Pelvic Exenteration - Past, Present and Future.

Background: Bearing in mind that the open procedure is already validated by multiple studies, the article aims to prove that pelvic exenteration performed in a minimally invasive fashion might offer better survival and to potentially identify prognostic factors for the outcome of these patients. Material and Methods: Data regarding past and present classifications and surgical indications are presented. Patient data were collected retrospectively. Results: The most frequent diseases treated with pelvic exenteration, in terms of the hystological type, were gynecological malignancy and squamous cell carcinoma. Recurrent pelvic disease was found in 68.2% of patients. R0 resection was achieved in 72.7% of patients in the MI group, and in 73.7% of patients in the OP group. Peri-operative morbidity was reported to be 56.6% for open surgery, and 18.1% for minimally invasive. Average DFS was 20.15 months, ranging from 1.5 to 70.3 months, while the OS was calculated to be 38.1 months (0.33 1508) up until November 2023. Conclusion: Pelvic exenteration is a continuously improving surgical procedure, open approach being favored to minimally invasive one. On the other hand, hospitalization and morbidity are reduced when choosing the latter. R0 and lymph node status are important predictors for overall survival, as well as major early postoperative complications. All in all, pelvic exenteration is still a promising surgical procedure to extend cancer patients lives.

A systematic review and meta-analysis on mortality rate following total pelvic exenteration in cancer patients.

BACKGROUND: Total pelvic exenteration (TPE), an en bloc resection is an ultraradical operation for malignancies, and refers to the removal of organs inside the pelvis, including female reproductive organs, lower urological organs and involved parts of the digestive system. The aim of this meta-analysis is to estimate the intra-operative mortality, in-hospital mortality, 30- and 90-day mortality rate and overall mortality rate (MR) following TPE in colorectal, gynecological, urological, and miscellaneous cancers. METHODS: This is a systematic review and meta-analysis in which three international databases including Medline through PubMed, Scopus and Web of Science on November 2023 were searched. To screen and select relevant studies, retrieved articles were entered into Endnote software. The required information was extracted from the full text of the retrieved articles by the authors. Effect measures in this study was the intra-operative, in-hospital, and 90-day and overall MR following TPE. All analyzes are performed using Stata software version 16 (Stata Corp, College Station, TX). RESULTS: In this systematic review, 1751 primary studies retrieved, of which 98 articles (5343 cases) entered into this systematic review. The overall mortality rate was 30.57% in colorectal cancers, 25.5% in gynecological cancers and 12.42% in Miscellaneous. The highest rate of mortality is related to the overall mortality rate of colorectal cancers. The MR in open surgeries was higher than in minimally invasive surgeries, and also in primary advanced cancers, it was higher than in recurrent cancers. CONCLUSION: In conclusion, it can be said that performing TPE in a specialized surgical center with careful patient eligibility evaluation is a viable option for advanced malignancies of the pelvic organs.

Assessment of secular trends of three major gynecologic cancers burden and attributable risk factors from 1990 to 2019: an age period cohort analysis.

BACKGROUND: This study aims to assess the long-term trends in the burden of three major gynecologic cancers(GCs) stratified by social-demographic status across the world from 1990 to 2019. To assess the trends of risk factor attributed mortality, and to examine the specific effects of age, period, cohort behind them in different regions. METHODS: We extracted data on the mortality, disability-adjusted life years(DALYs), and age-standardized rates(ASRs) of cervical cancer(CC), uterine cancer(UC), and ovarian cancer(OC) related to risks from 1990 to 2019, as GCs burden measures. Age-period-cohort analysis was used to analyze trends in attributable mortality rates. RESULTS: The number of deaths and DALYs for CC, UC and OC increased since 1990 worldwide, while the ASDRs decreased. Regionally, the ASDR of CC was the highest in low SDI region at 15.05(11.92, 18.46) per 100,000 in 2019, while the ASDRs of UC and OC were highest in high SDI region at 2.52(2.32,2.64), and 5.67(5.16,6.09). The risk of CC death caused by unsafe sex increased with age and then gradually stabilized, with regional differences. The period effect of CC death attributed to smoking showed a downward trend. The cohort effect of UC death attributed to high BMI decreased in each region, especially in the early period in middle, low-middle and low SDI areas. CONCLUSIONS: Global secular trends of attributed mortality for the three GCs and their age, period, and cohort effects may reflect the diagnosis and treatment progress, rapid socioeconomic transitions, concomitant changes in lifestyle and behavioral patterns in different developing regions. Prevention and controllable measures should be carried out according to the epidemic status in different countries, raising awareness of risk factors to reduce future burden.

