Textbook oncologic outcome is an easy-to-use composite quality measure that is strongly associated with survival in advanced-stage ovarian cancer.

OBJECTIVE: Textbook oncologic outcome (TOO) has been validated in surgical oncology as a composite quality measure correlated with oncologic outcomes. We aimed to assess the association between TOO and overall survival (OS) in patients undergoing primary treatment for advanced epithelial tubo-ovarian cancer (AEOC). METHODS: Patients undergoing surgery for AEOC between 2008 and 2019 were identified in the National Cancer Database (NCDB). Primary debulking surgery (PDS) and interval debulking surgery (IDS) cohorts were analyzed separately. TOO was defined as achieving complete debulking, length of hospital stay <10 days, no 30-day readmission, no death within 90 days, and initiation of adjuvant chemotherapy within 42 days. The Kaplan-Meier method was used to estimate 5-year OS by TOO status and Cox regression to evaluate the relationship between TOO and death within 5 years. RESULTS: A total of 21,657 patients were included: 51.4% in the PDS cohort and 48.6% in the IDS cohort. TOO was achieved (TOO+) in 20.5% of the PDS cohort and 39.2% of the IDS cohort. For the PDS cohort, achieving TOO was associated with improved 5-year OS: 59.0% TOO+ vs. 39.5% TOO- (HR 0.53, 95% CI 0.49-0.57). For the IDS cohort, a similar benefit was seen for 5-year OS: 43.9% TOO+ vs. 31.2% TOO- (HR 0.67, 95% CI 0.63-0.70). Multivariable analysis demonstrated that patients achieving TOO were at lower risk of death within 5 years in both the PDS cohort (HR 0.58, 95% CI 0.54-0.62) and the IDS cohort (HR 0.69, 95% CI 0.65-0.73). CONCLUSIONS: The TOO composite measure is associated with improved long-term survival and could be a useful quality assessment tool for patients undergoing primary treatment for AEOC, irrespective of surgical timing. This tool reflects the ability to deliver risk-based individualized decision-making using a multidisciplinary approach.

The Quality of Life after Endometrial Cancer Study: Baseline Characteristics and Patient-Reported Outcomes.

Endometrial cancer (EC) patients make up the second largest group of female cancer survivors. Patient-reported outcomes (PROs) including quality of life (QOL) and sexual function and satisfaction (SF and S) are critical facets of survivorship. This prospective, longitudinal study assesses associations between baseline characteristics and PROs after treatment. Herein, we report the baseline clinical characteristics and PROs prior to treatment initiation. Outcomes post-treatment over time will be reported separately. Patients with planned surgery for EC were prospectively enrolled in 2019-2021 and administered the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 30 (QLQ-C30), EORTC QLQ EC Module (EN24), Patient-Reported Outcomes Measurement Information System (PROMIS), and the Mayo Clinic lower extremity lymphedema (LEL) questionnaire. This study enrolled 198 patients with a mean (SD) age of 63.6 (9.8) years and body mass index of 35.5 (8.3) kg/m2. No significant differences in the PROs for the QOL were seen when compared to the reference means (SD) except for the lower interest in sexual activity (31.9 (9.8) vs. 47.5 (SE0.70)) and lower fatigue (21.3 (19.8) vs. 31.7 (25.9)). Increased obesity was associated with an increased likelihood of LEL (p < 0.01) and multiple QOL scales, including poorer global health status (p < 0.01) and physical functioning (p < 0.01). Prior to treatment initiation for EC, the patients had a similar QOL compared to that of the general population. The patients with increasing obesity, a known risk factor for EC, had worse overall global health status and physical functioning. A better understanding of these QOL measures is imperative for earlier identification and intervention of patients at risk of chronic impairments from EC treatment.

Treatment outcomes of vulvar and vaginal melanoma at an NCCN institution between 1993 and 2021.

