Showing papers in "International Journal of Gynecological Cancer in 2019"
TL;DR: This is the first updated Enhanced Recovery After Surgery (ERAS) Society guideline presenting a consensus for optimal perioperative care in gynecologic/oncology surgery, and the updated evidence base and recommendation are presented.
Abstract: BACKGROUND: This is the first updated Enhanced Recovery After Surgery (ERAS) Society guideline presenting a consensus for optimal perioperative care in gynecologic/oncology surgery.METHODS: A datab ...
390 citations
TL;DR: The European Society for Medical Oncology (ESMO) and European Society of Gynaecologia (ESGO) jointly developed clinically relevant and evidence-based recommendations in several selected areas in order to improve the quality of care for women with ovarian cancer.
Abstract: The development of guidelines is one of the core activities of the European Society for Medical Oncology (ESMO) and European Society of Gynaecologial Oncology (ESGO), as part of the mission of both societies to improve the quality of care for patients with cancer across Europe. ESMO and ESGO jointly developed clinically relevant and evidence-based recommendations in several selected areas in order to improve the quality of care for women with ovarian cancer. The ESMO–ESGO consensus conference on ovarian cancer was held on April 12–14, 2018 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of ovarian cancer. Before the conference, the expert panel worked on five clinically relevant questions regarding ovarian cancer relating to each of the following four areas: pathology and molecular biology, early-stage and borderline tumours, advanced stage disease and recurrent disease. Relevant scientific literature, as identified using a systematic search, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. The recommendations presented here are thus based on the best available evidence and expert agreement. This article presents the recommendations of this ESMO–ESGO consensus conference, together with a summary of evidence supporting each recommendation.
134 citations
TL;DR: The combined laparoscopic-vaginal technique for radical hysterectomy with avoidance of spillage and manipulation of tumor cells provides excellent oncologic outcome for patients with early cervical cancer.
Abstract: Objective Laparoscopic/robotic radical hysterectomy has been historically considered oncologically equivalent to open radical hysterectomy for patients with early cervical cancer. However, a recent prospective randomized trial (Laparoscopic Approach to Cervical Cancer, LACC) has demonstrated significant inferiority of the minimally invasive approach. The aim of this study is to evaluate the oncologic outcomes of combined laparoscopic-vaginal radical hysterectomy. Methods Between August 1994 and December 2018, patients with invasive cervical cancer were treated using minimally-invasive surgery at the Universities of Jena, Charite Berlin (Campus CCM and CBF) and Cologne and Asklepios Clinic Hamburg. 389 patients with inclusion criteria identical to the LACC trial were identified. In contrast to the laparoscopic/robotic technique used in the LACC trial, all patients in our cohort underwent a combined transvaginal-laparoscopic approach without the use of any uterine manipulator. Results A total of 1952 consecutive patients with cervical cancer were included in the analysis. Initial International Federation of Gynecology and Obstetrics (FIGO) stage was IA1 lymphovascular space invasion (LVSI+), IA2 and IB1/IIA1 in 32 (8%), 43 (11%), and 314 (81%) patients, respectively, and histology was squamous cell in 263 (68%), adenocarcinoma in 117 (30%), and adenosquamous in 9 (2%) patients. Lymphovascular invasion was confirmed in 106 (27%) patients. The median number of lymph nodes was 24 (range 2–86). Lymph nodes were tumor-free in 379 (97%) patients. Following radical hysterectomy, 71 (18%) patients underwent adjuvant chemoradiation or radiation. After a median follow-up of 99 (range 1–288) months, the 3-, 4.5-, and 10-year disease-free survival rates were 96.8%, 95.8%, and 93.1 %, and the 3-, 4.5-, and 10-year overall survival rates were 98.5%, 97.8%, and 95.8%, respectively. Recurrence location was loco-regional in 50% of cases with recurrence (n=10). Interestingly, 9/20 recurrences occurred more than 39 months after surgery. Conclusion The combined laparoscopic-vaginal technique for radical hysterectomy with avoidance of spillage and manipulation of tumor cells provides excellent oncologic outcome for patients with early cervical cancer. Our retrospective data suggest that laparoscopic-vaginal surgery may be oncologically safe and should be validated in further randomized trials.
124 citations
TL;DR: It is hypothesize that disease-free survival is non-inferior and health-related quality of life superior after Sentinel lymph node (SLN) biopsy compared with SLN biopsy + pelvic lymphadenectomy in early cervical cancer.
Abstract: Background Radical hysterectomy and complete pelvic lymphadenectomies are the most commonly performed procedures for women with early-stage cervical cancer. Sentinel lymph node (SLN) mapping could be an alternative to routine pelvic lymphadenectomy, aiming to diagnose accurately nodal extension and decrease lymphatic morbidity. Primary Objective To compare 3-year disease-free survival and health-related quality of life after SLN biopsy or SLN biopsy + pelvic lymphadenectomy in early cervical cancer. Study Hypothesis We hypothesize that disease-free survival is non-inferior and health-related quality of life superior after SLN biopsy compared with SLN biopsy + pelvic lymphadenectomy. Trial Design International, randomized, multicenter, single-blind trial. The study will be run by teams trained to carry out SLN biopsy, belonging to clinical research cooperative groups or recognized as experts in this field. Patients with an optimal mapping (Memorial Sloan Kettering Cancer Center [MSKCC] criteria) and a negative frozen section will be randomized 1:1 to SLN biopsy only or SLN biopsy + pelvic lymphadenectomy. Inclusion, Exclusion Criteria Patients with early stages (Ia1 with lymphovascular invasion to IIa1) of disease. Histological types are limited to squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma. Primary Endpoint Main endpoint will be co-primary endpoint, associating 3-year disease-free survival and quality of life (QLQ-C30 and QLQ-CX24). Sample Size 950 patients need to be randomized. Estimated dates for completing accrual and presenting results: study started on Q2 2018, last accrual is scheduled for Q2 2021, and last follow-up in Q2 2026. Trial registration ClinicalTrials.gov identifier: NCT03386734.
91 citations
TL;DR: TRUST is an international open, randomized, controlled multi-center trial investigating overall survival after primary cytoreductive surgery versus neoadjuvant chemotherapy and subsequent interval cytoreduction surgery in patients with FIGO stage IIIB–IVB ovarian, tubal, and peritoneal carcinoma.
