Average Time to Treatment in Lymphoma Patients Undergoing Ovarian Preservation: Experience from a Single Institution
Authors: Allen Pamela Blair , Pavone Mary Ellen , Smith Kristin M , Kazer Ralph , Rademaker Alfred W , Lawson Angela K , Moravek Molly , Confino Rafael , Gordon Leo I. , Winter Jane N. 
Published: October 2019

Abstract
Background:
Cryopreservation of oocytes or fertilized embryos prior to initiation of chemotherapy offers women with cancer an opportunity for future pregnancy if fertility is compromised by treatment. To investigate the actual delay in starting chemotherapy associated with fertility preservation protocols in young women with lymphoma, we performed a retrospective chart review of the Northwestern Medicine (NM) institutional experience.
Methods:
Subjects were identified from a log of women who contacted the fertility preservation patient care navigator (FPPCN) from May 2007 through December 2014. NM practitioners are required to address fertility in all newly diagnosed cancer patients, through the use of automated prompts. Patients were included in the analysis if they had newly diagnosed or relapsed/refractory lymphoma and were treated at NM, whether or not they attempted fertility preservation. The primary endpoint was time to treatment (TTT) initiation. In newly diagnosed patients, TTT was defined as time from NM hematology/oncology consult until the initiation of chemotherapy. In patients with relapsed disease, TTT was measured from time of biopsy at NM or time of consult if biopsy was performed at an outside institution. We used a one-tailed T test to compare independent means with a significance level of 0.05.
Results:
128 lymphoma patients contacted the FPPCN between 5/2007- 12/2014 and data on 28 of 36 women who proceeded with fertility preservation (FP) is available for analysis. 50 of 93 lymphoma patients who contacted the FPPCN but did not undergo ovarian stimulation served as a comparison group. The average length of follow up was 152 weeks (range: 14-388 weeks). Reasons patients were excluded from the analysis included lack of chemotherapy treatment records and no treatment received at NM. Among patients undergoing FP, 21 presented with a new diagnosis and 7 with relapsed/refractory disease. The average age was 26 years (range: 20-31). All had ECOG PS of 0/1. Histologies were: 17 HL, 8 DLBCL, and 3 other subtypes. 25 patients had stage I/II and 3 had stage III/IV disease. 4 HL patients had early favorable disease, 12 early unfavorable, and one had advanced disease.
Among 50 control patients, 37 presented with a new diagnosis and 13 with relapsed or refractory disease. The average age was 29 years (range 19-45). Histologies included 29 HL, 10 with DLBCL, 11 with other histologies. 31 patients were stage I/II and 15 were stage III/IV 15. 3 HL patients had early favorable disease, 19 had early unfavorable, and 6 had advanced disease with IPS scores ranging from 0-4.
Among 28 FP patients, median TTT was 28 days (range: 8-76) versus 15.5 days (range: 0-74) in controls (p-value <0.001). Among relapsed patients, the median TTT was 28 days (range 15-76) for FP patients versus 17 days (range: 0-55) for the control group (p-value = 0.04). 7 patients underwent random start protocol ovarian hyper-stimulation and 21 underwent cycle specific stimulation. The median TTT was 28 days among cycle specific (range 8-76) and 27 days (range 18-39) in random start protocols (p-value = 0.35). Eight of 28 patients in the fertility preservation group had progression/relapse of disease with a one year relapse free survival rate (RFS1) of 78%. Six of 50 patients in the control group progressed with an RFS1 of 94%. There was no difference between rates of progression (p-vale 0.07) between preserved and non-preserved patients.
Discussion:
Fertility preservation delayed treatment by a median of 13 days compared to controls. There was no difference in treatment delay among patients using the random start versus cycle specific protocols. However, all patients on the random start protocol were off oral contraceptives (OCP's) whereas almost all cycle specific patients were on OCP's, thus allowing them optimal timing of their cycle and reduced time to retrieval. The relapse free survival rate was lower among FP patients compared to controls (78% versus 94% respectively), however this did not meet statistical significance. Patients undergoing FP represent a selected group of patients with high risk disease, and baseline characteristics independent of FP may place them at increased risk of relapse. Whether or not the nearly two week delay required for fertility preservation results in adverse patient outcomes will require further investigation utilizing matched controls.

Disclosures
Gordon: Dr Leo I. Gordon: Patents & Royalties: Patent for gold nanoparticles pending; Northwestern University: Employment.