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Gynecologic Oncology

Organisations and Professional Societies
Specialist Journals
Recent Research Publications
Cervical Cancer
Endometrial (Uterus) Cancer
Fallopian Tube Cancer
Gestational Trophoblastic Cancer
Ovarian Cancer
Vaginal Cancer
Vulva Cancer
Uterine Sarcoma

Organisations and Professional Societies (32 links)

Specialist Journals (4 links)

See also: Oncology Journals

Recent Research Publications

Komatsu H, Oishi T, Sato S, et al.
Evaluating Chemotherapy-induced Nausea and Vomiting and Food Intake in Patients With Gynecologic Cancer.
Anticancer Res. 2019; 39(8):4555-4560 [PubMed] Related Publications
BACKGROUND/AIM: Treatments for controlling delayed nausea after chemotherapy are inadequate, potentially inciting malnutrition. We sought to determine the incidence of nausea, anorexia, and food intake after chemotherapy.
PATIENTS AND METHODS: Subjects were females with gynecological cancers who underwent chemotherapy between 2008 and 2013. Nausea, anorexia, and food intake in the acute (day 1) and delayed phases (days 2 and 3) were retrospectively evaluated.
RESULTS: Subjects included 156 females. Chemotherapies were highly (HEC; n=24) and moderately emetogenic (MEC; n=132). There were no significant between-group differences for anorexia control during either the acute or the delayed phase and both groups demonstrated significantly worse control of nausea during the delayed phase. In the HEC group, food intake was significantly reduced on days 2 and 3 compared with day 1.
CONCLUSION: Rates of nausea, anorexia, and food intake significantly worsened over time, particularly in the MEC group. Current supportive therapies appear inadequate and should be improved.

Namazov A, Volchok V, Liboff A, et al.
Sentinel Nodes Detection with Near-infrared Imaging in Gynecological Cancer Patients: Ushering in an Era of Precision Medicine.
Isr Med Assoc J. 2019; 21(6):390-393 [PubMed] Related Publications
BACKGROUND: The sentinel lymph node (SLN) biopsy procedure is a well-known method for identifying solid tumors such as breast cancer, vulvar cancer, and melanoma. In endometrial and cervical cancer, SLN has recently gained acceptance.
OBJECTIVES: To evaluate the detection rate of SLN with an indocyanine green and near-infrared fluorescent imaging (ICG/NIR) integrated laparoscopic system in clinically uterine-confined endometrial or cervical cancer.
METHODS: Patients with clinically early-stage endometrial or cervical cancer were included in this retrospective study. ICG was injected into the uterine cervix and an ICG/NIR integrated laparoscopic system was used during the surgeries. The National Comprehensive Cancer Network (NCCN) protocol was followed. SLN and/or suspicious lymph nodes were resected. Side-specific lymphadenectomy was performed when mapping was unsuccessful. Systematic lymphadenectomy was completed in patients with high-grade histology or deep myometrial invasion. Enhanced pathology using ultra-staging and immunohistochemistry were performed in all cases.
RESULTS: We analyzed 46 eligible patients: 39 endometrial and 7 cervical cancers. Of these, 44 had at least one SLN (93.6%). In 41 patients (89%) we detected bilateral SLN, in 3 (7%) only unilateral, and in 2 (4%) none were detected. Seven patients presented with lymph node metastasis. All were detected by NCCN/SLN protocol. Of these cases, two were detected with only pathological ultra-staging.
CONCLUSIONS: SLN mapping in endometrial and cervical cancer can easily be performed with a high detection rate by integrating ICG/NIR into a conventional laparoscopic system. Precision medicine in patients evaluated by SLN biopsy changes the way patients with endometrial or cervical cancer are managed.

Gil KM, Pugh SL, Klopp AH, et al.
Expanded validation of the EPIC bowel and urinary domains for use in women with gynecologic cancer undergoing postoperative radiotherapy.
Gynecol Oncol. 2019; 154(1):183-188 [PubMed] Related Publications
OBJECTIVE: Women with endometrial or cervical cancer at risk for recurrence receive postoperative radiation therapy (RT). A patient reported outcomes (PRO) instrument to assess bowel and urinary toxicities is the Expanded Prostate Cancer Index Composite (EPIC), which has been validated in men with prostate cancer. As this instrument specifically measures bowel toxicity and the degree to which this is a problem, it was used in NRG Oncology/RTOG 1203 to compare intensity modulated RT (IMRT) to standard RT. This paper reports on the expanded validation of EPIC for use in women receiving pelvic RT.
METHODS: In addition to the EPIC bowel domain, urinary toxicity (EPIC urinary domain), patient reported bowel toxicities (PRO-CTCAE) and quality of life (Functional Assessment of Cancer Therapy (FACT)) were completed before, during and after treatment. Sensitivity, reliability and concurrent validity were assessed.
RESULTS: Mean bowel and urinary scores among 278 women enrolled were significantly worse during treatment and differed between groups. Acceptable to good reliability for bowel and urinary domain scores were obtained at all time points with the exception of one at baseline. Correlations between function and bother scores within the bowel and urinary domains were consistently stronger than those across domains. Correlations between bowel domain scores and PRO-CTCAE during treatment were stronger than those with the FACT.
CONCLUSION: Correlations within and among the instruments indicate EPIC bowel and urinary domains are measuring conceptually discrete components of health. These EPIC domains are valid, reliable and sensitive instruments to measure PRO among women undergoing pelvic radiation.

