2011, Vol 9, No 4
Systemic treatment of HER2+ breast cancer patients. Part 1
CURR. GYNECOL. ONCOL. 2011, 9 (4), p. 227-237
ABSTRACT

In Poland, morbidity associated with breast cancer has been increasing over the past 40 years. Current advances in our understanding of breast cancer biology preclude considering this condition as a homogenous nosologic entity. Several subtypes of breast cancer: luminal A (ER+, PR+, HER2-), luminal B (ER+, PR+, HER2+), HER2-dependent (ER-, PR-, HER2+) and the so-called triple-negative or basic (ER-, PR-, HER2-) differ in clinical course and prognosis and require an individualized therapeutic approach. HER2 receptor is one of a family of human growth factor receptors. It may become expressed in different tissues, participating in growth and differentiation of cells. HER2 overexpression in breast cancer cells correlates with worse prognosis, but also enables implementation of targeted, anti-HER2 molecular therapies. As estimated, about 25% of breast tumors are HER2-positive and in these patients the use of “targeted” therapy should be considered. Therefore, at present, standard histological study of breast cancer should include immunohistochemical assessment of HER2 receptor expression. Patients with equivocal result of the IHC study (HER2 2+) require quantitative analysis of HER2 gene copies in cancer cells using the FISH technique. Only patients with HER2 receptor overexpression (HER2 3+) or HER2 gene amplification are candidates for targeted molecular treatment. The first drug of this kind is monoclonal antibody trastuzumab, binding with the HER2 receptor and blocking HER2-dependent intracellular processes, while triggering a cytotoxic cellular antibody-dependent immune reaction directed against cancer cells.

Keywords: HER receptor family, HER2 overexpression, HER2 gene amplification, prognostic factors in breast cancer, trastuzumab, antibody-dependent cellular cytotoxic reaction
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Systemic treatment of disseminated HER2-negative breast cancer
CURR. GYNECOL. ONCOL. 2011, 9 (4), p. 238-244
ABSTRACT

Breast cancer is the most frequent malignancy in the females and the main cause of malignancy-associated mortality. Patients with disseminated breast cancer are a heterogenous group and require different management strategies. This depends on several factors, first of all – tumor phenotype (steroid receptors), patient’s performance, dynamics of the neoplastic process, severity of symptoms and patient’s preferences. Treatment of disseminated breast cancer should include chemotherapy, hormonal therapy as well as supportive and symptomatic treatment. In patients with steroid receptors, low disease dynamics, localized lesions within soft tissues and bones, hormonal treatment should be considered in the first place. This type of therapy is based on antiestrogens (tamoxifen) as 1st line treatment in premenopausal women and tamoxifen or aromatase inhibitors in postmenopausal women; progestagens and fulvestrant are rarely administered. These classes of drugs are usually well tolerated and their toxicity is mild but variegated. Chemotherapy remains by far the most toxic modality and should be reserved for women with high dynamics of the disease, lack of steroid receptors, interstitial metastases or not responding to hormonal treatment. Cytostatics most effective against breast cancer include taxoids (docetaxel and paclitaxel), anthracycline-derived antibiotics (doxorubicin and epirubicin), vinorelbine and capecitabine. Usually, two-drug or three-drug protocols are administered, although sequenced monotherapy using particular drugs is also justified. Chemotherapy is associated with an elevated incidence of adverse events, thereof the commonest are nausea and vomiting, hair loss and bone marrow aplasia, resulting in neutropenia, anemia and thrombocytopenia. Every type of treatment of disseminated breast cancer requires close monitoring of both adverse effects and therapeutic response according to the RECIST criteria.

Keywords: breast cancer, metastatic disease, chemotherapy, hormone therapy, quality of life
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Role of Trivagin in restoration and maintenance of normal vaginal ecosystem in women treated for recurrent bacterial vaginosis
CURR. GYNECOL. ONCOL. 2011, 9 (4), p. 245-252
ABSTRACT

