Shreyaskumar R. Patel, MD: Leiomyosarcoma Differing From Those Arising at Other Sites

How does this patient’s leiomyosarcoma (IVC) differ from those arising at other sites (eg; GI tract)?

It is important to understand that this is a very heterogeneous group of diseases. In the subset of patients with smooth muscle tumors, you have benign tumors like leiomyoma and you have tumors that look benign but have metastatic potential, which are called metastasizing leiomyoma. Then there are tumors that do not have malignant characteristics but behave in a malignant fashion, which are called smooth muscle tumors of uncertain malignant potential. You also have leiomyosarcoma. Even before we get into the term leiomyosarcoma, it is important to recognize that this is a very heterogeneous group of tumors.

Within leiomyosarcomas, the site of origin does make a difference in terms of biologies, clinical behavior, and even their therapeutic sensitivity to different drugs. The common one arising in the uterus of the gynecologic tract of a young woman would be the more sensitive tumors to chemotherapy. You then have tumors arising from vascular structures like the one in this case, which you then have to differentiate from the ones arising in the GI tract. Tumors arising in GI tract have been renamed as GI stromal tumors. We know what the activiating mutations are, we know what drives those tumors to grow, and the therapeutic implications are therefore different.

CASE: Soft-Tissue Sarcoma (Part 1)

Rachel F is a 58-year-old school teacher from Roanoke, Virginia. Her medical history is notable for mild hypertension and total knee replacement in 2011

• In March of 2013, she presented to her PCP with abdominal fullness and distension of several months’ duration; physical exam showed mild abdominal discomfort on palpation; she denied any recent weight loss
• Initial abdominal sonography was inconclusive; subsequent CT scan showed a heterogeneously enhancing retroperitoneal mass along segment I of the inferior vena cava (IVC) and central necrosis
• She underwent contrast-enhanced CT with coronal and sagittal reconstructions, which showed encasement of the aorta and multiple hepatic metastases
• CT guided biopsy of the mass showed leiomyosarcoma that was immunohistochemically positive for desmin, smooth muscle actin, and vimentin, with a high proliferative rate (Ki67 > 60%)
• She underwent chemotherapy with gemcitabine and docetaxel for a total of 6 cycles, and experienced a minor response. Therapy was discontinued however, in November 2013 due to cumulative toxicity

Follow-up CT scan in January 2014 showed progression at multiple sites; at the time of follow up, her ECOG performance status was 1, with renal and hepatic function within normal limits

• She underwent six cycles of chemotherapy with anthracycline and dacarbazine, and her disease stabilized

In September of 2014 she returns for follow-up, unable to work with increasing fatigue and abdominal pain, and her CT scan was consistent with progressive disease

• She received treatment with pazopanib at 800 mg daily for metastatic disease
• Patient tolerated the treatment well, with mild fatigue and diarrhea, and her symptoms improved

After 4 months of therapy, she presents with worsening abdominal pain and declining performance status

• CT showed extensive progression of the primary tumor and hepatic metastases
• At progression, CBC, liver, and renal function were within normal limits, ECOG performance status was 2