Maru Y, Tanaka N, Itami M, Hippo Y
Efficient use of patient-derived organoids as a preclinical model for gynecologic tumors.
Gynecol Oncol. 2019; 154(1):189-198 [PubMed] Related Publications
OBJECTIVE: The relevance of patient-derived cancer cells has been recently increasing, particularly in terms of drug discovery and precision medicine. Whereas Matrigel-based organoid culture is a promising technique that enables infinite proliferation of cells from many types of organs in a physiological condition, its validity in gynecologic tumors remains to be established. To address this issue, we aimed at developing an efficient method for organoid culture of both ovarian and endometrial tumors.
METHODS: We conducted 3D culture of 21 gynecologic tumors following our original and modified protocol for Matrigel bilayer organoid culture. We investigated whether propagated organoids retained various features of the original tumors by histopathological examination and targeted genome sequencing.
RESULTS: We customized the protocol we previously optimized for murine normal and cancer tissues, so as to circumvent the digestion-resistant nature inherent to gynecologic tumors. Indeed, this modified protocol improved the success rate from 45 to 90%, for robust propagation of organoids from tumors with various stages and subtypes. Finally, 14 patient-derived organoids were established. The recovered organoids were enriched for cancer cells that retained many aspects of the original tumors, including histological features, mutation profiles, and intra-tumoral heterogeneity. A subset of the expanded organoids could develop xenografts in immunodeficient mice, potentially paving the way to drug screening in vivo. Drug response assay in vitro for paclitaxel and cisplatin was feasible using organoid-derived spheroids.
CONCLUSIONS: We showed that patient-derived organoids closely resembled the original gynecologic tumors, and thereby would serve as a promising resource for preclinical studies.

Liu K, Zhang Q, Pan F, et al.
Expression of circular RNAs in gynecological tumors: A systematic review.
Medicine (Baltimore). 2019; 98(20):e15736 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The rapid development of bioinformatic technology is boosting the discovery of components hiding in the darkness. As a type of universal, conservative, tissue-specific and stable molecules, circular RNA (circRNA) is a class of endogenous non-coding RNA that has no 5' cap and 3' poly(A) tail and forms a covalently closed continuous loop. At present, 3 types of circRNAs including exonic circRNA (ecRNA), intronic circRNA (ciRNA), and axon-intronic circRNA have been reported. Nowadays informatic technology and high-throughput sequencing have verified the abundance of endogenous circRNAs in eukaryocytes, with predominantly expressed in the cell cytoplasm. Their unique sequences endow them with special functions, such as miRNA sponge, selective transcription or splicing, and attaching to RNA-binding proteins.
DATA SOURCES: This review was based on articles published in PubMed databases up to January, 2019, with the following keywords: "circular RNA", "database", and "reproductive tumor" (Flow chart).
OBJECTIVES: Original articles and reviews on the topics were selected.
RESULTS: Studies have uncovered the interplay between circRNAs and the development of ovarian epithelial tumors, ovarian carcinoma, and cervical carcinoma, which suggesting the potential of circRNAs as biomarkers or therapeutic targets for human diseases.
CONCLUSIONS: Circular RNA has been found to play a role in gynecological tumors diseases. Meanwhile, we reviewed the studies on how CircularRNA participate in gynecological tumors, which provides a basis for the study of CircularRNA in gynecological tumors.

Spirtos NM, Enserro D, Homesley HD, et al.
The addition of paclitaxel to doxorubicin and cisplatin and volume-directed radiation does not improve overall survival (OS) or long-term recurrence-free survival (RFS) in advanced endometrial cancer (EC): A randomized phase III NRG/Gynecologic Oncology Group (GOG) study.
Gynecol Oncol. 2019; 154(1):13-21 [PubMed] Related Publications
OBJECTIVES: To determine if the addition of paclitaxel (P) to cisplatin and doxorubicin (CD) following surgical debulking and volume-directed radiation therapy improved long-term, recurrence-free survival (RFS) and overall survival (OS) in patients with advanced-stage endometrial cancer (EC).
METHODS: Prospective, randomized GOG trial comparing (CD) (50 mg/m
RESULTS: Since initial publication, 60 deaths occurred, leaving 311 patients alive with 290 (93.8%) recurrence- free. There was no significant decrease in the risk of recurrence or death associated with the CDP treatment regimen stratified for stage (p = 0.14, one-tail). The exploratory analysis for OS and the corresponding homogeneity tests for different effects across subgroups revealed only EFRT and EFRT & GRD status to have significantly different treatment effects (p = 0.027 and p = 0.017, respectively). Second primary malignancies were identified in 17/253 (6.4%) and 19/263 (7.0%) of patients treated with CD and CDP respectively. Breast (2.4%) followed by colon (1%) were the two cancers most frequently diagnosed in this setting.
CONCLUSION: No significant difference between treatment arms was identified. Subgroup analysis both in the initial and current reports demonstrated a trend towards improved RFS and OS in patients treated with CDP and EFRT. This long-term analysis of outcomes also identified the necessity of providing on-going cancer screening to patients enrolled in trials.

Bouberhan S, Shea M, Kennedy A, et al.
Financial toxicity in gynecologic oncology.
Gynecol Oncol. 2019; 154(1):8-12 [PubMed] Related Publications
OBJECTIVES: Financial toxicity is increasingly recognized as an adverse outcome of cancer treatment. Our objective was to measure financial toxicity among gynecologic oncology patients and its association with demographic and disease-related characteristics; self-reported overall health; and cost-coping strategies.
METHODS: Follow-up patients at a gynecologic oncology practice completed a survey including the COmprehensive Score for Financial Toxicity (COST) tool and a self-reported overall health assessment, the EQ-VAS. We abstracted disease and treatment characteristics from medical records. We dichotomized COST scores into low and high financial toxicity and assessed the correlation (r) between COST scores and self-reported health. We calculated risk ratios (RR) and 95% confidence intervals (CI) for the associations of demographic and disease-related characteristics with high financial toxicity, as well as the associations between high financial toxicity and cost-coping strategies.
RESULTS: Among 240 respondents, median COST score was 29. Greater financial toxicity was correlated with worse self-reported health (r = 0.47; p < 0.001). In the crude analysis, Black or Hispanic race/ethnicity, government-sponsored health insurance, lower income, unemployment, cervical cancer and treatment with chemotherapy were associated with high financial toxicity. In the multivariable analysis, only government-sponsored health insurance, lower income, and treatment with chemotherapy were significantly associated with high financial toxicity. High financial toxicity was significantly associated with all cost-coping strategies, including delaying or avoiding care (RR: 7.3; 95% CI: 2.8-19.1).
CONCLUSIONS: Among highly-insured gynecologic oncology patients, many respondents reported high levels of financial toxicity. High financial toxicity was significantly associated with worse self-reported overall health and cost-coping strategies, including delaying or avoiding care.

