l ong term outcomes of patients with leiomyosarcoma of uterine vs. extra - uterine origin srikanth...
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LONG TERM OUTCOMES OF PATIENTS WITH LEIOMYOSARCOMA OF UTERINE VS. EXTRA-UTERINE ORIGIN
Srikanth Divi, Medical Student, Univ. of Pittsburgh
Meghan Levy, Kurt Weiss MD, Mark Goodman MD, Richard McGough MD
BACKGROUND OF LEIOMYOSARCOMA (LMS)
Approximately 10,000 soft tissue sarcomas are diagnosed in the US annually1
LMS composes up to 10% (1000 cases) and is the third most frequent sarcoma after pleomorphic sarcoma NOS and liposarcoma2
Classification: visceral
gastrointestinal, separate from GIST uterine
somatic peripheral soft tissues (cutaneous, deep soft tissue) retroperitoneal (50%)
vascular bone (rare)
About 2/3 of retroperitoneal LMS occur in women, median age 60 y
Presenting symptoms nonspecific: abdominal mass, swelling, pain, weight loss, nausea, or vomiting
Presenting size often large (mean size and weight: 16 cm, 1600g)
In contrast, tumors of the extremities affect men and women equally
Significantly smaller (6 cm) than retroperitoneal tumors
BACKGROUND OF LEIOMYOSARCOMA (LMS)
Leiomyomas not necessarily associated with malignant transformation to LMS
Observation that significant number of tumors arise from small blood vessels
LMS also seen in the setting of hereditary retinoblastoma (abnormal Rb1 locus)
BACKGROUND OF LEIOMYOSARCOMA (LMS)
PROGNOSIS OF PATIENTS WITH SOMATIC SOFT TISSUE (SST) LMS
Farshid et al., 42 patients3 (2002) 8% developed local recurrence, 45% developed
mets Age > 62, size > 4cm, extensive necrosis correlated
with metastasis Conclusion: majority are of vascular origin (39/42
pts), disruption of tumor w/ biopsy is significant RF
Mankin et al., 66 patients4 (2004) 50% survival at 4.2 years, 62% developed mets Tumors with greater size (>500 cm3) had 82%
mortality rate Conclusion: presence of mets, size of tumor, MSTS
stage effect on survival outcomes
PROGNOSIS OF PATIENTS WITH SOMATIC LMS
Scandinavian Sarcoma Group, 225 pts (2006)5
10 year survival rate (with localized disease): 49%
Higher grade, larger tumor size, deeper location all significantly correlated with decreased survival
Overall prognosis is poor even with local control (w/ or w/o radiotherapy)
Abraham et al. 115 pts (2012)1
1, 5, and 10 year survival: 87%, 57%, 19% Histological grade, tumor depth, and mets
significant predictors of mortality
PROGNOSIS OF PATIENTS WITH SOMATIC LMS
Radkowski et al., 65 pts – 20125
Overall 1, 2, and 5 year survival: 91%, 87%, and 68%
Pts with deep lesions, grade 3 disease, and advanced stage have poorer prognosis
UTERINE LMS Uterine LMS is rare, it accounts for only 1% of all
uterine cancers6, however it represents up to 1/3 of all uterine sarcomas
30-35% of patients have evidence of extra-uterine disease at the time of presentation
5 year survival for metastatic disease is less than 40% with current therapies
Median age: 50 years, about 10 years older than the median age of presentation for leiomyoma7
Frequency of incidental LMS detected in women at various ages having surgery for presumed leiomyoma: 31-40 y: 0.2% 41-50 y: 0.9% 51-60 y: 1.4% 61-81 y: 1.7%
MOTIVATION FOR STUDY
Does extra-uterine LMS have the same prognosis as uterine LMS?
Some patients with extra-uterine LMS had hysterectomies in the past Difference in outcomes between those with and
those without hysterectomies?
Two distinct disease entities (uterine LMS and extra-uterine LMS) may actually overlap, with patients presenting decades later with recurrences of uterine LMS.
