University of Pittsburgh Medical Center Pittsburgh, PA
J. Shogan1, P. Sukumvanich2, M. M. Boisen2, M. Courtney-Brooks3, J. L. Berger2, S. Taylor2, A. Olawaiye4, J. Lesnock2, S. Rush4, A. Garrett5, H. Mahdi6, R. P. Edwards2, and J. A. A. Vargo IV1; 1UPMC Hillman Cancer Center, Department of Radiation Oncology, Pittsburgh, PA, 2UPMC Hillman Cancer Center, Department of Gynecologic Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 3UPMC Magee Womens Hospital, Pittsburgh, PA, 4UPMC Hillman Cancer Center, Department of Gynecologic Oncology, Pittsburgh, PA, 5Division of Gynecologic Oncology, Magee-Womens Hospital of UPMC, Pittsburgh, PA, 6University of Pittsburgh, Department of Gynecologic Oncology, Pittsburgh, PA
Purpose/Objective(s):Premature ovarian insufficiency (POI) is a challenging survivorship toxicity for patients treated with radiotherapy for locally advanced cervical cancer. Laparoscopic ovarian transposition can relocate the ovaries out of the pelvis potentially preserving ovarian function. However, it remains unclear what reasonable constraints are for sparing of the ovary and how soon following transposition it is safe to start radiotherapy. We hypothesize that our dose constraint of 5 Gy for the transposed ovary and starting within 1 week after transposition is optimal.Materials/
Methods: We performed a retrospective review of patients <50 years old diagnosed with cervical cancer treated with IMRT from 2010-2023. Included patients had undergone laparoscopic ovarian transposition of one or both ovaries prior to IMRT. Endpoints examined were incidence of POI (defined as FSH>30 IU/L or start of symptom directed medication), relapse in the ovary, and acute surgical complications (within 30 days) as it related to timing of radiotherapy. Results: 287 patients were reviewed; of these, 17 met inclusion criteria having undergone ovarian transposition prior to IMRT. Median age at diagnosis was 32 years (range 25-40). 35% of patients were staged IB1, 18% IB2, 6% IB3, 24% IIB, and 18% IIIC1. 71% (n=12) were prescribed 45 Gy to the pelvis, 29% (n=5) were prescribed 50.4 Gy. 76% (n=13) of patients also received a sequential intracavitary brachytherapy boost. 76% (n=13) received concurrent weekly cisplatin.Median follow up was 52.2 months (IQR 18.3-84.0). POI incidence was 71% (n=12). Among patients with POI, the median Dmean (mean dose) and Dmax (maximum dose) to the least affected ovary were 12.0 Gy (IQR 2.8-19.2) and 19.3 Gy (IQR 4.7-42.9), respectively. Among patients with no evidence of POI, the median Dmean and Dmax to the least affected ovary were 4.4 Gy (IQR 1.5-6.8) and 5.9 Gy (IQR 2.4-11.4), respectively. 100% of patients with a Dmean to the least affected ovary >8 Gy (n=7) developed POI compared with 50% of patients with a Dmean to the least affected ovary <8 Gy (n=10), (p=.03). POI developed in 100% of patients with a Dmax to the least affected ovary >16 Gy (n=6) compared with 54.5% of patients with a Dmax <16 Gy (n=11), (p=.05)There was one relapse in the ovary, however this patient was noted to have widely metastatic disease at the time of relapse. Three patients had died at the time of this analysis, 2 from disease progression. The median time from surgery to start of IMRT was 40 days. Three patients started radiotherapy within 1 week, none had an acute surgical complication. Conclusion: Our data suggest that patients receiving a mean dose >8 Gy or a maximum dose >16 Gy to the least affected ovary are at higher risk of POI. If these dose constraints cannot be met with IMRT, novel therapeutic strategies such as proton therapy may be considered to mitigate the risk of POI. Starting within 1 week of transposition was not associated with any identifiable increase in surgical complications.
