Adjuvant radiotherapy in carcinomas of the uterine cervix: the prognostic value of hemoglobin levels.

Anemia has been associated with a poorer treatment response and reduced survival in women undergoing primary radiotherapy (RT) or radiochemotherapy for advanced cervical carcinoma. This study aimed to determine the influence of anemia on outcome in patients with cervical carcinoma undergoing adjuvant RT. Medical records were reviewed for 183 cervical cancer patients who had received adjuvant RT because of risk factors after radical surgery (n= 109) or inadequate primary surgery (simple hysterectomy; n= 74). Kaplan-Meier and Cox regression analyses were used to study hemoglobin levels before and during adjuvant RT in relation to recurrence-free and overall survival. Hemoglobin values > or =11 g/dL were considered normal, while those <11 g/dL indicated anemia. Hemoglobin levels before RT influenced significantly overall survival and recurrence-free survival across the whole group (overall survival--log rank(all patients)= 7.5; df = 1; P= 0.006). However, subgroup analysis showed that the observed difference was mainly due to the group of women who had undergone inadequate primary surgery (overall survival--log rank(inadequate surgery)= 10.8; df = 1; P= 0.001). Multifactorial regression analyses comparing hemoglobin before RT with grading and tumor stage confirmed the prognostic value of hemoglobin values. Maintaining normal hemoglobin values before and during adjuvant RT seems to be important, especially in patients who have had inappropriate simple hysterectomy, which may resemble a therapeutic situation.

Role of dexamethasone dosage in combination with 5-HT3 antagonists for prophylaxis of acute chemotherapy-induced nausea and vomiting.

Dexamethasone (20 mg) or its equivalent in combination with 5-HT3 antagonists appears to be the gold-standard dose for antiemetic prophylaxis. Additional to concerns about the use of corticosteroids with respect to enhanced tumour growth or impaired killing of the tumour cells, there is evidence that high-dosage dexamethasone impairs the control of delayed nausea and emesis, whereas lower doses appear more beneficial. To come closer to the most adequate dose, we started a prospective, single-blind, randomized trial investigating additional dosage of 8 or 20 mg dexamethasone to tropisetron (Navoban), a 5-HT3 receptor antagonist, in cis-platinum-containing chemotherapy. After an interim analysis of 121 courses of chemotherapy in 69 patients, we have been unable to detect major differences between both treatment alternatives. High-dose dexamethasone (20 mg) had no advantage over medium-dose dexamethasone with respect to objective and subjective parameters of acute and delayed nausea and vomiting. In relation to concerns about the use of corticosteroids in non-haematological cancer chemotherapy, we suggest that 8 mg or its equivalent should be used in combination with 5-HT3 antagonists until further research proves otherwise.

Primary cancer of the fallopian tube. Treatment and results of 37 cases.

OBJECTIVE: A collective of 37 patients with primary cancer of the fallopian tube treated at the Gynecologic Clinic of the Justus Liebig University of Giessen, between 1976 and 1995 was retrospectively evaluated for stage, histo-pathology, treatment and results. PATIENTS: Median age was 61.5 years, FIGO stages: I 17 (45.9%), II 7 (18.9%,. III 12 (32.4%), and IV 1 (2.7%). Histopathology: adenocarcinoma 45.9%, papillary adenocarcinoma 27%, solid carcinoma 8.1%, undifferentiated carcinoma 5.4%, and others 13.6%. TREATMENT: 24 patients (64.9%) underwent complete bilateral salpingo-oophorectomy and hysterectomy (BSOH); 13 (35.1%) had incomplete surgery. POSTOPERATIVE TREATMENT: 31 patients (83.8%) had chemotherapy (since 1982 with platinum), 28 (75.7%) intraperitoneal radionuclides, 23 (62.2%) percutaneous irradiation, and 6 (16.2%) additional vaginal brachytherapy. RESULTS: The cumulative survival rates were 40% for the total of 37 patients, stage I 68%, stage II 29%, stage III 10%, stage IV 0%. From 1976 to 1985 the cumulative survival rate was 25%, from 1986 to 1995, 54%. Stage was a significant prognostic factor (p = 0.0001), surgery, age, chemotherapy and irradiation were not. Severe complications occurred in 7 patients (18.9%): 4 fistulas, 1 myelosuppression, 1 ileus, 1 peritonitis. CONCLUSION: Due to the long period of time and alterations in the mode of treatment the benefit of single treatment modalities could not be evaluated, but prognosis-dependent multimodality treatment (radical surgery, irradiation, platinum-containing chemotherapy) has resulted in higher 5-year survival rates for the last decade.

