39 year old teacher in rather good PS.  She has a Sertoli-Leydig-tumor G2 diagnosed 2007. She was operated twice by laparoscopy in an outside clinic, latest 10/2007. Then, immediately after the 2nd laparoscopy suspect liver nodules apeared and she was referred to a university clinic and had her 3rd surgery with partial liver and pancreas  resection , splenectomy etc. - all with Sertoli-Leydig tumor again.
The tumor was negative for ER, PR, EGF, c-kit, Her2neu, Inhibin A, and some other markers were negative. Inhibin A in the serum was positive and reflected somewhat "response". IHC for GnRH receptors should positivity in 50% of tumor cells.
Patient received (at my instiution from now onwards) 4 courses BEP 12/07-3/08.

8/08, after 4-5 months she recurred again in the liver (histologically confirmed).
8-9/08 we gave her 2 courses VAC and performed a CT after the 2nd course. This CT indicated progressive disease.
10-12/08 she received 8 course taxol weekly and bevacizumab bi-weekly.
The CT scan after this 8 weeks (and Inhibin A and sympotms) indicate progressive disease again.
What could I do next? The patient still wants maximum therapy and is in rather good PS (ECOG 0-1)
Does anybody has any good idea?
many thanks,
 Andreas du Bois

Response # 1:
If the liver lesions are localized, she might be palliated by liver lesion ablation of some type.

Bill Hoskins

Response # 2:
I fear no easy option hence this request

Some  non evidence-based thoughts for you

Conventional agents might include the weekly cisplatin/etoposide, no evidence but active in resistant EOC TIP also possible, at least ifos is not previously used

There was a PR reported to vorinostat in granulosa tumours in phase 1


Don’t know about good idea but maybe will stimulate some further discsussion and see if anyone else responds

Nick Reed

Response # 3:
We have some very interesting results with femara plus analog if patient was not very symptomatic (no biological hepatic abnormality)

Vorinostat could be try (one complete response published in 2007, we have also beautiful response with nexavar (ras pathway?)
Finally, gemzar plus docetaxel (sarcoma combination) could be try also patient received recently paclitaxel

best regards

Isabelle Ray-Coquard

Response # 4:
Dear Andreas,

 As far as I can see, you did all the realistic possibilities. Alternatives are (when in a good general condition) the use of dose-dense schedules, phase I studies with new drugs or comb inations or perhaps, althought as far as I know there is not much experience with it in Sertoli-Leydig cell tumors, with trabectidin.

Kind regards

Jan Vermorken

Response # 5:
GnRH antagonist

Kathy Look

Response # 6:
If it is confined to the liver we would irradiate.She has incurable disease and this may provide some useful long term palliation as it has for Granulosa Cell Tumours

Michael Quinn

Response # 7:
I am not sure if they respond as well as granulosa tumors to RT but if she were to have RT would suggest using Selective Internal Radiation Therapy (SIRT) which delivers high doses of radiation directly to the site of tumors. It is a minimally invasive treatment- radioactive SIR-Spheres microspheres are infused via a catheter into the liver where they selectively target liver tumors with a doses of internal radiation up to 40 times higher than conventional radiotherapy, while sparing healthy tissue.Works well for mets from colon .Would be worth considering if disease confined to liver.We have treated quite a few patients with non gynecological cancers .There is a radiologist in sydney who has extensive experience and you might wish to discuss with him regards

Michael Friedlander

Response # 8:
Dear Andreas,

I had two patients with metastatic Sertoli-Leydig tumor in the last 7 years with a very similar management to your patient (BEP/paclitaxel/doxorubicin based chemotherapy). We saw a partial remission and a minor remission to ifosfamide based chemotherapy in both patients. No responses were seen with gemcitabine or vinorelbine.

The last patient died several months ago. If you need more specific information I can review the records.

Do not hesitate to contact me for more information.

Good luck and best regards

Antonio González-Martín

Response # 9:
Localized radiotherapy +/- hormonal therapy +/- chemo but not TKI

Gillian Thomas

Response # 10:
GnRH - -> phase I (eg. mTor)

Stan Kaye

Response # 11:
Fusion molecule GnRH-Doxorubicine (protocol Gyn 5 - however, drug not available outside protocol and patient not eligible due to histology)


Response # 12:
Dear Andreas:

If there is frozen tumor available, why not do an expression array (I prefer protein array) to identify potential targets?  This makes more sense than pulling a drug out-of-the-air.  If you do have paraffin-embedded material, I can get a limited, RNA expression array done using a novel quantitative nuclease protection assay.

Warm regards,

David S. Alberts

Response # 13:
Dear David,

Nice suggestion if it works.

Kind regards

Jan Vermorken

Response # 14:
Dear Andreas,

Regarding the treatment with trabectedin, if you have paraffin embedded tumor you could determine the expression of BRCA1, ERCC1 and XPG. At least in sarcomas a low expression of BRCA1 and high expression of ERCC1 or XPG was associated with response.

I determined these predictive factors in one of my patients that I told to you. She had high expression of BRCA1, ERCC1 but low expression of XPG. Although only ERCC1 was favourable I treated the patient with trabectedine, but unfortunately she did not respond. She had responded to ifosfamide before the trabectedine trial.

Best regards

Antonio González-Martín

Response # 15:
Dear Professor duBois,

it sounds that the tumor situation is more multidocal, nevertheless it´s still palliative therapy, How are the liver function?, were are the liver metastasis are localized? In all lobes? what is the maximal size? Despite the negative hormonal receptor I will favour a therapy with high dose gestagen (egMPA) or GnRH analogues

Best regards
Jalid Sehouli

Update on Sertoli-Leydig tumor case:

I started with GnRH analogue and indicated PET-CT to see if localized radiotherapy would be a serious option. Furthermore, we wil try to get paraffine blocks and send to DAvid Alberts who generously offered some limited testing - let's see what comes out.

If GnRH fails, I plan to initiate an ifosfamide based treatment if nothing new comes up from the testing results, otherwise I would try to include her into a phase I trials and will ask, who has something open for this patient.

best wishes and many thanks