Case Conference January 31st 2018

31-Jan-2018, Divisi Ginekologi Onkologi RSCM

Mrs. D, 20 yo, P0A1, 4260078

Gestational Trophoblastic Neoplasia low risk Methotrexa

 

CASE DESCRIPTION (8 October 2017)

Mrs D, P0A1, came to the oncology clinic for routine follow up. Patient had no symptoms,  in 13/7/2017 patient had a curettage in RS islam Karawang due to 10 week gestational age of molar pregnancy (LMP: 04/05/2017), the diagnose was came from ultrasound finding, but the patient didn’t know the initial Beta HCG level. After curetage  the pathology result was conception tissue. After curettage patient didn’t cek Beta HCG level but patient have pregnancy test 5 time with all the test with positive result. The patient than referred to RSCM due to persistent Beta HCG with susp Gestational trophoblastic disease.

History of previous illness: patient denied have hypertension, DM, asthma and TB.

History of family illness : patient denied have hypertension, DM, asthma and TB

History of menstruation : menarche 13 year old, 4-5 day, regular, changing pad 2x/day, dismenorhea (-)

Marital Status : 1x, 2014

Obstetrical status : P0A1

Contraception : never

Social status : housewives. Husband employee

 

Physical examination :

BP : 112/84 HR: 99x/m RR: 20x/m T: 36,6

No lymph node palpables

Lung: vascular breath no wheezing, no rhales

Cor : regular heart sound I-II no murmur nor gallop

Abdomen : no pain nor abdominal mass

Extrimity : no pitting edema, sianosis, Capilary refill time < 2”

 

 

Gynecology status :

Inspection : vulva and external orifice normal

Inspeculo: portio was smooth closed OUE, fluksus and flour negative

VT: CUT anteflexed, size within normal limit, no adneksal mass were palpable, no nodul in the parametria, no portio movement tenderness.

 

Supportive examination

PA RS Islam Karawang 25/7/2017

Conception tissue

 

Lab result 3/10/2017 :

CBC: 12,8/37,9/6590/330000//82,9/26/37,8

Ur/cr: 13/0,4 SGOT/SGPT: 23/20 GDS 109 Beta-HCG : 59,69

 

US examination (4/10/2017)

Genitalia interna within normal limit, there is no vascular mass outside cavum uteri.

 

Ro Thorkas 03/10/2017

There is no radiologic anomaly found in lung and heart

 

 

 

Patient than got methotrexate 25 mg with β-HCG level during treatment

3/10/2017    59,69 à before treatment

1/11/2017    11,87 à after session 1 MTX

23/11/2017  11,12 à after session 2 MTX

14/12/2017  6,57 à after session 3 MTX

9/01/2018    10,96 à after session 4 MTX

24/01/2018  10,61 à after session 5 MTX

 

Assesment : gestational throphoblastic neoplasia low risk methothrexat resistans

Planning : second line chemotheraphy

 

CLINICAL QUESTION

 

In the management of getational throphoblastic disease low risk with methothrexat resistans, does single agent chemotheraphy or multiple agent chemotheraphy have a better outcome (remission,side effect) ?

 

What question did the study ask?	PICO Analysis
Patients	getational throphoblastic neoplasia low risk with methothrexat resistans
Intervention	Multiple agent chemotheraphy
Comparison	Single agent chemotheraphy
Outcome	Complete remission

 

 

METHODS

 

Search strategy

The search was conducted on Pubmed and ScienceDirect January 29th, 2017, using the search tool containing the keywords “Gestational Throphoblastic disease methotrexate resistans” (Table 1). Search results were filtered by the engine according to the following criteria: articles published in the past 5 years, human species, and English language. Search strategy, result, and the inclusion and exclusion criteria are shown in the flowchart (Figure 1).

 

Table 1. Search strategy used in Pubmed, Science Direct, and Uptodate, conducted on April 8th, 2017

 

Engine	Search Terms	Results
Pubmed     ScienceDirect	Gestational throphoblastic neoplasia low risk methothrexat resistance   Gestational throphoblastic neoplasia low risk methothrexat resistance	4     4

 

Figure 1. Flowchart of search strategy

 

Pubmed      n=4 Science direct        n=4

Papers for review of title and abstracts

Relevant n= 1 Discard   n=3 (no relevant title, no full text)

Papers for review of full text n= 4

Studies included n=1

Pubmed (Advance search)  Sciencedirect (advance search) Gestational trophoblastic Disease Low risk second line chemoheraphy (Title/Abstract)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

SELECTION

The titles of the filtered results from Pubmed and ScienceDirect were screened using the inclusion criteria. A second screening was conducted by reading the abstract, and finally 1 article were included.

 

CRITICAL APPRAISAL

 

	Questions	Remark
Validity	Is it a systematic review of high-quality studies? Does the methods section describe: a comprehensive search, and how the reviewers assesed the validity of each study? Are the studies consistent?	No (Retrospective)     Yes   Yes
Importancy	Are they clinically significant?	Yes
Applicability	Can the results help you?	Yes

 

 

RESULT

A retrospective study by M C Winter et all. 136 (35%) of 392 received second-line chemotherapy following methotrexate-resistance. 59 patients received single-agent dactinomycin with 53 (90%) patients achieving complete hCG response, 3 patients requiring combination chemotherapy or surgery, and 3 patients subsequently spontaneously resolving. 56 patients received EA chemotherapy with hCG complete response in 50 (89%) patients, and the remaining 6 patients were cured with further multi-agent chemotherapy or surgery. With carboplatin, 17/21 (81%) achieved an overall complete hCG response rate, with 4 patients requiring third-line EA. Carboplatin was well tolerated with no significant alopecia; myelosuppression was the most significant toxicity. Overall survival for all patients was 100%.

 

DISCUSSION

Clinicians treating GTN usually use the International Federation of Gynaecology and Obstetrics (FIGO 2000) scoring system to guide firstline treatment decisions and allow comparison of data. A score of 0–6 predicts for a low-risk of resistance to single-agent chemotherapy with methotrexate (MTX) or dactinomycin. Scores of ≥7 are deemed high-risk, with almost no chance of complete response to single-agent chemotherapy and therefore receive combination chemotherapy from the outset.¹ GTN is highly chemo-sensitive and the prognosis, particularly in low-risk disease, is excellent. Overall survival in low-risk disease is almost 100% and therefore a key aim is to optimise treatment by reducing exposure to both short and longer-term toxicities and minimise serious long-term adverse events including premature menopause and the small increased risk of leukaemia.²

Overall, approximately 75% of all women with low-risk GTN achieve complete marker remission with first-line treatment, with the risk of resistance to initial MTX chemotherapy increasing with higher FIGO scores, a diagnosis of choriocarcinoma, a higher pre-treatment hCG and the presence of metastatic disease.³ The selection of chemotherapy regimen in MTX-resistance depends on the volume of residual disease as indicated by the serum hCG value at the time.

Single-agent dactinomycin can be effectively used as second-line treatment for low-risk GTN following MTX resistance with lower hCG levels (currently <300 IU/L).⁴ As a strategy to minimise exposure to potentially carcinogenic combination chemotherapy and an increased risk of early menopause, single-agent carboplatin provides a simple, well-tolerated and effective alternative to combination chemotherapy and merits further evaluation in this setting. ⁵

 

CONCLUSION

 

Single-agent dactinomycin can be effectively used as second-line treatment for low-risk GTN following MTX resistance with lower hCG levels (currently <300 IU/L).

,

,