Recent Research Publications- April 2022
Liu JF, Brady MF, Matulonis UA, Miller A, Kohn EC, Swisher EM, Cella D, Tew WP, Cloven NG, Muller CY, Moore RG, Michelin DP, Waggoner SE, Geller MA, Fujiwara K, D'Andre SD, Carney M, Alvarez Secord A, Moxley KM, Bookman MA.
J Clin Oncol. 2022 Mar 15:JCO2102011. doi: 10.1200/JCO.21.02011. Epub ahead of print.
Purpose: Platinum-based chemotherapy is the standard of care for platinum-sensitive ovarian cancer, but complications from repeated platinum therapy occur. We assessed the activity of two all-oral nonplatinum alternatives, olaparib or olaparib/cediranib, versus platinum-based chemotherapy.
Patients and methods: NRG-GY004 is an open-label, randomized, phase III trial conducted in the United States and Canada. Eligible patients had high-grade serous or endometrioid platinum-sensitive ovarian cancer. Patients were randomly assigned 1:1:1 to platinum-based chemotherapy, olaparib, or olaparib/cediranib. The primary end point was progression-free survival (PFS) in the intention-to-treat population. Secondary end points included activity within germline BRCA-mutated or wild-type subgroups and patient-reported outcomes (PROs).
Results: Between February 04, 2016, and November 13, 2017, 565 eligible patients were randomly assigned. Median PFS was 10.3 (95% CI, 8.7 to 11.2), 8.2 (95% CI, 6.6 to 8.7), and 10.4 (95% CI, 8.5 to 12.5) months with chemotherapy, olaparib, and olaparib/cediranib, respectively. Olaparib/cediranib did not improve PFS versus chemotherapy (hazard ratio [HR] 0.86; 95% CI, 0.66 to 1.10; P = .077). In women with germline BRCA mutation, the PFS HR versus chemotherapy was 0.55 (95% CI, 0.32 to 0.94) for olaparib/cediranib and 0.63 (95% CI, 0.37 to 1.07) for olaparib. In women without a germline BRCA mutation, the PFS HR versus chemotherapy was 0.97 (95% CI, 0.73 to 1.30) for olaparib/cediranib and 1.41 (95% CI, 1.07 to 1.86) for olaparib. Hematologic adverse events occurred more commonly with chemotherapy; however, nonhematologic adverse events were higher with olaparib/cediranib. In 489 patients evaluable for PROs, patients receiving olaparib/cediranib scored on average 1.1 points worse on the NFOSI-DRS-P subscale (97.5% CI, -2.0 to -0.2, P = .0063) versus chemotherapy; no difference between olaparib and chemotherapy was observed.
Conclusion: Combination olaparib/cediranib did not improve PFS compared with chemotherapy and resulted in reduced PROs. Notably, in patients with a germline BRCA mutation, both olaparib and olaparib/cediranib had significant clinical activity.
Gupta P, Gallop R, Spitznagle T, Lai H, Tu F, Krieger JN, Clemens JQ, Yang C, Sutcliffe S, Moldwin R, Kreder K, Kutch J, Rodriguez LV.
J Urol. 2022 Mar 28:101097JU0000000000002679. doi: 10.1097/JU.0000000000002679. Epub ahead of print.
Purpose: 85% of women with interstitial cystitis/bladder pain syndrome (IC/BPS) and men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have concomitant pelvic floor muscle tenderness (PFT). The significance of this finding is incompletely understood. This study examines PFT among participants in the MAPP Research Network, and its relationship with urologic chronic pelvic pain syndrome (UCPPS) symptom severity, in order to determine whether this is a phenotypic predictor in UCPPS.
Materials and methods: Participants in the MAPP Network Symptom Patterns Study (SPS) underwent a standardized pelvic examination (PEX). Trained examiners palpated six locations evaluating the pelvic musculature for PFT. Participants were assigned a 0 to 6 PEX score based on the number of areas with tenderness on PEX. Using regression tree models, PEX scores were divided into low (0-1), mid (2,3,4,5), and high (6). The relationship between PFT and UCPPS symptoms was examined using several validated questionnaires.
Results: The study cohort consisted of 562 UCCPS participants (375 females and 187 males), and 69 controls. Diagnoses included IC/BPS (n=397), CP/CPPS (n=122), both (n=34), or no diagnosis (n=9). 81% of UCPPS participants had PFT on PEX compared to 9% of controls: 107 (19%) low, 312 (56%) mid, and 143 (25%) high. Participants with higher PFT scores had more severe disease burden (worse pelvic pain and urinary symptoms), worse quality of life, and more widespread distribution of non-pelvic pain.
