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Sarcoma – 3 – GIST, Kaposi

Sarcoma PART – 3
(All the articles published in past are available at
Question: Thank you Chiragbhai for explaining important points related to Sarcoma – tumors of connective tissue. Mainly 1. Sarcoma includes about 100 histology types. Treatment and prognosis however depend more on size, grade, site. 2. Few specific histology types dictate treatment however e.g. osteosarcoma, GIST…3. SOFT TISSUE Sarcomas are treated primarily by surgery. Tumors over 5 cm generally need postoperative radiotherapy. Preoperative radiotherapy is also used in case of very large tumors or to facilitate limb preservation. 4. Metastatic disease patients, especially with low volume, asymptomatic disease can be observed without active treatment. 5. Chemotherapy options have increased, and with better tolerability. Efficacy however remain about the same. 6. Some specific subtypes have remarkable improvement with new options however e.g. GIST.
Can you comment more about the major specific subtypes of sarcoma?
Ans: Certainly. Let us start with GIST – gastrointestinal stromal sarcoma. This is a classic example of how knowledge of pathophysiology, especially at molecular/genetic level can help decide treatment. GIST is a sarcoma, arising most commonly in stomach, occasionally other sites like intestine. An uncommon tumor, with surgery as the mainstay of treatment. Interestingly, this is one of the rare tumors where repeated surgery for debulking of major disease, especially if symptomatic, has a role. That means even in state 4 disease with metastases where almost all other cancers are NOT treated with surgery, GIST can be operated. This is feasible due to its unique biology. However for those who are inoperable, medically unfit or not willing, or have already undergone multiple surgeries, systemic treatment is required. Chemotherapy has traditionally been very poor in terms of efficacy for GIST.
In 2001, Imatinib was approved for CML, Chronic Myeloid Leukemia, a type of blood cancer. This drug Imatinib interestingly blocks KIT mutation, found in GIST as well. Based on this knowledge of tumor biology, Imatinib was tried in patients with GIST in 2002. And very surprisingly, a drug approved for blood cancer, actually worked in a sarcoma, and that too very well. Larger trials were done, and drug was officially approved in GIST. Imatinib increased median survival of metastatic disease with GIST, from median of about 15 months to 60 months i.e. by about 40 months, a rare achievement in oncology field, more so for stage 4 disease. And now it is the drug of choice for these patients. It is also very well tolerated.
Not only for metastatic disease, it is also approved for postoperative use based on large trials. For patients with high risk tumors (defined based on size and mitotic index), imatinib is given for 36 months postoperatively. Use for 36 months has shown improvement in relapse free survival as well as overall survival. Clinical trials for longer use are ongoing, due to late relapses seen after stopping drug, at the end of 36 months in some cases.
Since then, more targeted therapies are available to treat GIST. After progression from imatinib, approved options include Sunitinib, and more recently Regorafenib. Guidelines also include other options, with limited data however, sorafenib, nilotinib, dasatinib. Newer options like immunotherapy are also being studied, with Nivolumab showing early efficacy.
¬Que: This is amazing! Who would have thought of a blood cancer drug working in a rare Sarcoma! And that too with fantastic results. True impact of molecular pathology. What next?
Ans: One other typical sarcoma is Kaposi sarcoma. It is due to HHV-8 virus infection. It is seen in both non HIV and HIV patients. This diagnosis became very prominent due to widespread HIV infection, however the incidence and mortality has significantly reduced after introduction of active antiretroviral therapy (HAART). During my training days, this was a common diagnosis, with not so good outcome in HIV positive patients.
In non HIV patients, known as Classical Kaposi sarcoma, it is generally localized disease and is very slow growing. Most patients can be observed without any specific therapy for a long time. Patients with significant symptoms are treated with various local options, including but not limited to various topical applications, radiotherapy… Same applies to HIV patients with limited disease. They are more likely to develop widespread disease however. If they are not on HAART, it should be initiated first. Immune reconstitution following this therapy may control disease and obviate need for immediate therapy. For those with significant systemic disease requiring treatment, liposomal doxorubicin has been the treatment of choice since late ’90s. Taxanes are also highly effective, however.

August 14th 2019. Dr. Chirag A. Shah; M.D. Oncology/Hematology (USA), 079 26754001. Diplomate American Board of Oncology and Hematology. Ahmedabad.