Principles of chemotherapy and radiotherapy

Radiotherapy and chemotherapy are both widely used in the management of gynaecological malignancy. The reasons why tumours are destroyed and normal tissues recover after radiotherapy are complex and poorly understood. Therapeutic effects depend on differences in intrinsic radiosensitivity and the ability to repair and repopulate between normal and malignant tissue. Some tumours contain hypoxic cells, which are a source of radioresistance. At present, most radiotherapy treatments are carried out using a linear accelerator, which produces ‘skin sparing’ radiation and can treat deep-seated tumours. Brachytherapy (short-distance treatment) with implanted or internal radiation sources can also be used, and is an essential part of the radical radiotherapy for cervical carcinoma. Chemotherapeutic agents currently in use are cytotoxic and affect both normal and malignant cells. Side-effects include bone marrow suppression, nausea and vomiting, epilation, renal, cardiac and neurotoxicity. Ideally, agents with different mechanisms of action should be given in combination to overcome potential drug resistance. Multiple drugs should have differing patterns of toxicity so the highest tolerable doses can be given. Chemotherapy can also be given concurrently with radiotherapy to enhance the therapeutic effect. As most gynaecological chemotherapy treatments are palliative, patients should be selected with great care; the possible benefits of the treatment must be balanced against the risk of side-effects.     

Principles of chemotherapy and radiotherapy

The management of most malignancies is multidisciplinary with chemotherapy and radiotherapy widely employed. The reasons tumours are destroyed and normal tissues recover after radiotherapy are complex and thought to be due to differences in intrinsic radiosensitivity and ability to repair and repopulate. Linear accelerators, which produce “skin-sparing” photons (high energy X-rays), are used to treat deep-seated tumours. Brachytherapy (short distance treatment) with implanted or internal radiation sources can also be used.Chemotherapy consists of drugs of different classes and modes of action, which may be used in combination to prevent drug resistance. Cytotoxic agents affect normal and malignant cells leading to a variety of side-effects. Chemotherapy can be given with radiotherapy to enhance the therapeutic effect. With advances in the understanding of the molecular biology of cancer, targeted therapies are now being used in clinical practice. Chemotherapy can be used with curative or palliative intent.     

Restaging in gynaecological cancers

Regardless of recent technical developments in the scientific arena, stage is still the most important prognostic factor in gynaecological cancers. Surgical staging is performed in all types of gynaecologic cancers except for cervical cancer. Adjuvant therapies that contribute to survival are planned in the light of information obtained from staging procedures. Therefore, necessary information for further therapeutic management should be revealed by the end of surgical staging. A staging surgery that is not completed for any reason will not only deprive the patient of necessary treatments, but can also cause administration of unnecessary adjuvant treatments. This is especially important, given the undesired effects and cost of both chemotherapy and radiotherapy. A particularly relevant case in point is tumours that look like early stage; this is because upstaging up to 30% has been reported in ovarian and endometrial cancers. As for vulvar cancer, clinical staging has been reported to lead to about 15% over-diagnosis in comparison to surgical staging. Thus, the first step in all gynaecological cancers, except cervical cancer, should be to perform surgical staging when possible and unveil all surgical-pathological prognostic factors in the light of data obtained. Accordingly, restaging surgery should be considered in all cases that had incomplete staging. However, care should be taken to evaluate the benefits to be reaped together with the operative morbidity risk associated with the restaging procedure. This will both ensure accurate planning of postoperative treatment and provide a universal standard of approaching cancer patients and their treatments.     

Psychosexual function and impact of gynaecological cancer

A diagnosis of gynaecological cancer and its treatment are usually associated with many physical and psychological changes, both as a result of the diagnosis itself and of the usual treatments of surgery, radiotherapy and/or several months of chemotherapy. Patients often experience symptoms such as fatigue, abdominal swelling and pain, and suffer from emotional distress and disturbances of their life style. Sexual functioning can also be affected. Often there are physiological difficulties, such as vaginal dryness, together with psychological distress and relationship problems. This chapter discusses the ways in which gynaecological cancer can impact sexual functioning, and presents findings from a research project that was undertaken to begin to understand how sexual functioning can be affected by ovarian cancer. The article also makes recommendations for how health-care professionals can help women to cope better with psychosexual dysfunction following a diagnosis of a gynaecological cancer.     