Abstract: Background Primary cytoreductive surgery followed by chemotherapy has been considered standard management for patients with advanced ovarian cancer over decades. An alternative approach of interval debulking surgery following neoadjuvant chemotherapy was subsequently reported by two randomized phase III trials (EORTC‐GCG, CHORUS), which were criticized owing to important limitations, especially regarding the rate of complete resection. Primary Objective To clarify the optimal timing of surgical therapy in advanced ovarian cancer. Study Hypothesis Primary cytoreductive surgery is superior to interval cytoreductive surgery following neoadjuvant chemotherapy for overall survival in patients with advanced ovarian cancer. Trial Design TRUST is an international open, randomized, controlled multi-center trial investigating overall survival after primary cytoreductive surgery versus neoadjuvant chemotherapy and subsequent interval cytoreductive surgery in patients with FIGO stage IIIB–IVB ovarian, tubal, and peritoneal carcinoma. To guarantee adequate surgical quality, participating centers need to fulfill specific quality assurance criteria (eg, ≥50% complete resection rate in upfront surgery for FIGO IIIB–IVB patients, ≥36 debulking-surgeries/year) and agree to independent audits by TRUST quality committee delegates. Patients in the primary cytoreductive surgery arm undergo surgery followed by 6 cycles of platinum-based chemotherapy, whereas patients in the interval cytoreductive surgery arm undergo 3 cycles of neoadjuvant chemotherapy after histologic confirmation of the disease, followed by interval cytoreductive surgery and subsequently, 3 cycles of platinum-based chemotherapy. The intention of surgery for both groups is complete tumor resection according to guideline recommendations. Major Inclusion/Exclusion Criteria Major inclusion criteria are suspected or histologically confirmed, newly diagnosed invasive epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma FIGO stage IIIB–IVB (IV only if resectable metastasis). Major exclusion criteria are non-epithelial ovarian malignancies and borderline tumors; prior chemotherapy for ovarian cancer; or abdominal/pelvic radiotherapy. Primary Endpoint Overall survival. Sample Size 772 patients. Estimated Dates for Completing Accrual and Presenting Results Accrual completion approximately mid-2019, results are expected after 5 years9 follow-up in 2024. Trial Registration NCT02828618.
77 citations
TL;DR: The data suggest that gBRCA testing should be carried out in all patients with ovarian cancer, irrespective of the service provider’s professional position.
Abstract: Introduction BRCA gene mutations are associated with hereditary ovarian cancer. BRCA plays a key role in genome integrity, and mutations result in an increased risk for ovarian cancer. Although various guidelines recommend BRCA testing in patients with ovarian cancer, data on germline BRCA (gBRCA) mutation frequency in ovarian cancer in Japan are scarce. Objective This study aimed to determine gBRCA1/2 mutations in Japanese patients with ovarian cancer, stratified by clinicopathological characteristics, and to assess patients’ satisfaction with pre-test genetic counseling. Methods The CHARLOTTE study (CHARacterizing the cross-sectionaL approach to Ovarian cancer: geneTic TEsting of BRCA; UMIN000025597) is the first large multicenter epidemiological survey of Japanese women, aged ≥20, with newly diagnosed ovarian cancer (epithelial, primary peritoneal, or fallopian tube cancer), with histologically confirmed specimens. Patients were enrolled sequentially and underwent pre-test genetic counseling for BRCA testing. Blood samples were centrally tested for the presence or absence of known gBRCA mutations. A questionnaire was used to assess patient satisfaction with pre-test genetic counseling. Results A total of 634 patients with a mean age of 56.9 years were included. Most patients (84.2%) had epithelial ovarian cancer, and 51.1% had FIGO stage III–IV cancer. Nearly all patients (99.5%) received genetic counseling before the BRCA testing, either by an obstetrician-gynecologist (42.0%) or a clinical geneticist (42.0%). The overall prevalence of gBRCA1/2 mutations was 14.7% (93/634), with gBRCA1 mutations (9.9%) more common than gBRCA2 mutations (4.7%). High-grade serous carcinoma showed a prevalence of gBRCA mutations of 28.5%. Most patients were satisfied with pre-test counseling, irrespective of the service provider’s professional position. Discussion Patients with high-grade serous carcinoma and family history of ovarian cancer had a slightly higher prevalence of gBRCA mutations, but none of the subgroups had considerably high gBRCA mutation prevalence. These data suggest that gBRCA testing should be carried out in all patients with ovarian cancer.
71 citations
TL;DR: Robot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer post-operative complications and superior patient-reported outcomes in this study.
Abstract: Background Radical hysterectomy with pelvic lymphadenectomy represents the standard treatment for early-stage cervical cancer. Results from a recent randomized controlled trial demonstrate that minimally invasive surgery is inferior to laparotomy with regards to disease-free and overall survival. Primary Objective To investigate the oncologic safety of robot-assisted surgery for early-stage cervical cancer as compared with standard laparotomy. Study Hypothesis Robot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer post-operative complications and superior patient-reported outcomes. Trial Design Prospective, multi-institutional, international, open-label randomized clinical trial. Consecutive women with early-stage cervical cancer will be assessed for eligibility and subsequently randomized 1:1 to either robot-assisted laparoscopic surgery or laparotomy. Institutional review board approval will be required from all participating institutions. The trial is coordinated from Karolinska University Hospital, Sweden. Major Inclusion/Exclusion Criteria Women over 18 with cervical cancer FIGO (2018) stages IB1, IB2, and IIA1 squamous, adenocarcinoma, or adenosquamous will be included. Women are not eligible if they have evidence of metastatic disease, serious co-morbidity, or a secondary invasive neoplasm in the past 5 years. Primary Endpoint Recurrence-free survival at 5 years between women who underwent robot-assisted laparoscopic surgery versus laparotomy for early-stage cervical cancer. Sample Size The clinical non-inferiority margin in this study is defined as a 5-year recurrence-free survival not worsened by >7.5%. With an expected recurrence-free survival of 85%, the study needs to observe 127 events with a one-sided level of significance (α) of 5% and a power (1−β) of 80%. With 5 years of recruitment and 3 years of follow-up, the necessary number of events will be reached if the study can recruit a total of 768 patients. Estimated Dates for Completing Accrual and Presenting Results Trial launch is estimated to be May 2019 and the trial is estimated to close in May 2027 with presentation of data shortly thereafter. Trial Registration The trial is registered at ClinicalTrials.gov (NCT03719547).
67 citations
TL;DR: It seems that screening tools for ovarian cancer are currently not worthwhile for implementation into a national program, and an emphasis on reducing false positives rates, associated anxiety and subsequent overdiagnosis is needed.