HYPOTHESIS
Patients with uterine LMS have decreased survival compared to extra-uterine LMS
Of patients with extra-uterine LMS, those with prior hysterectomies have decreased survival
METHODS
Searched using MARS (Medical Archive Record System) in UPMC system from 1982-present Surgical pathology reports with designated
search terms Retrieved lists were filtered for correct diagnoses
Diagnosis of extra-uterine LMS 513 cases of extra-uterine LMS Included tumors from: GI, cutaneous, peripheral
soft tissue, retroperitoneal, vascular, etc. Diagnosis of uterine LMS
127 patients
METHODS
Patient characteristics identified: age at diagnosis tumor characteristics (size, # mitoses, %
necrosis, grade, FIGO stage) metastases
Survival data collected from: UPMC patient charts (inpatient and outpatient
visits) National and municipal registries
Censored survival data used to construct Kaplan Meier curves
RESULTS
Uterine
LMS Extra-uterine
LMS
Sample Size 127 513
Median Survival 4.97 4.28
5 yr 49.4% 46.7%
10 yr 31.5% 27.3%
15 yr 24.5% 20.0%
25 yr 18.4% 11.8%
Hazard Ratio: 1.042 [0.815, 1.333]
Logrank Test: χ2= 0.1074, p = 0.7431
RESULTS
RESULTS – ANALYSIS OF PATIENTS WITH EXTRA-UTERINE LMS
Of the 513 patients with extra-uterine LMS: 269 were females 177 with no documentation of hysterectomies 75 found to have hysterectomies prior to dx of
LMS 17 had hysterectomies after dx of LMS
75/269 = 27.9% of females with hysterectomies prior to dx of LMS
Differences in survival?
RESULTS – ANALYSIS OF PATIENTS WITH EXTRA-UTERINE LMS
Median Survival Time
Median
Estimate Std. Error
95% Confidence Interval
Lower Bound
Upper Bound
No hyst. 4.250 .713 2.852 5.648
Prior Hyst. 6.420 1.091 4.281 8.559
Overall 5.060 .696 3.696 6.424
Overall Comparisons
Chi-Square df Sig.
Log Rank (Mantel-Cox)
3.029 1 .082
DISCUSSION
Uterine vs. extra-uterine LMS has similar long term outcomes, not statistically significant Median survival: 4.97 y vs. 4.28 y HR 1.042, p = 0.74
Among extra-uterine LMS, those with prior hysterectomies had a longer survival time, not statistically significant Median: 6.42 y vs. 4.25 y p = 0.084
LIMITATIONS
Population heterogeneity
Does not stratify for commonly used clinical parameters: Margin status XRT Chemotherapy Other treatments
CONCLUSION
Retrospective review of 640 cases of LMS Uterine Extra-uterine
No difference in long term survival outcomes
Future directions: Evaluate contribution of clinical parameters Outcomes of patients with somatic soft tissue
LMS
REFERENCES Abraham et al. Outcomes and prognostic factors for a
consecutive case series of 115 patients with somatic leiomyosarcoma. J Bone Joint Surg Am. 2012 Apr 18; 94(8): 736-44
O’Sullivan et al. Radiological imaging features of non-uterine leiomyosarcoma. Br J Radiol. 2008 Jan; 81(961): 73-81
Farshid et al. Leiomyosarcoma of Somatic Soft Tissues. Am J Surg Pathol. 2002. 26(1): 14–24.
Mankin et al. Leiomyosarcoma of Somatic Soft Tissues. Clin Orthop Relat Res. 2004 Apr ; (421): 225-31
Radkowski et al. Leiomyosarcoma of the somatic soft tissues. J Surg Orthop Adv. 2012. 21(2): 96-101
Leitao et al. Surgical cytoreduction in patients with metastatic uterine leiomyosarcoma at the time of initial diagnosis. Gynecol Oncol. 2012 May. 125(2): 409-413
ACKNOWLEDGMENTS
Meghan Levy
Alma Heyl – Clinical Research Coordinator
Kurt Weiss, MD and Mark Goodman, MD
Richard McGough, MD – Project Mentor
THANK YOU