Herz-Lungen-Probleme bei und nach gynäkologisch-onkologischer Therapie

Gynaecological tumours frequently involve the heart and lung because of their closeness to the intrathoracic structures and the required toxic therapy. Under chemotherapy, particularly with Trastuzumab, heart failure leads the adverse effects. With radiotherapy, up to 60% of patients experience lung injury, but fewer have coronary vascular alterations. Another cause for reduced lung function are pleural effusions induced by gynaecological cancers. Taking this into consideration, evaluation of cardiac and pulmonary function is necessary both preoperatively and concomitant with chemotherapy and radiotherapy.     

Ovarian,fallopian tube and primary peritoneal cancer: an overview

Ovarian, fallopian tube and primary peritoneal cancer has the poorest survival outcomes of all gynaecological malignancies. The majority of women present with advanced stage, high grade disease following a period of generalized abdominal symptoms. There is currently no effective screening programme. Diagnosis is based on imaging and histology. Stratification of adnexal masses into benign and malignant categories has helped ensure patients are appropriately referred to the gynaecology oncology team. The mainstay of treatment is both surgery and chemotherapy, with removal of all residual disease being one of the most important prognostic factors. Recent advances in targeted therapies are also beginning to improve outcomes.Less common types of ovarian cancer, such as sex-cord stromal tumours and germ cell tumours are generally found to affect younger women and have an improved prognosis. They present with early stage disease, are amenable to fertility-sparing surgery and, in the case of germ-cell tumours, are often exquisitely chemotherapy sensitive.     

Oncologic and reproductive outcome after fertility-saving surgery in ovarian cancer

The rate of ovarian tumour diagnosis in reproductive age woman has increased parallel to the improvements in diagnostic methods and regular gynaecological visits. Because of this organ saving surgical procedures for the preservation of reproductive and endocrine functions have gained more interest. Conservative surgical approaches for ovarian tumours after surgical staging include cystectomy, unilateral salpingo-oophorectomy and unilateral salpingo-oophorectomy plus contralateral cystectomy. Ovarian tumours diagnosed in young ages tend to be low-stage low-grade malignancies. This not only enables but also necessitates preserving the fertility of women who have not completed their family. In invasive ovarian cancer, fertility saving surgery is confined to early-stage and low-grade disease. But, it also had been reported in advanced stages (up to Stage IIIc). Candidates for those procedures were selected according to the FIGO stage, grade, ploidy state, histological subtypes and patients' desire. Adjuvant chemotherapy is necessary for high-risk patients. The rate of recurrence following conservative and radical surgical procedures in low-stage and low-grade tumours are 9% and 11.6%, respectively; and disease-free and overall survival rates do not differ significantly. Prognosis of borderline ovarian tumours is excellent. Five and 20-year survival rates are 95% and 80%, respectively. Management of borderline tumours has evolved significantly in the last few decades. In contrast to invasive ovarian cancer, borderline tumours can be operated on conservatively at all stages. Chemotherapy is rarely prescribed even in advanced stages. Eighty percent of malignant germ cell tumours are diagnosed less than 30 years of age, and 70-75% of patients have Stage I disease. Conservative surgery is generally used in malignant germ cell tumours even in advanced stages. The relation between ovulation induction and tumour recurrence is not consistent in the literature. Spontaneous pregnancy rates following fertility saving surgery has been reported as 60-88%. Because of this over-treatment of these patients for fertility should be avoided. Briefly, fertility saving surgery can be performed safely in germ cell, borderline and early stage epithelial ovarian tumours in selected cases. Any increment in the rate of tumour recurrence following ovulation induction has not yet been demonstrated. Menstrual irregularities caused by chemotherapy are transient. The congenital malformation rate of ovarian cancer patients is slightly higher than that of the normal population, but no significant difference has been observed between patients who received or did not receive chemotherapy.     

