2019-09-15 Outline Background Methodology Results Discussion - PowerPoint PPT Presentation

COMPLIANCE AND OUTCOMES OF 5-DAY INTRAMUSCULAR METHOTREXATE FOR LOW RISK GESTATIONAL TROPHOBLASTIC NEOPLASIA AT KIGALI UNIVERSITY TEACHING HOSPITAL, RWANDA Investigator: Gilbert UWITONZE,MD Supervisor: LISA Bazzett-Matabele, MD, Gyn-Oncologist 2019-09-15

Outline • Background • Methodology • Results • Discussion • Conclusion 2019-09-15

Background  Gestational Trophoblastic disease (GTD) refers to a rare and curable group of tumours that develop from placental tissues  WHO classifies GTD into premalignant conditions(HM) and Malignant GTD or GTN  Gestational Trophoblastic Neoplasia (GTN) complicates approximately 15-20% of all Diagnosed Gestational Trophoblastic Diseases (GTD)*  Persistence of premalignant GTD  Evidenced by persistent elevation of human chorionic gonadotrophin(hCG)  C alled GTN, Untreated → it may metastasise → potentially fatal *Verhoef L, Baartz D, Morrison S, Sanday K, Garrett AJ. Outcomes of women diagnosed and treated for risk gestational trophoblastic neoplasia at the Queensland Trophoblast Centre ( QTC ). 2019-09-15

GTD Incidence • Indonesia ( 10 / 1000 pregnancies), • Mexico (4.6/ 1000) • Japan (2 /1000) • North America and Europe (<1 /1000) • Africa: Uganda (Mulago Hosp 2002: 3.2 /1000), S.A (king Eduard VIII, Durban ,2003 : 1.2/ 1000) Rwanda ( CHUK, 2014: 1.5/1000) 2019-09-15

GTN Classification  GTN are classified in Low risk and High risk group based on FIGO/ WHO Scoring system • A score of 0 – 6 : low risk of resistance to single agent chemotherapy • Treated with single agent, methotrexate or actinomycinD • A score of ≥7: high risk of resistance to single agent chemotherapy • Treated with multi-agent chemotherapy 2019-09-15

FIGO/WHO Scoring 2019-09-15

Methotrexate Regimens Regimens of methotrexate for low risk GTN  Methotrexate 0.4mg/kg IM for 5 days, repeated every 2 weeks  Methotrexate 50mg IM or 1mg/kg every other day for 4 doses with leucovorin 15mg or 0.1mg/kg 24 – 30 h after each dose of methotrexate  Methotrexate 50mg/m 2 IM given weekly 2019-09-15

Rationale of the study Since 2015 , 5-day Intramuscular Methotrexate regimen is used as protocol for treatment of Low risk GTN at CHUK and no studies have assessed compliance and outcomes on this regimen . 2019-09-15 *

Methodology  Retrospective cross-sectional study, chart review over a 2 year period (September 2015 to September 2017)  Inclusion criteria • W omen with low risk GTN, treated with 5D IM MTX (0.4mg/kg/day) • One year follow up for those with complete remission  IRB approval obtained before initiation of the study 2019-09-15

Methodology  Data collected through questionnaire • Demographics • Gestational event leading to GTN • Greatest tumor size • Location and number of metastasis • Pathologic diagnosis if available • Pre- treatment β -HCG • FIGO/WHO score • Side effects • Outcome on 5D IM MTX 2019-09-15

Results  44 patients (mean age=36 years)  3 patients (6.8%) lost to follow up  No case of disease relapse 2019-09-15

Demographics of study population Province 29.3 Frequency Kigali 12 Socio-demographics % (N=41) North 8 19.5 South 10 24.4 Age East 8 19.5 20-35 years 23 56.1 West 3 7.3 >35 years 18 43.9 Occupation Marital status 68.3 Farmer 28 Married 36 87.8 Government employee 1 2.4 Single 2 4.9 Divorced 2 4.9 Business/self employed 9 22.0 Cohabiting 1 2.4 Unemployed 3 7.3 2019-09-15

Characteristics of GTN Pre-Treatment B-HCG (mIU/ml) Variables Frequency % <1,000 1 2.4 Gestational event leading to GTN 1,000-10,000 6 14.6 Molar pregnancy 37 90.2 10,000-100,000 25 61.0 Abortion 3 7.3 >100,000 9 22.0 SVD 1 2.4 FIGO prognostic score Greatest tumor size 3&4 11 26.8 <3 cm 5 12.2 3-4 cm 32 78.0 5 15 36.6 >= 5cm 4 9.8 6 15 36.6 Pathological characteristics Metastasis (Lung n=1, vagina n=3) Choriocarcinoma 10 24.4 Yes 4 9.8 Invasive mole 31 75.6 No 37 90.2 2019-09-15

