Fertility Preservation in Female Cancer Patients

Transcription

1 Executive Summary Purpse: T prvide health care prviders at Princess Margaret Cancer Centre infrmatin abut fertility preservatin ptins fr female cancer patients and recmmendatins fr care delivery. Methds: A review f published literature frm January 2000 t June 2014 was cmpleted using MEDLINE. Frmal, published guidelines by recgnized assciatins were reviewed fr recmmendatins. Recmmendatins: All newly diagnsed cancer patients and patients beginning a new plan f care will be infrmed f the ptential risk f the prpsed treatment plan t their fertility as a standard part f a treatment cnsent discussin. Grade B. A reprductive specialist r health care prvider shuld be invlved t discuss FP interventins if a wman requests this infrmatin. will be infrmed f FP ptins - bth prven and unprven technlgies. Grade C. The decisin t pursue FP interventins is up t the patient and family; declining t pursue any interventin is acceptable. Grade C. Ocyte and/r embry preservatin are cnsidered standard practice and shuld be ffered t wmen at risk fr infertility and requesting fertility preservatin technlgies. Grade A. Ocyte preservatin shuld ccur befre the nset f cyttxic therapy in patients at risk fr acute varian failure (AOF). Grade A. Randm start (menstrual cycle day-independent) techniques are available t minimize nclgic treatment delays; cnsideratin f which varian stimulatin technique t use, and subsequent impact n treatment delay, is dependent n lcal fertility clinic expertise. Grade B. Limited data is available assessing subsequent cancer risk in wmen with hrmne sensitive cancers underging varian stimulatin; hwever, there des nt appear t be increased cancer recurrence risk as a result f stimulatin prtcls. Grade B. Prviders with apprpriate expertise shuld discuss ther fertility preservatin methds (such as varian transpsitin, cnservative gyneclgic surgery, cnservative radiatin therapy ptins and varian tissue crypreservatin and re-transplantatin) if apprpriate. Ovarian tissue crypreservatin and re-transplantatin is cnsidered experimental, this prcedure shuld be undertaken in a clinical trial. Grade C. Given the absence f cnsensus in the literature, and lack f clear harm, the use f GnRH analgs may be cnsidered in wmen in whm definitive fertility preservatin is nt pssible. Grade A. Page 1 f 14

2 Guideline 1.0 Intrductin The purpse f this guideline is t guide healthcare prviders abut fertility preservatin fr female cancer patients with cnditins r needing treatments that may place their fertility at risk. Target Users Physicians, Nurse Practitiners, Nurses, Pharmacists and Scial Wrkers. Target Patient Ppulatin Wmen diagnsed with cancer 42 years f age. requiring anti-cancer treatments that may put their fertility at risk, either due t direct effects f the treatment r the ptential teratgenic effects f chrnic anti-cancer treatment that delays child-bearing (e.g. tamxifen). 2.0 Definitins FP: Fertility Preservatin PMAYA: Princess Margaret Cancer Centre Adlescent and Yung Adult Prgram 3.0 Clinical Practice Recmmendatins Table 1: Grades f Recmmendatin A B C Recmmendatin supprted by at least ne randmized cntrlled trial, systematic review r meta-analysis. Recmmendatin supprted by at least ne chrt cmparisn, case study r ther experimental study. Recmmendatin supprted by expert pinin r experience f a cnsensus panel. Adapted frm Shekelle, 1999 [1] Page 2 f 14