Background: Vulvar melanoma and vaginal melanoma are rare and difficult to treat. We describe the last three decades in a cohort predominantly treated surgically with adjuvant therapy. Methods: All new patients between 1993 and 2021 followed until 2024. Collection of demographic and oncologic data allowed comparisons and Kaplan-Meier method was used to evaluate overall survival (OS) and progression free survival (PFS) stratified by adjuvant therapy type, diagnosis before and after 2011, and between vulvar and vaginal melanomas. Results: Consultation for 63/72 patients (87.5 %) were for primary treatment. Most patients had vulvar melanoma (50/72, 69.4 %), received surgery (65/72, 90.3 %), and adjuvant treatment (40/72, 55.6 %) with immunotherapy, chemotherapy, and/or targeted therapy. Median survival for 63 patients presenting for primary treatment was 54.2 months, and 9/13 patients who were disease free after five years later received adjuvant immunotherapy. Survival did not vary by adjuvant therapy type or diagnosis after 2011 but was significantly less for vaginal melanoma. Following recurrence seven patients experienced complete response including three patients receiving combined nivolumab with ipilimumab and two nivolumab alone experienced. Conclusions: Survival was not significantly different by adjuvant therapy type or after 2011. Most patients who were disease-free five years after surgery had received adjuvant therapy. Seven patients experienced complete responses to therapy after recurrence of whom five received immune checkpoint inhibitors. Although survival is not improved as in cutaneous melanomas by immune checkpoint inhibitors, signal continues for the use of immune checkpoint inhibitors in gynecologic melanomas.

Physical and psychological distress amongst patients undergoing neoadjuvant chemotherapy for advanced ovarian cancer.

OBJECTIVE: This study compares baseline clinical characteristics, physical function testing, and patient-reported outcomes for patients undergoing primary cytoreductive surgery versus neoadjuvant chemotherapy, with the goal of better understanding unique patient needs at diagnosis. METHODS: Patients with suspected advanced stage (IIIC/IV) epithelial ovarian cancer undergoing either primary cytoreductive surgery or neoadjuvant chemotherapy were enrolled in a single-institution, non-randomized prospective behavioral intervention trial of prehabilitation. Baseline clinical characteristics were abstracted. Physical function was evaluated using the Short Physical Performance Battery, Fried Frailty Index, gait speed, and grip strength. Patient-reported outcomes were evaluated using Patient-Reported Outcomes Measurement Information System metrics and the Perceived Stress Scale. RESULTS: There were no significant differences in demographics or clinical characteristics between cohorts at enrollment, with the exception of performance status, clinical stage, and albumin. While gait speed and grip strength were lower amongst neoadjuvant chemotherapy patients, there were no significant differences in physical function using the Short Physical Performance Battery and Fried Frailty Index. Patients in the neoadjuvant chemotherapy cohort reported decreased perception of physical function and increased fatigue on Patient-Reported Outcomes Measurement Information System metrics. A larger proportion of patients in the neoadjuvant cohort reported severe levels of emotional distress and anxiety, as well as greater perceived stress at diagnosis. CONCLUSIONS: Our findings suggest that patients undergoing neoadjuvant chemotherapy for advanced ovarian cancer present with increased psychosocial distress and decreased perception of physical function at diagnosis and may benefit most from early introduction of supportive care.

Artificial intelligence model for enhancing the accuracy of transvaginal ultrasound in detecting endometrial cancer and endometrial atypical hyperplasia.

OBJECTIVES: Transvaginal ultrasound is typically the initial diagnostic approach in patients with postmenopausal bleeding for detecting endometrial atypical hyperplasia/cancer. Although transvaginal ultrasound demonstrates notable sensitivity, its specificity remains limited. The objective of this study was to enhance the diagnostic accuracy of transvaginal ultrasound through the integration of artificial intelligence. By using transvaginal ultrasound images, we aimed to develop an artificial intelligence based automated segmentation model and an artificial intelligence based classifier model. METHODS: Patients with postmenopausal bleeding undergoing transvaginal ultrasound and endometrial sampling at Mayo Clinic between 2016 and 2021 were retrospectively included. Manual segmentation of images was performed by four physicians (readers). Patients were classified into cohort A (atypical hyperplasia/cancer) and cohort B (benign) based on the pathologic report of endometrial sampling. A fully automated segmentation model was developed, and the performance of the model in correctly identifying the endometrium was compared with physician made segmentation using similarity metrics. To develop the classifier model, radiomic features were calculated from the manually segmented regions-of-interest. These features were used to train a wide range of machine learning based classifiers. The top performing machine learning classifier was evaluated using a threefold approach, and diagnostic accuracy was assessed through the F1 score and area under the receiver operating characteristic curve (AUC-ROC). RESULTS: 302 patients were included. Automated segmentation-reader agreement was 0.79±0.21 using the Dice coefficient. For the classification task, 92 radiomic features related to pixel texture/shape/intensity were found to be significantly different between cohort A and B. The threefold evaluation of the top performing classifier model showed an AUC-ROC of 0.90 (range 0.88-0.92) on the validation set and 0.88 (range 0.86-0.91) on the hold-out test set. Sensitivity and specificity were 0.87 (range 0.77-0.94) and 0.86 (range 0.81-0.94), respectively. CONCLUSIONS: We trained an artificial intelligence based algorithm to differentiate endometrial atypical hyperplasia/cancer from benign conditions on transvaginal ultrasound images in a population of patients with postmenopausal bleeding.

