Gary K. Schwartz, MD – Soft Tissue Sarcoma

Question

What are the key factors that indicate a patient with soft tissue sarcoma (STS) is a good candidate for surgery?

Answer

Other than good physical condition, the major factor is resectability of the mass. The goal is to achieve an R0 resection (negative margins). In fact, for sarcomas, this is the only curative option. If disease is left behind with even microscopic positive margins, the surgery in noncurative. In addition, for lesions with positive margins, especially with sarcomas of the extremity, when possible we recommend re-resection to ensure that the margin is negative.

Question

What factors indicate that a patient is not a good candidate for radiation or surgery?

Answer

Poor physical condition, which is true of any surgery. Large tumors or tumors in hard-to-reach places, which are also difficult to excise. Any surgery in which the tumor is too big or in bad location that will result in a positive margin after resection.

There are no real contraindications for radiation. But radiation only diminishes the risk of local failure after surgical resection especially of extremity sarcoma. At times it is used to control the growth of sarcoma as form of palliation. It does not impact distant metastases, which are the cause of sarcoma death. It can also be used preoperatively to try and shrink large tumors to make them more resectable.

Question

What chemotherapeutic options are available to patients with sarcoma? What factors do you consider when recommending chemotherapy to patients?

Answer

With very compelling survival data, chemotherapy should be considered for all patients with locally advanced or metastatic sarcoma. The only exception would be the very sick or the patient with underlying organ dysfunction for whom specific chemotherapies may be contraindicated. The standard of care in the United States for the treatment of metastatic sarcoma is doxorubicin and olaratumab. Olaratumab, also called Latruvo, is an inhibitor of PDGFRa. This is the first doxorubicin-based chemotherapy combination to show a prolongation in survival in sarcoma. In fact, the improvement in survival exceeds anything preciously reported for sarcoma therapy. This effect was independent of sarcoma subtype. The results of a confirmatory phase 3 trial are pending. Some oncologists still prefer to use a more aggressive chemotherapy regimen called AIM, which combines ifosphamide and mesna with doxorubicin. However, now at least 2 large randomized trials have shown no survival benefit when compared to doxorubicin alone. In the absence of a survival benefit and with the superiority of doxorubicin and olaratumab there is generally very little reason to use AIM which has considerable toxicity. The only exception would be the situation where one is trying to reduce the size of a primary sarcoma in the non-metastatic setting to make it more resectable. When compared to doxorubicin alone, AIM has been shown to have a higher response rate and may increase the chance for resectability for those large and difficult-to-resect sarcomas. However, in view of the toxicity of AIM, this should only be done in otherwise fit patients with good performance status. Second-line therapy includes a combination of gemcitabine and docetaxel. This too has been shown to prolong survival when compared with gemcitabine alone but only for patients with ECOG 0 status as the combination can have toxicity. Other considerations include trabectedin for leiomyosarccoma, erubulin for liposarcoma, and pazopanib, the oral receptor tyrosine kinase inhibitor for all sarcomas other than liposarcoma. Of course, clinical trials should always be a consideration and patients should be encouraged to participate. This will be essential in order to advance the field.

There are other new agents that are showing promising and there is great hope for immunotherapy. So, in many ways, chemotherapy is an absolutely critical part of the treatment regimen for patients with sarcoma at all stages of their disease.

Question

What are the side effects that most frequently occur when patients are being treated for soft tissue sarcoma? How do you counsel patients and manage these side effects?

Answer

The side effects can be quite varied ranging from nausea to effects on the white blood counts (WBCs). But all of these are manageable with new antinausea drugs and drugs that stimulate the WBCs to fight infection. There really is no side effect that cannot be managed today with the right medications.

For surgery, there can be postoperative complications such as fluid collections or even bowel blockage, which is not dissimilar to any major surgery. For radiation therapy there can be burns to the skin, but these can be managed by topical creams and ointments.

Question

Are there any new or upcoming data that you are excited about for the treatment of patients with soft tissue sarcoma?

Answer

We are learning a lot about receptors on the surface of the sarcoma cell which may be amenable to new targeted therapy. Probably the greatest advances will come about by an increased understanding of the tumor microenvironment, which is the matrix around the tumor cells (rather than the tumor cells themselves). We are learning a lot about how the tumor microenvironment nourishes the sarcoma cell. There are also cells in the tumor microenvironment (ie, macrophages) that support the growth the tumor cells themselves. An understanding of these processes and how to modify them will have a great impact on future cancer therapies.

In addition, there is great interest in immunotherapy. The preliminary results in this area for sarcoma do not look as promising as those observed in other cancers such as melanoma or lung cancer. However, there may be some exceptions such as the very “inflamed” sarcoma called undifferentiated pleomorphic sarcoma that tends to respond to immunotherapy. There is also excitement about the development of cancer vaccines against particular sarcomas such as synovial cell sarcoma, which overexpress specific proteins that appear druggable with a cancer vaccine approach.

Question

Are there any other points that you think are important to make for oncologists who are treating patients with soft tissue sarcoma?

Answer

Sarcoma is not one disease. In fact, it is 60 different types of cancer and therapy must be tailored to the very specific sarcoma subtype. Some of these subtypes have no more than 100 patients in the United States. For this reason, it is important that a patient diagnosed with a sarcoma see a sarcoma specialist who has an understanding of this whole host of diseases and can personalize the therapy according to the patients’ specific sarcoma sub-type.

Furthermore, despite frustrations in the past, new treatment regimens are coming and a better understanding of the tumor microenvironment should help propel research in this area over the next decade.