3 3.1 Infertility Nmenclature Primary hypgnadism is defined by lw varian estrgen and prgesterne levels. The tw majr categries f primary hypgnadism include acute varian failure (AOF) and premature (r primary) varian failure (POF) [2]. wh lse varian functin during cancer therapy r shrtly after its cmpletin are classified as having acute varian failure (AOF)., wh retain varian functin after therapy cmpletin and then experience menpause befre the age f 40, are classified as POF [2]. Secndary hypgnadism, r central hypgnadism, results frm hypthalamic r pituitary defects, which subsequently impact gnadal functin. with secndary hypgnadism have lw varian estrgen and prgesterne levels, and serum LH and FSH cncentratins that are inapprpriately nrmal r lw. 3.2 Estimatin f Infertility Risk Estimating the risk f infertility in wmen after cancer therapy depends n several patient factrs including: cancer prfile (type, site f disease), general health, baseline fertility and patient age at expsure. Treatment factrs that influence fertility include: ttal cumulative dse f alkylating agents, cumulative gnadal txicity f multi-drug chemtherapy regimens, raditherapy field and dse, and surgery t rgans with a cntributin t fertility [3, 4]. The risk can be summarized as the chance f AOF with treatment, r POF in the years fllwing treatment. The knwn and ptential fertility risks f all cancer treatments shuld be cnsidered when cunseling patients regarding fertility impact. The decisin t pursue FP interventin may be influenced by the estimated risk t fertility [3]. shuld be advised f the uncertainty regarding chemtherapy-related infertility estimates. Mst data use return f menses as a surrgate fr fertility, which in itself may nt adequately estimate fertility. 3.3 Gnadtxicity versus Teratgenicity In additin t agents with gnadtxic ptential, cnsideratin f the impact f agents with teratgenic ptential shuld be given. Fr example, amng pre-menpausal wmen requiring adjuvant endcrine therapy, tamxifen is a cmmnly used medicatin. Althugh, tamxifen des nt have direct gnadtxic ptential, the agent is teratgenic and wmen taking this medicatin shuld nt attempt pregnancy. As tamxifen is used frm 5-10 years in the adjuvant setting; wmen are affected by the negative impact f increasing age n fertility [4]. Wmen requiring: (1) treatments that delay childbearing r (2) treatments with unknwn impact n gnadtxicity r teratgenicity shuld be cunseled accrdingly. Specifically, the wman s anticipated age at the end f treatment may impact the decisin t pursue FP interventins. Page 3 f 14

4 3.4 Disclsure f Infertility Risk and Cnsideratin f Referral t Reprductive Specialist All newly diagnsed cancer patients and patients beginning a new plan f care will be infrmed f the ptential risk f the prpsed treatment plan t their fertility as a standard part f a treatment and cnsent discussin [3]. Grade B. may require immediate initiatin f cancer therapy r may be t ill t underg FP prcedures. A patient shuld be infrmed f her ptential risks f cancer treatment t her fertility and be made aware f the reasn(s) why she is nt a suitable candidate fr FP interventins. Dcumentatin f this fertility discussin int the patient chart, prir t nset f treatment, shuld take place. Grade C. A reprductive specialist r health care prvider shuld be invlved t discuss FP interventins if a patient requests this infrmatin. Grade C. will be infrmed f FP ptins - bth prven and unprven technlgies [3]. Grade C. The decisin t pursue FP interventins is up t the patient and family; declining t pursue any interventin is acceptable. Grade C. 3.5 Fertility Preservatin Interventins A reprductive specialist r health care prvider shuld be invlved t discuss specific FP interventins if a patient requests this infrmatin. Grade C Optins fr Females Embry and/r Ocyte Preservatin Ocyte and/r embry preservatin can be ffered prir t cancer therapy r fllwing the cmpletin f cancer therapy [3]. A 6-12 mnth washut is recmmended pst therapy. Grade C. Ocyte preservatin shuld ccur befre the nset f cyttxic therapy in patients at risk fr acute varian failure AOF [3]. Grade A. Ocyte and embry preservatin are suitable fr pst-pubertal females and are bth cnsidered established, nn-experimental FP methds. Grade A. Depending n the phase f the patient s menstrual cycle, cyte preservatin may take 2 weeks t cmplete. This ptin may nt be suitable fr patients with clinical cnditins that preclude a delay in starting therapy [4-7]. Grade B. Cntrlled varian stimulatin requires daily subcutaneus injectins fr 9-13 days. Ocyte retrieval requires multiple transvaginal ultrasunds and bld tests, and transvaginal aspiratin under mild sedatin. Embry Preservatin Embry preservatin requires sperm (either frm a partner r sperm bank) [3, 4]. Ocyte Preservatin Ocyte preservatin is an ptin fr patients wh d nt have access t dnr sperm r have ethical r religius bjectins t embry preservatin [8]. Refer t a lcal Fertility and Reprductive Health clinic (link t referral frm). Cst assciated with these prcedures is the respnsibility f patient/family. Financial assistance may be available t families wh qualify (link t Fertile Future applicatin). Page 4 f 14