Zeng Y, Cheng ASK, Song T, et al.
Changes in functional brain networks and neurocognitive function in Chinese gynecological cancer patients after chemotherapy: a prospective longitudinal study.
BMC Cancer. 2019; 19(1):386 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Previous neurocognitive assessments in non-central nervous system cancers highlight the high incidence of neurocognitive dysfunction in this study population. However, there have been few studies exploring neurocognitive dysfunction induced by chemotherapy in gynecological cancer patients. This prospective longitudinal study was conducted to assess neurocognitive functioning and functional brain networks in Chinese gynecological cancer patients pre- and post-chemotherapy, while additionally including age-matched healthy subjects as the control group.
METHODS: All research participants were evaluated using a resting-state functional magnetic resonance imaging and neurocognition assessment. Behavioral data were conducted using SPSS for descriptive statistics, correlation and comparison analyses. Preprocessing of MRI (Magnetic Resonance Imaging) data and network analyses were performed using GRETNA (Graph Theoretical Network Analysis).
RESULTS: A total of 40 subjects joined this study, with 20 subjects in each group. With the exception of the mean of psychomotor speed, there was no significant difference pre-chemotherapy between patients and healthy controls in neurocognitive test mean scores (Ps > 0.05). During the post-chemotherapy assessment, there were significant differences in the mean scores of neurocognitive tests (including Digit Span tests, verbal memory, immediate recall, delayed recall, and information processing speed tests) (all Ps < 0 .05). Longitudinal graph analysis revealed statistically significant differences in the patient group, with significant decreases in both local efficiency (P < 0.01) and global efficiency (P = 0.04). Lower raw TMT-A scores were significantly associated with lower local efficiency (r = 0.37, P = 0.03). Lower verbal memory scores were statistically significant and associated with lower global efficiency (r = 0.54, P = 0.02) in the patient group, but not in the healthy control group.
CONCLUSIONS: This study found that the risk of brain function and neurocognitive changes following chemotherapy could potentially guide patients in making appropriate treatment decisions, and this study may identify a cohort that could be suited for study of an intervention.

Gore M, Hackshaw A, Brady WE, et al.
An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor.
Gynecol Oncol. 2019; 153(3):541-548 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: We evaluated four different treatment regimens for advanced-stage mucinous epithelial ovarian cancer.
METHODS: We conducted a multicenter randomized factorial trial (UK and US). Patients were diagnosed with primary mEOC: FIGO stage II-IV or recurrence after stage I disease. Treatment arms were paclitaxel-carboplatin, oxaliplatin-capecitabine, paclitaxel-carboplatin-bevacizumab, or oxaliplatin-capecitabine-bevacizumab. Chemotherapy was given 3-weekly for 6 cycles, and bevacizumab (3-weekly) was continued as maintenance (for 12 cycles). Endpoints included overall-survival (OS), progression-free survival (PFS), toxicity and quality of life (QoL).
RESULTS: The trial stopped after 50 patients were recruited due to slow accrual. Median follow-up was 59 months. OS hazard ratios (HR) for the two main comparisons were: 0.78 (p = 0.48) for Oxal-Cape vs. Pac-Carbo (each with/without bevacizumab), and 1.04 (p = 0.92) for bevacizumab vs. no bevacizumab. Corresponding PFS HRs were: 0.84 and 0.80. Retrospective central pathology review revealed only 45% (18/40) cases with available material had confirmed primary mEOC. Among these, OS HR for Oxal-Cape vs. Pac-Carbo was 0.36 (p = 0.14); PFS HR = 0.62 (p = 0.40). Grade 3-4 toxicity was seen in 61% Pac-Carbo, 61% Oxal-Cape, 54% Pac-Carbo-Bev, and 85% Oxal-Cape-Bev. QoL was similar between the four arms.
CONCLUSION: mEOC/GOG0241 represents an example of a randomized rare tumor trial. Logistical challenges led to early termination, including difficulties in local histopathological diagnosis and accessing drugs outside their labelled indication. There was misalignment between central funders who support clinical trials in rare cancers and the deprioritisation of such work by those managing and funding research at a local level. Rare cancer trials should include centralised pathology review before treatment. Clinical trial registry number: ISRCTN83438782.

Venturella G, Saporita P, Gargano ML
The Potential Role of Medicinal Mushrooms in the Prevention and Treatment of Gynecological Cancers: A Review.
Int J Med Mushrooms. 2019; 21(3):225-235 [PubMed] Related Publications
A review of scientific information about the potential role of medicinal mushrooms in the prevention and treatment of gynecological cancers, human immunodeficiency virus, and human papillomavirus infections is reported here. The results of in vivo and in vitro experiments on 16 different species of Basidiomycetes and three Ascomycetes, which possess chemopreventive potential and are effective in clinical application in combination with chemotherapy, are also discussed. Medicinal mushroom extracts confirm an evident efficacy on the reduction of tumor cell proliferation and side effects in patients with gynecological tumors who are undergoing chemotherapy treatments. This review, the first on the use of medicinal mushrooms in the prevention and treatment of gynecological cancers, aims to highlight the remarkable potential of mushrooms in integrated oncology.

