1 / 31

OncoFertility Fertility Preserving Options & Outcomes in Gynecologic Cancers

CAROLINE BILLINGSLEY, MD Thegos Annual Meeting June 1, 2014. OncoFertility Fertility Preserving Options & Outcomes in Gynecologic Cancers . Objectives. Background Prevalence of US population affected Etiology of cancer treatment-related fertility failure Chemotherapy Radiotherapy

ajay
Download Presentation

OncoFertility Fertility Preserving Options & Outcomes in Gynecologic Cancers

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. CAROLINE BILLINGSLEY, MD Thegos Annual Meeting June 1, 2014 OncoFertilityFertility Preserving Options & Outcomes in Gynecologic Cancers

  2. Objectives Background Prevalence of US population affected Etiology of cancer treatment-related fertility failure Chemotherapy Radiotherapy Surgery • Options for fertility preservation • Embryo cryopreservation • Oocyte cryopreservation • Ovarian tissue cryopreservation • Oophoropexy • GnRH analogue co-treatment • Candidates for fertility preservation • Breast cancer • Cervical cancer • Endometrial cancer • Ovarian cancer

  3. Gynecologic cancer incidence in reproductive age women Bleyer A et al. Cancer Epidemiology in Older Adolescents and Young Adults 15 to 29 Years of Age, Including SEER Incidence and Survival: 1975-2000. National Cancer Institute, NIH Pub. No. 06-5767. 2006

  4. Gynecologic cancer incidence in reproductive age women • Diagnosis and treatment of cancer often poses a threat to fertility SEER database, 5/2014 (http://seer.cancer.gov)

  5. Etiology of cancer treatment-related fertility failureChemotherapy

  6. Etiology of cancer treatment-related fertility failureRadiation Ovarian damage Radiation toxicity varies with the cell cycle Highest in G and M cycles Oocytes are particularly affected Dose related reduction in the primordial follicle pool Lethal Dose Dose >6 Gy usually causes irreversible gonadal failure1 LDL50 <2 Gy2 Dependent on age, extent, type/location and fractionation schedule 1Howell et al, 1998. 2Wallace et al, 1989, 2003.

  7. Etiology of cancer treatment-related fertility failureRadiation Uterine damage Obstetrical Increased risk of SAB Second trimester pregnancy loss Preterm birth Low birth weight Placenta accreta Risks dependent on dose, site, age Prepubertal uterus is particularly vulnerable Childhood Cancer Survivor Study1 Large, multicenter cohort Birth outcomes of childhood radiation survivors compared to sibling (no radiation exposure) controls 1264 cancer survivors 2201 singleton children 601 sibling controls (no radiation) 1175 singleton children 1Signorello et al, J Natl Cancer Inst 2006;26:98:1453

  8. Fertility Preserving Options • Options for fertility preservation • Embryo cryopreservation (via ovulation induction) • Oocyte cryopreservation • Ovarian tissue cryopreservation • Oophoropexy • GnRH analogue co-treatment

  9. Fertility Preserving Options: Embryo cryopreservation Definition Harvesting eggs, in vitro fertilization, and freezing of embryos for later implantation Comment Most established technique for fertility preservation in women Considerations Requires 10-14 days of ovarian stimulation from the beginning* of menstrual cycle * Random start ovarian stimulation Outpatient surgical procedure (egg retrieval) Requires partner or donor sperm Cost (range $4000-8000 per cycle, $350 for yearly storage fees) Medications Follicle stimulating hormone analogs Aromatase inhibitors Similar number of eggs and embryos and similar pregnancy outcomes 1 Selective estrogen receptor inhibitors Rates Success: Intact embryos after thawing have similar implantation rates as fresh embryos 59% pregnancy rate1 26% live birth rate1 1Rodriguez-Wallberg et al, Cancer Treatment Reviews. 2012;38:354-361.