5 Transmittable disease screening (Syphilis Screen VDRL, Hepatitis C Virus Serlgy, Hepatitis B surface antigen, HIV1/HIV2 serlgy) will be required. Ovarian Suppressin Therapy Gnadal prtectin thrugh hrmnal manipulatin with gnadtrpin-releasing hrmne (GnRH) analgs fr FP in wmen treating with gnadtxic chemtherapy has demnstrated cnflicting results [5, 9-20]. Published clinical guidelines frm clinical assciatins engaged in FP cnflict in their recmmendatins regarding GnRH analgs. The American Sciety f Clinical Onclgy des nt supprt the use f GnRH analgs hwever the Canadian Fertility and Andrlgy Sciety supprts their use in FP [5, 21]. Many meta-analyses have been cmpleted, sme f which demnstrate a ptential beneficial effect. and families shuld be made aware f this treatment and the cnflicting data in the literature regarding the use f GnRH analgs t prtect varian functin. Given the absence f cnsensus in the literature, and lack f clear harm, the use f GnRH analgs may be cnsidered in wmen in whm definitive fertility preservatin is nt pssible. Grade A. If undertaken, administratin f GnRH analgs shuld be undertaken by prescribing nclgists, as per the available literature, t crdinate with systemic therapy administratin. Ovarian Transpsitin (phrpexy) Ophrpexy is a treatment strategy t mve varies away frm the radiatin field when pelvic radiatin is perfrmed as part f cancer treatment [4, 5]. Due t radiatin scatter, varies are nt always prtected and patients shuld be advised f the pssibility f lack f success [5]. The prcedure shuld be perfrmed as clse t the time f radiatin treatment nset due t risk f migratin f the varies. There is cntrversial data regarding the efficacy f this prcedure [4, 22]. There is risk t the bld supply f the vary during this prcedure [4, 22] which in itself may diminish varian functin ver time. Cnservative gyneclgic surgery and radiatin therapy ptins Cnservative gyneclgic surgery is a strategy utilized t spare fertility by perfrming less radical surgeries with the intent f sparing as much f the reprductive rgans as pssible. Such strategies have been emplyed in early stage cervical, varian and endmetrial cancers [4, 23]. Such strategies shuld be discussed with all eligible patients. In situatins where such strategies are inapprpriate, a patient shuld be infrmed why she is nt a suitable candidate. Shielding f the gnadal regins is standard prcedure fr reducing scatter radiatin and varian damage [4]. Page 5 f 14

