Hormonal treatments in metastatic endometrial stromal sarcomas: the 10-year experience of the sarcoma unit of Royal Marsden Hospital
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Abstract:
Hormonal manipulation is sometimes recommended in the treatment of metastatic endometrial stromal sarcoma, but there are few data assessing the efficacy of endocrine therapies in this subtype of uterine sarcomas.We performed a retrospective electronic medical record review of patients with metastatic ESS treated with a hormonal agent at Royal Marsden Hospital between 1999 and 2011. We assessed progression-free survival (PFS), objective response and toxicity profile among patients with measurable disease.Thirteen patients with metastatic ESS were treated with hormonal therapies. Hormone receptor status (estrogen and progesterone receptors) was assessed in 9 out of 13 patients and in all of them it was moderately to strongly positive. Aromatase inhibitors (AIs) were prescribed as first endocrine line in 11/13 patients and progestins in the remainder, while in 2(nd) line treatment AIs were prescribed in 7/10 patients, followed by progestins and GnRH analogues. Median PFS for 1(st)line was 4.0 years (95% CI: 2.4 - 5.5 years) with 5-year progression-free rate of 30.8% (95% CI: 5.7 - 55.9%), both of which reflect the indolent natural history of ESS. Best objective response was partial response (PR) in 6/13 patients (46.2%; 95% CI: 19.2 - 74.9) and clinical benefit rate (defined as complete response + PR + stable disease ≥6 months) was 92.4% (95% CI: 64.0 - 99.8%; 12/13 patients). Median PFS for 2(nd) line was 3.0 years (95% CI: 2.0 - 4.1 years) with 2-year progression-free rate of 88.9% (95% CI: 68.3 - 100.0).In this cohort of metastatic ESS patients, 1st line endocrine treatment achieved objective response in 46.2% of them and clinical benefit in 92.4%. Tamoxifen and hormone replacement therapy should not be prescribed in patients with ESS due to their detrimental effects. Until more solid data are available, a reasonable recommendation would be that 1(st) line treatment with an endocrine treatment, preferably with an AI. Moreover, in view of the positive outcomes of our patients that received 2(nd)/3(rd)line endocrine treatments, all available hormonal options should be used in sequence in the management of ESS.Keywords:
Endometrial stromal sarcoma
Hormonal Therapy
Progression-free survival
Abstract Purpose: We reported previously that ≥5 circulating tumor cells (CTC) in 7.5 mL blood at baseline and at first follow-up in 177 patients with metastatic breast cancer (MBC) were associated with poor clinical outcome. In this study, additional follow-up data and CTC levels at subsequent follow-up visits were evaluated. Experimental Design: CTCs were enumerated in 177 MBC patients before the initiation of a new course of therapy (baseline) and 3 to 5, 6 to 8, 9 to 14, and 15 to 20 weeks after the initiation of therapy. Progression-free survival (PFS) and overall survival (OS) times were calculated from the dates of each follow-up blood draw. Kaplan-Meier plots and survival analyses were done using a threshold of ≥5 CTCs/7.5 mL at each blood draw. Results: Median PFS times for patients with <5 CTC from each of the five blood draw time points were 7.0, 6.1, 5.6, 7.0, and 6.0 months, respectively. For patients with ≥5 CTC, median PFS from these same time points was significantly shorter: 2.7, 1.3, 1.4, 3.0, and 3.6 months, respectively. Median OS for patients with <5 CTC from the five blood draw time points was all >18.5 months. For patients with ≥5 CTC, median OS from these same time points was significantly shorter: 10.9, 6.3, 6.3, 6.6, and 6.7 months, respectively. Median PFS and OS times at baseline and up to 9 to 14 weeks after the initiation of therapy were statistically significantly different. Conclusions: Detection of elevated CTCs at any time during therapy is an accurate indication of subsequent rapid disease progression and mortality for MBC patients.
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BACKGROUND: Metastatic breast cancer (MBC) is an incurable disease. AIM: The goal of therapy is to prolong survival and amelioration of quality of life. However, the benefit of later systemic treatment lines is not clear. METHODS: This was a retrospective study of 345 MBC patient., assessment of progression free survival (PFS) survival with first line of treatment and second, third, fourth, fifth, and sixth lines of therapy, and analysis of different prognostic factors. RESULTS: The median overall survival (OS) was 31.7 month. The median PFS was 8.1 versus 3 month for first line of treatment and beyond. Where median PFS1, PFS 2, PFS 3, PFS 4, PFS 5, and PFS 6 were 8.1, 5.8, 3.8, 4.8, 3.4, and 2.6, respectively. PFS of first line was significantly prolonged in hormone positive luminal subtype, bone only metastasis, age above 35, ECOG I-II, and oligometastatic (p = 0.041, 0.038, 0.023, 0.034, 0.0001, and 0.001, respectively). Post-progression survival was 23.4 months and it was significantly prolonged in hormone positive luminal subtype, bone only metastasis, age above 35, ECOG I-II and PFS more than 6 months with first line. CONCLUSION: PFS is reduced with using more treatment lines in MBC. Patients with luminal subtype, bone only metastasis, age above 35, ECOG I-II, and PFS more than 6 months with first line may have the best benefit from later lines.