Abstract: Ovarian cancer carries a lifetime risk of approximately 2% for women and is the leading cause of death from any gynecologic malignancy. Currently, no screening program for ovarian cancer exists for the general population in the UK. This review focuses on the evidence surrounding the efficacy of current markers and discusses future improvements in screening for this disease. One-off cancer antigen 125 (CA125) measurements for detecting ovarian cancer have been well researched. However, studies have highlighted low positive predictive values (5%) and high false positive rates leading to patient anxiety and unnecessary invasive follow-up. Commonly, in the UK, CA125 is combined with transvaginal ultrasound, but there is little evidence that this approach can decrease mortality from ovarian cancer. Recently the Risk of Ovarian Cancer Algorithm, involving a combination of serial CA125 measurements and age, has been shown to detect more early stage cancers. Nevertheless, these measures are not robust in decreasing mortality from ovarian cancer and are costly to implement. Newer markers, such as human epididymis protein 4, have shown greater specificity. Its combination with CA125 and menopausal status in the Risk of Ovarian Malignancy Algorithm can predict the risk of malignancy but provides no additional benefit as a screening tool. Advanced techniques are emerging, including ultrasound molecular imaging techniques using microbubbles targeted to kinase domain receptors, and fallopian tube cytology. To reduce mortality from ovarian cancer, detection of pre-invasive lesions is imperative as ovarian cancer may develop in the fallopian tube and spread to the peritoneal cavity before being detected systemically. It seems that screening tools for ovarian cancer are currently not worthwhile for implementation into a national program. An emphasis on reducing false positives rates, associated anxiety and subsequent overdiagnosis is needed.
65 citations
TL;DR: Multicenter tumor registries, such as the Neuroendocrine Cervical Tumor Registry (NeCTuR), are an opportunity to evaluate patterns of disease treatment and oncologic outcomes.
Abstract: Neuroendocrine carcinomas of the cervix account for less than 2% of all invasive cervical cancers and are classified as low-grade (carcinoid, atypical carcinoid tumor) or high-grade (known as small- and large-cell) neuroendocrine carcinomas. There are increasing data showing that cervical neuroendocrine carcinomas may be associated with the human papillomavirus (HPV), especially HPV18, and most will stain positive for p16. Immunohistochemistry markers such as synaptophysin and CD56 are the most sensitive markers. Although there are no commonly associated mutations, PIK3CA, KRAS, and TP53 are the most frequently found mutations in neuroendocrine tumors. Neuroendocrine cervical carcinomas are exceedingly aggressive tumors with a high tendency for nodal involvement and distant metastases. Age, lymph node metastases, smoking, pure small-cell histology, and tumor size are independent prognostic factors. Overall, the 5-year survival rate is 36% and the median overall survival ranges between 22 and 25 months. Treatment options are often extrapolated from small-cell lung cancer and limited retrospective studies. The preferred treatment is a multimodal approach of surgery, chemoradiation, and systemic chemotherapy. The most common chemotherapy regimen used as initial therapy is a combination of cisplatin and etoposide. In the setting of recurrent disease, a combination of topotecan, paclitaxel, and bevacizumab has demonstrated favorable outcomes. Multicenter tumor registries, such as the Neuroendocrine Cervical Tumor Registry (NeCTuR), are an opportunity to evaluate patterns of disease treatment and oncologic outcomes.
61 citations
TL;DR: Conservative surgery is oncologically safe in women with early stage, low-risk cervical carcinoma and recurrent disease has been diagnosed in 3 patients.
Abstract: Objective The objective of the ConCerv Trial was to prospectively evaluate the feasibility of conservative surgery in women with early-stage, low-risk cervical cancer. Methods From April 2010 to March 2019, a prospective, single-arm, multicenter study evaluated conservative surgery in participants from 16 sites in nine countries. Eligibility criteria included: (1) FIGO 2009 stage IA2–IB1 cervical carcinoma; (2) squamous cell (any grade) or adenocarcinoma (grade 1 or 2 only) histology; (3) tumor size Results 100 evaluable patients were enrolled. Median age at surgery was 38 years (range 23–67). Stage was IA2 (33%) and IB1 (67%). Surgery included conization followed by lymph node assessment in 44 women, conization followed by simple hysterectomy with lymph node assessment in 40 women, and inadvertent simple hysterectomy followed by lymph node dissection in 16 women. Positive lymph nodes were noted in 5 patients (5%). Residual disease in the post-conization hysterectomy specimen was noted in 1/40 patients—that is, an immediate failure rate of 2.5%. Median follow-up was 36.3 months (range 0.0–68.3). Three patients developed recurrent disease within 2 years of surgery—that is, a cumulative incidence of 3.5% (95% CI 0.9% to 9.0%). Discussion Our prospective data show that select patients with early-stage, low-risk cervical carcinoma may be offered conservative surgery.
56 citations
TL;DR: SENTIX is a prospective multicenter trial aiming to prove that less-radical surgery with SLN is non-inferior to treatment with systematic pelvic lymphadenectomy, and the quality of SLN pathology evaluation will be assessed by central review.
Abstract: Objective Sentinel lymph node (SLN) biopsy has been increasingly used in the management of early-stage cervical cancer. It appears in guidelines as an alternative option to systematic pelvic lymphadenectomy. The evidence about safety is, however, based mostly on retrospective studies, in which SLN was combined with systematic lymphadenectomy. Materials and methods SENTIX is a prospective multicenter trial aiming to prove that less-radical surgery with SLN is non-inferior to treatment with systematic pelvic lymphadenectomy. The primary end point is recurrence rate; the secondary end point is the prevalence of lower-leg lymphedema and symptomatic pelvic lymphocele. The reference recurrence rate was set up conservatively at 7% at 24 months after treatment. With a sample size of 300 patients treated per protocol, the trial is powered to detect a non-inferiority margin of 5% (90% power, p = 0.05) for recurrence rate, 30% reduction in the prevalence of symptomatic lymphocele or lower-leg lymphedema, with reference rates of 30% and 6% at 12 months (p = 0.025, Bonferroni correction). The patients eligible for SENTIX have stage IA1/LVSI+, IA2, IB1 ( IB1), or a positive intra-operative SLN assessment. The quality of SLN pathology evaluation will be assessed by central review. Three interim safety analyses are pre-planned when 30, 60, 150 patients complete 12 months' follow-up. Conclusions The first patient was enrolled into the study in June 2016 and, by June 2018, 340 patients had been enrolled. The first analysis of secondary outcomes should be available in 2019 and the oncological outcome of 300 patients at the end of 2021. The trial is registered as a CEEGOG trial (CEEGOG CX-01), ENGOT trial (ENGOT-Cx 2), and at the ClinicalTrials.gov database (NCT02494063).
TL;DR: Although sentinel lymph node navigation is a promising option, lymphadenectomy represents the primary treatment in many patients with endometrial cancer, however, comprehensive nodal dissection remains associated with a high rate of long term complications, such as lymphedema and lymphocele.