Physiologic vaginal bacterial flora is a dynamic balanced ecosystem encompassing microbes populating vaginal mucosa, products of their metabolism and secretions of vaginal glands. Normal composition of vaginal flora may be altered by pathogenic bacteria, fungi and yeasts, chemical factors, disturbed natural immune processes and also due to iatrogenic intervention, e.g. antibiotic therapy and surgical procedure. The aim of the present paper is to assess the role of Trivagin in restoring and maintaining normal vaginal flora in women with recurrent bacterial vaginosis (BV). Study population consisted of 60 women. Thereof, 30 women were patients with recurrent genital infections. Control group included randomly selected asymptomatic women. All patients underwent a standard gynecologic examination with assessment of vaginal secretion. Next, Trivagin has been administered for 20 days. Upon completion of treatment, vaginal secretion was re-assessed as direct sample study. Results obtained in both groups were compared. In the study population, signs and symptoms of BV resolved in 65% and subjective improvement was seen in 91% of the patients, according to the Amsel criteria. Conclusions: Trivagin promotes restoration and maintenance of physiologic vaginal flora in women with recurrent BV. Unique composition of the preparation (Lactobacillus rhamnosus, Lactobacillus gasseri, Lactobacillus fermentum, Lactobacillus plantarum) including species most frequently found in Polish females, enables an effective restoration of vaginal flora, while easy application by oral route significantly improves compliance and treatment outcomes.

Keywords: autologous hematopoietic stem cell transplantation, solid tumors, germ cell tumors, neuroblastoma, high-dose chemotherapy
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Treatment of steroid-resistant acute graft-versus-host diseas
CURR. GYNECOL. ONCOL. 2011, 9 (4), p. 253-263
ABSTRACT

Use of allogeneic hematopoietic stem cell transplantation is increasing continuously as a consequence of continuing progress of medical techniques, allowing implementation of this procedure even in patients where previously it was considered contraindicated. It is successfully used in the treatment of both several hematologic malignancies and other conditions. Still, a major concern remains the development of graft-versus-host disease (GvHD) as a complication of this kind of therapy. Treatment of choice in acute forms of stage II-IV GvHD are steroids (prednisolone, 1-2 mg/kg/d) combined with calcineurin inhibitors (cyclosporine A or tacrolimus). Steroid-resistant patients constitute a considerable therapeutic challenge, as they require enhanced immunosuppression. Standard management of these patients depends on experiences of particular center and usually an individual therapeutic strategy is warranted. No controlled clinical trials are available, documenting a favorable effect on survival of a particular salvage procedure in the setting of a steroid-resistant GvHD. In this situation, the following agents may be used: mycophenolate mofetil, methotrexate, pentostatin, mTOR inhibitors, anti-TNF-α and anti-IL-2 antibodies as well as mono- and polyclonal anti-T-lymphocyte antibodies. Non-pharmacological options include the use of extracorporeal photopheresis and infusion of allogeneic mesenchymal stem cells. In order to improve its effectiveness, salvage therapy should be instituted as quickly as possible, at best during the first 2 weeks after diagnosis of GvHD. Nevertheless, overall effectiveness and toxicity of most therapeutic modalities are far from satisfactory. Current research focuses on regulatory T-lymphocytes and small molecules affecting signal transmission between antigen-presenting cells and effector cells.

Keywords: acute graft-versus-host disease, salvage treatment, allogeneic hematopoietic stem cell transplantation, mesenchymal stem cells, extracorporeal photopheresis
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High dose rate brachytherapy in cervical cancer: an update
CURR. GYNECOL. ONCOL. 2011, 9 (4), p. 264-271
ABSTRACT

Selection of optimal treatment modality in a patient with cervical cancer depends on FIGO clinical stage. At stages IB2-IVA, the cornerstone of treatment is radiochemotherapy. As first step, patients undergo irradiation from external fields combined with chemotherapy (cisplatin, 40 mg/m2, QW). Brachytherapy is used as second-line treatment – an essential component thereof – enabling delivery of high dose of radiation to both genital organs and tumor. Quality of this treatment directly correlates with local control of the disease, long-term overall survival and quality of life of patients after completion of therapy. The paper presents current principles of high dose rate (HDR) brachytherapy in cervical cancer patients. Discussed are principles of two-dimensional (2D) planning, used to date in about 50% of brachytherapy centers worldwide, as well as three-dimensional (3D) magnetic resonance (MR)-based planning. As availability of MR in ours and many other oncology centers is limited, a computed tomography-based modification of gynecologic recommendations GIN GEC ESTRO has been suggested. Therapeutic areas are defined: high-risk clinical target volume (HR CTV) and intermediate risk clinical target volume (IR CTV) which may be safely contoured based on clinical exam and CT study, when no MRI is available. Acceptable doses for critical organs are listed. Based on own experience, indications and limitations for use of intraparenchymal (interstitial) and intracavitary applications were developed.

