Limitations of adjuvant radiotherapy for uterine sarcomas spread beyond the uterus

Dusenbery, Kathryn E.; Potish, Roger A.; Judson, Patricia L.

doi:10.1016/j.ygyno.2004.04.001

Cited by 35 publications

(34 citation statements)

References 29 publications

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“…17,18,19,20,21,22,23,24,25,26,27 Those that have involved postoperative pelvic EBRT have shown a consistent decrease in pelvic failures but no significant impact on overall patient survival. 17,19,20,21,22,23,24,27 However, two retrospective studies did claim an OS benefit with the addition of adjuvant pelvic irradiation for patients with surgical stage I and II disease. 25,26 When comparing the patterns of failure between WAI and CIM in GOG-150 for stages I/II/ III/IV, only vaginal recurrences appeared to be increased in the chemotherapy cohort versus the radiotherapy cohort.…”

Section: Discussionmentioning

confidence: 99%

A gynecologic oncology group randomized phase III trial of whole abdominal irradiation (WAI) vs. cisplatin-ifosfamide and mesna (CIM) as post-surgical therapy in stage I–IV carcinosarcoma (CS) of the uterus☆

Wolfson

Brady

Rocereto

et al. 2007

Gynecologic Oncology

243

154

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PURPOSE-After initial surgery, there has been no established consensus regarding adjunctive therapy for patients with uterine carcinosarcoma (CS). This study was designed to compare patient outcome following treatment with adjuvant whole abdominal irradiation (WAI) versus (vs) chemotherapy for patients with this rare group of female pelvic malignancies.PATIENTS AND METHODS-Eligible, consenting women with stage I-IV uterine CS, no more than 1 cm postsurgical residuum and/or no extra-abdominal spread had their treatments randomly assigned as either WAI or three cycles of cisplatin (C), ifosfamide (I), and mesna (M).RESULTS-232 patients were enrolled, of whom 206 (WAI=105; CIM=101) were deemed eligible. Patient demographics and characteristics were similar between arms. FIGO stage (both arms) was: I=64 (31%); II=26 (13%); III=92 (45%); IV=24 (12%). The estimated crude probability of recurring within 5 years was 58% (WAI) and 52% (CIM). Adjusting for stage and age, the recurrence rate was Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. CONCLUSION-We did not find a statistically significant advantage in recurrence rate or survival for adjuvant CIM over WAI in patients with uterine CS. However, the observed differences favor the use of combination chemotherapy in future trials. NIH Public Access

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Section: Discussionmentioning

confidence: 99%

A gynecologic oncology group randomized phase III trial of whole abdominal irradiation (WAI) vs. cisplatin-ifosfamide and mesna (CIM) as post-surgical therapy in stage I–IV carcinosarcoma (CS) of the uterus☆

Wolfson

Brady

Rocereto

et al. 2007

Gynecologic Oncology

243

154

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“…Eighty-one percent of women with stage III tumors will have tumor recurrence, and only 8% of women with stages II to IV tumors will survive 5 years (2,3). As uterine leiomyosarcoma is resistant to chemotherapy and radiotherapy (4,5), developing an efficient adjuvant therapy is expected to improve the prognosis of the disease.…”

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confidence: 99%

Oncogenic Property of Acrogranin in Human Uterine Leiomyosarcoma: Direct Evidence of Genetic Contribution in In vivo Tumorigenesis

Matsumura

Mandai

Miyanishi

et al. 2006

Clinical Cancer Research

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To identify potential oncogenes that contribute to the development of uterine leiomyosarcoma, we conducted a cDNA microarray analysis between normal uterine smooth muscle and uterine leiomyosarcoma. We found that acrogranin (also named PCDGF or progranulin) is overexpressed in uterine leiomyosarcoma. With immunohistochemical staining of 12 leiomyosarcoma cases, we verified acrogranin expression in tumor cells. Furthermore, the intensity of acrogranin expression correlated with high histologic grade and poor prognosis. To directly analyze the oncogenic properties of acrogranin, we established an immortalized uterine smooth muscle cell line by transfection of human telomerase reverse transcriptase into primary culture. This cell line retained the original characteristics of uterine smooth muscle cells, including spindle-shaped extension as well as expression of vimentin, estrogen receptor a, progesterone receptor, and a smooth muscle actin. Transfection of acrogranin into the immortalized uterine smooth muscle cells resulted in colony formation in soft agar, but the diameter of the colonies did not exceed 100 Am. Transfection of both acrogranin and SV40 early region (SV40ER) into the immortalized uterine smooth muscle cells resulted in an increased number of colonies and increased colony size in soft agar versus transfection of SV40ER alone. We show that only immortalized uterine smooth muscle cells expressing both acrogranin and SV40ER are capable of tumor formation in nude mice. Thus, acrogranin is overexpressed in uterine leiomyosarcoma cells, particularly in high-grade cases, and forced expression of acrogranin in immortalized uterine smooth muscle cells contributes to malignant transformation, which suggest that acrogranin plays an important role in the pathogenesis of uterine leiomyosarcoma.

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“…This combination produced a 27.8% RR, but its complexity and toxicity precluded further investigation, and the study was closed after the first stage of accrual (65). At present, surgical intervention is virtually the only means of treatment for this disease (6,66,67). Although adjuvant pelvic irradiation appears to reduce the rate of local recurrence, adjuvant therapy does not appear to significantly improve survival.…”

Section: Future Directionsmentioning

confidence: 99%

“…Since uterine LMS is resistant to chemotherapy and radiotherapy and surgical intervention is virtually the only means of treatment, the development of an efficient adjuvant therapy is expected to improve the prognosis of this disease (7)(8)(9). Matrix metallo-proteinases (MMPs), which degrade components of the extracellular matrix, appear to participate in tumour invasion and metastasis, and a trend towards prolonged disease-free survival has been seen in patients with MMP2-negative tumours (10,11).…”

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confidence: 99%

Molecular Pathology and Novel Clinical Therapy for Uterine Leiomyosarcoma

Hayashi

Kawano

Ichimura

et al. 2016

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Abstract. Patients with uterine leiomyosarcoma (LMS)typicallyUterine mesenchymal tumours have been traditionally divided into benign leiomyomas (LMA) and malignant leiomyosarcomas (LMS), based on cytological atypia, mitotic activity, and other criteria. Globally, uterine LMSs, which are some of the most common neoplasms in the female genital tract, are relatively rare mesenchymal tumours, having an estimated annual incidence of approximately one per 160,000 women (1). They account for approximately one-third of uterine sarcomas and 1.3% of all uterine malignancies, and are considered aggressive malignancies, with a 5-year survival rate of only 50% for patients with tumours confined to the uterus (2, 3). It is noteworthy that when adjusting for 4997 This article is freely accessible online.

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Limitations of adjuvant radiotherapy for uterine sarcomas spread beyond the uterus

Cited by 35 publications

References 29 publications

A gynecologic oncology group randomized phase III trial of whole abdominal irradiation (WAI) vs. cisplatin-ifosfamide and mesna (CIM) as post-surgical therapy in stage I–IV carcinosarcoma (CS) of the uterus☆

A gynecologic oncology group randomized phase III trial of whole abdominal irradiation (WAI) vs. cisplatin-ifosfamide and mesna (CIM) as post-surgical therapy in stage I–IV carcinosarcoma (CS) of the uterus☆

Oncogenic Property of Acrogranin in Human Uterine Leiomyosarcoma: Direct Evidence of Genetic Contribution in In vivo Tumorigenesis

Molecular Pathology and Novel Clinical Therapy for Uterine Leiomyosarcoma

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