Abstract: Objective To determine the incidence of long term lymphadenectomy complications in primary surgery for endometrial cancer and to elucidate risk factors for these complications. Methods A retrospective chart review was carried out for all patients with endometrial cancer managed at Parma University Hospital Unit of Gynecology and Obstetrics between 2010 and 2016. Inclusion criteria were surgical procedure including hysterectomy and lymphadenectomy (pelvic or pelvic and aortic). We identified patients with postoperative lymphocele and lower extremity lymphedema. Logistic regression analysis was used to identify predictive factors for postoperative complications. Results Of the 249 patients tested, 198 underwent pelvic lymphadenectomy (79.5%), and 51 (20.5%) of those underwent both pelvic and para-aortic lymphadenectomy. Among the 249 patients, 92 (36.9 %) developed lymphedema while 43 (17.3%) developed lymphocele. Multivariate analysis showed that addition of para-artic lymphadenectomy was an independent predictor for both lymphedema (odds ratio (OR) 2.764, 95% confidence interval (CI) 1.023 to 7.470) and lymphocele (OR 5.066, 95% CI 1.605 to 15.989). Moreover, postoperative adjuvant radiotherapy (OR 2.733, 95% CI 1.149 to 6.505) and identification of any positive lymph node (OR 19.391, 95% CI 1.486 to 253.0) were significantly correlated with lymphedema, while removal of circumflex iliac nodes (OR 8.596, 95% CI 1.144 to 65.591) was associated with lymphoceles occurrence. Conclusion Although sentinel lymph node navigation is a promising option, lymphadenectomy represents the primary treatment in many patients with endometrial cancer. However, comprehensive nodal dissection remains associated with a high rate of long term complications, such as lymphedema and lymphocele. Avoiding risk factors that are related to the development of these postoperative complications is often difficult and, therefore, the strategy to assess lymph nodal status in these women must be tailored to obtain the maximum results in terms of oncological and functional outcome.
TL;DR: Evidence of micrometastasis or isolated tumor cells in the SLN of untreated patients with early cervical cancer in the SENTICOL1 trial did not impact progression-free survival and there was a significant decrease in disease- free survival in patients aged >50 years.
Abstract: This prospective study is a 3-year follow-up of patients included in the prospective longitudinal SENTICOL (Ganglion Sentinelle dans le Cancer du Col) study. Objectives The primary outcome was disease-free survival; the secondary outcome was the predictive value of the presence of micrometastasis and isolated tumor cells for recurrence. Methods The study included patients with cervical carcinoma FIGO (International Federation of Gynecology and Obstetrics) stage IA1 with lymphovascular space invasion, stage IA2 and IB1, who participated in the prospective SENTICOL study. A centralized histological analysis with re-reading and ultrastaging was performed 3 months after the interventions; discovery of micrometastasis or isolated tumor cells in the sentinel and non-sentinel lymph nodes did not change the treatment that was previously planned. Patients were followed up after 3 years. Results were compared according to prognostic factors. Results We found 13 recurrences during the 3-year follow-up: two recurrences in patients with positive sentinel lymph nodes (one macrometastasis and one micrometastasis) and 11 recurrences in patients with negative lymph nodes (sentinel lymph nodes and non-sentinel lymph nodes). There was no statistically significant difference in disease-free survival in terms of prognostic factors in our cohort, except patient age: we found a significant decrease in disease-free survival in patients >50 years old (p=0.01). Among patients with sentinel lymph nodes positive for micrometastasis, only one had a recurrence (negative predictive value 89%). Conclusions Unlike previous retrospective studies, this prospective study showed no impact of micrometastasis or isolated tumor cells in sentinel lymph nodes on disease-free survival. However, due to the relatively short follow-up, some late recurrences may have been missed.
TL;DR: Minimally invasive surgery may be considered for the management of patients with advanced ovarian cancer who have undergone neoadjuvant chemotherapy, when surgery is limited to low-complexity standard cytoreductive procedures.
Abstract: Objectives The aim of this retrospective multicenter study was to investigate the extent, feasibility, and outcomes of minimally invasive surgery at the time of interval debulking surgery in different gynecological cancer centers. Methods/Materials In December 2016, 20 gynecological cancer centers were contacted by e-mail, to participate in the INTERNATIONAL MISSION study. Seven centers confirmed and five were included, with a total of 127 patients diagnosed with advanced epithelial ovarian cancer after neoadjuvant chemotherapy and minimally invasive interval surgery. Only women with a minimum follow-up time of 6 months from interval surgery or any cancer-related event before 6 months were included in the survival analysis. Baseline characteristics, chemotherapy, and operative data were evaluated. Survival analysis was evaluated using the Kaplan–Meier method. Results All patients had optimal cytoreduction at the time of interval surgery: among them, 122 (96.1%) patients had no residual tumor. Median operative time was 225 min (range 60 – 600) and median estimated blood loss was 100 mL (range 70 – 1320). Median time to discharge was 2 days (1–33) and estimated median time to start chemotherapy was 20 days (range 15 – 60). Six (4.7%) patients experienced intraoperative complications, with one patient experiencing two serious complications (bowel and bladder injury at the same time). There were six (4.7%) patients with postoperative short-term complications: among them, three patients had severe complications. The conversion rate to laparotomy was 3.9 %. Median follow-up time was 37 months (range 7 – 86): 74 of 127 patients recurred (58.3%) and 31 (24.4%) patients died from disease. Median progression-free survival was 23 months and survival at 5 years was 52 % (95% CI: 35 to 67). Conclusions Minimally invasive surgery may be considered for the management of patients with advanced ovarian cancer who have undergone neoadjuvant chemotherapy, when surgery is limited to low-complexity standard cytoreductive procedures.
TL;DR: A possible role for the composition of the vaginal microbiota as a modifier of high-risk HPV infection, and specific microbiota species may serve as sensors for changes in the cervical microenvironment associated with high- risk HPV infection is suggested.