6 Ovarian tissue crypreservatin and re-transplantatin This technique is cnsidered experimental. The use f tissue fr successful attainment f pregnancy is an unprven technlgy. Cnsideratin fr this prcedure shuld be undertaken in a clinical trial. Referred patients must be medically fit and able t underg a laparscpic abdminal prcedure. Ovarian tissue crypreservatin and future transplantatin is a ptential ptin fr wmen wh are unable t achieve cyte retrieval. This technique may be cnsidered, particularly in wmen underging pelvic surgery wh are destined t have adjuvant pelvic RT. There are cncerns with reintrductin f cancer cells with re-implanted varian tissue; this prcedure is cntraindicated in patients with leukemia Fertility Preservatin Risks Hrmne Sensitive Cancers Cncern has been raised in hrmnally sensitive malignancies (such as estrgen-sensitive breast and gyneclgic malignancies) that FP interventins (e.g. varian stimulatin regimens that increase estrgen levels) and/r subsequent pregnancy may increase the risk f cancer recurrence. Limited data, limited by selectin bias and shrt-term fllw-up, is available; current studies d nt indicate increased cancer recurrence risk as a result f stimulatin prtcls [24]. Grade B Fertility Preservatin Lgistics Timing f Fertility Treatment Onclgy treatment delays are cmmnly assciated with FP techniques. Ovarian stimulatin prtcls utilized fr cyte and embry preservatin are dependent n lcal expertise. Lcal stimulatin techniques currently utilized include menstrual cycle dayindependent (randm stimulatin) techniques; thus, wmen may nt need t be at the beginning f a menstrual cycle at the time f stimulatin. Randm stimulatin is currently a newer technique with less supprting evidence. Timing decisins will be made by the lcal fertility clinic with input frm the treating nclgist regarding urgency f treatment. Mst wmen will nt have enugh time t pursue mre than ne cycle f harvesting. Shuld the first cycle fail r lead t pr cyte retrieval, additinal cycles will further delay nclgic treatment. shuld be seen within 72 hurs f referrals t fertility specialists t minimize delays. Typical Ovarian Simulatin Prtcl IVF stimulatin prtcls generally invlve the use f 3-4 types f drugs: 1. A medicatin t suppress the luteinizing hrmne surge and vulatin (until the develping eggs are ready). A GnRH-agnist (gnadtrpin releasing hrmne agnist) such as Luprn r GnRH-antagnist may be used. 2. A fllicle stimulating hrmne (FSH) prduct t stimulate develpment f multiple eggs. 3. An LH cntaining prduct may be added t the regimen. 4. Human chrinic gnadtrpin (HCG) t cause final maturatin f the eggs. Page 6 f 14

7 Typical Timelines a patient may experience are as fllws: - Baseline tests are cnducted prir t any treatment. A baseline ultrasund examinatin and a bld test (usually fr FSH, estradil and antimullerian hrmne (AMH)). - Cycle day is determined by the IVF clinic. - Day 3 12: Ovarian Stimulatin. Daily injectable fertility medicatins begin n a day that is chsen by the cycle crdinatr. - Day 5 after stimulatin Cycle Mnitring. Regular ffice visits start and are cntinued every ne t tw days until fllicle aspiratin. - Day 8 t 12 after stimulatin Ovulatin Inductin. Ovulatin is triggered with an injectin f HCG, r a GnRH agnist, administered when the fllicles are judged t be mature based n ultrasund and hrmne criteria Hurs after HCG Egg Retrieval. Wmen will underg an aspiratin prcedure that takes less than 30 minutes. Wmen will arrive at the clinic ne hur befre the scheduled retrieval prcedure and g hme apprximately tw hurs afterwards. Likelihd f Success Embry and cyte preservatin success rates are specific t individual fertility clinics. Subsequent successful pregnancies are dependent n the quality f the eggs, which is inversely related t female age. Success is als related t the thawing prcess, the ability t fertilize the thawed cyte (fr thse wh underwent cyte preservatin alne) and the ability f the implanted embrys t develp int pregnancies. Embry: The verall IVF clinical pregnancy rate in Canada is 32% per cycle started, 34% per egg retrieval prcedure, and 39% per embry transfer prcedure. This des nt take int accunt the thawing prcess [25]. Ocyte: Success rates are clinic dependent and decline with age. Overall pregnancy rate ranges frm 7-25% [26]. Csts f Treatment Financial csts assciated with fertility treatments are specific t the prcedures undertaken, including number f cycles f harvest, medicatins required and the individual fertility clinic. Certain clinics ffer discunted rates fr nclgy patients. Average csts fr cyte preservatin and embry preservatin can range frm $5,000 - $7,000 CAD. Csts frm medicatins are additinal and may be cvered by private drug plans. Financial assistance may be available t families wh qualify (link t Fertile Future applicatin) Page 7 f 14