Impact of molecular classification on recurrence risk in endometrial cancer patients with lymph node metastasis: multicenter retrospective study.

OBJECTIVE: To assess the distribution of molecular classes and their impact on the risk of recurrence in endometrial cancer patients with lymph node metastasis at the time of primary surgery. METHODS: Endometrial cancer patients with lymph node micrometastasis or macrometastasis (International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IIIC) after surgical staging at five referral centers worldwide from October 2013 to September 2022 who underwent molecular classification were identified. Endometrial cancers were categorized into four molecular classes: POLE mutated, mismatch repair deficient, p53 abnormal, and no specific molecular profile. Survival analyses using Kaplan-Meier and Cox models (univariate and multivariate) were conducted to evaluate the relationship between molecular class and 5-year recurrence free survival. RESULTS: 131 patients were included: 55 (42.0%) no specific molecular profile, 46 (35.1%) mismatch repair deficient, 1 (0.8%) POLE mutated, and 29 (22.1%) p53 abnormal. During a 5 year follow-up period, 50 (38.2%) patients experienced a recurrence with a median time of 1.2 years (interquartile range (IQR) 0.5-1.8). Median follow-up for the remaining 81 patients was 3.1 years (IQR 1.3-4.5). Survival analysis revealed a significant difference in recurrence-free survival between no specific molecular profile, mismatch repair deficient, and p53 abnormal classes (log rank p<0.01). In a model adjusted for type of lymph node metastasis and tumor grade, the molecular class did not retain significance (p=0.13), while in a model adjusted for type of lymph node metastasis and adjuvant therapy, the molecular class retained significance (p<0.01). CONCLUSION: Among patients with stage IIIC endometrial cancer, POLE mutated tumors exhibited an extremely low prevalence, with no specific molecular profile emerging as the largest molecular subgroup. Despite the significant difference in recurrence-free survival between molecular classes, conventional histopathologic parameters retained crucial prognostic value. Our findings highlight the necessity of integrating molecular classes with pathological characteristics, rather than considering them in isolation as crucial prognostic factors in stage IIIC endometrial cancer.

White Matter Abnormalities Track Disease Progression in Multiple System Atrophy.

BACKGROUND: White matter (WM) abnormalities have been implicated in clinically relevant functional decline in multiple system atrophy (MSA). OBJECTIVE: To identify the WM and gray matter (GM) abnormalities in MSA and assess the utility of longitudinal structural and diffusion changes as surrogate markers for tracking disease progression in MSA. METHODS: Twenty-seven participants with early MSA [15 with clinically predominant cerebellar (MSA-C) and 12 with clinically predominant parkinsonian features (MSA-P)] and 14 controls were enrolled as a part of our prospective, longitudinal study of synucleinopathies. Using structural magnetic resonance imaging (MRI) and diffusion MRI (diffusion tensor and neurite orientation and dispersion density imaging), we analyzed whole and regional brain changes in these participants. We also evaluated temporal imaging trajectories based on up to three annual follow-up scans and assessed the impact of baseline diagnosis on these imaging biomarkers using mixed-effect models. RESULTS: MSA patients exhibited more widespread WM changes than GM, particularly in the cerebellum and brainstem, with greater severity in MSA-C. Structural and diffusion measures in the cerebellum WM and brainstem deteriorated with disease progression. Rates of progression of these abnormalities were similar in both MSA subtypes, reflecting increasing overlap of clinical features over time. CONCLUSION: WM abnormalities are core features of MSA disease progression and advance at similar rates in clinical MSA subtypes. Multimodal MRI imaging reveals novel insights into the distribution and pattern of brain abnormalities and their progression in MSA. Selected structural and diffusion measures may be useful for tracking disease progression in MSA clinical trials.