GTN characteristics and outcome Outcome Baseline B-hCG (mIU/ml) P Complete 0R (95% CI) <1,000 1 (100%) 0 (0.0%) Ref Resistance value remission 0.23 (0.01- 1,000-10,000 6 (100%) 0 (0.0%) 0.504 Gestational event leading to GTN 17.0) 8 0.86 (0.03- 5 0.8 (0.02- Molar pregnancy 29 (78.4%) 0.93 10,000-100,000 20 (80.0%) 0.898 (21.6%) 23.2) (20.0%) 22.6) 0.42(0.01- 3 1.6 (0.05- Abortion 3 (100.0%) 0 (0.0%) 0.703 >100,000 6 (66.7%) 0.785 33.5) (33.3%) 51.1) SVD 1 (100%) 0 (0.0%) Ref FIGO prognostic score Greatest tumor size 3&4 11 (100.0%) 0 (0.0%) Ref <3 cm 5 (100%) 0 (0.0%) Ref 3 6.4 (0.2- 7 3.2 (0.16- 5 12 (80.0%) 0.234 3-4 cm 25 (78.1%) 0.444 (20.0%) 138.6) (21.9%) 65.4) 5 12 (0.5- 1 4.7 (0.15- 6 10 (66.7%) 0.105 >= 5cm 3 (75.0%) 0.381 (33.3%) 245.3) (25.0%) 151) Metastasis (Lung n=1, vagina n=3) Pathological characteristics 1.4(0.12- 2 Yes 3 (75%) 1 (25%) 0.771 Choriocarcinoma 7 (77.8%) 15.8) (22.2%) 0.91 (0.15- 0.922 7 6 5.60) No 30 (81.1%) Invasive mole 23 (79.3%) (18.9%) (20.7%) 2019-09-15

Methotrexate cycles required for complete remission according to pre-treatment intervention 5D-Methotrexate cycles Outcome after 5D- Surgical intervention P value MTX ≤ 5 cycles 6-9 cycles 10-13 cycles Complete remission 10 (71.4%) 2 (14.3%) 2 (14.3%) Hysterectomy 0.013 013 Resistance 0 (0.0%) 3 (100.0%) 0 (0.0%) Complete remission 4 (21.1%) 12 (63.2%) 3 (15.8%) Evacuation or no 0.477 procedure Resistance 1 (20.0%) 2 (40.0%) 2 (40.0%) 2019-09-15

Side effects of Methotrexate and Impact on Treatment Methotrexate side effects and their impact on Treatment Frequency Percentage 60.9 Stomatitis 25 Neutropenia 17 41.5 Nausea 5 12.2 Impact on Treatment Dose reduction 14 34.1 Delayed cycles 13 31.7 2.3 cycles Mean number of cycles delayed 2019-09-15

Discussion  Primary remission rate for low risk GTN of 80.49% on a 5-Day IM Methotrexate regimen  Similar to the 81% primary remission rate observed at the Brewer Trophoblastic Disease Center of Northwestern University.  Kizaki et al, at Chiba University in Japan (1980 – 2009) and Tokyo Women's University (2010 – 2014)  Primary remission rate of 64.7% on 5D IM MTX 0.4mg/kg  Author associates this with high median pre-treatment β -HCG levels. 2019-09-15

Discussion  Molar pregnancy preceding pregnancy event in 90.2% of cases  FIGO/WHO risk score of 6 or hCG level of >100,000 mIU/ml  Higher rates of resistance to 5D IM methotrexate  66.7% of these patients achieving a complete remission  Loss to follow up rate was 6.8%  Attributed to inpatient only management during protocol initiation 2019-09-15

Discussion  Pre-treatment hysterectomy significantly decreased rate of resistance to 5D IM methotrexate regimen (P=0.013)  As also reported by Eysbouts et al in the Netherlands.  Gastrointestinal disorders most common side effects of MTX,  73% of patients.  Oral mucositis more frequent, 60.9%  Five-day IM Methotrexate  Feasible and safe with tolerable side effects  Pre-treatment HCG ≥100,000 mIU/mL and FIGO/WHO risk score of 6 influenced resistance 2019-09-15

Limitations  Single center study  No other accessible studies in the Region  Relatively small number of patients  Retrospective  Insufficient information on the gestational events preceeding GTN  The inconsistency in β -HCG results 2019-09-15

2019-09-15