Granulosa Cell Tumor and Letrozole therapy

[eelsel]

Hi!
I am writing on behalf of my sister. She has had Granulosa Cell Tumor since 2002. At that time she had only one ovary removed and no treatment. She had a recurrance of this in 2008 and underwent total hysterectomy (both surgeries were in Germany). Recently, in July, (here in the States) she has had another recurrance with surgical removal. The doctors are recommending either Chemo or letrozole therapies. My sister is against anything unnatural going into her body, so chemo is really out, especially since she hasn't found any studies that say that Chemo really works. Now, that leaves only the Letrozole therapy. She is very concerned about it causing osteoporosis, especially when she is so young...only 37 years old. Also, my sister really prefers to only do a ketogenic diet that she had read up on when in Germany...My family is very concerned about this not being a good enough treatment...

Here are my questions:
1. Since she has had 3 recurrances in a short amount of time, would it be necessary for her to undergo some sort of treatment to keep the GCT at bay?
2. Have you had any patients use Letrozole? If so, what do you recommend for treatment Osteoporosis? Anything else we should be aware of regarding use of this drug?
3. Have you had anyone use a ketogenic diet? Do you think the diet is helpful at all?
4. Since she has had so many recurrances already, is there a greater risk of mortality as well as a recurrance that  comes back sooner than later?

Thank you so much for your time!

[Annekathryn Goodman, M.D.]

Hi There
thank you for your good questions.

I would say that there is no information that the addition of therapy - whatever it is- int he absence of measurable disease will prevent recurrence.

So if your sister has had a complete surgical resection of the recurrence, close observation is reasonable.

If she continues to have signs of persistent cancer either from seeing unresectable tumor at surgery or by xray, then most people would consider adding therapy either with chemotherapy of hormone therapy.  There are some people who might watch a small tumor with therapy especially if it is slow growing.

I did a pub med search but do not see any compelling research to guide us. I like this little abstract which humbly makes this point

Case Rep Oncol. 2010 Jan 13;3(1):14-18.

Nearly 30 Years of Treatment for Recurrent Granulosa Cell Tumor of the Ovary: A Case Report and Review of the Literature.
Teoh D, Freedman R, Soliman PT.

Department of Gynecologic Oncology, Duke University, Durham, N.C., USA.

Abstract
A 30-year-old woman was diagnosed with a stage IA granulosa cell tumor (GCT) of the ovary in 1979. Following removal of the adnexal mass and complete surgical staging, she remained disease-free for 12 years. In 1991 she underwent a resection of a retroperitoneal mass, confirmed to be a recurrent GCT. Despite adjuvant radiation treatment at the time of recurrence, the patient presented five years later with abdominal pain, and was found to have a second recurrence. Over the next 10 years the patient had multiple recurrences and progressive disease despite surgical resection, cytotoxic, hormonal and targeted chemotherapy treatments. In conclusion, there is no standard management for recurrent GCT of the ovary. We review this patient's treatment in the context of the current literature.

Osteoporosis:  the most important interventions include calcium 1200 mg per day plus vitamin D 400  units per day plus daily weight bearing exercise.

other interventions include:
estrogen
biphosphonates
raloxifene
calcitonin


I am unfamiliar with the benefits of a ketogenic diet. There are many claims about diet and cancer but little science.

I understand your concern about prognosis with multiple recurrences.
Granulosa cell tumor is so rare that it is hard to make big generalizations. However, unlike other cancers, recurrence in granulosa cell tumors does not necessarily mean a reduced lifespan.Here is another nice abstract
best wishes

Eur J Gynaecol Oncol. 2010;31(1):94-8.

Granulosa cell tumors of the ovary: a clinicopathologic and immunohistochemical study of 21 cases.
Kondi-Pafiti A, Grapsa D, Kairi-Vassilatou E, Carvounis E, Hasiakos D, Kontogianni K, Fotiou S.

Pathology Laboratory, Aretaieion Hospital, Athens, Greece. ***@****

Abstract
PURPOSE: To further study the clinicopathologic and immunohistochemical features of ovarian granulosa cell tumors (GCTs).

METHODS: We retrospectively studied all cases of GCTs diagnosed in our laboratory over the last 10-year period. Immunohistochemistry for inhibin, vimentin, cytokeratin, Ki-67 and p53 was performed on archival paraffin blocks. Pathologic and immunohistochemical findings were correlated with the clinical records of the patients.

RESULTS: Twenty-one cases (15 of the adult and 6 of the juvenile type) were retrieved. All patients were FIGO Stage I at the time of diagnosis. Recurrent disease was detected in four patients (19%) during a median follow-up of 36 months (range 2-26 years). Pathology revealed a concomitant theca-cell component in three cases, a Sertoli-Leydig component in one case, and a thecoma in one case. Archival tissue material was available in 12 cases. Immunohistochemistry was positive for: beta-inhibin in 12/12 cases (100%), vimentin in 11/12 cases (91.7%), cytokeratin in 3/12 cases (25%), CD34 in 0 cases (0%), and p53 in 2/12 cases (16.7%). The Ki-67 index was < 5% in 12/12 cases (100%). No significant correlations were observed between the pathologic and immunohistochemical parameters examined and the clinical outcome.

CONCLUSIONS: Despite the relatively indolent nature and favorable prognosis of most GCTs, late recurrences are not a rare event even in Stage I patients, necessitating a close and long-term follow-up. The identification of novel prognostic markers, in addition to our traditional staging parameters such as clinical staging, is needed in order to more accurately predict probabilities of recurrence in these patients.

[eelsel]

I really appreciate the time that you took to answer my questions thoroughly. It is quite difficult to find adequate and reliable information and there is so much pressure to make the right decisions when health is involved. Thank you for what you are doing here!