Abstract: Objectives Since other genital infections enhance HIV susceptibility by inducing inflammation and evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of high-risk human papillomavirus (HPV) infections, we investigated the relationship between the composition of the vaginal microbiota and the risk of high-risk HPV infection. Methods The study included 151 healthy women (65 HPV-positive and 86 HPV-negative) aged 20–65 at enrollment. Total genome DNA from samples was extracted using the hexadecyltrimethylammonium bromide (CTAB) CTAB method. The vaginal microbiota composition was determined by sequencing barcoded 16S rDNA gene fragments (V4) on Illumina HiSeq2500. Results Of the 30 most abundant bacteria at the genus level, we found only six bacteria with a statistical difference between HPV-positive and HPV-negative women: Bacteroides, Acinetobacter, Faecalibacterium, Streptococcus, Finegoldia, and Moryella. Lactobacillus was the predominant genus and was detected in all women, but there was no significant difference between the two groups for L. iners, L. jensenii, and L. gasseri. Furthermore, we found 26 types of bacteria with a statistical difference at the species level between the two groups. Anaerobic bacteria such as Bacteroides plebeius, Acinetobacter lwoffii, and Prevotella buccae were found significantly more frequently in HPV-positive women, which is the most important finding of our study. Conclusion Our findings suggest a possible role for the composition of the vaginal microbiota as a modifier of high-risk HPV infection, and specific microbiota species may serve as sensors for changes in the cervical microenvironment associated with high-risk HPV infection. The exact molecular mechanism of the vaginal microbiota in the course of high-risk HPV infection and cervical neoplasia should be further explored. Future research should include intervention in the composition of the vaginal microbiota to reverse the course of high-risk HPV infection and the natural history of cervical neoplasia.
TL;DR: This study aims to evaluate the feasibility of preserving fertility in pre-menopausal women diagnosed with stage International Federation of Gynecology and Obstetrics IB2, 2–4 cm cervical cancer by assessing the rate of functional uterus defined as successful fertility-sparing surgery and no adjuvant therapy.
Abstract: Background There are limited data regarding the optimal management of pre-menopausal women with cervical lesions measuring 2–4 cm who desire to preserve fertility. Primary objectives To evaluate the feasibility of preserving fertility. Study hypothesis Neo-adjuvant chemotherapy will be effective in reducing the size of the tumor and will enable fertility-sparing surgery without compromising oncologic outcome. Trial design Pre-menopausal women diagnosed with stage International Federation of Gynecology and Obstetrics (FIGO) IB2, 2–4 cm cervical cancer who wish to preserve fertility will receive three cycles of platinum/paclitaxel chemotherapy. Patients with complete/partial response will undergo fertility-sparing surgery. Patients will be followed for 3 years to monitor outcome. Patients with suboptimal response (residual lesion ≥2 cm) will receive definitive radical hysterectomy and/or chemoradiation. Major eligibility criteria Patients must have histologically confirmed invasive cervical cancer, 2–4 cm lesion, by clinical examination and magnetic resonance imaging (MRI), negative node, and pre-menopausal (≤40 years old). Following three cycles of neo-adjuvant chemotherapy, patients must achieve a complete/partial response (residual lesion Primary endpoints Assess the rate of functional uterus defined as successful fertility-sparing surgery and no adjuvant therapy. Sample size A total of 90 evaluable patients will be needed to complete the study. Estimated dates for completing accrual and presenting results Expected complete accrual in 2022 with presentation of results by 2025. Trial registration number Pending ethics submission.
TL;DR: SLN with a cervical injection is gaining widespread acceptance for staging of endometrial cancer among gynecologic oncologists worldwide and standardization of the surgical approach with the National Comprehensive Care Network algorithm is applied by most users.
Abstract: Objective To explore the factors influencing adoption of the sentinel lymph node (SLN) technique for endometrial cancer staging among gynecologic oncologists. Methods A self-administered, web-based survey was sent via email (April 20 through May 21, 2017) to all members of European Society of Gynecologic Oncologists, International Gynecologic Cancer Society, and Society of Gynecologic Oncologists. Surgical and pathologic practices related to SLN and reasons for not adopting this technique were investigated. Results Overall, 489 attending physicians or consultants in gynecologic oncology from 69 countries responded: 201 (41.1%), 118 (24.1%), and 117 (23.9%) from Europe, the USA, and other countries, respectively (10.8% did not report a country). SLN was adopted by 246 (50.3%) respondents, with 93.1% injecting the cervix and 62.6 % using indocyanine green dye. The National Comprehensive Cancer Network SLN algorithm was followed by 160 (65.0%) respondents (USA 74.4%, Europe 55.4%, other countries 71.4%). However, 66.7% completed a backup lymphadenectomy in high-risk patients. When SLN biopsy revealed isolated tumor cells, 13.8% of respondents recommended adjuvant therapy. This percentage increased to 52% if micrometastases were detected. Among the 243 not adopting SLN, 50.2% cited lack of evidence and 45.3% stated that inadequate instrumentation fueled their decisions. Conclusions SLN with a cervical injection is gaining widespread acceptance for staging of endometrial cancer among gynecologic oncologists worldwide. Standardization of the surgical approach with the National Comprehensive Care Network algorithm is applied by most users. Management of isolated tumor cells and the role of backup lymphadenectomy for ‘high-risk’ cases remain areas of investigation.
TL;DR: A safe, reproducible, functional, and easy-to-apply multimodal prehabilitation program for gynecologic oncology practice based on patient-tailored pre-operative medical optimization, physical training, nutritional counseling, and psychological support is suggested.
Abstract: Patients undergoing major surgery are predisposed to a decrease in functional capacity as a response to surgical stress that can delay post-operative recovery. A prehabilitation program consists of patient preparation strategies before surgery, and include pre-operative measures to improve functional capacity and enhance post-operative recovery. Multimodal prehabilitation may include exercise, nutritional counseling, psychological support, and optimization of underlying medical conditions, as well as cessation of unfavorable health behaviors such as smoking and drinking. Currently, there are no standardized guidelines for prehabilitation, and the existent studies are heterogeneous; however, multimodal approaches are likely to have a greater impact on functional outcomes than single management programs. We have reviewed the literature on prehabilitation in general, and in gynecologic surgery in particular, to identify tools to establish an optimal prehabilitation program within an Enhanced Recovery After Surgery (ERAS) protocol for gynecologic oncology patients. We suggest a safe, reproducible, functional, and easy-to-apply multimodal prehabilitation program for gynecologic oncology practice based on patient-tailored pre-operative medical optimization, physical training, nutritional counseling, and psychological support. The analysis of the prehabilitation program implementation in an ERAS protocol should undergo further research in order to test the efficacy on surgical outcome and recovery after surgery.
TL;DR: The pregnancy and oncologic outcomes and factors of successful conception after hormone therapy for endometrioid endometrial cancer who underwent fertility-sparing treatment were defined and a lower grade might be a positive factor for future pregnancy.