8 3.5.4 Fertility Preservatin Strategies Table 2: Fertility Preservatin Strategies Dependent n Type f Treatment If the treatment includes: Cancer Surgery Radiatin Therapy t pelvis and gnads Cyttxic Treatment with high gnadtxicity Endcrine Therapy fr estrgen sensitive breast cancer Cnsider the fllwing Optins: 1. Fertility sparing surgery (gnad preservatin) 2. Uterus preservatin 3. Crypreservatin if high risk f gnadal damage anticipated 1. Shielding t reduce damage t varies 2. Ovarian transpsitin 3. Crypreservatin if high risk f gnadal damage anticipated 1. Crypreservatin 1. Crypreservatin if age at cmpletin f treatment is at a time when natural fertility is likely lw - > 33 years f age at start f treatment if 5 years planned - > 28 years f age at start f treatment if 10 years planned Adapted frm Rdriguez-Wallberg and Oktay, 2014 [4] Page 8 f 14

9 3.5.5 Fertility Preservatin Pathway Start: Cancer Diagnsis 1 Figure 1: Princess Margaret Cancer Centre Fertility Preservatin Prcess Seen by Onclgy Team AYA Referral Team Discusses Fertility Risk 2 Decisin t see Fertility Specialist N Inf entered n chart Yes r Unsure Cmplete lab wrk (t submit with referral) 3 Fertility Referral Sent Seen by Fertility Clinic A B Page 9 f 14

10 A B Decisin fr Fertility prcedure N Inf entered n chart Yes FP Prcedure Inf entered n chart Rutine Onclgic Care End: Fllw-up Care 4 Ntes: 1 Eligible : wmen < 45 years; men < 65 years 2 Regardless f fertility risk 3 AMH level, VDRL (syphilis screen), Hepatitis C serlgy, Hepatitis B antigen, HIV serlgy 4 Fllw-up Care: wmen varian functin checks (frequency t be determined); men yearly semen analysis Cntacts Princess Margaret Cancer Centre AYA Prgram aya@uhn.ca; Phne: ext Page 10 f 14

11 4.0 Implementatin Facilitatrs t implementatin The Princess Margaret Cancer Centre Adlescent and Yung Adult Prgram (PMAYA) is available fr cnsultatin t patients and families and t facilitate FP prcedures. Althugh the prgram frmally assesses patients < 40 years f age, referrals will be accepted fr lder patients wh may be candidates fr FP. The team may be reached at aya@uhn.ca The PMAYA is cnducting research investigating methds t imprve the delivery f infrmatin t patients and families regarding FP. The PMAYA is educating clinicians abut FP ptins fr patients. Organizatinal barriers t implementatin It has been reprted in the literature that patients are dissatisfied with the FP discussins that ccurred at the time f their diagnsis [27, 28]. It is als identified in the literature that health care prviders d nt cnsistently deliver FP infrmatin t all patients at risk [29-31]. A specific fertility clinic is nt recmmended; hwever, wmen referred t fertility specialists shuld be seen within 72 hurs f referral. Ptential ecnmic impact Crypreservatin f cytes, embrys and varian tissue will require additinal prcedure and clinic time at fertility clinics in additin t strage facilities. Apprpriate infrastructure supprt will be needed t ensure the necessary resurces are in place. Key review criteria/indicatrs fr mnitring and audit purpses The PMAYA will track the number f cnsultatins and prcedures perfrmed annually. Plans are underway t assess family/patient satisfactin with FP services. Educatinal mdules fr healthcare practitiners will als be develped, implemented and evaluated. 5.0 Related Dcuments Fertility clinic referral frm Pwer f Hpe referral frm Cancer Knwledge Netwrk: Oncfertility Referral Netwrk 6.0 Statement f Evidence This dcument was drafted by Amirrtha Srikanthan, MD, and reviewed and apprved by Drs. Abha Gupta and Ellen Greenblatt. This guideline is based n a search f relevant literature published in the last 10 years. The recmmendatins in the guideline are based n the guidelines published by the American Sciety f Clinical Onclgy fr fertility preservatin in cancer patients. The level f evidence fr this guideline is grade B/ C. This guideline will be reviewed by the PMAYA every tw years. As new infrmatin becmes available, this guideline will be updated as apprpriate. The authrs declare n cnflict f interest. Page 11 f 14