Conclusions: UCPPS patients with more widespread PFT have severe pain and urinary symptoms, worse quality of life, and a more centralized pain phenotype.
Prospective evaluation of genital hiatus in patients undergoing surgical prolapse repair.
Bonglack M, Maetzold E, Kenne KA, Bradley CS, Kowalski JT.
Int Urogynecol J. 2022 Mar 17:1–8. doi: 10.1007/s00192-022-05157-x. Epub ahead of print.
Introduction and hypothesis: Enlarged genital hiatus (GH) is associated with prolapse recurrence following prolapse repair. Perineorrhaphy is often performed to reduce GH. However, changes in GH between the time of surgery and follow up are poorly understood. Our primary aim was to compare the intra-operative resting GH at the conclusion of surgery with the resting GH 3 months post-operatively in patients who undergo perineorrhaphy. We hypothesized that the intra-operative resting GH would be sustained.
Methods: Patients planning apical prolapse surgery were prospectively enrolled. Perineorrhaphy was performed at the surgeon's discretion. GH was measured pre-operatively in clinic, intra-operatively before and after surgery (resting), and 3 months post-operatively (resting and Valsalva).
Results: Twenty-nine perineorrhaphy and 27 no perineorrhaphy patients completed 3-month follow-up. Groups were similar in age (63.9 y, SD 10.4), body mass index (28.3 kg/m2, SD 5.2) and prior prolapse surgery (19.6%). Median (interquartile range) baseline Valsalva GH was larger in the perineorrhaphy group (4.5 (4 - 5.5) vs 3.5 (3 - 4) cm, p < 0.01). Median resting GH at 3 months was 0.5 cm less than end of surgery in the perineorrhaphy group (p < 0.01). The median change in GH between baseline and 3-month follow up was greater with perineorrhaphy (-1.5 vs -0.5 cm, p < 0.01). This difference was not seen in the sacrocolpopexy subgroup (-1.75 vs -1.5, p = 0.14; n = 24).
Conclusions: Surgeons can be reassured that the intra-operative change in GH resulting from perineorrhaphy is sustained 3 months after surgery and similar to the more commonly measured preoperative to postoperative change in Valsalva GH.
Walhof ML, Leon J, , Knudson CM.
J Clin Lab Anal. 2022 Mar 3:e24323. doi: 10.1002/jcla.24323. Epub ahead of print.
Background: Hemolytic disease of the fetus and newborn (HDFN) is a potentially fatal complication in Rh-incompatible pregnancies and rarely occurs in the sensitizing pregnancy. Distinguishing RhIG from true anti-D identified is challenging. A case of severe HDFN in which a sample drawn at 28 weeks showed anti-D antibody (3+ strength) attributed to RhIG is described. RBC antibody testing early in pregnancy was negative. At birth, the infant was severely anemic and maternal anti-D titer was 1:256. This case represents a clinically significant anti-D in the sensitizing pregnancy that was missed due to confusion with RhIG.
Methods: To determine if agglutination strength could be helpful, a retrospective chart-review using both electronic and paper medical records was performed on 348 samples identified as RhIG and 52 true anti-D samples. The agglutination strength of antibody was recorded for each sample.
Results: For RhIG, there was an even distribution between the weak to moderate agglutination strength (w+, 1+, and 2+) results (35%, 26%, and 33%, respectively) and just 6% had a 3+ strength. Agglutination strength in patients with high titer (≥1:16) anti-D showed they often (44.4%) have 1+ or 2+ agglutination reactivity.
Conclusions: These results show that agglutination strength alone does not provide reliable evidence to distinguish RhIG from high titer anti-D antibodies. We recommend that in cases where there is any uncertainty about whether the anti-D reactivity is due to RhIG, titers should be performed to rule out clinically significant anti-D antibody.
Health Disparities in Uterine Cancer: Report From the Uterine Cancer Evidence Review Conference.
Whetstone S, Burke W, Sheth SS, Brooks R, Cavens A, Scott DM, Worly B, Chelmow D.
Obstet Gynecol. 2022 Mar 10;139(4):645–59. doi: 10.1097/AOG.0000000000004710. Epub ahead of print.
The Centers for Disease Control and Prevention recognized the need for educational materials for clinicians on the prevention and early diagnosis of gynecologic cancers. The American College of Obstetricians and Gynecologists convened a panel of experts in evidence review from the Society for Academic Specialists in General Obstetrics and Gynecology and content experts from the Society of Gynecologic Oncology to review relevant literature, best practices, and existing practice guidelines for the development of evidence-based educational materials for women's health care clinicians about uterine cancer. This article is the evidence summary of the literature review of health disparities and inequities related to uterine cancer. Substantive knowledge gaps are noted and summarized to provide guidance for future research.