Abstract: Objective Hormonal management is an alternative treatment for preserving fertility in patients with presumed early stage endometrioid endometrial cancer. This study aimed to define the pregnancy and oncologic outcomes and factors of successful conception after hormone therapy for endometrioid endometrial cancer. Methods We retrospectively analyzed patients presumed to have stage IA, grade 1–2 endometrioid endometrial cancer who underwent fertility-sparing treatment. Concurrent medroxyprogesterone and levonorgestrel-release intra-uterine devices were used for treatment. The pregnancy outcomes and oncologic outcomes were compared between the pregnant and non-pregnant groups. Results Seventy-one patients presumed to have stage IA, grade 1–2 endometrioid endometrial cancer had complete remission, and 49 of them tried to conceive. Twenty-two (44.9%) patients became pregnant; the total number of pregnancies was 30. These pregnancies resulted in seven abortions (23.3%), one pre-term birth (3.3%), and 20 full-term births (66.6%). The total live birth rate was 66.6 % (20/30). The median duration of hormonal treatment was 11.9 months (range 4–49) and 12.0 months (range 3–35) in the pregnant and non-pregnant groups, respectively. On multivariate analysis, age, body mass index, treatment duration, medroxyprogesterone dose, and number of dilatation and curettage biopsies were not significantly associated with pregnancy failure, but the association with grade (OR 6.2, 95% CI 1.0 to 38.9; P Conclusions A lower grade might be a positive factor for future pregnancy. Moreover, successful pregnancy might be a factor in preventing recurrence.
TL;DR: This study is the first, randomized, phase III trial to evaluate the potential impact of this combination on both progression-free survival and overall survival in patients presenting with advanced epithelial ovarian cancer, and will test the hypothesis that treatment with atezolizumab added to paclitaxel, carboplatin, and bevacizuab will prolong progression- free survival and Overall survival.
Abstract: Background There is mounting pre-clinical and clinical evidence that combinations of immunotherapy, specifically programed cell death-1 (PD-1) inhibition, with chemotherapy and anti-angiogenesis agents, such as bevacizumab, result in markedly improved outcomes across a variety of tumor types including endometrial cancer, renal cell cancer, and non-small cell lung cancer. IMagyn050/GOG 3015/ENGOT-OV39 is the first, randomized, phase III trial to evaluate the potential impact of this combination on both progression-free survival and overall survival in patients presenting with advanced epithelial ovarian cancer. Primary Objective The primary objective is to evaluate the efficacy of atezolizumab versus placebo in combination with paclitaxel + carboplatin + bevacizumab for front-line treatment of ovarian cancer among all patients and those with PD-L1+ tumors. Study Hypothesis This study will test the hypothesis that treatment with atezolizumab added to paclitaxel, carboplatin, and bevacizumab will prolong progression-free survival and overall survival compared with treatment with placebo plus paclitaxel, carboplatin, and bevacizumab. Trial Design This is a randomized, phase III, placebo-controlled study. Major Inclusion/Exclusion Criteria Eligible patients have a histologic diagnosis of advanced epithelial ovarain cancer, primary peritoneal, or fallopian tube cancer who either have residual disease after primary surgery or who are undergoing neoadjuvant chemotherapy with planned interval surgery. Ineligible patients include those who are cured with surgery alone or those for whom no gross residual disease remained following primary cytoreduction. Primary Endpoint There are two co-primary efficacy endpoints: investigator-assessed progression-free survival and overall survival. Sample Size 1300 patients. Estimated Dates for Completing Accrual and Presenting Results April 2020. Trial Registration NCT03038100.
University of Texas MD Anderson Cancer Center1, Memorial Sloan Kettering Cancer Center2, First Faculty of Medicine, Charles University in Prague3, Imperial College London4, Queen Elizabeth II Hospital5, Hospital Italiano de Buenos Aires6, Karolinska Institutet7, Scania AB8, Fudan University9, Copenhagen University Hospital10, Shanghai Jiao Tong University11
TL;DR: This study aims to compare disease-free survival between patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive (laparoscopic or robotic) radical trachelectomy.
Abstract: Background Radical trachelectomy is considered a viable option for fertility preservation in patients with low-risk, early-stage cervical cancer. Standard approaches include laparotomy or minimally invasive surgery when performing radical trachelectomy. Primary Objective To compare disease-free survival between patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive (laparoscopic or robotic) radical trachelectomy. Study Hypothesis We hypothesize that minimally invasive radical trachelectomy has similar oncologic outcomes to those of the open approach. Study Design This is a collaborative, multi-institutional, international, retrospective study. Patients who underwent a radical trachelectomy and lymphadenectomy between January 1, 2005 and December 31, 2017 will be included. Institutional review board approval will be required. Each institution will be provided access to a study-specific REDCap (Research Electronic Data Capture) database maintained by MD Anderson Cancer Center and will be responsible for entering patient data. Inclusion Criteria Patients with squamous, adenocarcinoma, or adenosquamous cervical cancer FIGO (2009) stages IA2 and IB1 (≤2 cm) will be included. Surgery performed by the open approach or minimally invasive approach (laparoscopy or robotics). Tumor size ≤2 cm, by physical examination, ultrasound, MRI, CT, or positron emission tomography (at least one should confirm a tumor size ≤2 cm). Centers must contribute at least 15 cases of radical trachelectomy (open, minimally invasive, or both). Exclusion Criteria Prior neoadjuvant chemotherapy or radiotherapy to the pelvis for cervical cancer at any time, prior lymphadenectomy, or pelvic retroperitoneal surgery, pregnant patients, aborted trachelectomy (intra-operative conversion to radical hysterectomy), or vaginal approach. Primary Endpoint The primary endpoint is disease-free survival measured as the time from surgery until recurrence or death due to disease. To evaluate the primary objective, we will compare disease-free survival among patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive radical trachelectomy. Sample Size An estimated 535 patients will be included; 256 open and 279 minimally invasive radical trachelectomy. Previous studies have shown that recurrence rates in the open group range from 3.8% to 7.6%. Assuming that the 4.5-year disease-free survival rate for patients who underwent open surgery is 95.0%, we have 80% power to detect a 0.44 HR using α level 0.10. This corresponds to an 89.0% disease-free survival rate at 4.5 years in the minimally invasive group.
TL;DR: A practical approach to selecting proper treatment for sexual dysfunctions in female cancer patients is proposed, which includes three main steps: knowledge, diagnosis, and sexual counseling.
Abstract: Sexual dysfunction in female cancer patients remains under-diagnosed and under-treated. As sexual dysfunction is becoming an increasingly common side effect of cancer treatments, it is imperative for healthcare providers and especially gynecologic oncologists to include a comprehensive evaluation of sexual health as a routine part of the workup of such patients. Although most oncologists are not experienced in treating sexual dysfunctions, simple tools can be incorporated into clinical practice to improve the management of these conditions. In this review, we propose a practical approach to selecting proper treatment for sexual dysfunctions in female cancer patients. This includes three main steps: knowledge, diagnosis, and sexual counseling. Knowledge can be acquired through a specific updating about sexual issues in female cancers, and with a medical training in female sexual dysfunctions. Diagnosis requires a comprehensive history and physical examination. Sexual counseling is one of the most important interventions to consider and, in some cases, it may be the only intervention needed to help cancer patients tolerate their symptoms. Sexual counseling should be addressed by oncologists; however, select patients should be referred for qualified psychological or sexological interventions where appropriate. Finally, a multidisciplinary team approach may be the best way to address this challenging issue.