12 7.0 References 1. Shekelle, P.G., et al., Clinical guidelines: develping guidelines. BMJ, (7183): p Metzger, M.L., et al., Female reprductive health after childhd, adlescent, and yung adult cancers: guidelines fr the assessment and management f female reprductive cmplicatins. J Clin Oncl, (9): p Lren, A.W., et al., Fertility Preservatin fr With Cancer: American Sciety f Clinical Onclgy Clinical Practice Guideline Update. Jurnal f Clinical Onclgy, Rdriguez-Wallberg, K.A. and K. Oktay, Fertility preservatin during cancer treatment: clinical guidelines. Cancer Manag Res, : p Lren, A.W., et al., Fertility preservatin fr patients with cancer: American Sciety f Clinical Onclgy clinical practice guideline update. J Clin Oncl, (19): p Fernbach, A., et al., Evidence-Based Recmmendatins fr Fertility Preservatin Optins fr Inclusin in Treatment Prtcls fr Pediatric and Adlescent Diagnsed With Cancer. J Pediatr Oncl Nurs, (4): p Ginsberg, J.P., Educatinal paper: the effect f cancer therapy n fertility, the assessment f fertility and fertility preservatin ptins fr pediatric patients. Eur J Pediatr, (6): p Practice Cmmittees f American Sciety fr Reprductive, M. and T. Sciety fr Assisted Reprductive, Mature cyte crypreservatin: a guideline. Fertil Steril, (1): p Chen, H., et al., Adjuvant gnadtrpin-releasing hrmne analgues fr the preventin f chemtherapy induced premature varian failure in premenpausal wmen. Cchrane Database Syst Rev, 2011(11): p. CD Clwse, M.E., et al., Ovarian preservatin by GnRH agnists during chemtherapy: a meta-analysis. J Wmens Health (Larchmt), (3): p Kim, S.S., et al., Use f hrmnal prtectin fr chemtherapy-induced gnadtxicity. Clin Obstet Gynecl, (4): p Del Mastr, L., et al., Gnadtrpin-releasing hrmne analgues fr the preventin f chemtherapyinduced premature varian failure in cancer wmen: systematic review and meta-analysis f randmized trials. Cancer Treat Rev, (5): p Badawy, A., et al., Gnadtrpin-releasing hrmne agnists fr preventin f chemtherapy-induced varian damage: prspective randmized study. Fertil Steril, (3): p Bedaiwy, M.A., et al., Gnadtrpin-releasing hrmne analg ctreatment fr preservatin f varian functin during gnadtxic chemtherapy: a systematic review and meta-analysis. Fertil Steril, (3): p e Yang, B., et al., Cncurrent treatment with gnadtrpin-releasing hrmne agnists fr chemtherapy-induced varian damage in premenpausal wmen with breast cancer: a meta-analysis f randmized cntrlled trials. Breast, (2): p Sverrisdttir, A., et al., Adjuvant gserelin and varian preservatin in chemtherapy treated patients with early breast cancer: results frm a randmized trial. Breast Cancer Res Treat, (3): p Page 12 f 14