子宫混合性恶性中胚叶瘤(附25例临床分析)

目的：探讨子宫混合性恶性中胚叶瘤的诊断及治疗方法对患者预后的影响。方法：回顾性分析1966～1995年经治疗的25例子宫混合性恶性中胚叶瘤患者的临床资料。结果：本组患者中，11例生存期≥2a，其中2例Ⅰ期早患者存活分别≥5a和≥10a。结论：子宫混合性恶性中胚叶瘤较少见，恶性程度高，患者预后不良。在诊断上，应重视术前诊刮和病理学检查。治疗方法上除Ⅰ期早可行单纯手术治疗外，其它各期均应在术前、术后辅以放疗、化疗等综合治疗。     

Surgical treatment in child gynecology. Germ cell tumors of the ovary in girls]

The authors presented 50 girls with germ cell tumours of the ovary. 9/50 (4.5%) were malignant germ-cell tumours. There were 5 patients with pure dysgerminomas, 1 with endotermal simus tumor, 3 with immature teratomas, 3 with gonadoblastoma, 38 with mature teratoma. Kariotype 46XY was present in patients. Authors prefer fertility sparing operative treatment. Primary postoperative therapy in malignant tumors was chemotherapy or radiotherapy. Authors recommend sift out ultrasonographic investigation. Girls should be individually considered for appropriate ovarian surgical procedures. The operative treatment should be as conservative as possible. Absence of follicle apparatus in the gonads require determination of levels of gonadotropin and kariotype.     

Clinical aspects of LHRH analogues in gynaecology: a review

LHRH agonists are synthetic peptide analogues of hypothalamic luteinizing hormone releasing hormone (LHRH) with superior potency and longer duration of gonadotrophin release. Paradoxically, repeated administration causes pituitary desensitization with diminished gonadotrophin and oestradiol secretion. A state of hypogonadotrophic hypogonadism is reversibly induced; plasma oestrogen can be reduced to castrate levels. LHRH agonists reliably induce anovulation but are unlikely to replace existing contraceptive methods in most normal women. By contrast these agents offer, for the first time, the prospect of inducing a reversible pseudomenopause essentially free of side-effects. LHRH analogues promise to have a profound impact upon the management of a diverse range of oestrogen-dependent gynaecological diseases both benign and malignant. In particular, they may shortly become the gynaecological treatment of choice in endometriosis, as well as becoming part of the management of common gynaecological disorders such as dysfunctional uterine bleeding and uterine fibroids.     

Clinical aspects of LHRH analogues in gynaecology: a review

Summary. LHRH agonists are synthetic peptide analogues of hypothalamic luteinizing hormone releasing hormone (LHRH) with superior potency and longer duration of gonadotrophin release. Paradoxically, repeated administration causes pituitary desensitization with diminished gonadotrophin and oestradiol secretion. A state of hypogonadotrophic hypogonadism is reversibly induced; plasma oestrogen can be reduced to castrate levels. LHRH agonists reliably induce anovulation but are unlikely to replace existing contraceptive methods in most normal women. By contrast these agents offer, for the first time, the prospect of inducing a reversible pseudomenopause essentially free of side-effects. LHRH analogues promise to have a profound impact upon the management of a diverse range of oestrogen-dependent gynaecological diseases both benign and malignant. In particular, they may shortly become the gynaecological treatment of choice in endometriosis, as well as becoming part of the management of common gynaecological disorders such as dysfunctional uterine bleeding and uterine fibroids.     

Clinical aspects of LHRH analogues in gynaecology: a review

Summary. LHRH agonists are synthetic peptide analogues of hypothalamic luteinizing hormone releasing hormone (LHRH) with superior potency and longer duration of gonadotrophin release. Paradoxically, repeated administration causes pituitary desensitization with diminished gonadotrophin and oestradiol secretion. A state of hypogonadotrophic hypogonadism is reversibly induced; plasma oestrogen can be reduced to castrate levels. LHRH agonists reliably induce anovulation but are unlikely to replace existing contraceptive methods in most normal women. By contrast these agents offer, for the first time, the prospect of inducing a reversible pseudomenopause essentially free of side-effects. LHRH analogues promise to have a profound impact upon the management of a diverse range of oestrogen-dependent gynaecological diseases both benign and malignant. In particular, they may shortly become the gynaecological treatment of choice in endometriosis, as well as becoming part of the management of common gynaecological disorders such as dysfunctional uterine bleeding and uterine fibroids.     

