2016, Vol 14, No 2
The prognostic significance of histology and treatment modality in stage IB1 squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma of the uterine cervix: SEER study 2004–2008
Curr Gynecol Oncol 2016, 14 (2), p. 78–84
DOI: 10.15557/CGO.2016.0008

Objective: To determine the significance of histology and treatment modality on overall survival and cause-specific survival in stage IB1 cervical carcinoma. Methods: Cases of stage IB1 squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma of the uterine cervix managed with either radical hysterectomy, definitive radiation therapy which may include external beam radiation therapy and/or vaginal brachytherapy, or total abdominal hysterectomy with adjuvant radiation therapy which may include external beam radiation therapy plus/minus vaginal brachytherapy were abstracted from the SEER database (2004–2008). Cause-specific survival was calculated using Kaplan–Meier, log-rank, and multivariable Cox regression analyses. Results: Five-year cause-specific survival for squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma were 94.4%, 97.3%, and 85.7%, respectively (p = 0.001 by log-rank test). On multivariable Cox regression analysis, patients with squamous cell carcinoma were not more likely to die of cervical cancer than patients with adenocarcinoma (hazard ratio = 1.12, 95% confidence interval = 0.53–2.39); but patients with adenosquamous cell carcinoma were more likely to die of cervical cancer than patients with adenocarcinoma (hazard ratio = 3.65, 95% confidence interval = 1.41–9.44). Five-year cause-specific survival was 96.9%, 80.0%, and 92.4% for patients receiving radical hysterectomy, definitive radiation therapy, and total abdominal hysterectomy plus radiation therapy, respectively (p < 0.0001 by log-rank test). On multivariable Cox regression analysis, patients who received definitive radiation therapy and patients who received total abdominal hysterectomy plus radiation therapy were more likely to die of cervical cancer than patients who received radical hysterectomy. Conclusion: In patients with stage IB1 cervical cancer, on multivariable Cox regression analysis, patients with squamous cell carcinoma were not more likely to die of cervical cancer than patients with adenocarcinoma; patients with adenosquamous cell carcinoma were more likely to die of cervical cancer than patients with adenocarcinoma. Patients who received either definitive radiation therapy or total abdominal hysterectomy plus radiation therapy were more likely to die of cervical cancer than patients who received radical hysterectomy.

Keywords: cervical cancer, radiation, surgery
Investigation of radiation therapy for gynecologic cancer patients with supraclavicular lymph node metastases
Curr Gynecol Oncol 2016, 14 (2), p. 85–88
DOI: 10.15557/CGO.2016.0009

Purpose: The aim of this study was to retrospectively investigate the benefit of radiotherapy for supraclavicular lymph nodes by determining the characteristics and survival of patients with recurrent gynecologic cancer after definitive radiotherapy. Material and methods: We reviewed the treatment outcomes of 18 gynecologic cancer patients with supraclavicular lymph nodes metastases treated. Twelve cervical cancer patients, 4 corporeal cancer patients and 2 ovarian cancer patients were investigated. Tumor responses, adverse events and the overall survival were examined. Results: The median overall survival was 12 months. The 1- and 2-year overall survival rates were 48.6% and 9.7%, respectively. The 2-year local control rate was 75.8%. Following therapy, the symptom of pain was relieved in 2 patients (2/2), and edema and swelling were improved in 6 out of 7 symptomatic patients. Eleven asymptomatic patients did not develop any symptoms during the follow-up period. Common Terminology Criteria for Adverse Events grade 2 toxicities were found in 5 patients (2 dermatitis and 4 hematologic toxicities), and grade 3 toxicities were found in 3 patients (3 hematologic toxicities). Conclusion: Radiotherapy for supraclavicular lymph nodes is effective as palliative irradiation. The 2-year local control rate was 75.8% in patients receiving this therapy, their symptoms improved and asymptomatic patients did not become symptomatic during the follow-up period. Radiotherapy for supraclavicular lymph nodes metastases is therefore recommended for preserving the patient’s life.

Keywords: palliative radiotherapy, gynecologic cancer, metastasis
Neoadjuvant chemoradiotherapy in advanced vulvar carcinoma
Curr Gynecol Oncol 2016, 14 (2), p. 89–96
DOI: 10.15557/CGO.2016.0010