Lee L, Matulonis U
Immunotherapy and radiation combinatorial trials in gynecologic cancer: A potential synergy?
Gynecol Oncol. 2019; 154(1):236-245 [PubMed] Related Publications
Immunotherapy (IO) is an important new pillar in the treatment of solid tumors, and the integration of IO agents with chemotherapy, targeted therapy, surgery and radiation has yet to be defined. As preclinical and clinical studies have described synergistic activity with the combination of radiation and immunotherapy, many clinical trials are underway to explore both the safety and efficacy of this approach both in the metastatic and definitive setting. Through immune priming, radiation may enhance local tumor control at the irradiated site, as well as induce a systemic response to control distant metastasis, known as the abscopal effect. On a mechanistic level, radiation therapy releases tumor neoantigens and activates an adaptive immune response that is mediated by cytotoxic T-cells, which then hone to sites of irradiated tumor as well as non-irradiated tumor metastases to induce immunogenic tumor cell death. Although the abscopal effect is rare in clinical practice, strategies that combine immune checkpoint blockade with radiation are being studied to overcome immune tolerance or suppression and increase systemic response rates to IO agents. Gynecologic cancers are attractive targets for immune checkpoint blockade, and IO agents may be used in combination with definitive chemoradiotherapy to enhance radiosensitivity and thus local control for unresected disease as well as control distant micrometastatic spread. For patients with metastatic disease, immune checkpoint blockade in combination with stereotactic radiotherapy is being evaluated as a strategy for immune activation and tumor cytoreduction. In this review, we highlight the current use of IO agents in gynecologic cancer, describe the immunogenic potential of radiation through clinical observation and preclinical study, and discuss strategies for combining IO and radiation in reported and ongoing clinical trials.

Gaillard SL, Andreano KJ, Gay LM, et al.
Constitutively active ESR1 mutations in gynecologic malignancies and clinical response to estrogen-receptor directed therapies.
Gynecol Oncol. 2019; 154(1):199-206 [PubMed] Related Publications
OBJECTIVE: Endocrine therapy is often considered as a treatment for hormone-responsive gynecologic malignancies. In breast cancer, activating mutations in the estrogen receptor (mutESR1) contribute to therapeutic resistance to endocrine therapy, especially aromatase inhibitors (AIs). The purpose of this study was to evaluate the frequency and clinical relevance of ESR1 genomic alterations in gynecologic malignancies.
METHODS: DNA from FFPE tumor tissue obtained during routine clinical care for 9645 gynecologic malignancies (ovary, fallopian tube, uterus, cervix, vagina, vulvar, and placenta) was analyzed for all classes of genomic alterations (base substitutions (muts), insertions, deletions, rearrangements, and amplifications) in ESR1 by hybrid capture next generation sequencing. A subset of alterations was characterized in laboratory-based transcription assays for response to endocrine therapies.
RESULTS: A total of 295 ESR1 genomic alterations were identified in 285 (3.0%) cases. mutESR1 were present in 86 (0.9%) cases and were more common in uterine compared to other cancers (2.0% vs <1%, respectively p < 0.001). mutESR1 were enriched in carcinomas with endometrioid versus serous histology (4.4% vs 0.2% respectively, p < 0.0001 in uterine and 3.5% vs 0.3% respectively, p = 0.0004 in ovarian carcinomas). In three of four patients with serial sampling, mutESR1 emerged under the selective pressure of AI therapy. Despite decreased potency of estrogen receptor (ER) antagonists in transcriptional assays, clinical benefit was observed following treatment with selective ER-targeted therapy, in one case lasting >48 months.
CONCLUSIONS: While the prevalence of ESR1 mutations in gynecologic malignancies is low, there are significant clinical implications useful in guiding therapeutic approaches for these cancers.

Lefkowits C, Bevis K, Carey EC, et al.
Gynecologic oncology providers endorse practice-changing impact of communication skills training.
Gynecol Oncol. 2019; 153(3):633-638 [PubMed] Related Publications
OBJECTIVE: Effective communication improves patient outcomes and is crucial to good patient care. Communication skills training (CST) has been shown to improve communication skills in non-gynecologic oncology specialties. We sought to develop and test CST for gynecologic oncology (GO) providers.
METHODS: We developed and conducted a two-day CST workshop with an interprofessional group of 20 GO providers over two years. Participants were surveyed pre-workshop, immediately post-workshop and one month post-workshop regarding self-assessed preparedness to handle challenging communication tasks, workshop evaluation and impact on practice. McNemar's tests were used for pre-post comparisons.
RESULTS: Of 12 challenging communication tasks assessed, all participants reported improvement in at least one, with a median of 10. The proportion of participants feeling more than "somewhat prepared" improved significantly for all communication tasks assessed (p < 0.05); improvement was sustained one month later. One month post-workshop, 86% reported thinking about what they had been taught at least weekly and 93% reported encountering situations where they used their CST skills at least weekly. Rates of reported practice-changing impact were >75% for each communication skill. All participants rated the CST educational quality very good or excellent and strongly agreed it should be required of all GO clinicians.
CONCLUSIONS: Participants felt the workshop provided high-quality, practice-changing education. As a result of the workshop, participants reported statistically significant, sustained improvement in preparedness to handle challenging communication tasks. CST for GO providers is feasible, with high rates of perceived effectiveness and impact on clinical practice. CST workshops should be integrated into GO training.

Horsboel TA, Kjaer SK, Johansen C, et al.
Increased risk for depression persists for years among women treated for gynecological cancers - a register-based cohort study with up to 19 years of follow-up.
Gynecol Oncol. 2019; 153(3):625-632 [PubMed] Related Publications
OBJECTIVE: Little is known about long-term risk of depression in women treated for gynecological cancers. We aim to investigate risk for depression among these women compared to women without a history of cancer.
METHODS: We followed 16,833 women diagnosed with gynecological cancers between 1998 and 2013 and 138,888 reference women in nationwide registers for up to 19 years. Women with a history of severe psychiatric disorders, and those who had redeemed a prescription for antidepressants three years before study entry were excluded from analyses. Regression analyses were applied to compare the risk for antidepressant use among patients compared to reference women, and to investigate associations between socio-demographic as well as clinical risk factors and use of antidepressants.
RESULTS: We found an increased risk for antidepressant use among women treated for ovarian (HR 4.14, 95% CI 3.74-4.59), endometrial (HR 2.19, 95% CI 1.97-2.45), and cervical cancer (HR 3.14, 95% CI 2.74-3.61) one year after diagnosis. This increased risk persisted years after diagnosis in all three groups, with the longest (up to eight years) found for ovarian cancer. Advanced disease was strongly associated with antidepressant use followed by short education, and comorbidity.
CONCLUSIONS: Women diagnosed with gynecological cancer have an increased risk for depression compared to reference women. The risk remains increased for years after diagnosis throughout and beyond standard oncological follow-up care. Advanced disease, short education, and comorbidity are factors associated with antidepressant use in this patient group.