Endometrial cancer

Endometrial cancers are the most common gynaecological malignancies in the UK with approximately 4500 new cases occur each year and the incidence is rising. Increasingly there is evidence-based management and centralized specialist care of women with endometrial cancer. Women with high grade disease, deep myometrial invasion or lymphadenopathy should be managed by specialist gynaecological oncologists as part of a multi-disciplinary team (MDT). Results from important clinical trials now guide the application of surgical and non-surgical treatments. Surgery remains the cornerstone of management with a trend towards increased use of minimal access surgery. Radiotherapy-related morbidity can now be reduced by the more selective use of external beam radiotherapy. There remain several unresolved issues however and it is important that relevant clinical trials are offered to eligible women. Women must have multi-disciplinary input before treatment, so that up-to-date and evidence-based treatments and inclusion in clinical trials can be considered.     

Radiotherapy and chemoradiotherapy for carcinoma of the vulva

Radiotherapy may be used in the treatment of vulval cancer as an alternative to surgery in unfit patients, as an adjuvant to surgery in patients with poor prognosis tumours and for the treatment of inoperable, recurrent and metastatic disease. High-energy X-rays, electrons and both superficial mould and interstitial brachytherapy may be integrated in the regimen to produce the maximum tumour control and minimum morbidity. Concomitant chemoradiotherapy has a high response rate and may be used before surgery to reduce the morbidity of otherwise sphincter-sacrificing procedures.This chapter presents the historical development of radiotherapy for vulval cancer, the role of radiotherapy in the treatment of the primary tumour and also the loco-regional nodes, both for prophylaxis and for proven node metastasis. Techniques for delivering radiotherapy are then discussed and are followed by protocols detailing radiotherapy and chemotherapy doses for different clinical situations.     

Gastrointestinal side effects of cytostatic treatment of gynecologic neoplasms

Gastrointestinal complaints are the most frequent side effects of antineoplastic chemotherapy behind the bonemarrow depressions. Nearly all cytostatic drugs, favourably used treating gynaecological malignant tumours, show a high complication rats on the part of the digestive organs. Primary an secondary damages can be so serious that the continuation of an effective tumour therapy becomes impossible. Whereas mucous excitement and motility disturbances are caused by local toxicity of cytostatic drugs, on the other hand central and psychogenic factors are of essential importance concerning nausea and vomiting. Therefore all these side effects could not be treated effective antiemetics alone. Only by an ingenious combination of medical treatment, psychological guidance and appropriate nutrition complaints can be relieved so far that the patients quality of life is interfered as less as possible and that a sufficient compliance may be reached.     

Ovarian cancer: current management and future directions

Of all the gynaecological malignancies ovarian cancer has the highest mortality. Different types of ovarian cancer vary significantly in their clinical and molecular characteristics and Epithelial ovarian cancer (EOC) is the most common subtype. Up to 20% of women with epithelial ovarian cancer have an inherited predisposition. The fallopian tubes are a potential source of high-grade serous cancer and risk reducing surgery can be an option. Routine screening with serum CA 125 and pelvic ultrasonography is still unproven. Diagnosis of ovarian tumours is usually made by pelvic ultrasonography and serum CA 125. The risk of malignancy index (RMI) is then calculated in order to decide where treatment takes place. Treatment of advanced ovarian cancer usually involves primary debulking surgery and adjuvant chemotherapy but neo-adjuvant chemotherapy with interval debulking surgery is equally effective. Survival is improved if surgery is performed by a specialist gynaecological oncologist. Recent evidence supports the value of radical surgery aiming to excise all macroscopic disease. Standard first line chemotherapy for epithelial ovarian cancer remains carboplatin with paclitaxel. BRAC mutation testing is frequently used to direct second line chemotherapy and molecular targeted treatments such as bevacizumab and PARP inhibitors have been added to the armoury against ovarian cancer. Treatment of advanced disease may prolong life and palliate symptoms but it is rarely curative. Novel drugs and approaches such as ultra-radical surgery, intra-peritoneal chemotherapy, and surgery for recurrent disease are being assessed.     