Survival prediction in patients with gynecological cancer irradiated for brain metastases.

BACKGROUND AND PURPOSE: This large population-based, retrospective, single-center study aimed to identify prognostic factors in patients with brain metastases (BM) from gynecological cancers. MATERIAL AND METHODS: One hundred and forty four patients with BM from gynecological cancer treated with radiotherapy (RT) were identified. Primary cancer diagnosis, age, performance status, number of BM, presence of extracranial disease, and type of BM treatment were assessed. Overall survival (OS) was calculated using the Kaplan-Meier method and the Cox proportional hazards regression model was used for multivariable analysis. A prognostic index (PI) was developed based on scores from independent predictors of OS. RESULTS: Median OS for the entire study population was 6.2 months. Forty per cent of patients died within 3 months after start of RT. Primary cancer with the origin in cervix or vulva (p = 0.001),  Eastern Cooperative Oncology Group (ECOG) 3-4 (p < 0.001), and the presence of extracranial disease (p = 0.001) were associated with significantly shorter OS. The developed PI based on these factors, categorized patients into three risk groups with a median OS of 13.5, 4.0, and 2.4 months for the good, intermediate, and poor prognosis group, respectively. INTERPRETATION: Patients with BM from gynecological cancers carry a poor prognosis. We identified prognostic factors and developed a scoring tool to select patients with better or worse prognosis. Patients in the high-risk group have a particular poor prognosis, and omission of RT could be considered.

The prognostic value of MEK pathway-associated estrogen receptor signaling activity for female cancers.

BACKGROUND: Other than for breast cancer, endocrine therapy has not been highly effective for gynecologic cancers. Endocrine therapy resistance in estrogen receptor positive gynecologic cancers is still poorly understood. In this retrospective study, we examined the estrogen receptor (ER) signaling pathway activities of breast, ovarian, endometrial, and cervical cancers to identify those that may predict endocrine therapy responsiveness. METHODS: Clinical and genomic data of women with breast and gynecological cancers were downloaded from cBioPortal for Cancer Genomics. Estrogen receptor alpha (ESR1) expression level and sample-level pathway enrichment scores (EERES) were calculated to classify patients into four groups (low/high ESR1 and low/high EERES). Correlation between ESR1/EERES score and survival was further validated with RNAseq data from low-grade serous ovarian cancer. Pathway analyses were performed among different ESR1/EERES groups to identify genes that correlate with endocrine resistance, which are validated using Cancer Cell Line Encyclopedia gene expression and Genomics of Drug Sensitivity in Cancer data. RESULTS: We identified a novel combined prognostic value of ESR1 expression and the corresponding estrogen response signaling (EERES score) for breast cancer. The combined prognostic value (ESR1/EERES) may be applicable to other gynecologic cancers. More importantly, we discovered that ER signaling can cross-regulate MEK pathway activation. We identified downstream genes in the MEK pathway (EPHA2, INAVA, MALL, MPZL2, PCDH1, and TNFRSF21) that are potential endocrine therapy response biomarkers. CONCLUSION: This study demonstrated that targeting both the ER and the ER signaling activity related MEK pathway may aid the development of endocrine therapy strategies for personalized medicine.

Computational image features of immune architecture is associated with clinical benefit and survival in gynecological cancers across treatment modalities.