Complex relationships of socioeconomic status with vascular and Alzheimer's pathways on cognition.

INTRODUCTION: AD and CVD, which frequently co-occur, are leading causes of age-related cognitive decline. We assessed how demographic factors, socioeconomic status (SES) as indicated by education and occupation, vascular risk factors, and a range of biomarkers associated with both CVD (including white matter hyperintensities [WMH], diffusion MRI abnormalities, infarctions, and microbleeds) and AD (comprising amyloid-PET and tau-PET) collectively influence cognitive function. METHODS: In this cross-sectional population study, structural equation models were utilized to understand these associations in 449 participants (mean age (SD) = 74.5 (8.4) years; 56% male; 7.5% cognitively impaired). RESULTS: (1) Higher SES had a protective effect on cognition with mediation through the vascular pathway. (2) The effect of amyloid directly on cognition and through tau was 11-fold larger than the indirect effect of amyloid on cognition through WMH. (3) There is a significant effect of vascular risk on tau deposition. DISCUSSION: The utilized biomarkers captured the impact of CVD and AD on cognition. The overall effect of vascular risk and SES on these biomarkers are complex and need further investigation.

Evaluating nutrition in advanced ovarian cancer: which biomarker works best?

BACKGROUND: Advanced epithelial ovarian cancer (OC) patients often present with malnutrition; however, the ideal nutritional evaluation tool is unclear. We aimed to evaluate the role of preoperative albumin, Prognostic Nutritional Index [PNI], neutrophil-to-lymphocyte ratio [NLR], and platelet-to-lymphocyte ratio [PLR] as independent predictors of severe postoperative complications and 90-day mortality in OC patients who underwent primary cytoreductive surgery to identify the ideal tool. METHODS: OC patients who underwent surgery at Mayo Clinic (2003-2018) were included; biomarkers were retrospectively retrieved and established cut-offs were utilized. Outcomes included severe complications (Accordion grade ≥ 3) and 90-day mortality. Univariate and multivariable logistic regression models were performed. Biomarkers were evaluated in separate models adjusted for age and American Society of Anesthesiologists (ASA) score for 90-day mortality, and adjusted for age, ASA score, stage, and surgical complexity for severe complications. RESULTS: Albumin <3.5 g/dL, PNI < 45, NLR > 6 and PLR ≥ 200 were univariately associated with 90-day mortality (all p < 0.05) in 627 patients that met inclusion criteria. Each marker remained significant in adjusted models with albumin having the highest OR: 6.04 [95% CI:2.80-13.03] and AUC (0.83). Univariately, PNI <45, NLR >6, and PLR ≥200 were significant predictors of severe complications(all p < 0.05), however failed to reach significance in adjusted models. Albumin was not associated with severe complications. CONCLUSION: All biomarkers were associated with 90-day mortality in adjusted models, with albumin being the easiest predictor to attain clinically; none with severe complications. Future research should focus less on methods of nutritional assessment and more on strategies to improve nutrition during OC tumor-directed therapy.

Incidence of sentinel lymph node metastases in apparent early-stage endometrial cancer: a multicenter observational study.

OBJECTIVE: Ultrastaging is accurate in detecting nodal metastases, but increases costs and may not be necessary in certain low-risk subgroups. In this study we examined the risk of nodal involvement detected by sentinel lymph node (SLN) biopsy in a large population of apparent early-stage endometrial cancer and stratified by histopathologic characteristics. Furthermore, we aimed to identify a subgroup in which ultrastaging may be omitted. METHODS: We retrospectively included patients who underwent SLN (with bilateral mapping and no empty nodal packets on final pathology) ± systematic lymphadenectomy for apparent early-stage endometrial cancer at two referral cancer centers. Lymph node status was determined by SLN only, regardless of non-SLN findings. The incidence of macrometastasis, micrometastasis, and isolated tumor cells (ITC) was measured in the overall population and after stratification by histotype (endometrioid vs serous), myometrial invasion (none, <50%, ≥50%), and grade (G1, G2, G3). RESULTS: Bilateral SLN mapping was accomplished in 1570 patients: 1359 endometrioid and 211 non-endometrioid, of which 117 were serous. The incidence of macrometastasis, micrometastasis, and ITC was 3.8%, 3.4%, and 4.8%, respectively. In patients with endometrioid histology (n=1359) there were 2.9% macrometastases, 3.2% micrometastases, and 5.3% ITC. No macro/micrometastases and only one ITC were found in a subset of 274 patients with low-grade (G1-G2) endometrioid endometrial cancer without myometrial invasion (all <1%). The incidence of micro/macrometastasis was higher, 2.8%, in 708 patients with low-grade endometrioid endometrial cancer invading <50% of the myometrium. In patients with serous histology (n=117), the incidence of macrometastases, micrometastasis, and ITC was 11.1%, 6.0%, and 1.7%, respectively. For serous carcinoma without myometrial invasion (n=36), two patients had micrometastases for an incidence of 5.6%. CONCLUSIONS: Ultrastaging may be safely omitted in patients with low-grade endometrioid endometrial cancer without myometrial invasion. No other subgroups with a risk of nodal metastasis of less than 1% have been identified.