Ovarian cancer – current management and future directions

Ovarian cancer has the highest mortality of all the gynaecological malignancies. Epithelial ovarian cancer is the most common subtype. Approximately 5–10% occurs in women with an inherited predisposition. These patients may benefit from prophylactic surgery. Diagnosis involves measurement of CA 125 and ultrasound. The results of both are combined to give a risk of malignancy index; this is used to decide where treatment takes place. Treatment of advanced epithelial ovarian cancer usually involves debulking surgery and chemotherapy. The correct order of these treatments is currently being evaluated. There are survival benefits if surgery is performed by a specialist gynaecological oncologist. Current standard chemotherapy for epithelial ovarian cancer is carboplatin with paclitaxel. Treatment may prolong life and palliate symptoms but it is rarely curative. New treatments are constantly being developed and offer the hope of improved outcomes. These include radical surgery, intraperitoneal chemotherapy and novel drug treatments.     

Ovarian cancer: current management and future directions

Ovarian cancer has the highest mortality of all the gynaecological malignancies. Epithelial ovarian cancer is the most common subtype. Approximately 5–10% occur in women with an inherited predisposition. These patients may benefit from prophylactic surgery. Diagnosis involves measurement of CA 125 and ultrasound. The results of both are combined to give a risk of malignancy index; this is used to decide where treatment takes place. Treatment of advanced epithelial ovarian cancer usually involves debulking surgery and chemotherapy. The correct order of these treatments is currently being evaluated. There are survival benefits if surgery is performed by a specialist gynaecological oncologist. Current standard chemotherapy for epithelial ovarian cancer is carboplatin with paclitaxel. Treatment may prolong life and palliate symptoms but it is rarely curative. New treatments are constantly being developed and offer the hope of improved outcomes. These include ultraradical surgery, intraperitoneal chemotherapy and novel drug treatments.     

The management of recurrent and drug-resistant gestational trophoblastic neoplasia (GTN)

Gestational trophoblastic neoplasia (GTN) comprises a spectrum of disease from low-risk disease which can be cured with simple relatively non-toxic treatment, to extremely aggressive tumours which require specialized management. The prognostic variables in patients with GTN are different from those in other gynaecological malignancies, and the major adverse prognostic variables include long interval from antecedent pregnancy, high concentrations of the pregnancy hormone, human chorionic gonadotrophin, metastases in brain and liver and failure of prior treatment. Patients who relapse after their prior treatment can also be categorized into different risk groups. Salvage treatment can vary from single agent actinomycin D to combination chemotherapy and, in selected cases, surgery. With appropriate management, the majority of patients can achieve long-term remission and, in most cases, preserve fertility. The late side-effects of more intensive treatment are a small risk of inducing second tumours and also of bringing forward the age of menopause.     

Gynaecological malignancies in pregnancy

Malignancies of the genital tract in pregnancy are uncommon. When they are encountered in pregnancy there is always a conflict between optimal maternal therapy and fetal well-being. In most instances the cancer should be managed as though the patient were not pregnant. Surgery is preferred for the various site-specific cancers; the timing and mode of delivery should be individualised. The commonest gynaecological cancer encountered is cervical cancer. Delivery by classical Caesarean section followed by radical hysterectomy appears to be the method of choice for cervical cancer; significantly poorer survivals were observed if this was delayed until the puerperium.Ovarian cancer, the second most common gynaecological cancer in pregnancy has a good prognosis due to early presentation in the majority. Malignant germ-cell tumours are just as common as epithelial ovarian cancers.The association of pregnancy with other gynaecological malignancies—carcinoma of endometrium, vagina, fallopian tube, vulva, and choriocarcinoma are discussed.Cytotoxic drugs are highly teratogenic in the first trimester; other fetal problems can arise when these are used after 12 weeks’ gestation. Therefore, cytotoxic chemotherapy is best avoided in pregnancy.