TL;DR: It is suggested that HSIL and dVIN are characterized by different underlying molecular alterations that may have important implications for treatment and follow-up of women diagnosed with vulvar squamous cell cancer.
Abstract: Vulvar intraepithelial neoplasia (VIN) is a precursor to vulvar squamous cell carcinoma and is defined histopathologically by the presence of atypia. VIN has been classified into two types: usual vulvar intraepithelial neoplasia (uVIN), which is also referred to as a vulvar high-grade squamous intra-epithelial lesion (HSIL), and differentiated VIN (dVIN). The former is associated with chronic infection by sub-types of the human papilloma virus (HPV), whereas dVIN is HPV-independent and frequently associated with lichen sclerosus. The distinction is important because dVIN has a greater risk of, and more rapid transit to, vulvar squamous cell carcinoma. Furthermore, dVIN-associated vulvar cancers have an increased risk of recurrence and higher mortality than those arising from HSIL. Molecular characterization of vulvar squamous cell carcinoma precursors using next-generation sequencing is a relatively novel, but rapidly advancing field. This review appraises recent studies that have investigated the risks of progression to vulvar malignancy associated with HSIL and dVIN, the prognosis of HPV-dependent and HPV-independent vulvar squamous cell carcinomas, and conducted next generation sequencing mutation analyses to elucidate the genomic profiles underlying VIN. These studies suggest that HSIL and dVIN are characterized by different underlying molecular alterations that may have important implications for treatment and follow-up of women diagnosed with vulvar squamous cell cancer.
TL;DR: Surgery and chemotherapy is increasingly used in the management of pregnant patients with cervical cancer and prognosis is similar to that of non-pregnant patients.
Abstract: Background Treatment of cervical cancer during pregnancy is often complex and challenging. This study aimed to analyze current patterns of practice in the management of pregnant patients diagnosed with cervical cancer. Methods This was a matched cohort study comprising patients managed for cervical cancer during pregnancy from six European centers. Patient information was retrieved from the dataset of the International Network for Cancer, Infertility and Pregnancy from 1990 to 2012. Each center matched its patients with two non-pregnant controls for age (±5 years) and International Federation of Gynecology and Obstetrics (FIGO) 2009 stage. Information on age, histological type, grade, lymphovascular space invasion, stage, tumor size, method of diagnosis, site of recurrence, delivery, date of recurrence, and date of death was recorded. Progression-free survival was compared using multivariable Cox proportional hazards regression. Results A total of 132 pregnant patients and 256 controls were analyzed. The pregnant patients (median age 34 years, range 21–43) were diagnosed at a median gestational age of 18.4 weeks of pregnancy (range 7–39). Stage distribution during pregnancy was 14.4% for stage IA, 47.0% for IB1, 18.9% for IB2, and 19.7% for II-IV. For treatment during pregnancy, 17.4% of the patients underwent surgery, 16.7% received neoadjuvant chemotherapy, 26.5% delayed their treatment, 12.9% had a premature delivery, and 26.5% had their pregnancy terminated. Median follow-up was 84 months (67 months for pregnant and 95 months for non-pregnant patients). The unadjusted hazard ratio of pregnancy for progression-free survival was 1.18 (95% confidence interval 0.74 to 1.88). Conclusion Surgery and chemotherapy is increasingly used in the management of pregnant patients with cervical cancer and prognosis is similar to that of non-pregnant patients.
TL;DR: Adding three to four pre-operative cycles of bevacizumab to neoadjuvant chemotherapy for unresectable disease did not improve the complete macroscopic response rate or surgical outcome, but improved surgical operability without increasing toxicity.
Abstract: Background Bevacizumab is an approved treatment after primary debulking surgery for ovarian cancer. However, there is limited information on bevacizumab added to neoadjuvant chemotherapy before interval debulking surgery. Objective To evaluate neoadjuvant bevacizumab in a randomized phase II trial. Methods Patients with newly diagnosed stage III/IV high-grade serous/endometrioid ovarian cancer were randomized to receive four cycles of neoadjuvant chemotherapy with or without ≥3 cycles of bevacizumab 15 mg/kg every 3 weeks. After interval debulking surgery, all patients received post-operative chemotherapy (three cycles) and bevacizumab for 15 months. The primary end point was complete macroscopic response rate at interval debulking surgery. Results Of 68 patients randomized, 64 completed four neoadjuvant cycles; 22 of 33 (67%) in the chemotherapy-alone arm and 31 of 35 (89%) in the bevacizumab arm (p=0.029) underwent surgery. The complete macroscopic response rate did not differ between treatment arms in either the intention-to-treat population of 68 patients (6.1% vs 5.7%, respectively; p=0.25) or the 55 patients who underwent surgery (8.3% vs 6.5%; p=1.00). There was no difference in complete cytoreduction rate or progression-free survival between the treatment arms. During neoadjuvant therapy, grade ≥3 adverse events were more common with chemotherapy alone than with bevacizumab (61% vs 29%, respectively; p=0.008). Intestinal (sub)occlusion, fatigue/asthenia, abdominal infection, and thrombocytopenia were less frequent with bevacizumab. The incidence of grade ≥3 adverse events was 9% in the control arm versus 16% in the experimental arm in the month after surgery. Conclusions Adding three to four pre-operative cycles of bevacizumab to neoadjuvant chemotherapy for unresectable disease did not improve the complete macroscopic response rate or surgical outcome, but improved surgical operability without increasing toxicity. These results support the early integration of bevacizumab in carefully selected high-risk patients requiring neoadjuvant chemotherapy for initially unresectable ovarian cancer.
TL;DR: Using metformin was significantly associated with a lower incidence and a better prognosis of ovarian cancer in patients with diabetes and well-designed interventional studies are warranted to confirm the findings.
Abstract: Background Some clinical and basic research studies have indicated that exposure to metformin might have protective effects against ovarian cancer. However, results from epidemiologic studies have been inconsistent. We performed a meta-analysis to evaluate the effect of metformin use on the risk of ovarian cancer occurrence and mortality. Methods Multiple databases were searched to identify studies on the association between use of metformin and risk of ovarian cancer or prognosis, up to August 2018. Relevant information for analysis was extracted. A random-effects model was used to calculate the pooled risk estimate. Results Thirteen articles were included, of which six articles focused on ovarian cancer incidence and the others focused on prognosis. The pooled OR for ovarian cancer occurrence and mortality comparing metformin use with non-use or use of other hypoglycemic drugs was 0.76 (95% CI 0.62 to 0.93, p = 0.008) and 0.55 (95% CI 0.36 to 0.84, p = 0.006), respectively. Moderate to substantial heterogeneity was observed across included studies. Conclusions Our findings demonstrate that use of metformin was significantly associated with a lower incidence and a better prognosis of ovarian cancer in patients with diabetes. Well-designed interventional studies are warranted to confirm our findings.
