The role of oophoropexy in patients with gynecological cancer who need radiation therapy.

Pelvic radiotherapy is an essential component of cancer therapy for patients with cervical and other gynecological malignancies. The ovaries are particularly radiosensitive, and even low radiotherapy doses may result in impaired or complete loss of ovarian function, causing hormonal disturbances and infertility. Recent advances in both surgery and radiotherapy have facilitated the ability of some patients to maintain ovarian function through ovarian transposition and careful radiotherapy planning. Multidisciplinary discussions should be undertaken to consider which candidates are appropriate for transposition. Generally, patients under age 35 should be considered due to ovarian reserve, likelihood of oophoropexy success, and radioresistance of ovaries. Those patients with small squamous cell tumors, minimal extra-uterine extension, and no lymphovascular invasion or lymph node involvement are ideal candidates to minimize risk of ovarian metastasis. Patients should be assessed and counseled about the risks of ovarian metastasis and the likelihood of successful ovarian preservation before undergoing oophoropexy and starting treatment. Oophoropexy should be bilateral if possible, and ovaries should be placed superior and lateral to the radiotherapy field. Studies limiting the mean ovarian dose to less than 2-3 Gray have demonstrated excellent preservation of ovarian function. Intensity modulated radiotherapy and volumetric modulated arc therapy techniques have the potential to further minimize the dose to the ovary with excellent outcomes. The addition of brachytherapy to the treatment regimen will probably cause minimal risk to transposed ovaries. Oophoropexy before radiotherapy may preserve the hormonal function of ovaries for a duration, and fertility might be possible through surrogate pregnancy. Successful ovarian transposition has the potential to improve the overall health and wellbeing, reproductive options, and potentially quality of life in patients with cervical and other gynecological cancers.

Sister Society Meeting on Global Education Development and Collaboration: Meeting Report.

OBJECTIVES: To identify common barriers to teaching and training and to identify strategies that would be useful in developing future training programs in gynecologic oncology in low- and middle- income countries. METHODS: There is a lack of overall strategy to meet the needs of education and training in gynecologic oncology in low- and middle- income countries, the leaderships of sister societies and global health volunteers met at the European Society of Gynecologic Oncology in October 23, 2015. The challenges of the training programs supported by gynecologic oncology societies, major universities and individual efforts were presented and discussed. Strategies to improve education and training were identified. RESULTS: Major challenges include language barriers, limited surgical equipment, inadequate internet access, lack of local support for sustainability in training programs, inadequate pathology and radiation oncology, finance and a global deficiency in identifying sites and personnel in partnering or developing training programs. The leaderships identified various key components including consultation with the local Ministry of Health, local educational institutions; inclusion of the program into existing local programs, a needs assessment, and the development of curriculum and regional centers of excellence. CONCLUSIONS: Proper preparation of training sites and trainers, the development of global curriculum, the establishment of centers of excellence, and the ability to measure outcomes are important to improve education and training in gynecologic oncology in low- and middle- income countries.

State of the science in cervical cancer: where we are today and where we need to go.

Invasive cervical cancer remains an important global cause of death, despite the declining prevalence within the United States. Definitive therapies, including surgical resection of early-stage disease and chemoradiation for locally advanced disease, can be curative. For women who experience local or distant recurrences, the prognosis remains poor and better treatments are required. On July 18, 2013, The Gynecologic Oncology Group sponsored a State of the Science in Cervical Cancer Symposium with experts, researchers, clinicians, and interested stakeholders. This article summarize the progress that has been made, questions that require further investigation, and contemporary genomic findings and innovative treatments that may help inform the next generation of clinical trials for patients with cervical cancer.

Cervical cancer management in a low resource setting: A 10-year review in a tertiary care hospital in Kenya.

