Recent Research Publications- April 2023
Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer.
Eskander RN, Sill MW, Beffa L, Moore RG, Hope JM, Musa FB, Mannel R, Shahin MS, Cantuaria GH, Girda E, Mathews C, Kavecansky J, Leath Iii CA, Gien LT, Hinchcliff EM, Lele SB, Landrum LM, Backes F, O'Cearbhaill RE, Al Baghdadi T, Hill EK, Thaker PH, John VS, Welch S, Fader AN, Powell MA, Aghajanian C.
N Engl J Med. 2023 Mar 27. doi: 10.1056/NEJMoa2302312. Epub ahead of print. PMID: 36972022.
Background: Standard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear.
Methods: In this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin. The administration of pembrolizumab or placebo was planned in 6 cycles every 3 weeks, followed by up to 14 maintenance cycles every 6 weeks. The patients were stratified into two cohorts according to whether they had mismatch repair-deficient (dMMR) or mismatch repair-proficient (pMMR) disease. Previous adjuvant chemotherapy was permitted if the treatment-free interval was at least 12 months. The primary outcome was progression-free survival in the two cohorts. Interim analyses were scheduled to be triggered after the occurrence of at least 84 events of death or progression in the dMMR cohort and at least 196 events in the pMMR cohort.
Results: In the 12-month analysis, Kaplan-Meier estimates of progression-free survival in the dMMR cohort were 74% in the pembrolizumab group and 38% in the placebo group (hazard ratio for progression or death, 0.30; 95% confidence interval [CI], 0.19 to 0.48; P<0.001), a 70% difference in relative risk. In the pMMR cohort, median progression-free survival was 13.1 months with pembrolizumab and 8.7 months with placebo (hazard ratio, 0.54; 95% CI, 0.41 to 0.71; P<0.001). Adverse events were as expected for pembrolizumab and combination chemotherapy.
Conclusions: In patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy resulted in significantly longer progression-free survival than with chemotherapy alone. (Funded by the National Cancer Institute and others; NRG-GY018 ClinicalTrials.gov number, NCT03914612.).
Whynott RM, Summers KM, Mejia RB, Segre LS, Ryan G, Pawlak SA.
F S Rep. 2023 Jan 7;4(1):61-71. doi: 10.1016/j.xfre.2023.01.002. PMID: 36959953; PMCID: PMC10028477.
Objective: Determine if group psychoeducational support can improve in vitro fertilization (IVF) patients' quality of life (QoL).
Design: Randomized controlled trial (NCT04048772).
Setting: University-affiliated IVF clinic.
Patients: Women (n = 76) and male partners undergoing initial autologous IVF cycle from August 2019, to December 2020.
Interventions: Couples were assigned to groups based on projected oocyte retrieval date. Groups were randomly assigned to the control or intervention arm. Clinic closures because of the COVID-19 pandemic delayed treatment for a portion of participants. Groups were conducted in person before and virtually during the pandemic.
Main outcome measures: The primary outcome was a change in fertility quality of life (FertiQoL) from baseline to 3 days after retrieval. Secondary outcomes were changes in depression (Patient Health Questionnaire 9), anxiety (Generalized Anxiety Disorder 7), resilience (Connor-Davidson Resilience scale), IVF knowledge scores, and the likelihood of return to treatment.
Results: Knowledge scores among women in Creating Affiliations, Learning, and Mindfulness (CALM) for IVF groups significantly increased compared with control (mean difference 13.19 [3.53 - 22.84]) before the pandemic. During the pandemic, women in CALM IVF had significant improvement in the social FertiQoL score compared with controls (10.42 [1.79 - 19.04]). Compared with controls, male CALM IVF participants had significantly greater improvement in total FertiQoL (mean difference 6.68 [0.39 - 12.98]), treatment FertiQoL (8.26 [0.69 - 15.82]), and resilience (Connor-Davidson 1.13 [0.54 - 1.72]). Immediate return to care did not significantly differ between arms.
Conclusions: For women undergoing IVF, group psychoeducational programs can improve IVF knowledge and social QoL during a pandemic. Participation in a group psychoeducational program can improve QoL and resilience in IVF dyad male partners.
Clinical trial registration number: Trial registration NCT04048772.
Kesic V, Carcopino X, Preti M, Vieira-Baptista P, Bevilacqua F, Bornstein J, Chargari C, Cruickshank M, Erzeneoglu E, Gallio N, Gultekin M, Heller D, Joura E, Kyrgiou M, Madić T, Planchamp F, Regauer S, Reich O, Esat Temiz B, Woelber L, Zodzika J, Stockdale C.
Int J Gynecol Cancer. 2023 Mar 23:ijgc-2022-004213. doi: 10.1136/ijgc-2022-004213. Epub ahead of print. PMID: 36958755.