Chung YS, Park SY, Lee JY, et al.
Outcomes of non-high grade serous carcinoma after neoadjuvant chemotherapy for advanced-stage ovarian cancer: a Korean gynecologic oncology group study (OV 1708).
BMC Cancer. 2019; 19(1):341 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Outcomes of patients with ovarian high-grade serous carcinoma (HGSC) treated with neoadjuvant chemotherapy (NAC) have been widely studied, but there is limited information on the outcomes of patients with non-HGSC. This study aimed to evaluate the outcomes of NAC in non-HGSC patients with advanced-stage ovarian cancer.
METHODS: We conducted a retrospective cohort study of patients who underwent NAC for advanced stage non-HGSC between 2002 and 2017 in 17 institutions. Demographics, surgical outcomes, and survival rates were evaluated according to histological subtypes.
RESULTS: A total of 154 patients were included in this study, comprising 20 cases (13.0%) of mucinous adenocarcinoma, 31 cases (20.1%) of endometrioid adenocarcinoma, 28 (18.2%) cases of clear cell carcinoma, 29 (18.8%) cases of low-grade serous carcinoma and 12 cases (7.8%) of carcinosarcoma. Complete remission/partial remission after the third cycle of NAC was achieved in 100 (64.9%) patients and optimal debulking surgery (residual disease ≤1 cm) at interval debulking surgery was achieved in 103 (66.9%) patients. The most common reason for performing NAC was high tumor burden (n = 106, 68.8%). The median progression-free survival (PFS) was 14.3 months and median overall survival (OS) was 52.9 months. In multivariate analyses, mucinous and clear cell carcinoma were negative prognostic factors for both PFS (p = 0.007 and p = 0.017, respectively) and OS (p = 0.002 and p = 0.013, respectively).
CONCLUSIONS: In this study, poor survival outcomes were observed in patients with mucinous and clear cell carcinoma undergoing NAC. Different treatment strategies are urgently required to improve survival outcomes for this disease subset.

Celio L, Saibene G, Lepori S, et al.
Short-course olanzapine to prevent delayed emesis following carboplatin/paclitaxel for gynecologic cancer: a randomised study.
Tumori. 2019; 105(3):253-258 [PubMed] Related Publications
PURPOSE: To explore efficacy of short-course olanzapine with or without low-dose dexamethasone for prevention of delayed emesis in gynecologic cancer patients receiving carboplatin/paclitaxel.
METHODS: This was a prospective study in 81 chemo-naive patients receiving 0.25 mg intravenous palonosetron, 16 mg dexamethasone, and 10 mg oral olanzapine before chemotherapy. On days 2 and 3, patients randomly received 10 mg olanzapine (arm A; n=27), 10 mg olanzapine plus 4 mg dexamethasone (arm B; n=27), or 8 mg dexamethasone (reference arm C; n=27). The primary endpoint was total control (TC; no vomiting, no rescue antiemetics, and no nausea) on days 2-5, using a diary. Secondary endpoints included proportion of patients with no emesis impact on daily life using the Functional Living Index-Emesis (FLIE) questionnaire, and patient's satisfaction with antiemetic coverage.
RESULTS: Fifty-two percent of patients in arm A (
CONCLUSIONS: In this exploratory study with a small sample size, we did not find any clue about better control of delayed emesis with either olanzapine regimen in gynecologic cancer patients treated with carboplatin/paclitaxel and receiving the same prophylaxis for acute emesis.

Shi X, Wang J, Lei Y, et al.
Research progress on the PI3K/AKT signaling pathway in gynecological cancer (Review).
Mol Med Rep. 2019; 19(6):4529-4535 [PubMed] Free Access to Full Article Related Publications
The phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (AKT) signaling pathway is involved in the regulation of multiple cellular physiological processes by activating downstream corresponding effector molecules, which serve an important role in the cell cycle, growth and proliferation. This is a common phenomenon; overactivation of the pathway is present in human malignancies and has been implicated in cancer progression, hence one of the important approaches to the treatment of tumors is rational drug design using molecular targets in the PI3K/AKT signaling pathway. In brief, the present review analyzed the effects of the PI3K/AKT signaling pathway on certain gynecological cancer types.

Lee EK, Liu JF
Antibody-drug conjugates in gynecologic malignancies.
Gynecol Oncol. 2019; 153(3):694-702 [PubMed] Related Publications
Antibody drug conjugates (ADCs) are an exciting class of oncologic therapeutics. ADCs have been FDA approved in hematologic malignancies and breast cancer and are a growing area of study in numerous solid malignancies. The desire for tumor-specific therapies with decreased systemic toxicity has driven over a decade of research into the design and optimization of ADCs, which are now in a third generation of development. Gynecologic malignancies in particular suffer a dearth of novel therapies. This review will examine the field of ADCs in gynecologic cancers, focusing on ADCs targeting folate receptor alpha (FRα), mesothelin, tissue factor, MUC16 (CA125), NaPi2B, and Trop2.

Nogami Y, Banno K, Adachi M, et al.
Profiling of the Causative Bacteria in Infected Lymphocysts after Lymphadenectomy for Gynecologic Cancer by Pyrosequencing the 16S Ribosomal RNA Gene Using Next-Generation Sequencing Technology.
Infect Dis Obstet Gynecol. 2019; 2019:9326285 [PubMed] Free Access to Full Article Related Publications
Background: Surgery for gynecologic cancer with lymphadenectomy and pelvic radiotherapy can produce lymphoceles that sometimes complicate with infection, resulting in abscesses. The true pathogenic bacteria of abscesses are not always found because of false-negative results due to administered antibiotics and difficulty with detection, including for anaerobic bacteria. Analyzing bacteria flora by next-generation sequencing (NGS) using 16S ribosomal DNA may reveal the true pathogenic bacteria in abscesses. This is the first report on causative pathogens for infectious lymphocele using this technology.
Methods: The subjects were patients who developed infectious lymphocele after surgery for gynecologic cancer at our hospital from July 2015 to September 2016. NGS analyses of bacterial flora were performed using specimens preserved at -80°C. Two steps of PCR were performed for purified DNA samples to obtain sequence libraries. Processing of sequence data, including operational taxonomic unit (OTU) definition, taxonomy assignment, and an OTU BLAST search were performed. All patients gave written informed consent and the study was approved by the institutional research ethics committee.
Results: Six patients underwent puncture and drainage. The result in most cases indicated a single causative pathogen, including