Introduction: In advanced vulvar carcinoma with unresectable lesions, permanent curing is rare. In the past, extensive exenteration surgeries offered a chance for improvement but led to considerable mutilation and impairment of functioning. An alternative method of treating advanced vulvar carcinoma is neoadjuvant chemoradiotherapy or sole chemoradiotherapy. At present, chemosensitivity of vulvar carcinoma is well-documented. The application of synchronous chemotherapy with total dosage reduction by 15–20% in relation to radiotherapy allows for obtaining a favorable diagnostic index. The aim of the study was to determine the position of chemoradiotherapy in preoperative treatment of vulvar carcinoma. Material and methods: From 2005 to 2013, radiation therapy was applied in 24 patients aged 48–81 (mean age was 64) with squamous cell carcinoma of the vulva in FIGO stage III and IV. The therapies were conducted in the Department of Gynecologic Oncology of the Marie Skłodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw (Poland). The patients’ vulvar region as well as inguinal and pelvic lymph nodes were irradiated with 15 MeV photons and/or 9–15 MeV electrons. The total doses used on vulva ranged from 54 to 65 Gy depending on the extensiveness of the infiltration. The dose used on the pelvic and inguinal lymph nodes ranged from 45 to 65 Gy. Chemotherapy: 750–1,000 mg/m2 of 5-FU administered as a 96-hour infusion and 50–75 mg/m2 of cisplatin on day 1 administered in the 1st and 5th weeks of radiotherapy. Results: Complete regression was obtained in 11 (46%) patients, partial regression in 12 (50%) patients and in 1 (4%) case, disease progression was observed. After the surgery, no carcinoma was detected in 3 (25%) out of 12 patients with partial regression; merely post-radiation damage was found. The instances of relapse were treated surgically and when the patient had not given consent or when the progression of the disease prevented surgery, systemic treatment was applied. Conclusions: In advanced vulvar carcinoma, neoadjuvant chemoradiotherapy with a high proportion of response should be a method of choice. Regression of carcinoma after irradiation allows for performing less mutilating surgeries. For optimal treatment selection, a decision concerning qualification for treatment in advanced vulvar carcinoma should be made together by a gynecologic oncologist and radiotherapist.

Keywords: advanced vulvar carcinoma, neoadjuvant chemoradiotherapy, tumor regression, radiation reaction
Effect of hyaluronate-containing preparations on certain parameters of urogenital organs statics disorders in women
Curr Gynecol Oncol 2016, 14 (2), p. 97–103
DOI: 10.15557/CGO.2016.0011

Urogenital organs statics disorders affect approximately 30–75% of women; their incidence increases with age. Among various causes, the generally recognized ones are deliveries experiences in the past, excessive physical effort, age-related estrogen deficiency, previous treatment, including irradiation (brachytherapy) – mainly due to uterine tumors. Dysfunctions in statics usually involve two anatomically and developmentally related systems: the reproductive system and the urinary system. In gynecologic practice, the most common pathologies involve a lowering the anterior vaginal wall (cystocele), stress urinary incontinence and polyuria. Study encompassed 78 women, aged 50 to 76, 11 of whom experienced earlier endometrial cancer and nine of whom were also subjected to brachytherapy. In 63 women OB intravaginal tampons were applied for three months, covered with a gel or cream containing hyaluronic acid; in some of them additionally estriolcontaining ointment was applied twice a week. Some women (15) were exclusively recommended to do the Kegel exercises. Evaluation of stress urinary incontinence as well as polyuria and nocturia was conducted 3 and 6 months after tampons stopped to be applied. The application of tampons covered with hyaluronic acid-containing preparations was found to reduce significantly the symptoms of stress urinary incontinence and polyuria and the symptoms of cystocele. The presented method is simple and evidently effective.

Keywords: stress urinary incontinence, polyuria, cystocele, Kegel exercises, hyaluronic acid
The results of cryotherapy and local application of povidone-iodine in the eradication of persistent highly oncogenic HPV
Curr Gynecol Oncol 2016, 14 (2), p. 104–108
DOI: 10.15557/CGO.2016.0012

Treatment covered 128 women aged 24–67 (37.5 on average), with abnormal cytology: in 77 patients atypical squamous cell of undetermined significance was detected, in 30 patients low-grade squamous intraepithelial lesions were identified while in 21 only the presence of koilocytes was demonstrated. In most cases, the cervix was without any clinical changes or ectropion lesions were detected. In all the patients, the presence of highly oncogenic human papillomavirus (HPV) was detected using viral genotyping reverse transcription polymerase chain reaction. In 45 (35%) patients, a single strain of HPV was detected, HPV 16 (40% of the patients) was most common. In 29 (22.6%) patients, two types of the virus were identified, most frequently HPV 16 or 18. In the remaining 54 (42.1%) patients, multiple types of HPV were detected. The employed therapeutic scheme involved two applications of cryotherapy with liquid nitrogen for 3 minutes, covering the mucosal surface (in the case of ectropion) with the transient zone and cervical canal. Following each application of cryotherapy, povidone-iodine (Betadine) globules were used. In 7 patients, electrocoagulation using the LEEP system was additionally performed (in the case of bleeding ectropion). Two months after the last procedure, HPV was marked again using the RT-PCR method. HPV was not detected in any of the treated patients. In 10 patients due to persistent ectropion lesion on the cervix, electroconization was conducted and histopathology demonstrated no HPV-related lesions. Cryotherapy – accompanied by the application of povidone-iodine – is effective in the prophylaxis and eradication of persistent infection with highly oncogenic HPV.