Background: Cervical cancer is one of the leading causes of cancer mortality among women in Kenya due to late presentations, poor access to health care, and limited resources. Across many low- and middle-income countries infrastructure and human resources for cervical cancer management are currently insufficient to meet the high population needs therefore patients are not able to get appropriate treatment. Objective: This study aimed to describe the clinicopathological characteristics and the treatment profiles of cervical cancer cases seen at Moi Teaching and Referral Hospital (MTRH). Methods: This was a retrospective cross-sectional study conducted at MTRH involving the review of the electronic database and medical charts of 1541 patients with a histologically confirmed diagnosis of cervical cancer between January 2012 and December 2021. Results: Of the 1541 cases analyzed, 91% were squamous cell carcinomas, 8% were adenocarcinomas, and 1% were other histological types. Thirty-eight percent of the patients were HIV infected and less than 30% of the women had health insurance. A majority (75%) of the patients presented with advanced-stage disease (stage IIB-IV). Only 13.9% received chemoradiotherapy with curative intent; of which 33.8% received suboptimal treatment. Of the 13% who received surgical treatment, 45.3% required adjuvant therapy, of which only 27.5% received treatment. Over 40% of the women were lost to follow-up. Conclusion: Most of the patients with cervical cancer in Kenya present at advanced stages with only a third receiving the necessary treatment while the majority receive only palliative treatment or supportive care.

Surgical management of a suspicious adnexal mass: a systematic review.

OBJECTIVE: To systematically review the existing literature in order to determine the optimal recommended protocols for the surgical management of adnexal masses suspicious for apparent early stage malignancy. METHODS: A review of all systematic reviews and guidelines published between 1999 and 2009 was conducted as a first step. After the identification of two systematic reviews on the topic, searches of MEDLINE for studies published since 2004 were also conducted to update and supplement the evidentiary base. RESULTS: The updated literature search identified 31 studies that met the inclusion criteria. A bivariate random effects analysis of 15 frozen section diagnosis studies yielded an overall sensitivity of 89.2% (95% CI, 86.3 to 91.5%) and specificity of 97.9% (95% CI, 96.6 to 98.7%). The surgical evidence suggests that systematic lymphadenectomy and proper surgical staging improve survival. Conservative fertility-preserving surgical approaches are an acceptable option in women with low malignant potential tumours. The accuracy and the adequacy of surgical staging by laparotomy or laparoscopic approaches appear to be comparable, with neither approach conferring a survival advantage. Intraoperative tumour rupture was indeed reported to occur more frequently in patients undergoing laparoscopy versus laparotomy in two retrospective cohort studies. CONCLUSIONS: The best available evidence was collected and included in this rigorous systematic review. The abundant evidentiary base provided the context and direction for the surgical management of adnexal masses suspicious for apparent early stage malignancy.

Preoperative identification of a suspicious adnexal mass: a systematic review and meta-analysis.

OBJECTIVE: To systematically review the existing literature in order to determine the optimal strategy for preoperative identification of the adnexal mass suspicious for ovarian cancer. METHODS: A review of all systematic reviews and guidelines published between 1999 and 2009 was conducted as a first step. After the identification of a 2004 AHRQ systematic review on the topic, searches of MEDLINE for studies published since 2004 was also conducted to update and supplement the evidentiary base. A bivariate, random-effects meta-regression model was used to produce summary estimates of sensitivity and specificity and to plot summary ROC curves with 95% confidence regions. RESULTS: Four meta-analyses and 53 primary studies were included in this review. The diagnostic performance of each technology was compared and contrasted based on the summary data on sensitivity and specificity obtained from the meta-analysis. Results suggest that 3D ultrasonography has both a higher sensitivity and specificity when compared to 2D ultrasound. Established morphological scoring systems also performed with respectable sensitivity and specificity, each with equivalent diagnostic competence. Explicit scoring systems did not perform as well as other diagnostic testing methods. Assessment of an adnexal mass by colour Doppler technology was neither as sensitive nor as specific as simple ultrasonography. Of the three imaging modalities considered, MRI appeared to perform the best, although results were not statistically different from CT. PET did not perform as well as either MRI or CT. The measurement of the CA-125 tumour marker appears to be less reliable than do other available assessment methods. CONCLUSION: The best available evidence was collected and included in this rigorous systematic review and meta-analysis. The abundant evidentiary base provided the context and direction for the diagnosis of early-staged ovarian cancer.

