Treatment of Sarcoma

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Soft Tissue Sarcoma Treatment

The soft tissue sarcoma treatment usually depends on many factors, including but not limited to the type of sarcoma, stage of disease, the location of the disease, performance status, patient’s preference, along with other factors. Following are the preferred treatment approaches for different stages of soft tissue sarcoma, but the final decision is taken after clinical assessment of the patient by an oncologist.

Stage I

Stage I STSs are low-grade tumors of any size. If possible, surgical resection with negative margins is considered as the standard treatment. In a case when negative margins were not obtained, further surgical resection to remove all cancerous tissue is the preferred approach. If further surgery is not possible, radiotherapy may be employed to decrease the chances of disease recurrence.

If the tumor is present at such a location (e.g. retroperitoneum, trunk, and head and neck,) that it cannot be entirely removed without functional disability, radiotherapy may be employed as the first-line treatment. This may cause the tumor to shrink sufficiently that it can be removed surgically.

Stage II or III

Most Stage II- and III STSs are high-grade tumors that tend to spread quickly and some of them have already spread to nearby lymph nodes. If possible (without any significant functional disability), surgical resection with negative margins is considered as the standard treatment. Any lymph node with the sign of disease spread should also be removed. Radiotherapy with/without chemotherapy may be considered after complete removal of the tumor.

If tumor is too large or present at such a location (e.g. retroperitoneum, trunk, and head and neck,) that it cannot be entirely removed without functional disability, or if surgery is not possible due to overall health of the patient, radiotherapy with or without chemotherapy may be employed as the first-line treatment.

This may cause the tumor to shrink sufficiently that it can be removed with surgery. Further treatment, such as more radiotherapy/chemotherapy and/or supportive care or any other treatment may be provided based on the response to initial treatment.

Stage IV

Stage IV STSs are cancers that have spread to a distant body parts.

For patients with a single site of disease spread and a small primary tumor that can be entirely removed with surgery, a surgical resection with the negative surgical margins for the primary tumor and the distant site is considered as the preferred treatment. As appropriate, tumor ablation, embolization, or radiotherapy may be employed instead of surgical resection for the secondary tumors.

For patients with a widespread disease or when the primary and secondary tumors cannot be removed by surgery, chemotherapy is usually employed. Any other suitable treatment may be employed as palliative treatment.

Targeted Therapy for Sarcoma

Targeted drugs works differently than chemotherapy drugs that they target a specific gene or protein characteristic of the cancer cells that help them to divide and grow indefinitely.

Tyrosine Kinase Inhibitors

Sorafenib

sorafenib Sorafenib is a kinase inhibitor that is active against a variety of kinases including KIT, VEGFR-1–3, and PGDFR beta.

It has shown clinical benefit for the treatment of patients with unresectable, KIT-positive GISTs who have received prior treatment with imatinib and sunitinib.

It is also used in patients with solitary fibrous tumor, advanced epithelioid hemangioendothelioma, desmoid tumors (aggressive fibromatosis), angiosarcoma, and solitary fibrous tumor (Hemangiopericytoma).

Pazopanib

pazopanib Pazopanib is a multitargeted TKI that inhibit several kinases including VEGFR-1–3, PDGFR alpha and beta, KIT and others. It has been approved for the treatment of advanced soft tissue sarcomas other than adipocytic tumors and GISTs that have not responded to chemotherapy.

Nilotinib

Some clinical studies have reported that nilotinib can confer clinical benefit in patients with unresectable, KIT-positive GIST who have received imatinib and sunitinib and progressed on these drugs, especially with KIT exon 17 mutations and not with KIT exon 9 mutation.

Dasatinib

Dasatinib is another kinase inhibitor that has demonstrated activity against PDGFRA D842V mutation that is commonly involved in the development of resistance to imatinib treatment. Thus, it could be a potentially effective treatment option for patients with imatinib-resistant GIST.

mTOR Inhibitors

Perivascular epithelioid cell tumors (PEComas) are mostly benign but can be malignant or aggressive, such as in the case of advanced-sage or recurrent lymphangioleiomyomatosis or angiomyolipomas.

In most cases, PEComa tumors show dysregulated mammalian target of rapamycin (mTOR) signaling due to a mutation in the TSC1 or TSC2 genes leading to the tumor development and progression.

The mutation in the indicated genes may be inherited or sporadic. Targeted drugs directed towards mTOR, for example, sirolimus, temsirolimus, and everolimus have shown benefit in the treatment of advanced-stage PEComas. Sirolimus has been approved by US FDA for treatment of patients with pulmonary lymphangioleiomyomatosis.

Monoclonal Antibodies

Following are the 2 monoclonal antibodies which are currently recommended for the treatment of STSs:

Olaratumab

Olaratumab is a novel monoclonal antibody that binds to and inhibits PDGFR alpha. The activation of PDGFR alpha is thought to drive tumorigenesis and disease progression in STSs.

Olaratumab, in combination with doxorubicin (a chemotherapeutic drug), has been approved for the treatment of patients with untreated, unresectable, or metastatic STS. Interestingly, the reported clinical benefit was consistent among all patients including those with the presence or absence of PDGFR alpha expression.

Side effects of combined treatment (olaratumab + doxorubicin) include infusion reactions, fatigue, nausea, musculoskeletal pain, hair loss, vomiting, diarrhea, decreased appetite, abdominal pain, neuropathy, and headache.

Bevacizumab

Bevacizumab Bevacizumab is a monoclonal antibody that binds to vascular endothelial growth factor (VEGF) and inhibits its interaction with VEGFR.

The drug has shown clinical benefit as single agent treatment for patients with highly vascular tumors, such as angiosarcoma and solitary fibrous tumor (hemangiopericytoma), or in combination with temozolomide (a chemotherapeutic drug) in patients with malignant SFT.

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