Does dexamethasone enhance the efficacy of alizapride in cis-platinum-induced delayed vomiting and nausea?

At the present time 5-HT3 antagonists in combination with corticosteroids represent the best prophylaxis and treatment of acute vomiting and nausea in highly emetogenic cancer chemotherapy. However, 24 h after chemotherapy 5-HT3 antagonists are no longer superior to benzamides for prevention of delayed symptoms. All recommendations for use of corticosteroids in delayed nausea and vomiting basically rely on one small study by Kris et al. [J Clin Oncol 1989;7:108-114]. Since the use of corticosteroids in cancer chemotherapy remains controversial, this single-blind, randomised, prospective trial was initiated to re-evaluate the benefits of corticosteroids during the days after chemotherapy. Thus patients treated for ovarian cancer received 5 mg tropisetron (Navoban) plus 20 mg dexamethasone for the prevention of acute vomiting and nausea in cis-platinum-containing chemotherapy (50 mg). Twenty-four hours after the beginning of chemotherapy 49 patients were randomised to receive 3 x 100 mg alizapride (Vergentan) plus a placebo medication (group A) and 47 patients to receive 3 x 100 mg alizapride plus 3 x 4 mg dexamethasone (group B) for 3 days depending on the incidence of acute vomiting beginning on day 2. The well-being of both groups was compared using objective and subjective parameters (Rotterdam Symptom Checklist). Major control of acute vomiting was achieved in 87.5% of the cases. The study was stopped after this interim analysis of 96 patients revealed no advantage of corticosteroids during the days after chemotherapy. Significant differences between both groups were detected only on a few days (day 6: objective nausea in favour of group A, day 4: objective vomiting in favour of group B, day 6: objective vomiting in favour of group A, day 3: constipation in favour of group A, days 4 and 5: difficulty concentrating in favour of group A, day 3: dry mouth in favour of group B). In contrast to acute nausea and vomiting the addition of corticosteroids is not beneficial in the prevention of delayed nausea and vomiting. Until better strategies are available the best prophylaxis of delayed symptoms is the control of acute nausea and vomiting using 5-HT3 antagonists plus corticosteroids. The use of benzamides has to be considered efficacious in the prevention of delayed vomiting and nausea.

Epicutaneous breast forms. A new system promises to improve body image after mastectomy.

Mastectomies will remain a treatment alternative for breast cancer in spite of efforts to perform more breast-conserving treatment. Restoration of body symmetry may then be an important issue, which can be achieved by surgical breast reconstruction or with an epicutaneous breast prosthesis. A new improved system has recently been developed, which is self-adhesive to the thorax wall. In this study we investigated the advantages and disadvantages of the new system. The body image of 55 patients after unilateral mastectomy was assessed before they entered the study and after approximately 6 months of experience with the system. The "Frankfurter Körperkonzeptskalen" plus additional questions concerning problems after mastectomy and the handling of the new breast form were used for the assessment. About 50% of the patients had problems with the adhesiveness of the breast form, which remains a problem to be solved. Patients who suffered badly from mastectomy, have a smooth and plane mastectomy scar, and who were not suffering from hot flushes, which can impair the adhesiveness of the prosthesis, were more likely to profit from the new self-supporting breast forms. Significant differences were observed in the scales "self-acceptance of the body", acceptance of the body by others" for the subsets of patients mentioned above. The differences were less pronounced in patients who were already familiar with another type of epicutaneous breast form, which is attached to an adhesive plate on the thorax wall by nylon touch and close fasteners. Most (90.7%) of the patients would recommend this new type of breast prosthesis for other patients with mastectomy. The concept of self-supporting breast forms is an improvement with respect to social and psychological rehabilitation. According to the manufacturer, the problem with adhesion has meanwhile been solved.