Epidemiological profile and clinico-pathological features of pediatric gynecological cancers at Moi Teaching & Referral Hospital, Kenya.

Background: The main pediatric (0-18 years) gynecologic cancers include stromal carcinomas (juvenile granulosa cell tumors and Sertoli-Leydig cell tumors), genital rhabdomyosarcomas and ovarian germ cell. Outcomes depend on time of diagnosis, stage, tumor type and treatment which can have long-term effects on the reproductive career of these patients. This study seeks to analyze the trends in clinical-pathologic presentation, treatment and outcomes in the cases seen at our facility. This is the first paper identifying these cancers published from sub-Saharan Africa. Method: Retrospective review of clinico-pathologic profiles and treatment outcomes of pediatric gynecologic oncology patients managed at MTRH between 2010 and 2020. Data was abstracted from gynecologic oncology database and medical charts. Results: Records of 40 patients were analyzed. Most, (92.5%, 37/40) of the patients were between 10 and 18 years. Ovarian germ cell tumors were the leading histological diagnosis in 72.5% (29/40) of the patients; with dysgerminomas being the commonest subtype seen in 12 of the 37 patients (32.4%). The patients received platinum-based chemotherapy in 70% of cases (28/40). There were 14 deaths among the 40 patients (35%). Conclusion: Surgery remains the main stay of treatment and fertility-sparing surgery with or without adjuvant platinum-based chemotherapy are the standard of care with excellent prognosis following early detection and treatment initiation. LMICs face several challenges in access to quality care and that affects survival of these patients. Due to its commonality, ovarian germ cell cancers warrant a high index of suspicion amongst primary care providers attending to adnexal masses in this age group.

Phase II study of fulvestrant in recurrent/metastatic endometrial carcinoma: a Gynecologic Oncology Group study.

OBJECTIVES: To evaluate the activity and toxicity of fulvestrant in advanced, recurrent, or persistent endometrial carcinoma. METHODS: Eligible patients with advanced, recurrent or persistent endometrial carcinoma not amenable to curative therapy were treated with fulvestrant at a dose of 250 mg by IM injection every 4 weeks for at least 8 weeks. Therapy was continued until evidence of progressive disease, or adverse effects prohibited further therapy. Response was assessed in patients with at least one target lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Immunohistochemical analysis of tumor tissue (histology or cytology) for estrogen and progesterone receptors was required from the metastatic or recurrent site. RESULTS: Sixty-seven patients were enrolled in this study. Upon review, 14 patients were excluded. In the 22 estrogen receptor (ER) negative patients, no patients demonstrated either a complete or partial response, and 4 (18%) demonstrated stable disease (as best response). In the 31 ER positive patients, 1 (3%), 4 (13%) and 9 (29%) patients demonstrated a complete, partial response, and stable disease (as best response), respectively. The median progression free survival and overall survival in the ER negative patients were 2 and 3 months and in the ER positive patients 10 and 26 months. Treatment was well tolerated, and no patient discontinued therapy due to toxicity. CONCLUSIONS: Fulvestrant has minimal activity in advanced, recurrent, or persistent endometrial carcinoma.

Assessment of Sentinel Lymph Node Biopsy vs Lymphadenectomy for Intermediate- and High-Grade Endometrial Cancer Staging.

