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Reversion of Hormone Treatment Resistance with the Addition of an mTOR Inhibitor in Endometrial Stromal Sarcoma.

Martin-Liberal J, Benson C, Messiou C, Fisher C, Judson I - Case Rep Med (2014)

Bottom Line: Results.Conclusion.This observation is highly encouraging and deserves further investigation.

View Article: PubMed Central - PubMed

Affiliation: The Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK.

ABSTRACT
Background. Endometrial stromal sarcomas (ESS) are a subtype of gynaecological sarcomas characterized by the overexpression of hormone receptors. Hormone treatment is widely used in ESS but primary or acquired resistance is common. The mammalian target of rapamycin (mTOR) pathway has been suggested to play a key role in the mechanisms of hormone resistance. Recent studies in breast and prostate cancer demonstrate that this resistance can be reversed with the addition of an mTOR inhibitor. This phenomenon has never been reported in ESS. Methods. We report the outcome of one patient with pretreated, progressing low grade metastatic ESS treated with medroxyprogesterone acetate in combination with the mTOR inhibitor sirolimus. Results. Partial response was achieved following the addition of sirolimus to the hormone treatment. Response has been maintained for more than 2 years with minimal toxicity and treatment is ongoing. Conclusion. This case suggests that the resistance to the hormone manipulation in ESS can be reversed by the addition of an mTOR pathway inhibitor. This observation is highly encouraging and deserves further investigation.

No MeSH data available.


Related in: MedlinePlus

Axial contrast enhanced CT images show a peritoneal deposit within the left side of the abdomen (arrows). Prior to commencing sirolimus, the deposit progressed by RECIST 1.1 over a period of 6 months ((a) and (b)). CT staging at 4 months (c) and 13 months (d) on treatment with sirolimus showed that the deposit had reduced in size but was within the limits of stable disease by RECIST v1.1. A further pelvic deposit (not shown) also reduced in size but overall disease remained stable by RECIST v1.1. However, assessment by Choi criteria which incorporates attenuation changes classified disease status as partial response at 4 months and further partial response at 13 months.
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fig1: Axial contrast enhanced CT images show a peritoneal deposit within the left side of the abdomen (arrows). Prior to commencing sirolimus, the deposit progressed by RECIST 1.1 over a period of 6 months ((a) and (b)). CT staging at 4 months (c) and 13 months (d) on treatment with sirolimus showed that the deposit had reduced in size but was within the limits of stable disease by RECIST v1.1. A further pelvic deposit (not shown) also reduced in size but overall disease remained stable by RECIST v1.1. However, assessment by Choi criteria which incorporates attenuation changes classified disease status as partial response at 4 months and further partial response at 13 months.

Mentions: Two years following ovarian surgery, the patient presented with right-sided abdominal pain. A new CT scan showed a 5 × 3 cm mass in the inferior pelvis and another mass of similar characteristics in the right iliac fossa. A second operation was performed and the 2 lesions were resected and the pathological analysis demonstrated relapse of her previous ESS with strong HR expression. Postoperative close surveillance and leuprorelin injections, a gonadotropin-releasing hormone (GnRH) analog, were advised. Almost 1 year later, a further relapse in the form of several peritoneal deposits and recurrence of the pelvic mass was diagnosed on a CT scan. The disease was considered unresectable so the patient started treatment with an AI, letrozole 2.5 mg once daily (od). Her disease remained stable for 4 months and the patient did not experience any significant side effects. However, a new CT scan demonstrated progression of her pelvic disease. In addition, the patient reported new abdominal discomfort. A different hormonal manoeuvre was considered and medroxyprogesterone acetate 400 mg od was started. The abdominal symptoms completely disappeared soon after starting treatment in spite of not finding significant tumour changes in regular CT scans, being classified as stable disease (SD) by RECIST v1.1. Moreover, the patient tolerated the treatment well. Nevertheless, progression by RECIST v1.1 in the dominant peritoneal nodule located anteromedial to the splenic flexure was noted after 1 year of treatment: 2.8 cm in maximum diameter compared to 1.4 cm in previous CT scan (Figure 1). The pelvic mass showed no significant changes.