[Violations of chemotherapy protocols for ovarian cancer--reasons and consequences]. / Verletzungen des Therapieplans und des Chemotherapieprotokolls beim Ovarialkarzinom--Gründe und Konsequenzen.

In times when colony-stimulating factors were not available, delays of treatment or dose reductions were necessary, to assure that chemotherapy could be safely administered. In a retrospective analysis the effects of chemotherapy protocol violations on the survival of patients with ovarian cancer was evaluated. The serial courses of leukocyte counts were often the determinants for a protocol adequate chemotherapy in contrary to the thrombocytes but the serial platelet counts had no influence on protocol violations. Only time-related protocol violations have been found in 7.6% of the cases. There seems to be no apparent influence on patients' survival. However, accomplishment of treatment schedules, which may be regarded as a reaction towards unsatisfactory tumour response, at the initial visit alone or in combination with time-related protocol violations as well as tumour stage, course of tumour markers (CA 125) had a strong impact on survival while higher dosage levels produces only a trend towards improved survival. The use of growth factors will probably reduce the percentage of protocol violations caused by neutropenia, but it is questionable if it will reduce mortality due to tumour progression.

Changes in self-concept and body image during alopecia induced cancer chemotherapy.

Alopecia as a result of cancer chemotherapy has been reported to cause changes to the self-concept and body image. In a prospective longitudinal study, self-concept and body image were analysed in 29 patients after histological confirmation of gynaecological malignancy, mainly ovarian cancer, who were assigned to receive a complete-alopecia-inducing PEC combination chemotherapy (cisplatin 50 mg/m2, epirubicin 60 mg/m2, and cyclophosphamide 500 mg/m2 in 1 day every 28 days). The analysis was performed before the commencement of treatment and repeated when alopoecia was complete and after completion of therapy when patients had already experienced regrowth of hair, using the Frankfurt self-concept scales (FSKN) and Frankfurt body concept scales (FKKS). Significant differences were observed in the various evaluation scales FSAP (general ability to solve problems), FSSW (general self-esteem), SGKB (state of health), and SKEF (physical fitness). For all scales the results worsened during chemotherapy but did not return to normal or improve when patients experienced regrowth of hair. It was found that 73.3% of the patients did not feel as self-confident as before treatment and that for 46.6% alopecia was the most traumatic side effect of chemotherapy. Since there is no chemotherapeutic regimen or any other effective treatment that can prevent alopecia, either of the following conclusions can be drawn: the observed differences may not be related exclusively to alopecia, but also associated with coping processes initiated by chemotherapy and perhaps enhanced by alopecia; or the changes persist even after the discontinuation of chemotherapy. Regrowth of hair and other adaptive processes do not normalize or improve the impaired body image and self-concept.

Serum CA 125 levels and survival in advanced ovarian cancer.

We made a retrospective analysis of 85 patients with elevated serum CA 125 after surgery for ovarian cancer. Absolute CA 125 serum levels were a poor guide to prognosis. However, the ratio between the serum CA 125 after the first, second, or third course of treatment and the postoperative value was an excellent guide to prognosis. These were also independent and stable in the Cox Regression analysis.

[The behavior of the activation parameters of plasma coagulation under HDR-afterloading therapy in patients with endometrial carcinoma]. / Verhalten der Aktivierungsparameter der plasmatischen Gerinnung unter HDR-Afterloading-Therapie bei Patientinnen mit Endometriumkarzinom.

BACKGROUND: In the radium era heparin prophylaxis was necessary to avoid thromboembolic events. Today with high-dose-rate (HDR) afterloading thromboembolic events are rare. Coagulation activation parameters were monitored during HDR afterloading to evaluate the necessity of heparin prophylaxis. PATIENTS AND METHODS: Twenty patients with uterine carcinoma and no postoperative tumor residuals were randomized before their first 10 Gy OD HDR-afterloading application. Ten patients received heparin prophylaxis, the other ten patients received no prophylaxis. Blood samples were taken before, immediately after, 6 and 24 hours after HDR afterloading. D-Dimer, TAT, and F 1 + 2 were measured. RESULTS: No significant activation of the coagulation system was observed over the investigated time period and no differences have been detected between both groups. None of the patients of either group developed thromboembolic complications. CONCLUSIONS: HDR afterloading has no direct influence on the plasmatic coagulation system. From this point of view heparin prophylaxis does not seem necessary.