  10. Fertility Preserving Options: Oocyte cryopreservation Definition Retrieving and freezing unfertilized eggs through a vitrification process Comment Previously considered experimental Now considered a standard practice per ASCO 2013 guidelines Considerations Requires 10-14 days of ovarian stimulation from the beginning* of menstrual cycle * Random start ovarian stimulation Outpatient surgical procedure (egg retrieval) Cost (range $4000-8000 per cycle, $350 for yearly storage fees) Medications Follicle stimulating hormone analogs (FolliStim) Aromatase inhibitors Similar number of eggs and embryos and similar pregnancy outcomes 1 Selective estrogen receptor inhibitors Rates Antinori et al: The fertilization, pregnancy, and implantation rates were 92.9%, 32.5%, and 13.2%, respectively2 Three hundred thirty-seven live births resulting from 857 thawed cycles (39.3% pregnancy rate) were reported across all centers3 1Loren et al, J ClinOncol. 2013;31. 2Antinori et al, RBM Online. 2007;14:72–79. 3Rudick et al, FertilSteril. 2010 Dec;94(7):2642-6.

  11. Fertility Preserving Options: Ovarian tissue cryopreservation Definition Freezing of ovarian tissue and reimplantation after cancer treatment Reimplant: Orthotopic: reimplant to the medullary portion of the remaining ovary, or to the peritoneum of the ovarian fossa Heterotopic: to forearm, abdominal wall, chest wall *No live births reported for heterotopic Comment Poor survival of ovarian stroma is a limiting factor Same day outpatient surgical procedure Considerations Considered experimental Not appropriate if the risk of ovarian involvement is high Leukemia Risk of reintroduction of malignant cells No reports of cancer recurrence in humans1 Rates In women who have survived cancer, at least 24 live births have been reported using cryopreserved ovarian tissue1,2,3 Preparing the tissue for freezing Transplantation of ovarian tissue Reimplantation 1Loren et al, J ClinOncol. 2013;31. 2Donnez et al. FertilSteril. 2013;99:1503-15. 3Fertil Steril 2014 May;101(5):1237-43.

  12. Fertility Preserving Options: Ovarian tissue cryopreservation American Society of Reproductive Medicine: 2014 Committee Opinion1 “an option in patients who must urgently undergo aggressive chemotherapy and/or radiation, or who have medical conditions requiring treatment that may threaten ovarian function and subsequent fertility. Ovarian tissue cryopreservation may be the only option for prepubertal girls undergoing such treatments. However, these techniques are still considered to be experimental and should be offered to carefully selected patients as an experimental protocol”. 1Fertil Steril. 2014 May;101(5):1237-43.

  13. Fertility Preserving Options: Ovarian transposition (Oophoropexy) Definition Surgical repositioning of ovaries away from a planned radiation field Comment Same day surgical procedure Must occur just prior to radiation therapy to prevent migration of ovaries to original position May need repositioning or IVF to conceive Risks Ovarian torsion Chronic ovarian pain Infarction of fallopian tube Need for re-operation Efficacy Menstruation 50% success rate1 altered blood flow to the ovary scattered radiation (panumbra) Age of the patient Dose and extent of radiation Pregnancy Variable Morice et al2 37 patients Ovarian transposition Uterine conservation Overall pregnancy rate: 12/37 (32%) 18 pregnancies in 12 patients 1Loren et al, J ClinOncol. 2013;31.2Morice et al,Hum Reprod. 1998 Mar;13(3):660-3.

  14. Fertility Preserving Options: GnRH analogue co-treatment Definition Use of hormonal therapies to protect ovarian tissue during chemotherapy and radiation therapy Comment Injections prior to and during gonadotoxic treatments Risks Side effects Efficacy Meta-analysis, 20111 6 RCTs Conclusion: May be beneficial Menstruation: Increased incidence spontaneous menstruation (OR 3.46, CI 1.13-10.57) Increased incidence spontaneous ovulation (OR 5.70, 95% CI 2.29-14.20) NO difference in spontaneous pregnancy rate OPTION2 Menstruation: No difference between ovarian suppression and no treatment with GnRH analogue ASCO 2013 GnRH is not an effective method of fertility preservation Should not solely be relied upon for fertility preservation 1Bedaiwyi et al, FertilSteril. 2011;95(3):906. 2Leonard et al, J ClinOncol. 2010;28: .

