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