2011, Vol 9, No 3
Changes in the Treg lymphocyte population levels in patients being treated for ovarian cancer with chemotherapy
CURR. GYNECOL. ONCOL. 2011, 9 (3), p. 139-146
ABSTRACT

Regulatory T lymphocytes CD4+CD25+FOXP3+ or Treg cells play a major role in immune system surveillance and tolerance. Treg cells are critical for controlling the immunological system because they inhibit the cytotoxic response. Moreover, it has been found that Treg cell recruitment into the tumor microenvironment reduces the chances of survival in cancer patients and that an increase in Treg cells in the peripheral blood correlates with the progression of ovarian cancer. In our study we addressed Treg cell population changes in cases of ovarian cancer where the patients were treated with chemotherapy. Using flow cytometry we determined the levels of CD4+CD25+FOXP3+ lymphocytes in the peripheral blood of the patients prior to chemotherapy, after 3 courses of chemotherapy, and then after 6 courses (the respective regimens were: TK – 13, CP – 1, TPT – 1 patient). We observed that the Treg lymphocyte levels of ovarian cancer patients decreased after 3 courses of chemotherapy though the difference (p=0.3) was not statistically significant. After 6 chemotherapy courses, however, levels did increase to a statistically significant degree (p=0.02). We have therefore concluded that a measurement of the Treg cell population could be helpful in estimating the impact of chemotherapy on a patient’s host immune system during the systemic treatment of ovarian cancer.

Keywords: CD4+CD25+FOXP3+, Treg, ovarian cancer, chemotherapy, immune tolerance
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Treatment of advanced ovarian cancer: cost-effectiveness analysis
CURR. GYNECOL. ONCOL. 2011, 9 (3), p. 147-157
ABSTRACT

Aim of paper: Retrospective pharmacoeconomic cost-effectiveness analysis of treatment of patients with FIGO stage III-IV ovarian cancer using two protocols: cisplatin + paclitaxel (PT) or cisplatin + cyclophosphamide (PC). Material and methods: Analysis was based on medical records of 80 patients treated at the Center of Oncology in Bydgoszcz. The main criterion of therapeutic response was survival time over a 5-years’ follow-up period. Analyzed direct medical costs included: hospitalization, ambulatory treatment, diagnostic tests, drugs, radiotherapy, medical consultations and treatment of hematologic complications. The study focused on the following: pharmacoeconomic analysis of cost-effectiveness, incremental cost-effectiveness ratio and sensitivity analysis. Results: Cost of hospitalization was the major component of total cost of both treatment protocols (PT – 58% , PC – 56%). In the one-day setting, share of hospital costs was also similar in both cases (PT – 13.30%, PC – 13.49). Share of costs of pharmacotherapy and radiotherapy was 17.62% (PC) and 18.97% (PT). The least expensive were medical consultations and treatment of hematologic complications. The PT protocol was more effective but also more expensive, with mean total cost of treatment per patient 19 620.30 PLN and mean survival time 27.6 months. Mean cost of treatment per patient by the PC protocol was 18 700.26 PLN and mean survival time – 25.9 months. Incremental analysis revealed that additional cost of one month of survival (incremental coefficient of cost-effectiveness) when replacing protocol PC by PT is 541.20 PLN per patient. Conclusions: From the pharmacoeconomic point of view, use of the PT protocol in the treatment of advanced ovarian cancer is justified.

Keywords: cost-effectiveness analysis, pharmacoeconomics, treatment costs, ovarian cancer, chemotherapy
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Venous thromboembolic disease and gynecologic malignancy
CURR. GYNECOL. ONCOL. 2011, 9 (3), p. 158-168
ABSTRACT