Keywords: HPV infection, cryotherapy, povidone-iodine
Influence of recreational psychoactive substances on the development of gynecologic cancers
Curr Gynecol Oncol 2016, 14 (2), p. 109–116
DOI: 10.15557/CGO.2016.0013

Tea and coffee, beverages most commonly consumed by people, contain flavonoids, which have an antioxidant effect. It has been proven that green tea consumption protects against both precancerous lesions and cervical cancer. Black tea consumption is associated with a reduced risk of ovarian and breast cancer development in postmenopausal women. Drinking coffee lowers the risk of type I endometrial cancer. The majority of studies on postmenopausal women with breast cancer show a protective role of coffee, which seems to be related to the state of hormonal receptors. Alcoholic beverages, on the other hand, are classified as class 1 carcinogens and their metabolism generates harmful free radicals. Alcohol is also associated with an increased risk of HPV infection, which is in turn causally responsible for the development of precancerous cervical lesions. In addition, alcohol increases the risk of recurrence of cervical cancer. In the case of endometrial cancer the views are rather divergent. Some studies suggest that beer and wine may reduce the risk of cancer, while other studies show that other alcoholic beverages consumed in greater quantities increase that risk. While the consumption of wine is believed to reduce the risk of development of endometrioid ovarian cancer, there is no proof of the same effect on other histopathological types of this disease. This phenomenon may be associated with the protective effect of resveratrol. Various types of alcohol, on the other hand, have been proven to be conducive to the development of breast cancer.

Keywords: tea, coffee, alcohol, cervical cancer, endometrial cancer, ovarian cancer, breast cancer
The role of PD-1 – a programmed cell death receptor 1 – and its ligands in ovarian cancer immunotherapy
Curr Gynecol Oncol 2016, 14 (2), p. 117–120
DOI: 10.15557/CGO.2016.0014

The immune system plays an important role in both cancer development and destruction. Tumor cells have developed mechanisms to evade an effective immune response. One of these involves the use of immune checkpoint pathways, which modulate the intensity and duration of such responses. There are two immune checkpoint receptors that have been most thoroughly studied: CTLA-4 (cytotoxic T lymphocyte-associated antigen 4) and PD-1 (programmed cell death protein 1 pathway), involved in regulatory T cell responses. The anti-CTLA-4 antibody is used in the treatment of many malignancies, including non-small-cell lung cancer, prostate cancer and melanoma. PD-1 and its ligands, PD-L1 and PD-L2, represent an immune axis protecting cancer cells against regulatory T cells (cytotoxic CD8+ cells and CD4+ helper cells). Nivolumab, a monoclonal antibody, blocks PD-1 and, as a result, its binding to its ligands. Consequently, T cell antitumor activity is restored, which appears promising in clinical trials involving patients with malignancies in multiple locations, including non-small-cell lung cancer, melanoma and ovarian cancer, clear cell ovarian carcinoma in particular. Nivolumab therapy is not devoid of adverse effects, which affect about 40% of patients with ovarian cancer. These include e.g. arrhythmia, fever, anemia and decreased lymphocyte count. It is believed that combining a therapy that blocks the key immune checkpoints with other anticancer agents, including chemotherapy, radiation therapy or other targeted therapies, will improve treatment efficacy in malignancies, including ovarian cancer.

Keywords: PD-1/PD-L1, nivolumab, ovarian cancer, immunotherapy
Therapeutic options in radiation-induced rectovaginal fistula
Curr Gynecol Oncol 2016, 14 (2), p. 121–132
DOI: 10.15557/CGO.2016.0015

A pathological communication between the rectum and the vagina, referred to as rectovaginal fistula, can develop as a result of a number of factors. Fistula caused by ionizing energy treatment, which belongs to the most serious late radiation-induced complications, is a special type of this abnormality. This type of fistulas are classified as complex fistulas. Their surgical treatment is very difficult and shows poor efficacy as well as high rate of recurrence. Therefore, it is still a serious and current problem of women after radiation therapy for gynecologic cancer. The quality of life in patients with this complication is dramatically poor. Despite completed cancer treatment, women with radiation-induced rectovaginal fistula are often unable to resume their previous social roles, including work. Therefore, it is important to determine the optimal management strategy in these patients. Although it may seem impossible to develop a simple diagnostic and therapeutic algorithm due to different fistula locations and sizes, the knowledge on the basic management strategies increases the chance of success. A surgery using the transabdominal approach described by Parks is the primary surgical technique. However, new reports on repair techniques, particularly less invasive ones, occasionally occur in literature. Therefore, we present a current literature review of treatment options in radiation-induced rectovaginal fistulas.

Keywords: rectovaginal fistula, radiation-induced fistula, radiation-induced complications