A high-fat eucaloric diet induces reprometabolic syndrome of obesity in normal weight women.

We examined the effects of 1 month of a eucaloric, high-fat (48% of calories) diet (HFD) on gonadotropin secretion in normal-weight women to interrogate the role of free fatty acids and insulin in mediating the relative hypogonadotropic hypogonadism of obesity. Eighteen eumenorrheic women (body mass index [BMI] 18-25 kg/m2) were studied in the early follicular phase of the menstrual cycle before and after exposure to an HFD with frequent blood sampling for luteinizing hormone (LH) and follicle-stimulating hormone (FSH), followed by an assessment of pituitary sensitivity to gonadotropin-releasing hormone (GnRH). Mass spectrometry-based plasma metabolomic analysis was also performed. Paired testing and time-series analysis were performed as appropriate. Mean endogenous LH (unstimulated) was significantly decreased after the HFD (4.3 ± 1.0 vs. 3.8 ± 1.0, P < 0.01); mean unstimulated FSH was not changed. Both LH (10.1 ± 1.0 vs. 7.2 ± 1.0, P < 0.01) and FSH (9.5 ± 1.0 vs. 8.8 ± 1.0, P < 0.01) responses to 75 ng/kg of GnRH were reduced after the HFD. Mean LH pulse amplitude and LH interpulse interval were unaffected by the dietary exposure. Eucaloric HFD exposure did not cause weight change. Plasma metabolomics confirmed adherence with elevation of fasting free fatty acids (especially long-chain mono-, poly-, and highly unsaturated fatty acids) by the last day of the HFD. One-month exposure to an HFD successfully induced key reproductive and metabolic features of reprometabolic syndrome in normal-weight women. These data suggest that dietary factors may underlie the gonadotrope compromise seen in obesity-related subfertility and therapeutic dietary interventions, independent of weight loss, may be possible.

Vascular risk, gait, behavioral, and plasma indicators of VCID.

INTRODUCTION: Cost-effective screening tools for vascular contributions to cognitive impairment and dementia (VCID) has significant implications. We evaluated non-imaging indicators of VCID using magnetic resonance imaging (MRI)-measured white matter (WM) damage and hypothesized that these indicators differ based on age. METHODS: In 745 participants from the Mayo Clinic Study of Aging (≥50 years of age) with serial WM assessments from diffusion MRI and fluid-attenuated inversion recovery (FLAIR)-MRI, we examined associations between baseline non-imaging indicators (demographics, vascular risk factors [VRFs], gait, behavioral, plasma glial fibrillary acidic protein [GFAP], and plasma neurofilament light chain [NfL]) and WM damage across three age tertiles. RESULTS: VRFs and gait were associated with diffusion changes even in low age strata. All measures (VRFs, gait, behavioral, plasma GFAP, plasma NfL) were associated with white matter hyperintensities (WMHs) but mainly in intermediate and high age strata. DISCUSSION: Non-imaging indicators of VCID were related to WM damage and may aid in screening participants and assessing outcomes for VCID. HIGHLIGHTS: Non-imaging indicators of VCID can aid in prediction of MRI-measured WM damage but their importance differed by age. Vascular risk and gait measures were associated with early VCID changes measured using diffusion MRI. Plasma markers explained variability in WMH across age strata. Most non-imaging measures explained variability in WMH and vascular WM scores in intermediate and older age groups. The framework developed here can be used to evaluate new non-imaging VCID indicators proposed in the future.