BACKGROUND: We present a computational approach (ArcTIL) for quantitative characterization of the architecture of tumor-infiltrating lymphocytes (TILs) and their interplay with cancer cells from digitized H&E-stained histology whole slide images and evaluate its prognostic role in three different gynecological cancer (GC) types and across three different treatment types (platinum, radiation and immunotherapy). METHODS: In this retrospective study, we included 926 patients with GC diagnosed with ovarian cancer (OC), cervical cancer, and endometrial cancer with available digitized diagnostic histology slides and survival outcome information. ArcTIL features quantifying architecture and spatial interplay between immune cells and the rest of nucleated cells (mostly comprised cancer cells) were extracted from the cell cluster graphs of nuclei within the tumor epithelial nests, surrounding stroma and invasive tumor front compartments on H&E-stained slides. A Cox proportional hazards model, incorporating ArcTIL features was fit on the OC training cohort (N=51), yielding an ArcTIL signature. A unique threshold learned from the training set stratified the patients into a low and high-risk group. RESULTS: The seven feature ArcTIL classifier was found to significantly correlate with overall survival in chemotherapy and radiotherapy-treated validation cohorts and progression-free survival in an immunotherapy-treated validation cohort. ArcTIL features relating to increased density of TILs in the epithelium and invasive tumor front were found to be associated with better survival outcomes when compared with those patients with an increased TIL density in the stroma. A statistically significant association was found between the ArcTIL signature and signaling pathways for blood vessel morphogenesis, vasculature development, regulation of cell differentiation, cell-substrate adhesion, biological adhesion, regulation of vasculature development, and angiogenesis. CONCLUSIONS: This study reveals that computationally-derived features from the spatial architecture of TILs and tumor cells are prognostic in GCs treated with chemotherapy, radiotherapy, and checkpoint blockade and are closely associated with central biological processes that impact tumor progression. These findings could aid in identifying therapy-refractory patients and further enable personalized treatment decision-making.

Pelvic exenteration for gynecologic malignancies: The experience of a tertiary center from Greece.

BACKGROUND: Pelvic exenteration is an ultraradical procedure that is performed for locally advanced pelvic malignancies. Despite its rarity, the rates of the procedure increase during the last years due to the gain of surgical expertise. Data on survival rates remain; however, scarce in the literature. METHODS: We retrospectively reviewed the records of all patients who underwent exenterative procedures for advanced gynecologic malignancies between 2006 and 2020. Major and minor perioperative complications were documented according to the Clavien-Dindo classification only when they occurred during a time limit of 30 days from the operation. Cox regression analysis and Kaplan-Meier survival curves were used for the analysis of survival outcomes. RESULTS: Overall, we identified 138 patients who were offered a pelvic exenteration procedure that were followed up for a median of 42 months (range 6-60 months). Seventy-five patients recurred (54.3%) during the follow-up period within 35.04 months (95% CI 31.01, 39.07 months). After examining several potential factors that might influence survival rates, we observed that only patients with positive margins had increased risk of recurrence (HR 1.66, 95%CI 1.10, 2.56 p = .016), although this was not associated with a decrease in overall survival. Overall survival outcomes were available for 112 patients of whom 62 died (55.4%) within 38.84 months (95% CI 35.02, 42.67). Major complications were detected in 21 patients. Reoperation was required in 18 patients. Anastomotic leakage was observed in 7 cases (5%) of whom 4 patients required reoperation. CONCLUSION: In summary, the findings of our study suggest that women undergoing pelvic exenteration for gynecologic malignancies have a significant survival probability that is accompanied by acceptable rates of operative morbidity.

Early referral to a palliative team improves end-of-life care among gynecological cancer patients: a retrospective, population-based study.

OBJECTIVE: To assess end-of-life care among patients with gynecological cancer, and to describe the association between timing of palliative care referral and patterns of care. METHODS: All women with residence in Oslo, Norway, who died of gynecological cancer between January 1, 2015 and December 30, 2017 (36 months), were identified. Patients were primarily treated at the Norwegian Radium Hospital and clinical data on end-of-life care were retrospectively extracted from the medical records. RESULTS: We identified 163 patients with median age 70.1 years at death (range 26-100) with the following diagnoses: ovarian (n=100), uterine (n=40), cervical (n=21), and vulvar cancer (n=2). 53 (33%) of patients died in a palliative care unit, 34 patients (21%) died in nursing homes without palliative care, and 48 (29%) patients died in hospital. Only 15 (9%) patients died at home. 25 (15%) patients received chemotherapy in the last 30 days before death, especially ovarian cancer patients (n=21, 21%). 103 patients (61%) were referred to a palliative team prior to death. Referral to a palliative team was associated with a significantly reduced risk of intensive care unit admission (OR 0.11, 95% CI 0.02 to 0.62) and higher likelihood of a structured end-of-life discussion (OR 2.91, 95% CI 1.03 to 8.25). Palliative care referral also seemed to be associated with other quality indicators of end-of-life care (less chemotherapy use, more home deaths). CONCLUSIONS: End-of-life care in patients with gynecological cancer suffers from underuse of palliative care. Chemotherapy is still commonly used towards end-of-life. Early palliative care referral in the disease trajectory may be an important step towards improved end-of-life care.