TL;DR: Different classifications of TP53 mutations did not show an impact on outcomes in this study, and immunohistochemistry was a good predictor for TP53 mutation.
Abstract: Objective Mutations in TP53 are found in the majority of high grade serous ovarian cancers, leading to gain of function or loss of function of its protein product, p53, involved in oncogenesis. There have been conflicting reports as to the impact of the type of these on prognosis. We aim to further elucidate this relationship in our cohort of patients. Methods 229 patients with high grade serous ovarian cancer underwent tumor profiling through an institutional molecular screening program with targeted next generation sequencing. TP53 mutations were classified using methods previously described in the literature. Immunohistochemistry on formalin-fixed paraffin embedded tissue was used to assess for TP53 mutation. Using divisive hierarchal clustering, we generated patient clusters with similar clinicopathologic characteristics to investigate differences in outcomes. Results Six different classification schemes of TP53 mutations were studied. These did not show an association with first platinum-free interval or overall survival. Next generation sequencing reliably predicted mutation in 80% of cases, similar to the proportion detected by immunohistochemistry. Divisive hierarchical clustering generated four main clusters, with cluster 3 having a significantly worse prognosis (p Conclusions Different classifications of TP53 mutations did not show an impact on outcomes in this study. Immunohistochemistry was a good predictor for TP53 mutation. Cluster analysis showed that a subgroup of patients with gain of function mutations (cluster 3) had a worse prognosis.
TL;DR: Adjuvant radiotherapy and adjuvant chemotherapy appear to improve overall survival and total hysterectomy and bilateral oophorectomy is the standard treatment for high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas.
Abstract: Objective High grade endometrial stromal sarcoma and undifferentiated uterine sarcomas are associated with a very poor prognosis. Although large surgical resection is the standard of care, the optimal adjuvant strategy remains unclear. Methods A retrospective analysis of patients with localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas (stages I–III) treated in 10 French Sarcoma Group centers was conducted. Results 39 patients with localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas treated from 2008 to 2016 were included. 24/39 patients (61.5%) were stage I at diagnosis. 38/39 patients underwent surgical resection, with total hysterectomy and bilateral oophorectomy completed in 26/38 (68%). Surgeries were mostly resection complete (R0, 23/38, 60%) and microscopically incomplete resection (R1, 6/38, 16%). 22 patients (58%) underwent postoperative radiotherapy (including brachytherapy in 11 cases), and 11 (29%) underwent adjuvant chemotherapy. After a median follow-up of 33 months (range 2.6–112), 17/39 patients were alive and 21/39 (54%) had relapsed (9 local relapses and 16 metastases). The 3 year and 5 year overall survival rates were 49.8% and 31.1%, respectively, and 3 year and 5 year disease free survival rates were 42.7% and 16.0%, respectively. Median overall survival and disease free survival were 32.7 (95% CI 16.3–49.1) and 23 (4.4–41.6) months, respectively. Medians were, respectively, 46.7 months and 39.0 months among those who underwent adjuvant radiotherapy and 41.0 months and 10.3 months for those who underwent adjuvant chemotherapy. In multivariate analysis, adjuvant radiotherapy was an independent prognostic factor for overall survival (P=0.012) and disease free survival (P=0.036). Chemotherapy, International Federation of Gynecology and Obstetrics I–II stages, and Eastern Cooperative Oncology Group-performance status 0 correlated with improved overall survival (P=0.034, P=0.002, P=0.006), and absence of vascular invasion (P=0.014) was associated with better disease free survival. Conclusions The standard treatment of primary localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas is total hysterectomy and bilateral oophorectomy. The current study shows that adjuvant radiotherapy and adjuvant chemotherapy appear to improve overall survival. A prospective large study is warranted to validate this therapeutic management.
TL;DR: Compliance with an ERAS pathway exceeding 80% was associated with lower complication rates and shorter length of stay without impacting on re-operations or readmissions.
Abstract: Objective The aim of this study was to evaluate if varying levels of compliance with an enhanced recovery after surgery (ERAS) protocol impacted post-operative outcomes (length of stay, complications, readmissions, and re-operations) in gynecologic surgery at a tertiary center. Methods We included 584 patients who had open gynecologic surgery between November 1, 2014 and December 31, 2016. Patients were categorized into subgroups according to their date of surgery from the time of the ERAS protocol implementation. Patients were categorized by their per cent compliance into two groups: Results Overall compliance was 72.3%. Patients with compliance ≥80% had significantly less complications (P Conclusions Compliance with an ERAS pathway exceeding 80% was associated with lower complication rates and shorter length of stay without impacting on re-operations or readmissions.
TL;DR: Predictive models for EC patients using the Naïve Bayes machine learning algorithm for LNI prediction suggest machine learning may have a place in the decision tree for the management of EC.
Abstract: Objective The necessity of lymphadenectomy and the prediction of lymph node involvement (LNI) in endometrial cancer (EC) have been hotly-debated questions in recent years. Machine learning is a broad field that can produce results and estimations. In this study we constructed prediction models for EC patients using the Naive Bayes machine learning algorithm for LNI prediction. Methods The study assessed 762 patients with EC. Algorithm models were based on the following histopathological factors: V1: final histology; V2: presence of lymphovascular space invasion (LVSI); V3: grade; V4: tumor diameter; V5: depth of myometrial invasion (MI); V6: cervical glandular stromal invasion (CGSI); V7: tubal or ovarian involvement; and V8: pelvic LNI. Logistic regression analysis was also used to evaluate the independent factors affecting LNI. Results The mean age of patients was 59.1 years. LNI was detected in 102 (13.4%) patients. Para-aortic LNI (PaLNI) was detected in 54 (7.1%) patients, of which four patients had isolated PaLNI. The accuracy rate of the algorithm models was found to be between 84.2% and 88.9% and 85.0% and 97.6% for LNI and PaLNI, respectively. In multivariate analysis, the histologic type, LVSI, depth of MI, and CGSI were independently and significantly associated with LNI (p Conclusions Machine learning may have a place in the decision tree for the management of EC. This is a preliminary report about the use of a new statistical technique. Larger studies with the addition of sentinel lymph node status, laboratory findings, or imaging results with machine learning algorithms may herald a new era in the management of EC.