Neurite-based white matter alterations in MAPT mutation carriers: A multi-shell diffusion MRI study in the ALLFTD consortium.

We assessed white matter (WM) integrity in MAPT mutation carriers (16 asymptomatic, 5 symptomatic) compared to 31 non-carrier family controls using diffusion tensor imaging (DTI) (fractional anisotropy; FA, mean diffusivity; MD) and neurite orientation dispersion and density imaging (NODDI) (neurite density index; NDI, orientation and dispersion index; ODI). Linear mixed-effects models accounting for age and family relatedness revealed alterations across DTI and NODDI metrics in all mutation carriers and in symptomatic carriers, with the most significant differences involving fronto-temporal WM tracts. Asymptomatic carriers showed higher entorhinal MD and lower cingulum FA and patterns of higher ODI mostly involving temporal areas and long association and projections fibers. Regression models between estimated time to or time from disease and DTI and NODDI metrics in key regions (amygdala, cingulum, entorhinal, inferior temporal, uncinate fasciculus) in all carriers showed increasing abnormalities with estimated time to or time from disease onset, with FA and NDI showing the strongest relationships. Neurite-based metrics, particularly ODI, appear to be particularly sensitive to early WM involvement in asymptomatic carriers.

Relationship between frailty and nutrition: Refining predictors of mortality after primary cytoreductive surgery for ovarian cancer.

OBJECTIVE: We aimed to examine the interplay between frailty and nutritional status on 90-day mortality after primary cytoreductive surgery (PCS) for ovarian cancer (OC). METHODS: Patients with OC who underwent PCS from 1/2/2006-4/30/2018 at a single institution were identified. Frailty index (FI) includes 30 items and is calculated summing across all the item scores and dividing by the total; frailty was defined as FI ≥0.15. Nutritional status was considered impaired when preoperative serum albumin was <3.5 g/dL. Logistic regression was used to analyze the association between FI (continuous) and albumin status (binary) and 90-day postoperative mortality. RESULTS: A total of 533 patients (mean age, 64.4 years) were included, the majority were stage IIIC disease and serous histology. Albumin was <3.5 g/dL in 87 patients (16.3%) and 113 patients (21.2%) were considered frail. Median FI was 0.07 (IQR 0.03, 0.13). Postoperative 90-day mortality occurred in 24 patients (4.5%). Mortality within 90 days was higher amongst patients with low albumin (12/87, 13.8%), regardless of frailty status (13.8% [9/65] non-frail and 13.6% [3/22] frail patients). Ninety-day mortality in patients with normal albumin (n = 446) was over twice as likely in frail versus non-frail patients (5.5% [5/91] vs. 2.0% [7/355], respectively, p = 0.08). A model to assess 90-day mortality that included both FI and low albumin significantly improved the overall discrimination compared to low albumin alone (AUC 0.76 vs. 0.68 p = 0.03). CONCLUSION: Our findings suggest that frailty and nutrition are both related to 90-day mortality. Preoperative interventions to improve functional and nutritional characteristics are needed.

Let go of the myth: safety of indocyanine green for sentinel lymph node mapping in endometrial cancer.

OBJECTIVE: Sentinel lymph node mapping by intracervical indocyanine green injection is the preferred method for surgical staging in endometrial cancer. Adverse reactions to indocyanine green are extremely rare, and information about the safety of this tracer in patients with a history of other allergies, asthma, or comorbidities is limited. We aim to evaluate the rate of adverse reactions to indocyanine green injected during sentinel lymph node mapping in patients with endometrial cancer and review the etiology of such reactions. METHODS: All patients with endometrial cancer undergoing sentinel lymph node mapping with indocyanine green cervical stroma injection at the Mayo Clinic in Rochester, Minnesota between June 2014 and December 2018 were retrospectively evaluated. Any adverse reaction occurring intra-operatively or within 7 days after surgery was identified. A thorough chart review was performed by an allergy specialist physician for any patient with an allergic-type reaction. RESULTS: We included 923 patients of which 565 (61.2%) had a history of allergy to antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), other medications, and/or environmental exposures. Of 490 patients who had previously received contrast media, 25 (5.1%) had a history of an adverse reaction. No immediate anaphylaxis or other allergic reactions were observed after indocyanine green injection. 10 (1.1%) patients developed a transient skin reaction within 7 days after surgery. None of these patients had a history of contrast media reaction. Based on timing and clinical/peri-operative history of affected patients, it was determined that skin reactions were likely induced by other newly prescribed medications or contact sensitivity, not administration of indocyanine green. CONCLUSION: Indocyanine green injection for sentinel lymph node mapping in patients with endometrial cancer caused no immediate/delayed anaphylactic or other severe allergic reactions. This included patients with a history of other allergies, asthma, and comorbidities. The myth of iodine's relationship to allergic reactions must be refuted to allow indocyanine green use in patients with a history of contrast media or shellfish allergy.

