Does the choice of platinum doublet matter? A study to evaluate the impact of platinum doublet choice for treatment of platinum-sensitive ovarian cancer recurrence on the development of future PARP inhibitor and platinum resistance.

OBJECTIVES: The use of a platinum doublet for the treatment of platinum-sensitive epithelial ovarian cancer (EOC) recurrence is well established. The impact of the non­platinum chemotherapy used as part of a platinum doublet on PARP inhibitor (PARPi) and platinum sensitivity it not known. We aimed to describe oncologic outcomes in cases of recurrent EOC receiving PARPi as maintenance therapy based on preceding platinum doublet. METHODS: Retrospective study of patients with platinum-sensitive recurrent ovarian, fallopian tube or primary peritoneal cancer treated with platinum doublet followed by maintenance PARPi from 1/1/2015 and 1/1/2022. Comparisons were made between patients receiving carboplatin + pegylated liposomal doxorubicin (CD) versus other platinum doublets (OPDs). Descriptive statistics, Kaplan-Meier and univariate survival analyses were performed. RESULTS: 100 patients received PARPi maintenance following a platinum doublet chemotherapy regimen for platinum-sensitive recurrence. 25/100 (25%) received CD and 75/100 (75%) received OPDs. Comparing CD and OPDs, median progression-free survival was 8 versus 7 months (p = 0.26), median time to platinum resistance was 15 versus 13 months (p = 0.54), median OS was 64 versus 90 months (p = 0.28), and median OS from starting PARPi was 25 versus 26 months (p = 0.90), respectively. CONCLUSIONS: Using pegylated liposomal doxorubicin as part of a platinum doublet preceding maintenance PARPi for platinum-sensitive recurrence does not seem to hasten PARPi resistance or platinum resistance compared to OPDs. Although there was a non-significant trend towards increased OS among patients who received a platinum doublet other than CD prior to PARPi, the OS from PARPi start was similar between groups. Given the retrospective nature of this study and small study population, further research is needed to evaluate if the choice of platinum doublet preceding PARPi maintenance impacts PARPi resistance, platinum resistance and survival.

Assessment of the feasibility of same-day discharge following minimally invasive hysterectomy in the elderly population.

Objective: To determine the safety and feasibility of same-day discharge (SDD) following minimally invasive hysterectomy (MIH) for elderly patients and to evaluate associations between age, frailty, and postoperative outcomes. Methods: Retrospective review was conducted of patients aged ≥ 70 who underwent MIH within a single gynecologic oncology institution from 2018 to 2020. Demographics, peri-operative factors, postoperative complications, and 30-day readmission rates were collected. Frailty was determined by an 11-point modified frailty index ≥ 2. Outcomes were compared between SDD and observation groups using Fisher's exact and Wilcoxon rank-sum tests. Results: Of 169 patients included in the analysis, 8.9% (n = 15) underwent SDD, and 91.1% (n = 154) were admitted for OBS following MIH. Demographics, peri-operative factors, and frailty rates (33% SDD vs 43.5% observation; p = 0.59) were similar between groups. 86.7% (n = 13) of SDD cases were completed before 12PM, and none were completed after 6PM. No SDD patients had early post-operative complications or hospital readmissions. Early postoperative complications were diagnosed in 9 (5.8%) patients admitted for OBS, and the 30-day hospital readmission rate for patients who underwent OBS was 8.4% (n = 13). While elderly patients who met objective frailty criteria (n = 72) did not have a higher likelihood of early post-operative complications (44.4% vs 55.6%; p = 0.909), they did have a higher likelihood of ED visit within 30 days of discharge (15.3 vs 3.1%; p = 0.009), and a trend was noted toward a higher rate of 30-day hospital readmission (12.5% vs 4.1%; p = 0.080). Conclusions: Elderly patients undergoing SDD following MIH did not have increased morbidity or mortality. Elderly patients who meet objective criteria for frailty, however, represent a more vulnerable population.

Safety and feasibility of same-day discharge following minimally invasive hysterectomy in the morbidly obese patient population.