Unconventional cancer therapy--survey of patients with gynaecological malignancy.

Although the benefits remain unproven, a considerable number of cancer patients use unconventional therapy, in many cases without the knowledge of the oncologist. At the oncological out-patient department of the women's clinic of the Justus-Liebig-University Giessen we conducted a survey of the various unconventional methods used. 38.8% (80/206) of the patients used unconventional therapies, mainly mistletoe extracts (50%), trace minerals (46%), megavitamins (39%), and enzymes (22%). The perceived etiology of cancer determined the choice for the various methods (p = 0.00074). Users of unconventional methods suffered significantly more from conventional therapy, had less faith in their doctors, and felt more nervous and emotionally unstable after the diagnosis of "cancer".

Radio-chemotherapeutic treatment of advanced ovarian cancer.

BACKGROUND: The role of irradiation seems to be not very important in the post-operative treatment of cancer of the ovaries compared to chemotherapy although it has proved to be highly effective. MATERIALS AND METHODS: In a retrospective study 37 patients with advanced cancer of the ovaries Stages IIIb and IIIc (FIGO) undergoing post-operative consecutive radio-chemotherapy consisting of two series of whole abdominal radiation (WAR) applied in sandwich technique with 6 courses of cisplatin-epirubicin-cyclophosphamide (PEC) were evaluated. For the effectiveness of WAR and PEC-chemotherapy changes of CA 125 serum levels were noted. RESULTS: Both WAR and PEC-chemotherapy proved to be effective in 50.5% of the patients, either WAR and PEC-chemotherapy were effective in 16.2% neither one affected the course of disease in 8.1%. Statistical analysis shows a good correlation between the effectiveness of WAR and survival but no such correlation as to the effectiveness of PEC-chemotherapy. CONCLUSION: The role of irradiation in the treatment of ovarian cancer is underestimated. The addition of WAR at the beginning of the post-operative treatment can prolong the survival time in advanced stages of ovarian cancer.

Serum levels of squamous cell carcinoma antigen and ovarian carcinoma antigen (CA 125) in patients with benign and malignant diseases of the uterine cervix.

In the present study we evaluated the clinical usefulness of the tumor antigens, squamous cell carcinoma antigen (SCC) and ovarian carcinoma antigen (CA 125), in populations of patients with benign and malignant cervical disease. SCC and CA 125 levels were determined in the serum of 59 patients with invasive carcinoma of the uterine cervix and in 21 patients with benign cervical diseases. Before treatment of cervical cancer, SCC levels were elevated in 63% of the patients with squamous cell cancer while all 5 patients with adenocarcinoma had normal levels. CA 125 levels were elevated in 21% of the patients with cervical squamous cell cancer and in 3 of the 5 cases of adenocarcinoma of the cervix. In patients with benign cervical diseases, only 1 had a positive SCC level and none were positive for CA 125. No correlation was found between SCC levels and histological differentiation or clinical stage. In positive patients, serial SCC determinations correlated with the clinical course in 72.2%. Increasing levels were always associated with progression and increased on average 3 months before there was clinical evidence for disease progression. It is concluded from these studies that SCC levels are a useful marker for cervical cancer progression and recurrence. Levels of CA 125 were more likely to be elevated in patients with adenocarcinoma than squamous cell carcinoma, but when elevated in these latter patients, it also tended to predict tumor recurrence.

[Ovarian carcinoma antigen (CA 125) and ovarian cancer (clinical follow-up and prognostic studies)]. / Ovarium carcinoma antigén (CA 125) és a petefészekrák. (Klinikai ellenörzö és prognosztikai vizsgálatok).