Prognostic value of isolated tumor cells in sentinel lymph nodes in low risk endometrial cancer: results from an international multi-institutional study.

OBJECTIVE: The prognostic significance of isolated tumor cells (≤0.2 mm) in sentinel lymph nodes (SLNs) of endometrial cancer patients is still unclear. Our aim was to assess the prognostic value of isolated tumor cells in patients with low risk endometrial cancer who underwent SLN biopsy and did not receive adjuvant therapy. Outcomes were compared with node negative patients. METHODS: Patients with SLNs-isolated tumor cells between 2013 and 2019 were identified from 15 centers worldwide, while SLN negative patients were identified from Mayo Clinic, Rochester, between 2013 and 2018. Only low risk patients (stage IA, endometrioid histology, grade 1 or 2) who did not receive any adjuvant therapy were included. Primary outcomes were recurrence free, non-vaginal recurrence free, and overall survival, evaluated with Kaplan-Meier methods. RESULTS: 494 patients (42 isolated tumor cells and 452 node negative) were included. There were 21 (4.3%) recurrences (5 SLNs-isolated tumor cells, 16 node negative); recurrence was vaginal in six patients (1 isolated tumor cells, 5 node negative), and non-vaginal in 15 (4 isolated tumor cells, 11 node negative). Median follow-up among those without recurrence was 2.3 years (interquartile range (IQR) 1.1-3.0) and 2.6 years (IQR 0.6-4.2) in the SLN-isolated tumor cell and node negative patients, respectively. The presence of SLNs-isolated tumor cells, lymphovascular space invasion, and International Federation of Obstetrics and Gynecology (FIGO) grade 2 were significant risk factors for recurrence on univariate analysis. SLN-isolated tumor cell patients had worse recurrence free survival (p<0.01) and non-vaginal recurrence free survival (p<0.01) compared with node negative patients. Similar results were observed in the subgroup of patients without lymphovascular space invasion (n=480). There was no difference in overall survival between the two cohorts in the full sample and the subset excluding patients with lymphovascular space invasion. CONCLUSIONS: Patients with SLNs-isolated tumor cells and low risk profile, without adjuvant therapy, had a significantly worse recurrence free survival compared with node negative patients with similar risk factors, after adjusting for grade and excluding patients with lymphovascular space invasion. However, the presence of SLNs-isolated tumor cells was not associated with worse overall survival.

Re-Evaluating Chemotherapy Dosing Strategies for Ovarian Cancer: Impact of Sarcopenia.

We investigated the impact of sarcopenia on adjuvant chemotherapy dosing in advanced epithelial ovarian cancer (EOC). The chemotherapy dosing and toxicity of 173 eligible patients who underwent cytoreductive surgery and adjuvant chemotherapy at a single institution were analyzed. Patients with a skeletal muscle index less than 39 cm2/m2 measured on a CT scan were considered sarcopenic. Sarcopenic and non-sarcopenic patients were compared with regard to relative dose intensity (RDI), completion of scheduled chemotherapy, toxicity, and survival. A total of 62 (35.8%) women were sarcopenic. Sarcopenic women were less likely to complete at least six cycles of chemotherapy (83.9% vs. 95.5%, p = 0.02). The mean RDI for both carboplatin (80.4% vs. 89.4%, p = 0.03) and paclitaxel (91.9% vs. 104.1%, p = 0.03) was lower in sarcopenic patients compared to non-sarcopenic patients. Despite these differences in chemotherapy, there was no difference in neutropenia or median overall survival (3.99 vs. 4.57 years, p = 0.62) between the sarcopenic and non-sarcopenic women, respectively. This study highlights the importance of considering lean body mass instead of body weight or surface area in chemotherapy dosing formulas for sarcopenic women with advanced EOC. Further research is needed to optimize chemotherapy strategies based on individual body composition, potentially leading to improved dosing strategies in this population.

