technically easier and the complications require less radical surgical treatment. The operation should only be done on narrow indications in the hope of achieving a cure, and the selection of patients must thus be stringent.     

Platelet-derived endothelial cell growth factor as a prognostic factor for radiotherapy outcome in patients with adenocarcinoma of the uterine cervix

OBJECTIVE: The aim of this study was to evaluate the platelet-derived endothelial cell growth factor (PD-ECGF) and VEGF expressions of tumor cells as prognostic factors for radiotherapy outcome in patients with adenocarcinoma of the uterine cervix. METHODS: In 47 formalin fixed, paraffin-embedded tissues from adenocarcinoma of the uterine cervix which had been treated with radiation (1970-1995), PD-ECGF and VEGF expressions were determined using immunohistochemistry, and the relationships between PD-ECGF or VEGF expressions and local control or survival were assessed. RESULTS: PD-ECGF and VEGF expressions were successfully detected in the cytoplasm and/or nucleus of adenocarcinoma cells of the uterine cervix. Of the 47 patients, 44.6 (21/47 cases) and 57.4% (27/47 cases) were positive for PD-ECGF and VEGF, respectively. There was no correlation between PD-ECGF or VEGF expressions and age, grade, or histologic subtypes. Stage and high expression of PD-ECGF showed a significant correlation to local control (P = 0.0025, P = 0.0057, respectively) and were significant independent prognostic factors for 5-year survival in multivariate analysis (P = 0.0039, P = 0.0032, respectively). CONCLUSION: This study demonstrated that PD-ECGF expression was a significant prognostic factor for radiotherapy outcome in patients with adenocarcinoma of the uterine cervix. Preradiation assessment of PD-ECGF expression may be helpful in selecting high-risk patients, providing them with opportunities to receive more sophisticated and individualized treatments.     

Human anti-murine antibody responses in ovarian cancer patients undergoing radioimmunotherapy with the murine monoclonal antibody OC-125

Human anti-murine antibody (HAMA) responses were monitored in 23 patients with recurrent or persistent epithelial ovarian carcinoma undergoing single-dose intraperitoneal radioimmunotherapy (RIT) with the murine monoclonal antibody OC-125. Sera of patients receiving escalating doses of OC-125 F(ab')2 (10-70 mg) radiolabeled with 18 to 141 mCi of iodine-131 were assayed for HAMA by a protein A-based radioimmunoassay. Overall, 70% of patients (16/23) developed HAMA within 10 to 46 days (median = 29) postinfusion, with peak values (23 +/- 6 to 325 +/- 10 micrograms/ml) at 32 to 102 days (median = 38). HAMA was undetectable prior to infusion in all cases and persisted up to 76 weeks. Of patients receiving a dose of 123 mCi or less, 80% (16/20) developed HAMA, whereas in the 140-mCi group, none of the three patients had detectable levels. Two patients in the 140-mCi group demonstrated dose-limiting bone marrow toxicity (severe thrombocytopenia and neutropenia). It is concluded that a single intraperitoneal dose of monoclonal antibody leads to a high incidence of HAMA production. The results also suggest that the likelihood of HAMA formation in patients who either had undergone recent chemotherapy or had received the highest dose of the radioimmunoconjugate is reduced. These observations may be of significance in designing multiple-dose therapy trials as HAMA has been demonstrated to decrease antibody-to-tumor binding and may potentially increase renal, hepatic, and hematologic toxicity associated with radioimmunotherapy.     

Hemostatic radiotherapy in carcinoma of the uterine cervix

Objective: To evaluate the treatment of hemorrhagic carcinoma of the uterine cervix with hemostatic radiotherapy (external and intracavitary radiotherapy). Method: Twenty cases of refractory hemorrhagic carcinoma of the uterine cervix receiving hemostatic radiotherapy between April 1987 and May 1992 were analyzed. The age of the patients ranged between 30 and 60 years with a median of 42 years. Results: The mean tumor volume was 130 mm³; all cases were classified as FIGO stage IIb (n = 8), IIIb (n = 11) or IVa (n = 1). Radiotherapy was carried out either by the external or intracavitary technique. The control of hemorrhage was 100% within 12–48 h after radiotherapy. However 85% of patients failed locally in the form of residual, recurrent pelvic or metastatic disease, within 24 months of follow-up. Conclusion:Hemorrhagic cervical cancer has a poor prognosis.