Venous thromboembolism is a multifactorial disease and a frequent complication in patients affected with malignant tumors. The risk of venous thrombosis in oncologic patients increases seven-fold and is particularly high during the first few months after diagnosis. Molecular mechanisms of tumor – thrombosis correlation are relatively well known. Main factors responsible for hypercoagulation state are tissue factor and tumor procoagulant. Incidence of venous thromboembolic syndrome differs depending on location of the tumor, being the most frequent in gastrointestinal tumors of the mucous variety, lung cancer, ovarian cancer, endometrial cancer, breast cancer and leukemias. Among patients with gynecologic malignancy, thromboembolic complications usually coexist with ovarian cancer and endometrial cancer, as these are frequently of the adenomatous tumors of the mucous variety. Patients affected with gynecologic malignancy are at high-risk of thromboembolism not only because of the disease itself, but also due to the fact that pelvic surgery is the type of surgery second only to orthopedic procedures in terms of risk of thromboembolic complications. Furthermore, there are several common risk factors for gynecologic malignancies and venous thromboembolism. Thromboembolic complications significantly contribute to worsen the prognosis of oncologic patients. Standards of management should be developed concerning antithrombotic prevention in the group of patients with gynecologic malignancies at a particularly high risk of venous thromboembolism, as to date there is no consensus as to the optimal way of preventing these complications.

Keywords: venous thromboembolism, gynecologic malignancy, risk factors, complications, treatment
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Autologous hematopoietic cell transplantation in the treatment of solid tumors
CURR. GYNECOL. ONCOL. 2011, 9 (3), p. 169-185
ABSTRACT

High-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) has been used in the treatment of solid tumors since the ‘80s. Standard indications include breast cancer, ovarian cancer and germ cell tumors. Results of several phase II trials confirmed a beneficial effect of this therapeutic strategy on recurrence-free survival and total survival compared with conventional chemotherapy. Unfortunately, in most types of solid tumors, this effect has not been confirmed by phase III trials. Subsequently, the number of autologous transplantations in breast cancer decreased considerably. There is no evidence for any favorable effect of HDC in brain tumors and small cell lung cancer. According to 2006 EBMT recommendations, HDC followed by administration of hematopoietic cells is a therapeutic option in cases of therapy-resistant or recurrent primarily extragonadal germ cell tumors. A matter of debate is the use of this technique with similar indications in patients with germ cell tumors originating in the gonads. The first report on the effectiveness of HDC as first-line treatment of non-epithelial soft tissue tumors was by Pritchard et al. (1998). They documented improved event-free survival and total survival after administration of high doses of melphalan in children with stage IV neuroblastoma, achieving complete or very favorable partial remission after completed induction chemotherapy and surgical treatment. To date, neuroblastoma remains the only neoplasm, where randomized trials in children confirmed a favorable effect of transplantation of autologous hematopoietic cells on final treatment outcome.

Keywords: autologous hematopoietic stem cell transplantation, solid tumors, germ cell tumors, neuroblastoma, high-dose chemotherapy
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Sources of hematopoietic stem cells for transplantation
CURR. GYNECOL. ONCOL. 2011, 9 (3), p. 186-198
ABSTRACT

Bone marrow transplantation dates back to the ‘50s, but greatest progress in this therapeutic modality applied successfully in the treatment of several conditions took place mostly during the past 25 years. Among all organ transplantations, bone marrow transplants are second only to kidney transplants. In Poland this therapeutic technique also undergoes a rapid development. During the past 10 years, absolute numbers of various forms of transplantation increased 100-fold, starting from 6 procedures in 1989 to over 700 at present. Essentially, the term bone marrow transplantation (BMT), present in names of international associations and registers, is in fact a colloquialism (e.g. European Group for Blood and Marrow Transplantation). A much more appropriate term would be hematopoietic cell transplantation (HCT). This is because progenitor cells for transplantation may be obtained not only from bone marrow, but also from peripheral blood and umbilical cord blood. The term hematopoietic cell transplantation has a much broader meaning and includes: classic transplantation of bone marrow obtained at surgery, transplantation of peripheral blood stem cells (PBSCT) and umbilical cord blood-derived stem cells. All hematopoietic stem cells express on their surface the CD34+ antigen and glycosylated transmembrane protein, a member of the family of adhesion molecules. In healthy persons, expression of this antigen in bone marrow cells is at the level of 1-3%, while in peripheral blood – 0.01-0.1%, and in umbilical cord blood – 0.1-0.4%. The first source (transplantation material) of hematopoietic progenitor cells was bone marrow, while transplantation of stem cells obtained from peripheral blood and umbilical cord blood started much later (during the ‘80s of the past century).