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Hormonal Therapy
Endometrial stromal sarcoma
Progestin
Hormone Therapy
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The objective of this study is to assess the therapeutic importance of surgical castration, adjuvant hormonal treatment and lymphadenectomy in endometrial stromal sarcoma (ESS). A retrospective and multicentric search was performed. Clinicopathologic data were retrieved from cases that were confirmed to be ESS after central pathology review. The protocol was approved by the Ethical Committee. ESS was confirmed histopathologically in 34 women, but follow-up data were available in only 31 women. Surgical treatment (n=31) included hysterectomy with or without bilateral salpingo-oophorectomy (BSO) in 23 out of 31 (74%) and 8 out of 31 (26%) cases, respectively. Debulking surgery was performed in 6 out of 31 cases (19%). Stage distribution was as follows: 22 stage I, 4 stage III and 5 stage IV. Women with stage I disease recurred in 4 out of 22 (18%) cases. Among stage I women undergoing hormonal treatment with or without BSO, 3 out of 15 (20%) and 1 out of 7 (14%) relapsed, respectively. Among stages III–IV women receiving adjuvant hormonal treatment or not, 1 out of 5 (20%) and 3 out of 4 (75%) relapsed, respectively (differences=55.0%, 95% CI=−6.8–81.2%). Kaplan–Meier curves show comparable recurrence rates for stage I disease without adjuvant hormonal treatment when compared to stages III–IV disease treated with surgery and adjuvant hormonal treatment. Furthermore, women taking hormones at diagnosis have a better outcome when compared to women not taking hormonal treatment. Three out of 31 (9%) patients had a systematic lymphadenectomy whereas 3 out of 31 (9%) had a lymph node sampling. In one case, obvious nodal disease was encountered at presentation. Isolated retroperitoneal recurrence occurred in 1 out of 31 (3%) of all cases and in 1 out of 8 (13%) recurrences. This single woman later also developed lung and abdominal metastases. Leaving lymph nodes in situ does not appear to alter the clinical outcome of ESS. Although numbers are low, the retrospective data suggest that the need for surgical castration (BSO) in premenopausal women with early-stage disease should be discussed with the patient on an individual basis. The data support the current practice in some centres to administer adjuvant hormonal treatment.
Lymphadenectomy
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Endometrial stromal sarcoma
Debulking
Oophorectomy
Adjuvant Therapy
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Endometrial stromal sarcoma
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HER2 negative
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Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), metastatic breast cancer (MBC) accounts for 73% of all MBCs. Endocrine therapy (ET) is the basis of first-line (1L) therapy for patients with HR+/HER2- MBC. Novel therapies have demonstrated improvements in progression-free survival (PFS) compared to ET. The clinical relevance of PFS is being debated, as there is no proven direct correlation with overall survival (OS) benefit to date. We reviewed studies of HR+/HER2- MBC to assess PFS and other factors that influence OS and treatment response, and health-related quality of life (HRQoL).
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Palbociclib
Letrozole
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Introduction: We surveyed the use of adjuvant hormonal therapy in patients with endometrial stromal sarcomas. Material and methods: A questionnaire was circulated among the 130 members of an Internet-based endometrial stromal sarcoma support group. The questions pertained to age at diagnosis, organs involved at diagnosis, recurrences, metastases, current disease status, and treatment protocols, with special focus on hormonal therapy. Results: The questionnaire was returned by 64 of 120 women (49%). At the time of the study 48 patients (mean follow-up 2.4 (range, 1-9) years) had no evidence of disease (NED) and 16 (mean follow-up 6.2 (range, 1-22) years) were alive with disease (AWD). Of the 16 women AWD, 15 (95%) were being treated with hormones as opposed to ten of 48 (21%) women with NED. Hormone treatment consisted of progestins (15 patients), aromatase inhibitors [9], aromatase inhibitor plus GnRH analog [I], or tamoxifen [1]. Discussion: Adjuvant hormonal therapy presently appears to be used predominantly in women with advanced or recurrent endometrial stromal sarcomas but is also a potential option for patients after surgery without residual tumor.
Endometrial stromal sarcoma
Hormonal Therapy
Adjuvant Therapy
Hormone Therapy
Aromatase inhibitor
Anastrozole
Estrogen therapy
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Purpose of review Low-grade endometrial stromal sarcomas are steroid receptor positive tumors with slow tumor progression and high recurrence rates, which lack established treatment protocols. We present an update on hormonal therapy options. Recent findings In the past, hormonal therapy consisted of progestins for advanced/recurrent/metastatic low-grade endometrial stromal sarcomas. Aromatase inhibitors and gonadotropin-releasing hormone analogues have become new effective alternatives for first and second line treatment. The high recurrence rates after short disease free intervals in low-grade endometrial stromal sarcoma patients were partly due to inadvertent growth stimulation during estrogen-containing hormone replacement therapy and tamoxifen treatment, which – according to current knowledge – are contraindicated. Recently, hormonal therapy has been introduced for the prevention of recurrences. Aromatase inhibitors are becoming the treatment of choice, since progestins are poorly tolerated due to side effects. The effective duration of preventive hormonal therapy is still undetermined. Summary Hormonal therapy with progestins, aromatase inhibitors and gonadotropin-releasing hormone analogues has become an effective treatment alternative to radiation and chemotherapy for low-grade endometrial stromal sarcoma patients. Preventive hormonal therapy is of particular interest in the setting of concomitant endometriosis.
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