Importance: Whether sentinel lymph node biopsy (SLNB) can replace lymphadenectomy for surgical staging in patients with high-grade endometrial cancer (EC) is unclear. Objective: To examine the diagnostic accuracy of, performance characteristics of, and morbidity associated with SLNB using indocyanine green in patients with intermediate- and high-grade EC. Design, Setting, and Participants: In this prospective, multicenter cohort study (Sentinel Lymph Node Biopsy vs Lymphadenectomy for Intermediate- and High-Grade Endometrial Cancer Staging [SENTOR] study), accrual occurred from July 1, 2015, to June 30, 2019, with early stoppage because of prespecified accuracy criteria. The study included patients with clinical stage I grade 2 endometrioid or high-grade EC scheduled to undergo laparoscopic or robotic hysterectomy with an intent to complete staging at 3 designated cancer centers in Toronto, Ontario, Canada. Exposures: All patients underwent SLNB followed by lymphadenectomy as the reference standard. Patients with grade 2 endometrioid EC underwent pelvic lymphadenectomy (PLND) alone, and patients with high-grade EC underwent PLND and para-aortic lymphadenectomy (PALND). Main Outcomes and Measures: The primary outcome was sensitivity of the SLNB algorithm. Secondary outcomes were additional measures of diagnostic accuracy, sentinel lymph node detection rates, and adverse events. Results: The study enrolled 156 patients (median age, 65.5 years; range, 40-86 years; median body mass index [calculated as weight in kilograms divided by height in meters squared], 27.5; range, 17.6-49.3), including 126 with high-grade EC. All patients underwent SLNB and PLND, and 101 patients (80%) with high-grade EC also underwent PALND. Sentinel lymph node detection rates were 97.4% per patient (95% CI, 93.6%-99.3%), 87.5% per hemipelvis (95% CI, 83.3%-91.0%), and 77.6% bilaterally (95% CI, 70.2%-83.8%). Of 27 patients (17%) with nodal metastases, 26 patients were correctly identified by the SLNB algorithm, yielding a sensitivity of 96% (95% CI, 81%-100%), a false-negative rate of 4% (95% CI, 0%-19%), and a negative predictive value of 99% (95% CI, 96%-100%). Only 1 patient (0.6%) was misclassified by the SLNB algorithm. Seven of 27 patients with node-positive cancer (26%) were identified outside traditional PLND boundaries or required immunohistochemistry for diagnosis. Conclusions and Relevance: In this prospective cohort study, SLNB had acceptable diagnostic accuracy for patients with high-grade EC at increased risk of nodal metastases and improved the detection of node-positive cases compared with lymphadenectomy. The findings suggest that SLNB is a viable option for the surgical staging of EC.

Phase III trial of weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia: a gynecologic oncology group study.

PURPOSE: There is no consensus on the best regimen for the primary treatment of low-risk gestational trophoblastic neoplasia (GTN). PATIENTS AND METHODS: Two commonly used single-drug regimens were compared with respect to the proportion of patients meeting the criteria for a complete response (CR) in a randomized phase III trial conducted by the Gynecologic Oncology Group. Eligibility was purposefully broad to maximize the generalizability of the results and included patients with a WHO risk score of 0 to 6 and patients with metastatic disease (limited to lung lesions < 2 cm, adnexa, or vagina) or choriocarcinoma. RESULTS: Two hundred forty women were enrolled, and 216 were deemed eligible. Biweekly intravenous dactinomycin 1.25 mg/m² was statistically superior to weekly intramuscular (IM) methotrexate 30 mg/m² (CR: 70% v 53%; P = .01). Similarly, in patients with low-risk GTN as defined before the 2002 WHO risk score revisions (risk score of 0 to 4 and excluding choriocarcinoma), response was 58% and 73% in the methotrexate and dactinomycin arms, respectively (P = .03). Both regimens were less effective if the WHO risk score was 5 or 6 or if the diagnosis was choriocarcinoma (CR: 9% and 42%, respectively). There were two potential recurrences; one at 4 months (dactinomycin) and one at 22 months (methotrexate). Not all patients completed follow-up. Both regimens were well tolerated. CONCLUSION: The biweekly dactinomycin regimen has a higher CR rate than the weekly IM methotrexate regimen in low-risk GTN, a generally curable disease.