Stereotactic radiosurgery for brain metastases from pelvic gynecological malignancies: oncologic outcomes, validation of prognostic scores, and dosimetric evaluation.

INTRODUCTION: Stereotactic radiosurgery is a well-established treatment option in the management of brain metastases. Multiple prognostic scores for prediction of survival following radiotherapy exist, but are not disease-specific or validated for radiosurgery in women with primary pelvic gynecologic malignancies metastatic to the brain. The aim of the present study is to evaluate the feasibility, safety, outcomes, and impact of established prognostic scores. METHODS: We retrospectively identified 52 patients treated with radiotherapy for brain metastases between 2008 and 2021. Stereotactic radiosurgery was utilized in 31 patients for an overall number of 75 lesions; the remaining 21 patients received whole-brain radiotherapy. Kaplan-Meier survival analysis and the log-rank test were used to calculate and compare survival curves and univariate and multivariate Cox regression to assess the influence of cofactors on recurrence, local control, and prognosis. RESULTS: With a median follow-up of 10.7 months, overall survival rates post radiosurgery were 65.3%, 51.3%, and 27.7% for 1, 2, and 5 years, respectively, which were significantly higher than post whole-brain radiotherapy (p=0.049). Five local failures (6.7%) were detected, resulting in 1 and 2 year local cerebral control rates of 97.4% and 94.0%, respectively. Univariate factors for prediction of superior overall survival were high performance status (p=0.030) and application of three prognostic scores, especially the Recursive Partitioning Analysis score (p=0.028). Uni- and multivariate analysis revealed that extracranial progression prior to radiosurgery was significant for inferior overall survival (p<0.0001). Radionecrosis was diagnosed in five women (16%); long-term neurotoxicity was significantly worse after whole-brain radiotherapy compared with radiosurgery (p=0.023). CONCLUSION: Stereotactic radiosurgery for brain metastases from pelvic gynecologic malignancies appears to be safe and well tolerated, achieving promising local cerebral control. Prognostic scores were shown to be transferable and radiosurgery should be recommended as primary intracranial treatment, especially in women with no prior extracranial progression and Recursive Partitioning Analysis class I.

Statin use and incidence and mortality of breast and gynecology cancer: A cohort study using the National Health Insurance claims database.

Previous studies have reported inconsistent findings concerning the impact of statin use on cancer prevention. Our study examined the association between statin use and cancer incidence and mortality related to breast and gynecologic cancers in South Korea. A population-based cohort study was conducted using the National Health Insurance claims database. Women aged 45 to 70 years old who had taken statins for at least 6 months were compared to statin non-users of the same age from January 2005 to June 2013. The primary outcomes were cancer incidence and mortality related to breast cancer, total gynecologic cancers, cervix uteri cancer and ovarian cancer. Cox proportional hazards regression was conducted to calculate the adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs). Out of 587 705 women, there were 3591 cases of breast cancer, 2239 cases of gynecologic cancers and 565 breast and total gynecologic cancer deaths during 7.6 person-years. The aHRs for the association between the risk of each cancer and statin use were 0.88 (95% CI 0.79-0.97) for breast cancer and 0.83 (95% CI 0.67-0.99) for cervix uteri cancer. Statin use was associated with decreased breast cancer mortality (HR = 0.65, 95% CI 0.43-0.99) and total gynecologic cancer mortality (HR = 0.70, 95% CI 0.50-0.98). A dose-response relationship was only found for all-cancer mortality. Statin use for at least 6 months was significantly associated with a lower risk of breast and cervix uteri cancer incidence, and with lower mortality of breast and gynecologic cancers. Further research on these associations will be needed.

How do age and social environment affect the dynamics of death hazard and survival in patients with breast or gynecological cancer in France?