13 17. Gerber, B., et al., Effect f luteinizing hrmne-releasing hrmne agnist n varian functin after mdern adjuvant breast cancer chemtherapy: the GBG 37 ZORO study. J Clin Oncl, (17): p Del Mastr, L., et al., Effect f the gnadtrpin-releasing hrmne analgue triptrelin n the ccurrence f chemtherapy-induced early menpause in premenpausal wmen with breast cancer: a randmized trial. JAMA, (3): p Munster, P.N., et al., Randmized trial using gnadtrpin-releasing hrmne agnist triptrelin fr the preservatin f varian functin during (ne)adjuvant chemtherapy fr breast cancer. J Clin Oncl, (5): p Elgindy, E.A., et al., Gnadatrphin suppressin t prevent chemtherapy-induced varian damage: a randmized cntrlled trial. Obstet Gynecl, (1): p Wallace, W.H., et al., Predicting age f varian failure after radiatin t a field that includes the varies. Int J Radiat Oncl Bil Phys, (3): p Lange, S., D. Tait, and M. Matthews, Oncfertility: an emerging discipline in bstetrics and gyneclgy. Obstet Gynecl Surv, (8): p Wallberg, K.A., V. Kers, and O. Hvatta, Clinical aspects f fertility preservatin in female patients. Pediatr Bld Cancer, (2): p Azim, A.A., M. Cstantini-Ferrand, and K. Oktay, Safety f fertility preservatin by varian stimulatin with letrzle and gnadtrpins in patients with breast cancer: a prspective cntrlled study. J Clin Oncl, (16): p Canadian Fertility and Andrlgy Sciety. Human Assisted Reprductin 2013 Live Birth Rates fr Canada [cited 2014 August 21]; Available frm: &catid=929%3Apress-releases&Itemid= Cil, A.P., H. Bang, and K. Oktay, Age-specific prbability f live birth with cyte crypreservatin: an individual patient data meta-analysis. Fertil Steril, (2): p e Partridge, A.H., et al., Web-based survey f fertility issues in yung wmen with breast cancer. J Clin Oncl, (20): p Yee, S., et al., Addressing ncfertility needs: views f female cancer patients in fertility preservatin. J Psychsc Oncl, (3): p Andersn, R.A., et al., D dctrs discuss fertility issues befre they treat yung patients with cancer? Hum Reprd, (10): p Yee, S., et al., A natinal study f the prvisin f ncfertility services t female patients in Canada. J Obstet Gynaecl Can, (9): p Yee, S., et al., Fertility preservatin practices amng Ontari nclgists. J Cancer Educ, (2): p Page 13 f 14

14 8.0 Guideline Grup and Reviewers Guideline Grup Membership: 1. Amirrtha Srikanthan, MD, FRCPC, Medical Onclgist, Clinical Fellw, Medical Onclgy and AYA Prgram 2. Abha Gupta, MD, MSc, FRCPC, Staff Onclgist, Haematlgy/Onclgy, Medical Directr PMAYA Prgram 3. Ellen Greenblatt, MDCM, FRCSC, Staff Obstetrician and Gyneclgist, Obstetrics and Gyneclgy, Fertility and Reprductive Health Internal Reviewers: 1. Eitan Amir, MB ChB, PhD, Staff Onclgist, Medical Onclgy 2. Philippe Bedard, MD, FRCPC, Staff Onclgist, Medical Onclgy 3. Meredith Giuliani, MBBS, Med, FRCPC, Staff Onclgist, Radiatin Onclgy 4. David Hdgsn, MD, MPH, FRCPC, Staff Onclgist, Radiatin Onclgy 5. Stephane Laframbise, MD, MSc, FRCSC, Staff Onclgist and Gyneclgist, Gyneclgy Onclgy 6. Anca Prica, MD, MSc, FRCPC, Staff Hematlgist, Hematlgy Onclgy 7. Karen Yee, MD, FRCPC, Staff Hematlgist, Hematlgy Onclgy External Reviewers: 1. Page 14 f 14