Keywords: hematopoietic stem cells transplantation, bone marrow, peripheral blood, umbilical cord blood, mobilization of hematopoietic stem cells, growth factors
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Cervical adenocarcinoma with bilateral adnexal metastases
CURR. GYNECOL. ONCOL. 2011, 9 (3), p. 199-205
ABSTRACT

Cervical cancer is the second, after breast cancer, most frequent malignancy in the females worldwide. Annually, about 500 000 new cases are diagnosed and about 275 000 women die thereof. Most cases of cervical cancer are epithelial in origin, while only 15-35% are adenomatous. Recent epidemiological data indicate a gradually increasing incidence of adenocarcinoma with concomitant reduction planoepithelial cancer. The paper presents a case of a 50-year-old patient diagnosed with a cervical adenocarcinoma with bilateral adnexal metastases and concomitant ascites. Clinical signs and intraoperative findings initially suggested an ovarian cancer at FIGO stage IIIC. Based on histological studies, the final diagnosis of adenocarcinoma with adnexal metastases was made. Tumor metastases from the genitals usually originate from ovarian or endometrial cancer. Metastases from the cervical cancer are much less frequent. There are few publications dealing with this issue in the world literature. Furthermore, available papers provide widely divergent data concerning the incidence of metastases to the ovaries and oviducts. Some authors highlight the necessity to exclude the reverse situation – metastases of ovarian cancer to the uterine cervix. Such data only confirm complexity of this issue. Therefore we decided to present the following case report.

Keywords: cervical adenocarcinoma, adnexal metastases, complications, ascites, ovarian cancer, tumors
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Primary small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) in a young woman: case report, review of the literature and management options
CURR. GYNECOL. ONCOL. 2011, 9 (3), p. 206-215
ABSTRACT

Primary small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an extremely rare neoplasm of the neuroendocrine tumor (NET) family, diagnosed mainly in young women in their second and third decade. In 50-75% of the cases it coexists with mostly asymptomatic hypercalcemia. Due to highly non-specific and cryptic course, much like ovarian cancer, in about half of the cases it is detected in far-advanced clinical stages. Determination of final diagnosis is possible only after surgery, based on comprehensive microscopic and immunohistochemical studies. Management of a primary SCCOHT diagnosed in a 19-year-old woman is discussed in detail. Initial surgical treatment did not result in a correct histological diagnosis. The patient underwent combined treatment, including surgery and chemotherapy. Over 3 years’ follow-up, she has been operated on six-fold. Even using several protocols of adjuvant chemotherapy after surgery, consecutive recurrences of the disease could not be prevented. To date, no uniform management protocol has been developed, due mainly to great rarity of this tumor type and its extremely aggressive behavior. Advanced cases require aggressive surgical treatment, including hysterectomy with adnexectomy and omentectomy. Considerable clinical dilemma is posed by young women, who wish to preserve fertility. Some authors suggest that faced with such an aggressive tumor type, even in early-stage cases, preservation of fertility in young women should not be taken into account. In late-stage cases, cytoreduction is recommended. Adjuvant and neoadjuvant chemotherapy of the pulmonary type (cisplatin + etoposide) is an important part of the therapy. In view of very aggressive behavior of the tumor, selected cases may require high-dose chemotherapy with autologous stem cell rescue (HD-SCR) as first-line adjuvant treatment or, even more frequently, as consolidation treatment. In early-stage cases, great hope is associated with the use of adjuvant radiotherapy after surgery and chemotherapy. SCCOHT is a rare condition with an aggressive clinical course and poor prognosis, where treatment outcomes are still far from satisfactory. In spite of treatment, most patients die during the first two years. Inability to perform large-scale randomized trials results in lack of optimal and universally accepted management protocol. Close cooperation of highly specialized oncologic centers is necessary to promote our understanding of biology of this tumor type.

Keywords: small cell carcinoma of the ovary – hypercalcemic type, diagnosis, treatment, recurrence, prognosis
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