Several studies have investigated the association between net survival (NS) and social inequalities in people with cancer, highlighting a varying influence of deprivation depending on the type of cancer studied. However, few of these studies have accounted for the effect of social inequalities over the follow-up period, and/or according to the age of the patients. Thus, using recent and more relevant statistical models, we investigated the effect of social environment on NS in women with breast or gynecological cancer in France. The data were derived from population-based cancer registries, and women diagnosed with breast or gynecological cancer between 2006 and 2009 were included. We used the European deprivation index (EDI), an aggregated index, to define the social environment of the women included. Multidimensional penalized splines were used to model excess mortality hazard. We observed a significant effect of the EDI on NS in women with breast cancer throughout the follow-up period, and especially at 1.5 years of follow-up in women with cervical cancer. Regarding corpus uteri and ovarian cancer patients, the effect of deprivation on NS was less pronounced. These results highlight the impact of social environment on NS in women with breast or gynecological cancer in France thanks to a relevant statistical approach, and identify the follow-up periods during which the social environment may have a particular influence. These findings could help investigate targeted actions for each cancer type, particularly in the most deprived areas, at the time of diagnosis and during follow-up.

COVID-19 outcomes of patients with gynecologic cancer in New York City: An updated analysis from the initial surge of the pandemic.

BACKGROUND: Despite significant increase in COVID-19 publications, characterization of COVID-19 infection in patients with gynecologic cancer remains limited. Here we present an update of COVID-19 outcomes among people with gynecologic cancer in New York City (NYC) during the initial surge of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]). METHODS: Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 NYC area hospital systems between March and June 2020. Multivariable logistic regression was utilized to estimate associations between factors and COVID-19 related hospitalization and mortality. RESULTS: Of 193 patients with gynecologic cancer and COVID-19, the median age at diagnosis was 65.0 years (interquartile range (IQR), 53.0-73.0 years). One hundred six of the 193 patients (54.9%) required hospitalization; among the hospitalized patients, 13 (12.3%) required invasive mechanical ventilation, 39 (36.8%) required ICU admission. Half of the cohort (49.2%) had not received anti-cancer treatment prior to COVID-19 diagnosis. No patients requiring mechanical ventilation survived. Thirty-four of 193 (17.6%) patients died of COVID-19 complications. In multivariable analysis, hospitalization was associated with an age ≥ 65 years (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.11, 4.07), Black race (OR 2.53, CI 1.24, 5.32), performance status ≥2 (OR 3.67, CI 1.25, 13.55) and ≥ 3 comorbidities (OR 2.00, CI 1.05, 3.84). Only former or current history of smoking (OR 2.75, CI 1.21, 6.22) was associated with death due to COVID-19 in multivariable analysis. Administration of cytotoxic chemotherapy within 90 days of COVID-19 diagnosis was not predictive of COVID-19 hospitalization (OR 0.83, CI 0.41, 1.68) or mortality (OR 1.56, CI 0.67, 3.53). CONCLUSIONS: The case fatality rate among patients with gynecologic malignancy with COVID-19 infection was 17.6%. Cancer-directed therapy was not associated with an increased risk of mortality related to COVID-19 infection.

Outcomes after targeted treatment based on somatic tumor genetic testing for women with gynecologic cancers.

OBJECTIVE: Molecular tumor profiling and next-generation sequencing are being increasingly utilized, but there are limited data on the therapeutic implications and potential benefits of targeted treatments. We aim to characterize gynecologic oncology patients referred for somatic tumor genetic mutation testing and assess survival outcomes, efficacy, and toxicities of those receiving targeted therapy. METHODS: We conducted a retrospective chart review of gynecologic oncology patients referred for somatic tumor testing by next generation sequencing between 1/1/2012-8/23/2019. The primary objective was to compare overall and progression free survival between those treated with targeted therapy (group 1) versus traditional treatment (group 2). RESULTS: Most patients (70%) had additional treatment options available based on actionable mutations. The median number of somatic mutations identified was 5 (range 0-53). Patients in group 1 had more actionable somatic mutations (median 2 versus 0, p < 0.001). There was no difference in OS (median 64 versus 76 months, p = 0.97) or PFS (median 2 versus 8 months, p = 0.05) between the groups. While fewer patients in group 1 experienced neuropathy (0 versus 5, p = 0.02), grade I/II thrombocytopenia (7 versus 13, p = 0.03), grade III/IV thrombocytopenia (0 versus 4, p = 0.02), and grade III/IV neutropenia (1 versus 9, p = 0.002), all other non-hematologic toxicities were similar in the two groups. CONCLUSIONS: Most gynecologic cancer patients have actionable mutations and may benefit from a personalized targeted therapy treatment plan. Next generation sequencing can be used to identify clinically actionable mutations in gynecologic cancers and guide the selection of treatments, thereby expanding treatment options without worsening survival or toxicity.