Keywords: cervical cancer, HDR brachytherapy, principles of treatment, 3D planning, computed tomographye treatment, allogeneic hematopoietic stem cell transplantation, mesenchymal stem cells, extracorporeal photopheresis
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Skin care during and after radiotherapy
CURR. GYNECOL. ONCOL. 2011, 9 (4), p. 272-275
ABSTRACT

Radiotherapy is, besides surgery and chemotherapy, an established modality in the treatment of breast cancer and genital malignancy in the females as well as prostate cancer in the males. Ionizing radiation may cause post-radiation dermatitis of varying severity. This may result in itching, pain, burning, epithelial exfoliation and inflammatory reaction, which may considerably compromise the patients’ quality of life during radiotherapy, sometimes even necessitating interruption of treatment. In view of such a serious side effect of radiotherapy, protection of irradiated skin and treatment of radiation-induced skin lesions are an important task, both for radiotherapists and for their patients. Preventive measures and treatment of radiation-induced skin reaction should begin on the first day of radiotherapy and continue for several (at least three) months after its termination. Non-compliance may result in exacerbation of radiation-induced lesions, longer healing of skin damaged by ionizing radiation and, in extreme cases, may lead to ulcerations, scars and skin necrosis. Effective care of skin areas exposed to radiotherapy includes wearing proper undergarments and dress, appropriate daily hygiene and avoidance of overheating. We recommend the use of proper dermocosmetics, which facilitate skin regeneration and accelerate healing, i.e. exerting a soothing, hydrating, nourishing, protecting and radiation-induced reaction-alleviating effects. This paper reviews current principles of care of irradiated skin – the key factor in prevention and treatment of radiation dermatitis.

Keywords: radiotherapy, radiation dermatitis, skin care, post-radiation skin reaction, dermocosmetics
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Desmoplastic small round cell tumor: characteristics and treatment options
CURR. GYNECOL. ONCOL. 2011, 9 (4), p. 276-282
ABSTRACT

Desmoplastic small round cell tumor (DSRCT) is an extremely rare malignancy rated among the sarcomas. It was first described in 1989. As there are only a few hundred cases reported in world literature, to date there are no uniform standards of management of patients presenting with such a diagnosis. This malignancy is characterized by a extremely aggressive clinical course. The disease affects mainly young males in their second and third decade. Most often described primary location of DSRCT is abdominal cavity. Identified cytogenetic marker of DSRCT is translocation t(11;22)(p13q12). Therapy relies in surgery, radiotherapy and chemotherapy. In spite of continuous progress in the treatment of DSRCT, prognosis in this group of patients is still very poor. High propensity to dissemination already at the time of first diagnosis considerably reduces the effectiveness of surgical excision and all patients require systemic treatment. Chemotherapy usually resorts to cyclophosphamide, doxorubicin, vincristine, ifosfamide and etoposide (their combination is known as “protocol P6”). Other cytostatics of confirmed effectiveness in the treatment of DSRCT are cisplatin, carboplatin, topotecan, vinorelbine and irinotecan. In spite of clear clinical activity of chemotherapeutics, eventually all patients develop resistance to implemented treatment and suffer disease progression. Therefore, selection of optimal treatment for this group of patients remains a considerable clinical challenge.

Keywords: desmoplastic small round cell tumor, symptoms, diagnosis, treatment, chemotherapy
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Tumor-related internal hemorrhage in late-stage post-chemotherapy cervical cancer patient: case report
CURR. GYNECOL. ONCOL. 2011, 9 (4), p. 283-288
ABSTRACT

Genital tract bleeding is among the most frequent and life-threatening complications of cervical cancer, potentially resulting in severe hemodynamic disturbances, including death. Bleeding may occur at any clinical stage, but is most frequent in women affected with late-stage tumor (FIGO stages IIIB-IVA). There are many literature reports of genital tract bleeding in patients treated by radio- or radiochemotherapy. The past decade provided a large body of evidence indicating high effectiveness of chemotherapy in both adjuvant and neoadjuvant treatment of patients with late-stage cervical cancer. Our experience with chemotherapy in the treatment of locally advanced tumors of various locations confirmed a risk of hemorrhagic complications, which are paradoxically a side effect of an otherwise favorable therapeutic response. The paper reports on an uncommon complication – internal hemorrhage in a patient with FIGO stage IV chemotherapy-treated cervical cancer. Based on this case discussed are conservative and surgical options for controlling genital tract hemorrhage. Prognosis in these patients is very poor; there is always a risk of hemorrhage, independent on treatment modality chosen. Management of internal hemorrhage in patients with genital malignancies poses a considerable challenge for surgeon’s expertise and requires an advanced technical support. The reported further case confirms the necessity of treating cervical cancer patients in multi-specialty centers.

Keywords: cervical cancer, genital tract bleeding, internal hemorrhage, chemotherapy complications, iliac vessel ligation
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