  15. Candidates for fertility preservation • Candidates • Breast cancer • Cervical cancer • Endometrial cancer • Ovarian cancer

  16. Candidates for fertility preservationBreast Cancer Breast Cancer 232,340 women will be diagnosed in 20141 30% prior to age 44 Treatment Multi-agent, mainly cyclophosphamide based, cytotoxic chemotherapy regimens Timing 6 week interval from surgery to chemotherapy Concerns Hormone responsive (ER, PR) Options Ovulation induction Aromatase inhibitors SERMs- Tamoxifen Tissue cryopreservation Rare metastasis to ovaries 1 http://seer.cancer.gov/csr/ 1975_2011/results_single/ sect_01_table.01.pdf

  17. Candidates for fertility preservationBreast Cancer Azim, et al 20081 Risk of letrozole and FSH on recurrence 215 breast cancer patients Prospective, non-randomized trial, 2002-2007 79 patients : letrozole + FSH 136 patients: controls, no fertility treatments Mean follow up after chemotherapy: 23.4 months vs 33 months (control) Recurrence PFS: No difference (HR 0.56, CI 95% .17-1.9) Conclusion Use of letrozole + FSH for ovarian stimulation does not appear to increase the risk of recurrence in the short term Longer follow up is needed Relapse-free survival in women with breast cancer stimulated with letrozole versus control group. Kaplan-Meier plot (hazard ratio 0.56, 95% CI 0.17–1.9). 1AzimAA et al., J ClinOncol 2008;26:2630–5

  18. Candidates for fertility preservationCervical Cancer Cervical Cancer 12,360 women will be diagnosed in 20141 Treatment Early Stage: Radical surgery, lymphadenectomy Possible adjuvant chemoradiation Concerns Ovarian involvement2,3 SCC: 0.5-0.79% Adenocarcinoma: 1.7%-5.31% 1http://seer.cancer.gov/csr/ 1975_2010/results_single/ sect_01_table.01.pdf, 2Sutton et al, Am. J. Obstet. Gynecol. 1992;166:50–53, 3Shimada et al, Gynecol Oncol. 2006;101(2):234-7. 4Lu et al, Gynecol Oncol. 2013;04:470.

  19. Candidates for fertility preservationCervical Cancer Options Surgical Radical trachelectomy, lymphadenectomy Vaginal Laparoscopic or robotic The intent of the radical abdominal trachelectomy was to resect the cervix, upper 1–2 cm of the vagina, parametrium, and paracolpos in a similar manner to a type III radical abdominal hysterectomy but sparing the uterine corpus Reconstruction of the uterine corpus to upper vagina after the cerclage is placed 1http://seer.cancer.gov/csr/ 1975_2010/results_single/ sect_01_table.01.pdf, 2Sutton et al, Am. J. Obstet. Gynecol. 1992;166:50–53, 3Shimada et al, Gynecol Oncol. 2006;101(2):234-7. 4Lu et al, Gynecol Oncol. 2013;04:470.

  20. Candidates for fertility preservationCervical Cancer Radical abdominal trachelectomy— the cervical tissue and parametria are separated from the fundus

  21. Candidates for fertility preservationCervical Cancer The uterus is reattached to the vaginal apex

  22. Candidates for fertility preservationCervical Cancer The reconstructed fundus with remaining blood supply from the intact utero-ovarian ligaments—uterine serosa without evidence of fundal ischemia

  23. Candidates for fertility preservationCervical Cancer Obstetric outcomes >250 live births have been reported1 Plante et al, 20082, 20113 Survival outcomes Recurrence Mortality 1Lu et al, Gynecol Oncol. 2013;04:470. 2Plante et al, Gynecol Oncol. 2008;111:S105. 3Plante et al, Gynercol Oncol. 2011;121:290-7.

  24. Candidates for fertility preservationCervical Cancer Oncologic outcomes Plante et al, 20081, 20112 Recurrence risk factors: 2008 Lesions larger than 2 cms (29 vs 1%) Presence of LVSI (12 vs 2%) 2011 Lesions larger than 2 cms 1Plante et al, Gynecol Oncol. 2008;111:S105. 3Plante et al, Gynercol Oncol. 2011;121:290-7.