DiSilvestro PA
Shaping the standard of care in ovarian cancer management: A review of Gynecologic Oncology Group (GOG)/NRG oncology clinical trials of the past twenty years.
Gynecol Oncol. 2019; 153(3):479-486 [PubMed] Related Publications
The Gynecologic Oncology Group (GOG), now part of the NRG Oncology network since the re-alignment of the National Clinical Trials Network in 2014, has played a fundamental role in creating the standard of care for women with ovarian cancer. GOG/NRG Oncology has had a series of achievements that have contributed to how we treat this disease; the approval of bevacizumab in frontline therapy, defining the role of intraperitoneal chemotherapy, optimal chemotherapy for early stage disease and the role of surgery in primary and recurrent disease management. Going forward, GOG/NRG Oncology is positioned to meet the ever changing knowledge that we have about the molecular background of this disease and the expanding repertoire of drugs/interventions in development.

Moss HA, Melamed A, Wright JD
Measuring cause-and-effect relationships without randomized clinical trials: Quasi-experimental methods for gynecologic oncology research.
Gynecol Oncol. 2019; 152(3):533-539 [PubMed] Related Publications
Clinical research in gynecologic oncology has seen a proliferation of studies that investigate the effectiveness of treatments using existing data sources such as cancer registries, electronic health records, and insurance claims. These observational studies are often feasible when randomized trial may not be, and may be more generalizable than randomized trials, because of greater diversity in the study populations. While statistical methods such as multivariable regression, matching, stratification, and weighting can adjust for the confounding in observational studies, statistical adjustment cannot control for confounders that are unmeasured in the data. Observational studies comparing the effectiveness of treatments for gynecologic malignancies are susceptible to bias from unmeasured confounding because factors like functional status, frailty and disease burden, which influence treatment selection and outcome, are often not reported in existing data sources. Like randomized trials, quasi-experimental designs attempt to account for both measured and unmeasured confounding by exploiting natural experiments arising in the real world. These methods are underutilized in gynecologic oncology research and are particularly relevant to studies that use large datasets to study the effectiveness of treatments. In this review, we consider methodological challenges that arise in the analysis of non-randomized studies, and describe how application of quasi-experimental methodology can estimate unbiased treatment effects even in the presence of unmeasured confounders.

Gressel GM, Dioun SM, Richley M, et al.
Utilizing the Patient Reported Outcomes Measurement Information System (PROMIS®) to increase referral to ancillary support services for severely symptomatic patients with gynecologic cancer.
Gynecol Oncol. 2019; 152(3):509-513 [PubMed] Related Publications
OBJECTIVE: The Patient-Reported Outcomes Measurement Information System (PROMIS®) Network has developed a comprehensive repository of electronic patient reported outcomes measures (ePROs) of major symptom domains that have been validated in cancer patients. Their use for patients with gynecologic cancer has been understudied. Our objective was to establish feasibility and acceptability of PROMIS ePRO integration in a gynecologic oncology outpatient clinic and assess if it can help identify severely symptomatic patients and increase referral to supportive services.
METHODS: English-speaking patients with a confirmed history of gynecologic cancer completed PROMIS ePROs on iPads in the waiting area of an outpatient gynecologic oncology clinic. Symptom scores were calculated for each respondent and grouped using documented severity thresholds. Response data was compared with clinicopathologic characteristics across symptom domains. Severely symptomatic patients were offered referral to ancillary services and asked to complete post-exposure surveys assessing acceptability of the ePRO.
RESULTS: Of the 336 patients who completed ePROs, 35% had active disease and 19% had experienced at least one disease recurrence. Sixty-nine percent of the cohort demonstrated moderate to severe physical dysfunction (60%), pain (36%), fatigue (28%), anxiety (9%), depression (8%), and sexual dysfunction (32%). Thirty-nine (12%) severely symptomatic patients were referred to services such as psychiatry, palliative care, pain management, social work or integrative oncology care. Most survey respondents identified the ePROs as helpful (78%) and easy to complete (92%).
CONCLUSIONS: Outpatient PROMIS ePRO administration is feasible and acceptable to gynecologic oncology patients and can help identify severely symptomatic patients for referral to ancillary support services.

Wang XS, Shi Q, Williams LA, et al.
Validation and application of a module of the MD Anderson Symptom Inventory for measuring perioperative symptom burden in patients with gynecologic cancer (the MDASI-PeriOp-GYN).
Gynecol Oncol. 2019; 152(3):492-500 [PubMed] Article available free on PMC after 01/03/2020 Related Publications
OBJECTIVE: Using patient-reported outcomes (PROs) in perioperative care is increasingly common. We report the development, validation, and application of an MD Anderson Symptom Inventory version for use in patients undergoing surgery for gynecologic cancer or benign conditions (MDASI-PeriOp-GYN).
METHODS: Our process included: (1) generating PeriOp-GYN-specific candidate items from qualitative interviews with patients, followed by input from an expert panel; (2) dropping items that lacked independent clinical relevance; (3) validating psychometric properties (reliability, validity) of the resulting MDASI-PeriOp-GYN; and (4) conducting cognitive debriefing interviews with patients to confirm ease of comprehension, relevance, and acceptability.
RESULTS: Qualitative interviews with 40 patients generated 9 new PeriOp-GYN symptom items (bloating, abdominal cramping, constipation, hot flashes, dizziness, grogginess/confusion, urinary pain, difficulty urinating, and diarrhea) that, along with the core MDASI items, formed the new MDASI-PeriOp-GYN. A total of 150 patients (minimally invasive surgery (MIS) = 69, open surgery = 81) participated in the validation study; 121 patients also provided retest data. Cronbach alphas were 0.89 for symptoms and 0.86 for interference. Test-retest reliability was 0.88 for all symptom severity items. Known-group validity was supported by the detection of significant differences in symptom and interference levels by performance status (P < 0.01) and for all symptoms by surgery type (P < 0.01). Cognitive debriefing with 20 of the 150 patients demonstrated that the MDASI-PeriOp-GYN is an easy-to-use and understandable tool.
CONCLUSIONS: The MDASI-PeriOp-GYN is a valid, reliable, concise tool for measuring symptom severity and functional interference in patients undergoing gynecologic surgery and can be useful in assessing postoperative symptom burden via PROs.

