Research Spotlight

Wall, A.E., Johannesson, L., Sok, M., Warren, A.M., Gordon, E.J. and Testa, G. (2021). “The journey from infertility to uterus transplantation: A qualitative study of the perspectives of participants in the Dallas Uterus Transplant Study.” Bjog Dec 9. [Epub ahead of print].

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OBJECTIVE: To assess how absolute uterine factor infertility affects women who undergo uterus transplantation, how uterus transplantation impacts women with absolute uterine factor infertility and how uterus transplant recipients view uterus transplantation in terms of their reproductive autonomy. DESIGN: Qualitative semi-structured interview study. SETTING: Uterus transplant programme in a large academic medical centre in the USA. POPULATION/SAMPLE: Twenty one uterus transplant recipients. METHODS: A medical chart review was conducted to collect patient demographic information and clinical outcomes. Semi-structured interviews collected information regarding participants’ experience. MAIN OUTCOME MEASURE(S): The outcomes of interest were participants’ experience of infertility, experience with uterus transplantation and general perceptions of uterus transplantation. RESULTS: Six participants were pregnant (one with a second child), six had experienced early graft failure and removal, five had delivered a healthy baby, and four had a viable graft and were awaiting embryo transfer. The primary themes identified were: the negative impact of absolute uterine factor infertility diagnosis on psychological wellbeing, relationships and female identity; the positive impact of uterus transplantation on healing the emotional scars of absolute uterine factor infertility, female identity and value of research trial participation and the perception of uterus transplantation as an expansion of reproductive autonomy. All participants reported that uterus transplantation was worthwhile, regardless of individual outcome. CONCLUSION: Absolute uterine factor infertility has a negative impact on women from a young age, affects multiple relationships and challenges female identity. Uterus transplantation helps to reverse this impact, transforming women’s life narrative of infertility and enhancing female identity. TWEETABLE ABSTRACT: Absolute uterine factor infertility (AUFI) adversely affects women. Uterus transplantation helps mitigate the negative impact of AUFI, by transforming women’s life narratives of infertility and enhancing female identity.

Weadick, C.S., Duffy, A.G. and Kelly, R.J. (2022). “Recent advances in immune-based approaches for the treatment of esophagogastric cancer.” Expert Opin Emerg Drugs: 1-13.

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INTRODUCTION: The year 2021 will be remembered as a transformational year in the management of both esophageal and gastric cancers. Decades of failed clinical trials had seen limited therapeutic advances beyond refinement of the traditional combined modality approach. Targeted strategies against specific molecular alterations did not – with the exception of Her2 – yield the desired breakthroughs, and it was unclear what immune-based approaches would bring to this group of cancers. The presence of tumor-infiltrating lymphocytes in esophagogastric cancer demonstrates that an endogenous immune response is already occurring and potentially amplifiable by immune checkpoint inhibition. Recent data have validated this with FDA approvals in both the locoregional (CheckMate 577) and metastatic disease (CheckMate 649, KeyNote 590 and KeyNote 811) setting which have altered the therapeutic landscape. AREAS COVERED: Here we discuss recent data and ongoing research efforts to better define the role of immune-based approaches and select the patient cohorts who might gain the most benefit from them. EXPERT OPINION: Immunotherapy, and specifically the incorporation of the immune checkpoint inhibitors (ICI) drug class, has altered the therapeutic paradigm of many cancers in recent years. Anti-PD-1 therapies are now the new standard of care for patients with local and advanced disease.

Wall, A.E., McKenna, G.J., Onaca, N., Ruiz, R., Bayer, J., Fernandez, H., Martinez, E., Gupta, A., Askar, M., Spak, C.W. and Testa, G. (2022). “Utilization of a SARS-CoV-2-positive donor for liver transplantation.” Proc (Bayl Univ Med Cent) 35(1): 62-63.

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Liver transplantation rates have been negatively affected by the pandemic caused by coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current practice in the liver transplant community is to avoid utilizing SARS-CoV-2-positive donors for liver transplantation unless there is a compelling reason such as recipient illness severity. In this case, we report the use of a donor who had a positive exposure to and symptom history for COVID-19 and tested positive for SARS-CoV-2 on admission for a liver transplant recipient with primary sclerosing cholangitis and a Model of End-Stage Liver Disease score of 23 with no known COVID-19 exposures. We focus on the decision to accept this particular organ, as well as the discussion with the recipient about the unknowns of disease transmission and risk associated with this donor. The current case argues that transplant programs should begin to consider low-risk donors with positive SARS-CoV-2 testing for recipients who have the potential to benefit from liver transplantation, which may not only be those with the most severe illness.