The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vaginal intraepithelial neoplasia (VaIN). The management of VaIN varies according to the grade of the lesion: VaIN 1 (low grade vaginal squamous intraepithelial lesions (SIL)) can be subjected to follow-up, while VaIN 2-3 (high-grade vaginal SIL) should be treated. Treatment needs individualization according to the patient's characteristics, disease extension and previous therapeutic procedures. Surgical excision is the mainstay of treatment and should be performed if invasion cannot be excluded. Total vaginectomy is used only in highly selected cases of extensive and persistent disease. Carbon dioxide (CO2) laser may be used as both an ablation method and an excisional one. Reported cure rates after laser excision and laser ablation are similar. Topical agents are useful for persistent, multifocal lesions or for patients who cannot undergo surgical treatment. Imiquimod was associated with the lowest recurrence rate, highest human papillomavirus (HPV) clearance, and can be considered the best topical approach. Trichloroacetic acid and 5-fluorouracil are historical options and should be discouraged. For VaIN after hysterectomy for cervical intraepithelial neoplasia (CIN) 3, laser vaporization and topical agents are not the best options, since they cannot reach epithelium buried in the vaginal scar. In these cases surgical options are preferable. Brachytherapy has a high overall success rate but due to late side effects should be reserved for poor surgical candidates, having multifocal disease, and with failed prior treatments. VaIN tends to recur and ensuring patient adherence to close follow-up visits is of the utmost importance. The first evaluation should be performed at 6 months with cytology and an HPV test during 2 years and annually thereafter. The implementation of vaccination against HPV infection is expected to contribute to the prevention of VaIN and thus cancer of the vagina. The effects of treatment can have an impact on quality of life and result in psychological and psychosexual issues which should be addressed. Patients with VaIN need clear and up-to-date information on a range of treatment options including risks and benefits, as well as the need for follow-up and the risk of recurrence.
Cafun RG, Merrill A, Bhagavathi SM, Summers KM, Bettendorf BA, Van Voorhis BJ.
Fertil Steril. 2023 Mar 25:S0015-0282(23)00235-2. doi: 10.1016/j.fertnstert.2023.03.026. Epub ahead of print. PMID: 36972747.
Greenwood A, Nora A, Hartman C, Summers K, Syrop C, Haugsdal M.
Proc Obstet Gynecol. 2023;12(1): Article 4 [14 p.]. DOI: https://doi.org/10.17077/2154-4751.31886
The WHO defines social determinants of health (SDoH) as the conditions in which we are born, grow, work, and live as well as other large systems that positively or negatively affect our health. Many healthcare systems currently lack the resources and strategies required to accurately assess and address SDoH. Action must be taken because studies have found that chronic diseases, including cancer, are affected by SDoH. The aim of this study is to identify the incidence of social needs in an inpatient gynecologic oncology population and its relation to patient demographics and clinical diagnostic data to guide and inform future intervention. Patients agreeing to participate in the study completed a needs assessment survey during their inpatient stay at the hospital between November 2020 to March 2021. The survey contained seven questions, six of which were questions screening for social needs including food and housing security, transportation means, financial stability, health literacy, and social support. Responses were considered positive if any degree of need was reported. Demographic and cancer diagnosis data were then collected and included zip code, race, cancer stage and age at diagnosis, treatment history, and number of hospital admissions and length of stay over the past 12 months. The most substantial reported needs across all gynecologic malignancies were social support (65%), health literacy (37%), and financial need (22%). Less need was reported in the categories of food (11%), housing (7%), and transportation (4%). SDoH have been studied in the outpatient gynecologic population and the needs seen in this study are similar to the needs of that population. However, there are likely different challenges and frequencies of unmet need in the different types of gynecologic cancers that may affect the stage at which their cancer is diagnosed as well as the number of hospital admissions related to their cancer care.
Prevalence of maternal complications and neonatal outcomes at a Midwest academic health center.
Swartz SR, Kenne KA, Steffen HA, Bujimalla PV, Wendt LH, Jackson JB, Rysavy MB.
Proc Obstet Gynecol. 2023;12(1): Article 5 [12 p.]. DOI: https://doi.org/10.17077/2154-4751.31887
Introduction: The University of Iowa Hospitals and Clinics (UIHC) serves as the main referral center for Iowa and has seen increased delivery volumes following many hospital closures across the state. Maternal characteristics are also shifting as pre-pregnancy obesity of reproductive-age women is increasing nationally and in Iowa; average maternal age at first delivery has also increased over time. The aim of the current study was to characterize the outcomes of the delivering population at UIHC over a one-year period to better understand the population we serve, as well as compare our population to state and national delivering populations.
Methods: This study is a secondary analysis of a pre-existing prospectively gathered database related to COVID-19 in pregnancy. The current study included all pregnant patients who delivered or underwent procedures for a spontaneous or induced second-trimester abortion on the labor and delivery unit at UIHC between May 1, 2020, and April 30, 2021. Demographic and clinical data including maternal characteristics, delivery information, maternal complications, and neonatal outcomes were obtained from the electronic medical record and double entered in a Research Electronic Data Capture (REDCap) database. Continuous and categorical variables were summarized using medians and ranges.
Results: The median maternal age among the 2497 delivering patients was 30 (IQR 26, 33). The median pre-delivery body mass index (BMI) was 32 (IQR 28, 37), which included 439 patients (17.6%) with BMI >40 at time of delivery. 1769 (70.8%) patients listed White as their self-defined race and 2275 (91.0%) listed English as their preferred language. 23% had hypertensive disease of pregnancy. The patients delivered a total of 2603 neonates, with 907 (34.8%) born by cesarean section. 18.7% of deliveries were preterm and 16.6% of neonates had low birth weight.
Discussion: The delivering population at UIHC has a high rate of obesity and preeclampsia, both of which place patients at higher risk for other obstetric complications. The cesarean section rate was significantly higher than the national rate of 31.8% (p=0.0017). Understanding common complications in our changing population will better equip providers to care for these patients; providing these data also creates a resource for other researchers.