  25. Candidates for fertility preservationEndometrial Cancer Endometrial Cancer It is estimated that 52,630women will be diagnosed in 20141 Candidates Early stage uterine cancer, FIGO Ia Low grade histology (endometrioid) No myometrial involvement (MRI) Treatment Progestin Medroxyprogestone Megestrol acetate Levonorgestrel IUD Meta-analysis2 Regression rate Resolution of 76% of 408 patients Live birth rate: 28% live birth rate Recurrence rate: 41% of 267 of evaluable patients had recurred 1 http://seer.cancer.gov/csr/ 1975_2010/results_single/ sect_01_table.01.pdf. 2Gallos et al, Am J Obstet Gynecol. 2012;207:(266):e1-2.

  26. Candidates for fertility preservationEndometrial Cancer Gunderson et al, 20121 Medical management (progestins) 45 studies, 391 patients 31.7 years old (median age) Treatment: Medroxyprogesterone (49%), Megace (25%), IUD (19%) 1Gunderson et al, GynecolOncol. 2012;125;477-482.

  27. Candidates for fertility preservationOvarian Cancer Ovarian cancer >22,000 women will be diagnosed in 20141 15% will be younger than 40 Candidates Borderline tumors Early stage ovarian cancers Germ cell Sex cord stromal Epithelial? Treatment Surgical USO, omentectomy, washings, peritoneal biopsies, pelvic and aortic lymphadenectomy Preservation of one ovary, uterus Park, et al 20092 Borderline ovarian tumors Recurrence Rate: 4.9% (SOC) vs 5.1% (fert sparing) Disease free survival 10 yr DFS: 92% (SOC) vs 95% (fert sparing) Overall survival 10 yr OS: 97% (SOC) vs 98% (fert sparing) Pregnancy 34 term pregnancies 1 http://seer.cancer.gov/csr/ 1975_2010/results_single/ sect_01_table.01.pdf 2 Park et al, GynecolOncol. 2009;113:75-82.

  28. Candidates for fertility preservationOvarian Cancer Epithelial Ovarian cancer? Candidates Stage IA Stage IC, grade 1-2, favorable histologic type Serous, mucinous, endometrioid Ineligible Stage >IC Grade III Unfavorable histologic type Clear cell Poorer survival Nam, et al 20131 918 patients Recurrence: 109 (11.9%) Death: 48 (5.2%) Obstetrical: 177 patients242 pregnancies 214 term births (88%), 1 preterm (0.4%) SAB rate: 25/242 (10%) Ectopic rate: 2/42 (0.8%) No congenital anomalies 1Nam et al, GynecolObstet Invest. 2013;76(1):14-24.

  29. American Society of Clinical Oncology (ASCO)Clinical Oncology Clinical Practice Guidelines 2006 ASCO1 Key Recommendations: Discussion of fertility preservation Refer patients who express interest to REI specialists Address fertility preservation early, before treatment starts Document fertility preservation discussions in the medical record Answer basic questions whether fertility preservation may have an impact on successful cancer treatment Refer patients to psychosocial providers if they experience distress about potential infertility Encourage patient to participate in clinical trials 2006 ASCO1 Adult Female specific recommendations Present embryo cryopreservation as an established fertility preservation method Discuss ovarian transposition (oophoropexy) when pelvic radiation therapy is planned Inform patients of conservative gynecologic surgery and radiation therapy options Inform patients that there is insufficient evidence regarding the effectiveness of ovarian suppression (GnRH analogs) as a fertility preservation method, and cannot be relied upon Inform patients that other methods (ovarian tissue preservation, oocyte cryopreservation) are still experimental 2013 ASCO2 Recommendation changes Oocyte cryopreservation is considered a standard practice, and no longer experimental 1Lee et al, J ClinOncol. 2006;24:2917-2931. 2Loren et al, J Clin Oncol. 2013 Jul 1;31(19):2500-10.

  30. Fertility matters, even with a cancer diagnosis • Patients are concerned, and want to discuss options • Refer early. At the time of a cancer diagnosis, consider a referral to REI, as time is often limited between diagnosis and treatment • Physicians are not addressing the fertility concerns with patients • OncoFertility • Still in its infancy • Additional, long term studies are needed to know the effects of these treatments on cancer recurrence and survival Summary

  31. Thank You • Cuterus- the adorable uterus!

More Related