Serum concentrations of ovarian carcinoma antigen (CA 125) were determined by Abbot CA 125-EIA Monoclonal kit from 66 patients with malignant ovarian tumor. The preoperative serum levels of CA 125 were elevated (> 35.0 IU/ml) in 93% (27/29). After the laparotomy and before the irradiation or chemotherapy in 36% (24/36) of patients had elevated levels. No significant correlation was seen between elevated levels and histology, tumor grade and clinical stage. However, the rate of positive cases were significantly higher in advanced stages than in the 1st stage (p < 0.05). No significant correlation was found between the preoperative levels of CA 125 and the clinical course. The postoperative elevated levels indicated bad prognosis. Good conformity was found between CA 125 levels and the therapy response. Serological follow up revealed a correlation with the clinical course of ovarian carcinoma in 84% (44/52). In patients with tumor progression the CA 125 levels increased before clinical signs of progression with median lead time of 97 days. The second look laparotomy proved, that residual tumor larger than 2 cm of diameter cause elevated levels. Smaller tumors remained marker negatives. CA 125 determination before operation, during and after therapy provide a useful tool in detecting progression and persistence of ovarian carcinoma.

[Significance of determination of squamous cell carcinoma antigen in the follow up of patients with cancer of the uterine cervix]. / Squamosus sejtes carcinoma antigén vizsgálatának jelentösége cervix carcinomás betegek ellenörzése során.

The serum concentrations of squamous cell carcinoma antigen (SCC) were determined in 59 patients with invasive carcinoma of the uterine cervix, in 21 patients with benign cervical diseases. Pretherapeutic SCC levels were elevated (> 2.5 ng/ml) in 63% (34/54) of the patients with squamous cervical carcinoma. 5 patients with adenomatosus cervical carcinoma had not elevated levels. In 21 patients with benign cervical diseases, 4.8% (1/21) of SCC values were above the normal range. There were no correlation of SCC levels and the degree of the histological differentiation or clinical stages. Serial SCC determinations revealed a correlation with the clinical course of disease in 72.2% (26/36) with squamous cervical carcinoma. Rising levels were always associated with progression. The SCC level increased before clinical signs of progression with a median lead time of 3 months. Patients with cervical adenocarcinoma for follow up CA 125 determination was recommended. The determination of SCC is a useful tool checking the patients, detecting early progression of squamous cervical tumor.

[Immunologic studies in patients with ovarian carcinoma during radio-chemotherapy. I. Studies of lymphocyte subpopulations]. / Immunologische Untersuchungen bei Patientinnen mit Ovarialkarzinom unter Radio-Chemotherapie. Mitteilung I: Untersuchungen der Lymphozytensubpopulationen.

In this article we have studied the behaviours of different lymphocyte subpopulations (T11, T8, T4, B4 and B1) in the peripheral blood of 60 patients suffering from ovarian cancer during radio- and chemotherapy with the APAAP-technique. The most important results of our study are that compared with the chemotherapy the radiotherapy causes greater lymphocyte depression, that the subpopulations of T-lymphocyte with the exception of T8 show greater radio-sensitivities than B-lymphocyte, that T8-subpopulation is not radio-sensitive, and that the T11-, T4-, B4- and B1-subpopulations of the patients at stage I and II can recover from the depression caused by radiation much better than the corresponding subpopulations of the patients at stage III and IV.

Initial experience with placental protein 4 (PP-4) as tumor marker in cervical and endometrial cancer.

PP-4, a recently characterized glycoprotein from human placenta was studied using a specific double-antibody radioimmunoassay in sera of 130 volunteers, 74 cervical cancer patients and 43 endometrial cancer patients. Elevated levels (greater than 3 micrograms/l) were found in 35 (47.3%) cervical cancer patients and in 18 (41.9%) endometrial cancer patients. Degree of elevation were not correlated with clinical stage, histology, and histological degree of differentiation. 36 patients with cervical cancer and 20 patients with endometrial cancer were monitored on two to seven occasions during four to 50 weeks. Rising, remaining unchanged of falling levels of PP-4 correlated with progression, stabilization or regression of disease 55.5% in patients with cervical and 65.0% in patients with endometrial cancer. During and some months after external telecobalt irradiation therapy wide range of PP-4 levels were observed in some patients. The study suggest that PP-4 can be regarded as a tumor associated protein which most likely can serve as tumor marker in cervical and endometrial cancer.