Reversion of Hormone Treatment Resistance with the Addition of an mTOR Inhibitor in Endometrial Stromal Sarcoma.

Martin-Liberal J, Benson C, Messiou C, Fisher C, Judson I - Case Rep Med (2014)

Axial contrast enhanced CT images show a peritoneal deposit within the left side of the abdomen (arrows). Prior to commencing sirolimus, the deposit progressed by RECIST 1.1 over a period of 6 months ((a) and (b)). CT staging at 4 months (c) and 13 months (d) on treatment with sirolimus showed that the deposit had reduced in size but was within the limits of stable disease by RECIST v1.1. A further pelvic deposit (not shown) also reduced in size but overall disease remained stable by RECIST v1.1. However, assessment by Choi criteria which incorporates attenuation changes classified disease status as partial response at 4 months and further partial response at 13 months.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4109292&req=5

fig1: Axial contrast enhanced CT images show a peritoneal deposit within the left side of the abdomen (arrows). Prior to commencing sirolimus, the deposit progressed by RECIST 1.1 over a period of 6 months ((a) and (b)). CT staging at 4 months (c) and 13 months (d) on treatment with sirolimus showed that the deposit had reduced in size but was within the limits of stable disease by RECIST v1.1. A further pelvic deposit (not shown) also reduced in size but overall disease remained stable by RECIST v1.1. However, assessment by Choi criteria which incorporates attenuation changes classified disease status as partial response at 4 months and further partial response at 13 months.
Mentions: Two years following ovarian surgery, the patient presented with right-sided abdominal pain. A new CT scan showed a 5 × 3 cm mass in the inferior pelvis and another mass of similar characteristics in the right iliac fossa. A second operation was performed and the 2 lesions were resected and the pathological analysis demonstrated relapse of her previous ESS with strong HR expression. Postoperative close surveillance and leuprorelin injections, a gonadotropin-releasing hormone (GnRH) analog, were advised. Almost 1 year later, a further relapse in the form of several peritoneal deposits and recurrence of the pelvic mass was diagnosed on a CT scan. The disease was considered unresectable so the patient started treatment with an AI, letrozole 2.5 mg once daily (od). Her disease remained stable for 4 months and the patient did not experience any significant side effects. However, a new CT scan demonstrated progression of her pelvic disease. In addition, the patient reported new abdominal discomfort. A different hormonal manoeuvre was considered and medroxyprogesterone acetate 400 mg od was started. The abdominal symptoms completely disappeared soon after starting treatment in spite of not finding significant tumour changes in regular CT scans, being classified as stable disease (SD) by RECIST v1.1. Moreover, the patient tolerated the treatment well. Nevertheless, progression by RECIST v1.1 in the dominant peritoneal nodule located anteromedial to the splenic flexure was noted after 1 year of treatment: 2.8 cm in maximum diameter compared to 1.4 cm in previous CT scan (Figure 1). The pelvic mass showed no significant changes.

Bottom Line: Results.Conclusion.This observation is highly encouraging and deserves further investigation.

View Article: PubMed Central - PubMed

Affiliation: The Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK.

ABSTRACT
Background. Endometrial stromal sarcomas (ESS) are a subtype of gynaecological sarcomas characterized by the overexpression of hormone receptors. Hormone treatment is widely used in ESS but primary or acquired resistance is common. The mammalian target of rapamycin (mTOR) pathway has been suggested to play a key role in the mechanisms of hormone resistance. Recent studies in breast and prostate cancer demonstrate that this resistance can be reversed with the addition of an mTOR inhibitor. This phenomenon has never been reported in ESS. Methods. We report the outcome of one patient with pretreated, progressing low grade metastatic ESS treated with medroxyprogesterone acetate in combination with the mTOR inhibitor sirolimus. Results. Partial response was achieved following the addition of sirolimus to the hormone treatment. Response has been maintained for more than 2 years with minimal toxicity and treatment is ongoing. Conclusion. This case suggests that the resistance to the hormone manipulation in ESS can be reversed by the addition of an mTOR pathway inhibitor. This observation is highly encouraging and deserves further investigation.

No MeSH data available.


Related in: MedlinePlus