OBJECTIVES: To determine whether morbid obesity should serve as an independent factor in the decision for same day discharge following minimally invasive hysterectomy. METHODS: Retrospective review was performed of patients with BMI ≥ 40 who underwent minimally invasive hysterectomy within a single comprehensive cancer center between January 2018 - August 2020. Demographics, perioperative factors, post-operative monitoring, complications, and readmissions were compared between patients who underwent same day discharge and overnight observation using Fisher's exact tests and Wilcoxon rank-sum tests. RESULTS: 374 patients with BMI ≥ 40 were included. Eighty-three (22.2%) patients underwent same day discharge, and 291 (77.8%) patients underwent overnight observation. Factors associated with increased likelihood of same day discharge included younger age (median age 53 vs 58; p = 0.001), lower BMI (median BMI 45 vs 47; p = 0.005), and fewer medical co-morbidities (Charlson Co-Morbidity Index 2 vs 3; p < 0.001). On multivariate regression analysis, frailty (OR 2.16 [1.14-4.11], p = 0.019) and surgical completion time after 12 PM (OR 3.67 [2.16-6.24], p < 0.001) were associated with increased risk of overnight observation. Few patients admitted for routine overnight observation required medical intervention (n = 14, 4.8%); most of these patients were frail (64.3%). The overall hospital readmission rate within 30 days of discharge was 3.2% (n = 12), with no patients discharged on the day of surgery being readmitted. CONCLUSIONS: Morbid obesity alone should not serve as a contraindication to same day discharge following minimally invasive hysterectomy. Admission for observation was associated with low rates of clinically meaningful intervention, and patients who underwent same day discharge were not at increased risk of adverse outcome.

The effect of applying orthogonal projection technique in short window segments to obtain fetal magnetocardiogram.

Non-invasive recordings of fetal heart and brain have been possible for almost a decade with the advancement in biomagnetic sensors using the SQUID (Superconducting Quantum Interference Device) technology. Techniques such as orthogonal projection and ICA have been applied to attenuate interference from other biological sources such as maternal heart. Successful application of such techniques among other factors depend on the non-stationary characteristics of the signals. To minimize the effect of non-stationarity due to maternal and/or fetal movement in long duration datasets, we proposed to investigate the minimal time window that is needed to obtain averaging with good SNR to apply the orthogonal projection technique to attenuate maternal magnetocardiogram (MCG) and obtain fetal MCG. The quantifying measure is based on spectral power of signals from 151-channel SQUID array system.

Differences in the sleep states of IUGR and low-risk fetuses: An MCG study.

BACKGROUND: Intrauterine growth restriction (IUGR) is a fetal condition characterized by growth-rate reduction. Afflicted fetuses tend to display abnormalities in heart rate. OBJECTIVE: To study the differences in the heart-rate variability of low-risk fetuses and IUGR fetuses during different behavioral states. METHODS: A total of 40 fetal magnetocardiograms were analyzed from 20 low-risk and 20 IUGR fetuses recorded using a 151-sensor SQUID-array system. The maternal cardiac signals were attenuated using signal-space projection. Fetal R waves were identified using an adaptive Hilbert transform approach and fetal heart rate was calculated. In each three-minute window, the heart rate was classified into patterns reflective of quiet sleep (pattern A) and active sleep (pattern B) using the criteria of Nijhuis. Two adjacent 3-min windows exhibiting the same pattern were selected for analysis from every dataset. Heart-rate variability in that 6-min window was characterized using three measures, standard deviation of normal to normal (SDNN), root mean square of successive differences (RMSSD) and phase plane area (PPA). RESULTS: All three measures tended to be lower in the IUGR group compared to the low-risk group. However, when the measures were analyzed in patterns, only PPA showed significant difference between the risk groups in pattern A, whereas both PPA and SDNN showed highly significant risk-group differences in pattern B. RMSSD did not show any significant risk-group difference. CONCLUSION: The result signifies that the heart-rate variability of IUGR fetuses is different from that of low-risk fetuses, and only PPA was able to capture the HRV differences in both quiet and active states. The difference between these two groups of fetuses shows that the fetal-activity states are potential confounders when characterizing heart-rate variability.

Phase plane based identification of fetal heart rate patterns.

Using a phase plane analysis (PPA) of the spatial spread of trajectories of the fetal heart rate and its time-derivative we characterize the fetal heart rate patterns (fHRP) as defined by Nijhuis. For this purpose, we collect 22 fetal magnetocardiogram using a 151 SQUID system from 22 low-risk fetuses in gestational ages ranging from 30 to 37 weeks. Each study lasted for 30 minutes. After the attenuation of the maternal cardiac signals, we identify the R waves using an adaptive Hilbert transform approach and calculate the fetal heart rate. On these datasets, we apply the proposed approach and the traditionally used approaches such as standard deviation of the normal to normal intervals (SDNN) and root mean square of the successive difference (RMSSD). Heart rate patterns are scored by an expert using Nijhuis criteria and revealed A, B, and D patterns. A receiver operator characteristic (ROC) curve is used to assess the performance of the metric to differentiate the different patterns. Results showed that only PPA was able to differentiate all pairs of fHRP with high performance.