Nonsurgical management of early-stage endometrial cancer due to obesity: a survey of the practice patterns of current Society of Gynecologic Oncology members.

Objective: Nonsurgical management for endometrial cancer in patients with class 3 obesity (BMI ≥ 40 kg/m2) is a challenging scenario given lack of consensus on patient selection and treatment options. Our objective was to evaluate trends in practice patterns and physician opinions in the Society of Gynecologic Oncology (SGO) on nonsurgical management of endometrial cancer and complex atypical hyperplasia due to obesity. Methods: An online survey was sent to all gynecologic oncologist members of the SGO with questions centered on decision-making for nonsurgical approaches for patients with class 3 obesity patients. Fisher's exact tests were used to assess the associations between offering nonsurgical management and geographic region, practice type, and time in practice. Results: 255 (19.8 %) members from 6 geographic regions responded, of which 183 (71.8 %) offered primary nonsurgical management of endometrial cancer to patients with class 3 obesity and 72 (28.2 %) do not. The choice to offer initial nonsurgical management did not vary based on geographic region, time in practice or practice type. When asked to select BMI cutoff, the majority (65.2 %) started to offer nonsurgical management was BMI 60-64 kg/m2. Progesterone intrauterine device was the preferred treatment (68.3 %, 125/183). Of those who offered nonsurgical management, 97.3 % (178/183) recommended resampling in 3-6 months. Conclusion: Primary nonsurgical management of endometrial cancer in patients with class 3 obesity is offered by most gynecologic oncologists in SGO. However, almost one-third of gynecologic oncologists indicated they do not offer nonsurgical management for endometrial cancer for obesity alone. Additional data are needed to determine the safety of both approaches in these complex patients.

Mohs surgery for female genital Paget's disease: a prospective observational trial.

BACKGROUND: Extramammary Paget's disease recurs often after traditional surgical excision. Margin-controlled surgery improves the recurrence rate for male genital disease but is less studied for female anatomy. OBJECTIVE: This study aimed to compare surgical and oncologic outcomes of margin-controlled surgery vs traditional surgical excision for female genital Paget's disease. STUDY DESIGN: We conducted a prospective observational trial of patients with vulvar or perianal Paget's disease treated with surgical excision guided by Mohs micrographic surgery between 2018 and 2022. The multidisciplinary protocol consisted of office-based scouting biopsies and modified Mohs surgery followed by surgical excision with wound closure under general anesthesia. Modified Mohs surgery cleared peripheral disease margins using a moat technique with cytokeratin 7 staining. Medial disease margins (the clitoris, urethra, vagina, and anus) were assessed using a hybrid of Mohs surgery and intraoperative frozen sections. Surgical and oncologic outcomes were compared with the outcomes of a retrospective cohort of patients who underwent traditional surgical excision. The primary outcome was 3-year recurrence-free survival. RESULTS: Three-year recurrence-free survival was 93.3% for Mohs-guided excision (n=24; 95% confidence interval, 81.5%-100.0%) compared to 65.9% for traditional excision (n=63; 95% confidence interval, 54.2%-80.0%) (P=.04). The maximum diameter of the excisional specimen was similar between groups (median, 11.3 vs 9.5 cm; P=.17), but complex reconstructive procedures were more common with the Mohs-guided approach (66.7% vs 30.2%; P<.01). Peripheral margin clearance was universally achieved with modified Mohs surgery, but positive medial margins were noted in 9 patients. Reasons included intentional organ sparing and poor performance of intraoperative hematoxylin and eosin frozen sections without cytokeratin 7. Grade 3 or higher postoperative complications were rare (0.0% for Mohs-guided excision vs 2.4% for traditional excision; P=.99). CONCLUSION: Margin control with modified Mohs surgery significantly improved short-term recurrence-free survival after surgical excision for female genital Paget's disease. Use on medial anatomic structures (the clitoris, urethra, vagina, and anus) is challenging, and further optimization is needed for margin control in these areas. Mohs-guided surgical excision requires specialized, collaborative care and may be best accomplished at designated referral centers.