Kumar A, Nesbitt KM, Bakkum-Gamez JN
Quality improvement in gynecologic oncology: Current successes and future promise.
Gynecol Oncol. 2019; 152(3):486-491 [PubMed] Related Publications
Quality improvement in healthcare has accelerated over the past two decades, including in gynecologic oncology. Improvements have been made on a practice, institution, system and national scale, and efforts have focused on improving safety, efficiency, and cost of care. Gynecologic oncology practitioners ought to engage in this work to improve patient outcomes, comply with federal regulation, and continue to meet required educational requirements of training programs. In gynecologic oncology there are already many examples of successful quality improvement initiatives that have resulted in improved patient care, including the implementation of enhanced recovery after surgery programs, reduction in blood transfusion, and increases in guideline adherent cancer care. Quality improvement methodology is born out of industrial engineering and includes Six Sigma and Lean; both are frameworks for implementing quality improvement as a process and can be adopted in healthcare settings to achieve the desired outcomes. Six Sigma is a system that aims to have a 99.9997% defect free process, and uses the DMAIC (Define-Measure-Analyze-Improve-Control) framework to guide stakeholders in their work. Lean is a concept aimed at reducing waste in process. Regardless of methodology used, the most important aspect of successful quality improvement is the use of change-management theory to achieve stakeholder buy-in and institutional participation. The physician champion is a key element to this. Finally, once a project has been completed, successfully or not, it is important to disseminate the experience. This will allow for adoption and replication in other institutions. It also can serve as a mechanism for academic recognition and advancement. Quality improvement is an important and growing field in medicine, and has an important role in the future of gynecologic oncology.

Nguyen JMV, Sadeghi M, Gien LT, et al.
Impact of a preventive bundle to reduce surgical site infections in gynecologic oncology.
Gynecol Oncol. 2019; 152(3):480-485 [PubMed] Related Publications
OBJECTIVE: To assess the impact of a surgical site infection (SSI) prevention bundle for Gynecologic Oncology patients at a large academic tertiary centre in Toronto, Canada.
METHODS: A SSI prevention bundle was implemented in February 2017 including: preoperative chlorhexidine shower, prophylactic antibiotics, glycemic control, normothermia, and separate closing tray. Data were collected prospectively using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) institutional data, and chart review of surgeries between January 2016 and September 2017 was performed. The primary outcome was rate of SSIs, secondary outcomes were: superficial, deep and organ space SSIs, sepsis, wound disruption, length of stay, 30-day readmission and reoperation. Logistic regression analysis was conducted to identify predictors of SSIs.
RESULTS: 339 baseline and 224 post-intervention patients were included. 53 incurred one or more SSIs: 43 superficial, 6 deep, and 14 organ-space. The bundle decreased overall SSIs by 55% (12.1% to 5.4%, p = 0.008) and superficial SSIs by 54% (9.7% to 4.5%, p = 0.023). Improvement was sustained for 6 quarters. No significant difference was found in other secondary outcomes. On multivariable analysis, surgery in the pre-bundle period, BMI ≥30, laparotomies and longer operative duration were independent risk factors for overall SSIs (OR 2.23, 95% CI 1.06-5.06, -OR 3.01, 95% CI 1.57 - 5.87, OR 3.70, 95% CI 1.56 - 10.18 and - OR 2.16, 95% 1.11 - 4.19, respectively).
CONCLUSIONS: This prevention bundle successfully decreased SSIs in patients undergoing gynecologic cancer surgery. We recommend improving quality of care by wide implementation of SSI prevention bundles in Gynecologic Oncology patients.

Chen HH, Ting WH, Lin HH, Hsiao SM
Predictors of Lymphoceles in Women Who Underwent Laparotomic Retroperitoneal Lymph Node Dissection for Early Gynecologic Cancer: A Retrospective Cohort Study.
Int J Environ Res Public Health. 2019; 16(6) [PubMed] Article available free on PMC after 01/03/2020 Related Publications

Murakami R, Matsumura N, Michimae H, et al.
The mesenchymal transition subtype more responsive to dose dense taxane chemotherapy combined with carboplatin than to conventional taxane and carboplatin chemotherapy in high grade serous ovarian carcinoma: A survey of Japanese Gynecologic Oncology Group study (JGOG3016A1).
Gynecol Oncol. 2019; 153(2):312-319 [PubMed] Related Publications
OBJECTIVE: Recently, we established new histopathological subtypes of high-grade serous ovarian cancer (HGSOC) that include the mesenchymal transition (MT) type, the immune reactive (IR) type, the solid and proliferative (SP) type and the papillo-glandular (PG) type. Furthermore, we identified that the mesenchymal transcriptome subtype might be sensitive to taxane. We investigated whether these different histopathological subtypes of HGSOC require individualized chemotherapy for optimal treatment.
METHODS: We conducted the Japanese Gynecologic Oncology Group (JGOG) 3016A1 study, wherein we collected hematoxylin and eosin slides (total n = 201) and performed a histopathological analysis of patients with HGSOC registered in the JGOG3016 study, which compared the efficacy of conventional paclitaxel and carboplatin (TC) and dose-dense TC (ddTC). We analyzed the differences in progression-free survival (PFS) and overall survival (OS) among the four histopathological subtypes. We then compared the PFS between the TC group and the ddTC group for each histopathological subtype.
RESULTS: There were significant differences in both PFS and OS among the four histopathological subtypes (p = 0.001 and p < 0.001, respectively). Overall, the MT subtype had the shortest PFS (median 1.4 y) and OS (median 3.6 y). In addition, the MT subtype had a longer PFS in the ddTC group (median 1.8 y) than in the TC group (median 1.2 y) (p = 0.01). Conversely, the other types had no significant difference in PFS when the two regimens were compared.
CONCLUSIONS: The MT type of HGSOC is sensitive to taxane; therefore, the ddTC regimen is recommended for this histopathological subtype.