Executive Summary of the Uterine Cancer Evidence Review Conference.
Chelmow D, Brooks R, Cavens A, , Scott DM, Sheth SS, Whetstone S, Worly B, Burke W.
Obstet Gynecol. 2022 Mar 10;139(4):626–43. doi: 10.1097/AOG.0000000000004711. Epub ahead of print.
The Centers for Disease Control and Prevention recognized the need for educational materials for clinicians on the prevention and early diagnosis of gynecologic cancers. The American College of Obstetricians and Gynecologists convened a panel of experts in evidence review from the Society for Academic Specialists in General Obstetrics and Gynecology and content experts from the Society of Gynecologic Oncology to review relevant literature, best practices, and existing practice guidelines as a first step toward developing evidence-based educational materials for women's health care clinicians about uterine cancer. Panel members conducted structured literature reviews, which were then reviewed by other panel members and discussed at a virtual meeting of stakeholder professional and patient advocacy organizations in January 2021. This article is the evidence summary of the relevant literature and existing recommendations to guide clinicians in the prevention, early diagnosis, and special considerations of uterine cancer. Substantive knowledge gaps are noted and summarized to provide guidance for future research.
Cancer genetics and breast cancer.
Huber-Keener KJ.
Best Pract Res Clin Obstet Gynaecol. 2022 Jan 31:S1521-6934(22)00016-5. doi: 10.1016/j.bpobgyn.2022.01.007. Epub ahead of print.
The risk of developing breast cancer is multifactorial and, at times, modifiable. However, the risk imposed by family history and hereditary pathogenic variants in a person's genetic code is, at present, an important fixed variable. Therefore, it is imperative to identify patients at risk for hereditary breast cancer and to understand the current evidence-based approach to the management of that risk. This chapter focuses on how genes play a role in breast cancer risk, why certain genes are commonly involved in hereditary breast cancer, and what are the specific genes and genetic syndromes that put patients at risk for breast cancer. Hereditary cancer susceptibility syndromes, including Hereditary Breast and Ovarian Cancer Syndrome (HBOC - BRCA1/2), Cowden Syndrome (CS - PTEN), Li-Fraumeni Syndrome (LFS - TP53), Peutz-Jegher Syndrome (PJS - STK11), Neurofibromatosis Type 1 (NF1), and Diffuse Hereditary Gastric Cancer Syndrome (CDH1) will be discussed along with individual genes not associated with a particular syndrome (ATM, BARD1, CHEK2, and PALB2).
Vieira-Baptista P, Pérez-López FR, López-Baena MT, , Preti M, Bornstein J.
J Low Genit Tract Dis. 2022 Mar 10. doi: 10.1097/LGT.0000000000000673. Epub ahead of print.
Objective: Vulvar lichen sclerosus (VLS) and possibly vulvar lichen planus (VLP) are associated with an increased vulvar cancer (VC) risk. We analyzed the risk of VC and its precursors after a diagnosis of VLS or VLP.
Materials and methods: A search was performed to identify articles describing the development of vulvar neoplasia in women with VLS or VLP. This systematic review was registered with the PROSPERO database.
Results: Fourteen studies on VLS included 14,030 women without a history of vulvar neoplasia. Vulvar cancer, differentiated vulvar intraepithelial neoplasia (dVIN), and vulvar high-grade squamous intraepithelial lesion occurred in 2.2% (314/14,030), 1.2% (50/4,175), and 0.4% (2/460), respectively. Considering women with previous or current VC, the rate was 4.0% (580/14,372). In one study, dVIN preceded VC in 52.0% of the cases. Progression of dVIN to VC was 18.1% (2/11).The risk was significantly higher in the first 1-3 years after a biopsy of VLS and with advancing age; it significantly decreased with ultrapotent topical steroid use.For the 14,268 women with VLP (8 studies), the rates of VC, dVIN, and vulvar high-grade squamous intraepithelial lesion were 0.3% (38/14,268), 2.5% (17/689), and 1.4% (10/711), respectively.
Conclusions: Vulvar lichen sclerosus is associated with an increased risk of VC, especially in the presence of dVIN and with advancing age. Ultrapotent topical steroids seem to reduce this risk. An increased risk of developing VC has been suggested for VLP. Hence, treatment and regular life-long follow-up should be offered to women with VLS or VLP.