External validation of a prognostic nomogram for overall survival in women with uterine leiomyosarcoma

Abstract

Background There is no validated system to identify prognostically distinct cohorts of women with uterine leiomyosarcoma (ULMS). Using an independent, pooled, multi-institutional, international patient cohort, we validated a recently proposed ULMS nomogram. Methods The ULMS nomogram incorporates 7 clinical characteristics (age, size, grade, cervical involvement, locoregional metastases, distant metastases, and mitotic index (per 10 HPF) to predict overall survival (OS) following primary surgery. Independent cohorts from two sarcoma centers were included. Eligible women underwent at minimum a hysterectomy for primary, locally advanced, or metastatic ULMS and received part of their care at one of the centers between 1994 and 2010. Results We identified 187 women with ULMS who met the above criteria (median age, 51 years; median tumor size, 9 cm; median mitotic index, 20). Tumors were generally high grade (88%), FIGO stage I-II (61%) without cervical involvement (93%) and without locoregional (77%) or distant metastases (83%). Median OS and the 5-year OS rate were 4.5 years (95% CI 3.2–5.3) and 46%, respectively; 65 women (35%) were alive at last follow-up. The nomogram concordance index was 0.67(SE=0.02), which was as high as the concordance index from the initial cohort used for nomogram development. The concordance between actual OS and nomogram predictions suggests excellent calibration since predictions were within 1% of actual 5-year OS rates for patients with a predicted 5-year OS of less than 0.68. Conclusions The ULMS nomogram was externally validated using independent cohorts. These findings support the international use of the ULMS nomogram prognostic of OS in ULMS.

Does Lymphadenectomy Improve Survival in Uterine Leiomyosarcoma?

“…Also, another report of 187 patients with uterine LMS validated this prognostic model. 29 In our study, although stage and mitotic count were significantly associated with OS in univariate model (P G 0.001 and P = 0.001, respectively), they were correlated factors in multivarate regression analysis. In the presented study, significant prognostic factors for DFS were stage, grade, and mitotic count, and they were stage and mitotic count for OS in univariate analyses.…”

Practical issues in uterine pathology from banal to bewildering: the remarkable spectrum of smooth muscle neoplasia

“…A third system has been developed focusing on patient 5-year outcome based on specific parameters that include age at diagnosis, tumor size, histologic grade, mitotic index, cervical involvement, extrauterine spread, and distant metastases, 8,9 which appears to have been validated using external cohorts. 10 As immunohistochemistry (mostly p16 and p53), and molecular tools including MED12 mutations have currently a very limited role in the classification of smooth muscle tumors as benign or malignant, morphologic examination remains the cornerstone in the diagnosis of these tumors. 11 Uterine leiomyosarcoma, the most frequent uterine sarcoma, is seen as a large solitary mass (average 10 cm) or within a "fibroid" uterus.…”

A phase 2 study of alisertib (MLN8237) in recurrent or persistent uterine leiomyosarcoma: An NRG Oncology/Gynecologic Oncology Group study 0231D

“…1 Although patients are often diagnosed with FIGO stage 1 (uterine confined) disease, recurrence rates are estimated to be between 50-70%. 2,3 To date, the mainstay of treatment for patients who develop unresectable metastatic disease is cytotoxic chemotherapy with response rates to first-line multidrug chemotherapy ranging from 27-53%. 4-9 The efficacy of second-line chemotherapy drops significantly with most regimens offering response rates of 10-15%.…”