Romanyukha A, Carrara M, Mazzeo D, et al.
An innovative gynecological HDR brachytherapy applicator system for treatment delivery and real-time verification.
Phys Med. 2019; 59:151-157 [PubMed] Related Publications
The multichannel vaginal cylinder (MVC) applicator employed for gynecological high dose rate (HDR) brachytherapy increases dose delivery complexity, and thus makes the treatment more prone to errors. A quality assurance (QA) procedure tracking the source throughout dose delivery can detect dwell position and time errors in the multiple channels of the applicator. A new MVC system with integrated real time in vivo treatment delivery QA has been developed based on diodes embedded on the outer surface of the MVC. It has been pre-calibrated and verified using a non-clinical treatment plan with consecutive test positions and dwell times within each catheter, followed by the delivery of ten clinical plans of adjuvant vaginal cuff brachytherapy following hysterectomy for endometrial cancer. The non-clinical verification showed overall mean dwell position and time discrepancies between the nominal and measured treatment of -0.2 ± 0.5 mm and -0.1 ± 0.1 s (k = 1), respectively. The clinical plans showed mean positional discrepancies of 0.2 ± 0.4 and 0.0 ± 0.8 mm, for the central and peripheral catheters, respectively, and mean dwell time discrepancies of -0.1 ± 0.2 and -0.0 ± 0.1 s for central and peripheral catheters, respectively. The innovative prototype of the MVC system has shown the ability to track the source with sub-mm and sub-second accuracy, and demonstrated potential for its incorporation into the clinical routine.

Brooks RA, Tritchler DS, Darcy KM, et al.
GOG 8020/210: Risk stratification of lymph node metastasis, disease progression and survival using single nucleotide polymorphisms in endometrial cancer: An NRG oncology/gynecologic oncology group study.
Gynecol Oncol. 2019; 153(2):335-342 [PubMed] Article available free on PMC after 01/03/2020 Related Publications
OBJECTIVES: The ability to stratify a patient's risk of metastasis and survival permits more refined care. A proof of principle study was undertaken to investigate the relationship between single nucleotide polymorphisms (SNPs) in literature based candidate cancer genes and the risk of nodal metastasis and clinical outcome in endometrioid endometrial cancer (EEC) patients.
METHODS: Surgically-staged EEC patients from the Gynecologic Oncology Group or Washington University School of Medicine with germline DNA available were eligible. Fifty-four genes represented by 384 SNPs, were evaluated by Illumina Custom GoldenGate array. Association with lymph node metastases was the primary outcome. Progression-free survival (PFS) and overall survival (OS) was also evaluated.
RESULTS: 361 SNPs with high quality genotype data were evaluated in 337 patients with outcome data. Five SNPs in CXCR2 had an odds ratio (OR) between 0.68 and 0.70 (p-value ≤ 0.025). The A allele rs946486 in ABL had an OR of 1.5 (p-value = 0.01) for metastasis. The G allele in rs7795743 in EGFR had an OR for metastasis of 0.68 (p-value = 0.02) and hazard ratio (HR) for progression of 0.66 (p-value = 0.004). Importantly, no SNP met genome wide significance after adjusting for multiple test correcting and clinical covariates. The A allele in rs2159359 SNP in NME1 and the G allele in rs13222385 in EGFR were associated with worse OS. Both exhibited genome wide significance; rs13222385 remained significant after adjusting for prognostic clinical variables.
CONCLUSION: SNPs in cancer genes including rs2159359 SNP in NME1 and rs13222385 in EGFR may stratify risk in EEC and are prioritized for further investigation.

Arquiette JM, Moss HA, Truong T, et al.
Impact of a documentation intervention on health-assessment metrics on an inpatient gynecologic oncology service.
Gynecol Oncol. 2019; 153(2):385-390 [PubMed] Related Publications
OBJECTIVE: Accurate documentation is critical for patient care and hospital reimbursement. We sought to improve the accuracy of severity of illness (SOI) and risk of mortality (ROM) scores through implementation of documentation initiatives.
METHODS: We performed a pre- versus post-implementation analysis to assess the impact of a documentation intervention bundle on calculated admission/discharge SOI/ROM scores on an inpatient gynecologic oncology service. Introduced in January 2017, the bundle included educational in-service, introduction of problem-based progress notes, a documentation tip ID badge and video, and weekly chart audits. Admission/discharge SOI/ROM scores (range 1-4) were obtained from hospital performance services. Demographics and 30-day mortality were collected from electronic medical records for all inpatients in historic (calendar year 2015) and intervention (2017) cohorts. Primary outcomes (discharge SOI/ROM) were modelled using ordinal and multinomial logistic regressions, controlling for confounders. 30-day observed/expected mortality ratios were reported for each cohort.
RESULTS: 629 patients were included: 378 (60%) in 2015, 251 (40%) in 2017. Increased odds of having higher SOI score were observed in the intervention cohort for medical (OR = 2.22; 95% CI 1.38, 3.58) and surgical admissions (OR = 2.63; 95% CI 1.47, 4.40). Surgical (OR = 5.54; 95% CI 1.29, 23.96), but not medical (OR = 1.45; 95% CI 0.46, 4.57), admissions in the intervention cohort had higher odds of having the worst ROM score. Observed/expected mortality was 0.24 in the intervention compared to 0.37 in historic cohort (p = 0.58, NS).
CONCLUSION: An intervention bundle to improve physician documentation accuracy resulted in higher discharge SOI scores for medical and surgical admissions.

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