Determining post-operative morbidity and mortality following gynecological oncology surgery: protocol for a multicenter, international, prospective cohort study (Global Gynaecological Oncology Surgical Outcomes Collaborative-GO SOAR).

BACKGROUND: The Global Gynaecological Oncology Surgical Outcomes Collaborative (GO SOAR) aims to develop a network of gynecological oncology surgeons, surgical departments, and other interested parties that will have the long-term ability to collaborate on outcome studies. The protocol for the first collaborative study is presented here. PRIMARY OBJECTIVE: To evaluate international variation in 30-day post-operative morbidity and mortality following gynecological oncology surgery between very high/high and medium/low human development index country settings. HYPOTHESIS: There is no variation in post-operative morbidity and mortality following gynecological oncology surgery between very high/high and medium/low human development index country settings. STUDY DESIGN: International, multicenter, prospective cohort study. Patient data will be collected over a consecutive 30-day period through gynecological oncology multidisciplinary teams/tumor boards and clinics across different human development index country groups. All data are collected on a customized, secure, password protected, central REDCap database. MAJOR INCLUSION/EXCLUSION CRITERIA: Inclusion criteria include women aged ≥18 years undergoing elective/emergency, curative/palliative surgery for primary/recurrent tubo-ovarian/peritoneal, endometrial, cervical, vulval, vaginal, gestational trophoblastic malignancies. Surgical modality may be open, minimal access (laparoscopic/robotic), or vaginal. PRIMARY ENDPOINT: 30-day post-operative morbidity and mortality defined as per Clavien-Dindo classification system. SAMPLE SIZE: 1100 (550/arm). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: It is estimated recruitment will be completed by 2022 and results published by 2023. TRIAL REGISTRATION: ClinicalTrials.gov registry: NCT04579861 (https://clinicaltrials.gov/ct2/show/NCT04579861).

Mesonephric adenocarcinomas in female genital tract: A case series.

ABSTRACT: Mesonephric adenocarcinoma (MNAC) is a very rare tumor that originates from mesonephric duct remnants of the female genital tract. Only a few cases were reported in the literature, and most of them occurred in the cervix, extremely rare in the uterine body and ovary. MNAC was rarely reported to arise in the uterine corpus, but never was reported in the ovary. Mesonephric-like adenocarcinomas are recently suggested to describe these neoplasms arising from the uterine corpus and ovary. Due to the rareness of the disease, little is known regarding clinical characteristics, pathological diagnosis, prognosis, and optimal management strategy of MNAC in the female reproductive system. We report a series of MNACs arising from the vagina, cervix, uterine corpus, ovary, and fallopian tube, to summarize the clinical characteristics, pathological diagnosis, treatment, and prognosis.We retrospectively analyzed all MNACs in the female genital tract derived from our institute from January 2010 till January 2020. Patients' clinical details and follow-up were obtained from hospital records and scans were obtained from picture archiving and communication system.A total of 11 patients were included. The median age of onset of symptoms was 52 years. All patients underwent total hysterectomy and bilateral salpingo-oophorectomy, and lymph node dissections were performed in 7/11 (63.6%) patients. Two/eleven (18.2%) received neoadjuvant chemotherapy before surgery and 7/11 (63.6%) received adjuvant chemotherapy after primary surgery. Of the 11 patients, only 1 patient received adjuvant radiation therapy. One patient died at the end point of this study, 9 patients (81.8%) survived and 1 patient was lost to follow-up. The mean follow-up duration was 33.5 months.Although there is no consensus for the optimal treatment of this rare disease, radical surgery is considered to be the initial choice for localized lesion. Given the high malignancy, the majority of MNAC or mesonephric-like adenocarcinoma patients who underwent adjuvant chemotherapy received 4 to 8 cycles of carboplatin/paclitaxel as a first-line treatment after primary surgery with a median progression-free survival of 12 months. Treatment for recurrent disease in these patients included gemcitabine, carboplatin, and paclitaxel. Radiation was very limited in the treatment of the disease.

Pelvic exenteration for recurrent or persistent gynecologic malignancies: Clinical and histopathologic factors predicting recurrence and survival in a modern cohort.