Tan, A.R., Wright, G.S., Thummala, A.R., Danso, M.A., Popovic, L., Pluard, T.J., Han, H.S., Vojnović, Ž., Vasev, N., Ma, L., Richards, D.A., Wilks, S.T., Milenković, D., Xiao, J., Sorrentino, J., Horton, J. and O’Shaughnessy, J. (2021). “Trilaciclib prior to chemotherapy in patients with metastatic triple-negative breast cancer: final efficacy and subgroup analysis from a randomized phase II study.” Clin Cancer Res Dec 9;clincanres.2272.2021. [Epub ahead of print].

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PURPOSE: We report final antitumor efficacy results from a phase II study of trilaciclib, an intravenous cyclin-dependent kinase 4/6 inhibitor, administered prior to gemcitabine plus carboplatin (GCb) in patients with metastatic triple-negative breast cancer (NCT02978716). EXPERIMENTAL DESIGN: Patients were randomized (1:1:1) to group 1 (GCb [days 1, 8]; n = 34), group 2 (trilaciclib prior to GCb [days 1, 8]; n = 33), or group 3 (trilaciclib [days 1, 8] and trilaciclib prior to GCb [days 2, 9]; n = 35). Subgroup analyses were performed according to CDK4/6 dependence, level of PD-L1 expression, and RNA-based immune signatures using proportional hazards regression. T-cell receptor (TCR) β CDR3 regions were amplified and sequenced to identify, quantify, and compare the abundance of each unique TCR β CDR3 at baseline and on treatment. RESULTS: Median overall survival (OS) was 12.6 months in group 1, not reached in group 2 (hazard ratio [HR] 0.31; P = 0.0016), 17.8 months in group 3 (HR 0.40; P = 0.0004), and 19.8 months in groups 2 and 3 combined (HR 0.37; P < 0.0001). Efficacy outcomes were comparable regardless of cancer CDK4/6 dependence status and immune signatures. Administering trilaciclib prior to GCb prolonged OS irrespective of PD-L1 status but had greater benefit in the PD-L1-positive population. T-cell activation was enhanced in patients receiving trilaciclib. CONCLUSIONS: Administering trilaciclib prior to GCb enhanced antitumor efficacy, with significant improvements in OS. Efficacy outcomes in immunologic subgroups and enhancements in T-cell activation suggest these improvements may be mediated via immunologic mechanisms.

Squiers, J.J., DiMaio, J.M., Schaffer, J.M., Baxter, R.D., Gable, C.E., Shinn, K.V., Harrington, K., Moore, D.O., Shutze, W.P., Brinkman, W.T. and Gable, D.R. (2022). “Surgical Debranching versus Branched Endografting in Zone 2 Thoracic Endovascular Aortic Repair.” J Vasc Surg Jan 5;S0741-5214(21)02748-8. [Epub ahead of print].

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INTRODUCTION: Left subclavian artery (LSA) revascularization is recommended in patients undergoing elective thoracic endovascular aortic repair (TEVAR) with proximal zone 2 landing requiring coverage of the LSA. The gold-standard remains surgical LSA revascularization, but recently the feasibility of branched endografts has been demonstrated. We compared the perioperative and mid-term outcomes of these approaches. METHODS: A retrospective review of consecutive patients undergoing TEVAR with proximal zone 2 landing at a single center from 2014-2020 was performed. Patients were divided into cohorts for comparison: those undergoing surgical revascularization (SR-TEVAR group) and those undergoing thoracic branched endografting with an investigational device (TBE group). Patients who did not receive LSA revascularization were excluded. Perioperative outcomes including procedural success, death, stroke, limb ischemia, and length of stay were compared. Kaplan-Meier survival curves were compared with the log-rank test. The cumulative incidences of device-related endoleak (type I and III) and device-related reintervention, accounting for death as a competing hazard, were compared with the Fine-Gray test. RESULTS: A total of 55 patients were included: 31 (56%) SR-TEVAR and 24 (44%) TBE. Preoperative demographics and comorbidities were similar between the groups. Procedural success was 100% in both cohorts, and there were no periprocedural strokes or left upper extremity ischemic events. One operative/30-day mortality (TBE 4.2% vs SR-TEVAR 3.2%, p=0.99) occurred in each cohort. Total operative time (minutes, TBE 203 ± 79 vs SR-TEVAR 250 ± 79 p=0.03) and total length of stay (days, TBE 5.2 ± 3.6 vs SR-TEVAR 9.9 ± 7.2, p=0.004) were both significantly shorter in the TBE group. There was no difference in mid-term survival (log-rank p=0.50), nor the cumulative incidence of device-related endoleak (Fine-Gray p=0.51) or reintervention (Fine-Gray p=0.72). There have been no occlusions of the TBE graft nor surgical bypass/transpositions after a mean follow-up for 28 ± 16 and 34 ± 24 months, respectively. CONCLUSIONS: Thoracic branched endografting can be performed with similar procedural success and comparable safety profile to TEVAR with surgical revascularization, while reducing total length of stay, in patients requiring proximal zone 2 coverage. Mid-term outcomes of each approach are also similar. Prospective, randomized comparisons of these techniques are warranted.