O002/#185 Uterine transposition: feasibility study

Abstract

Objectives In locally-advanced cervical cancer (LACC), platinum-based chemoradiotherapy (CRT) has been the standardof-care treatment for >20 years. CALLA is the first global Phase 3 study evaluating immune checkpoint inhibition (durvalumab) versus placebo in combination with and following CRT in LACC (NCT03830866). Methods Newly-diagnosed, untreated patients with LACC (FIGO 2009 stages IB2-IIB node positive, IIIA-IVA with any node status) were randomized 1:1 to durvalumab (1500 mg IV) or placebo Q4W, for a total of up to 24 months, in combination with and following CRT. CRT comprised concurrent weekly IV cisplatin with EBRT and brachytherapy. RT quality was monitored, with variations evaluated for clinical significance. The primary endpoint is PFS; secondary endpoints include OS, objective response rate, local/distant disease progression incidence, and safety. Results 770 patients were randomized (N=385 per arm) at 120 sites in 15 countries. Median age was 49 years; median follow-up was 18.5 months. Durvalumab+CRT did not show a statistically significant improvement in PFS vs placebo+CRT (HR 0.84 [95% CI, 0.65-1.08]; P=0.174); there was no detriment to OS, although data were immature and not formally tested. Adverse events of grade 3-4 occurred in 51.7% and 51.0% of patients in the durvalumab+CRT and placebo+CRT arms, respectively; 12.5% and 9.6% of patients discontinued treatment due to AEs possibly related to study drug. Conclusions Durvalumab in combination with and following CRT did not significantly improve PFS in patients with LACC. Safety of durvalumab+CRT was generally comparable to CRT alone, with no new or unexpected toxicity. Funding: AstraZeneca.

Utero-ovarian transposition before pelvic radiation in a patient with rectal cancer: a case report and systemic literature review

“…A total of 14 cases have been reported in 10 articles ( Table 1 ). In addition, as reported in a congress paper, Ribeiro et al performed UOT in 11 further patients with non-gynecological cancers ( 19 ). Since this represents the largest case series of UOT, we decided to report these data, but due to the limited information, they have not been integrated into the table.…”

“…Cervical stenosis is a potential complication associated with UOT, especially in the case of trachelectomy for cervical cancer ( 11 , 12 , 17 , 19 ). The partial dehiscence of uterine anastomosis needing re-suturing was reported once ( 12 ).…”

“…Perfusion issues (e.g., thrombosis) associated with the dissection of infundibulopelvic ligaments, their mobilization, and the alteration of the anatomical path of their vessels could be responsible for these functional disorders. Uterine necrosis after UOT has been reported only once ( 19 ), but the risk of less serious postoperative utero-ovarian functional disorders could not be excluded, even if their potential incidence is currently difficult to predict. Low-molecular-weight-heparin, with or without aspirin, has been administered to mitigate the risk of thrombosis and subsequent utero-ovarian hypoperfusion ( 16 , 26 ).…”

“…Due to the limited number of reported cases of UOT and their relatively short follow-up, this risk is currently difficult to evaluate. Currently, only one case of a patient's death from cancer progression with carcinomatosis for non-gynecological cancer 4 months after UOT was reported ( 19 ).…”

The Young: Early-Onset Colon Cancer

“…Large prospective studies are lacking, particularly in the United States; however, small cohort studies have demonstrated up to 90% preserved ovarian function after pelvic radiation with these procedures. 50 51 52 In one prospective study evaluating uterine transposition, eight patients (seven with rectal cancer) underwent uterine transposition followed by radiation therapy. The uterus was successfully preserved in six patients and two patients achieved spontaneous pregnancies and healthy cesarean deliveries without complication.…”