OBJECTIVES: To explore pre-operative factors and their impact on overall survival (OS) in a modern cohort of patients who underwent pelvic exenteration (PE) for gynecologic malignancies. METHODS: A retrospective review was performed for all patients who underwent a PE from 1/1/2010 through 12/31/2018 at our institution. Inclusion criteria were exenteration due to recurrent or progressive carcinoma of the uterus, cervix, vagina or vulva, with histologically confirmed complete surgical resection of the malignancy. Exclusion criteria included PE for palliation of symptoms without recurrence, and for ovarian or rare histologic malignancies. Univariable and multivariable analysis were performed to identify factors predicting prolonged survival. RESULTS: Overall, 71 patients met the inclusion criteria. Median age at time of exenteration was 62 years (range, 28-86 years). Vulvar cancer was the most common primary diagnosis (32%); 30% had cervical cancer; 23%, uterine cancer; 15%, vaginal cancer. Median OS was 55.1 months (95% confidence interval (CI): 36-not estimable) with a median follow-up time of 40.8 months (95% CI: 1-116.1). On univariable analysis, age > 62 years (hazard ratio (HR) 2.71, 95% CI 1.27-5.79), American Society of Anesthesia (ASA) 3-4 (HR: 3.41 (95% CI 1.03-11.29), and vulvar cancer (HR 4.19 (95% CI 1.17-14.96) predicted worse OS. Tumor size and prior progression-free interval (PFI) did not meet statistical significance in OS analyses. On multivariable analysis, there were no significant factors associated with worse OS. CONCLUSIONS: PE performed with curative intent may be considered a treatment option in well-counseled, carefully selected patients, irrespective of tumor size and PFI before exenteration.

Intraoperative electron beam radiotherapy and perioperative high-dose-rate brachytherapy in previously irradiated oligorecurrent gynecological cancer: clinical outcome analysis

Background Pelvic recurrences from previously irradiated gynecological cancer lack solid evidence for recommendation on salvage. Methods A total of 58 patients were included in this clinical analysis. Salvage surgery was performed for locoregional relapse within previously irradiated pelvic area after initial surgery and adjuvant radiotherapy or radical external beam radiotherapy. The primary tumor diagnosis included cervical cancer (n = 47, 81%), uterine cancer (n = 4, 7%), and other types (n = 7, 12%). Thirty-three patients received adjuvant IOERT (1984–2000) at a median dose of 15 Gy (range 10–20 Gy) and 25 patients received adjuvant PHDRB (2001–2016) at a median dose of 32 Gy (range 24–40 Gy) in 6, 8, or 10 b.i.d. fractions. Results The median follow-up was 5.6 years (range 0.5–14.2 years). Twenty-nine (50.0%) patients had positive surgical margins. Grade ≥ 3 toxic events were recorded in 34 (58.6%) patients. The local control rate at 2 years was 51% and remained stable up to 14 years. Disease-free survival rates at 2, 5, and 10 years were 17.2, 15.5, and 15.5%, respectively. Overall survival rates at 2, 5, and 10 years were 58.1, 17.8, and 17.8%, respectively. Conclusions IOERT and PHDRB account for an effective salvage in oligorecurrent gynecological tumors. Patients with previous pelvic radiation suitable for salvage surgery and at risk of inadequate margins could benefit from adjuvant reirradiation in form of IOERT or PHDRB. However, the rate of severe grade ≥ 3 toxicity associated with the entire treatment program is relevant and needs to be closely counterbalanced against the expected therapeutic gain (AU)

The impact of marital status on stage at diagnosis and survival of female patients with breast and gynecologic cancers: A meta-analysis.

The aim of this meta-analysis is to evaluate the effect of marital status on the stage at diagnosis and survival of female patients with breast and gynecologic cancers. A systematic literature search was conducted on electronic databases (PubMed, Cochrane and EMBASE) till December 31, 2020. Publications investigating the association of marital status with stage at diagnosis and/or cancer-specific mortality (CSM) and/or overall survival (OS) in female patients with breast or gynecologic cancers were retrieved. After studies were selected according to inclusion criteria, data extraction, quality assessment and data analysis were performed. 55 articles were eligible for inclusion, consisting of 1,195,773 female cancer patients with breast, vulvar, cervical, endometrial and ovarian cancers. Unmarried female cancer patients had higher odds of being diagnosed at later stage [odds ratio (OR) = 1.28, 95% confidence interval (CI): 1.22-1.36)] and worse survival outcomes in CSM [hazard ratio (HR) = 1.22, 95% CI: 1.16-1.28] and OS (HR = 1.20, 95% CI: 1.14-1.25). This estimate did not vary by level of social support, number of adjustment factors, or between America and Europe. Being married is associated with timely diagnosis and favorable prognosis in most women's cancers. Unmarried female cancer patients have a higher risk of late-stage diagnosis and worse survival outcomes than the married. Greater concern shall be demonstrated towards unmarried female cancer patients. Furthermore, the impact of lacking economic and emotional support on survival outcomes in unmarried female cancer patients deserves particular attention.

Self-management and adherence to recommended follow-up after gynaecological cancer: results from the international InCHARGE study.

OBJECTIVE: To assess the relationship between self-management skills and adherence to follow-up guidelines among gynecological cancer survivors in the Netherlands, Norway, and Denmark, and to assess the relationship between adherence to follow-up programs and use of additional healthcare services. METHODS: For this international, multicenter, cross-sectional study, we recruited gynecological cancer survivors 1-5 years after completion of treatment. Information on follow-up visits, use of healthcare resources, self-management (measured by the Health Education Impact Questionnaire), clinical characteristics, and demographics were obtained by validated questionnaires. Participants were categorized as adherent if they attended the number of follow-up visits recommended by national guidelines, non-adherent if they had fewer visits than recommended, or over-users if they had more visits than recommended. RESULTS: Of 4455 invited survivors, 2428 (55%) returned the questionnaires, and 911 survivors were included in the analyses. Survivors with high self-management most frequently adhered to recommended follow-up. Non-adherent survivors showed lower self-management in the health-directed activity domain (OR 1.54, 95% CI 1.03 to 2.32) than adherent survivors. No other associations between self-management and follow-up adherence were revealed. Non-adherent survivors tended to have endometrial cancer, surgical treatment only, be older, and be Danish residents. Over-users reported more follow-up visits and also used additional healthcare services more frequently than adherent survivors. CONCLUSION: Low self-management appears to reduce the likelihood of adherence to national guidelines for gynecological cancer follow-up. Focusing on patient education for survivors at risk of low self-management to ensure adherence to recommended follow-up may improve personalization of follow-up.

Intraoperative electron beam radiotherapy and perioperative high-dose-rate brachytherapy in previously irradiated oligorecurrent gynecological cancer: clinical outcome analysis.

BACKGROUND: Pelvic recurrences from previously irradiated gynecological cancer lack solid evidence for recommendation on salvage. METHODS: A total of 58 patients were included in this clinical analysis. Salvage surgery was performed for locoregional relapse within previously irradiated pelvic area after initial surgery and adjuvant radiotherapy or radical external beam radiotherapy. The primary tumor diagnosis included cervical cancer (n = 47, 81%), uterine cancer (n = 4, 7%), and other types (n = 7, 12%). Thirty-three patients received adjuvant IOERT (1984-2000) at a median dose of 15 Gy (range 10-20 Gy) and 25 patients received adjuvant PHDRB (2001-2016) at a median dose of 32 Gy (range 24-40 Gy) in 6, 8, or 10 b.i.d. fractions. RESULTS: The median follow-up was 5.6 years (range 0.5-14.2 years). Twenty-nine (50.0%) patients had positive surgical margins. Grade ≥ 3 toxic events were recorded in 34 (58.6%) patients. The local control rate at 2 years was 51% and remained stable up to 14 years. Disease-free survival rates at 2, 5, and 10 years were 17.2, 15.5, and 15.5%, respectively. Overall survival rates at 2, 5, and 10 years were 58.1, 17.8, and 17.8%, respectively. CONCLUSIONS: IOERT and PHDRB account for an effective salvage in oligorecurrent gynecological tumors. Patients with previous pelvic radiation suitable for salvage surgery and at risk of inadequate margins could benefit from adjuvant reirradiation in form of IOERT or PHDRB. However, the rate of severe grade ≥ 3 toxicity associated with the entire treatment program is relevant and needs to be closely counterbalanced against the expected therapeutic gain.