Soft tissue sarcoma is a common tumor with an incidence of 8,680 (10,390) cases in the United States in 2004 (2008) and an annual mortality rate of an average of 3,660 (3,680) cases. The overall 5-year survival rate for soft tissue sarcoma is 50-60%, and currently, gastrointestinal mesenchymal tumors account for approximately 5,000 cases per year in the United States.
Soft tissue sarcomas are mainly located in the limbs, accounting for more than 50% of all cases, and mainly include malignant fibrous histiocytoma, liposarcoma, smooth muscle sarcoma and undifferentiated sarcoma, synovial sarcoma and malignant peripheral nerve sheath tumor, but also 50% of cases present as histologic subtypes, with common metastatic sites in the lung, liver, etc. In 2002, the AJCC reclassified soft tissue tumors in the guidelines for diagnosis and treatment In 2002, the AJCC reclassified soft tissue tumors in its guidelines.
Principles of surgical treatment.
Since surgery is the main treatment for sarcoma, the basic principles of treatment include.
(1) Adequate surgical margins are the key to prevent local recurrence, which should include fascial or muscle in normal tissue.
(2) While removing the tumor to the maximum extent possible, the function should be preserved as much as possible, and limb-preserving surgery can also get good results.
(3) If surgical treatment is not suitable, preoperative chemotherapy or radiotherapy can be applied to control the lesion before deciding on further treatment.
(4) The pathology section should be reviewed and reported by an experienced pathologist, especially for the first pathology classification. The pathology report should include the cut edge of the specimen, and the basal cut edge. Immunohistochemistry and molecular biology diagnosis are required for sarcoma with diagnostic difficulties.
Limb soft tissue sarcoma.
Before treatment of limb tumors, a professional treatment team should formulate the whole treatment plan. Imaging examinations including ultrasound, CT and MRI are needed, especially in tumors above 5 cm, this examination should be performed, and it is generally believed that CT is suitable for abdominal and pelvic cavity, and MRI is suitable for limb tumors. Routine chest X-ray is needed to exclude metastasis.
CT-PET PET/CT can be used according to the situation, especially for disseminated epithelioid sarcoma.
Fine needle aspiration cytology can be applied to certain cases of metastases. The primary tumor should be punctured with caution. For small tumors with stage I surgery, puncture is not necessary, while large tumors should be punctured within 24 hours before treatment, and if they are confirmed to be malignant, surgery or radiotherapy or chemotherapy should be implemented as early as possible to prevent medical proliferation. Preoperative biopsy should also try to articulate with treatment in a timely manner and should ensure 1×1×1cm3 size for pathological diagnosis.
Generally experienced doctors can assess the following three elements based on a series of examinations before surgery.
1.Tumor can be resected
2.Tumor is unresectable but no distant metastasis
3.Coexistence of primary and metastatic foci
Resectable primary tumor.
Tumors in T1a-1b, No, Mo stage (superficial, small, low malignancy) can be considered with margins larger than 2-3 cm. If there are sufficient margins for pathological examination without tumor residue, no radiotherapy can be given.
Stage T2a-b, No, Mo tumors (low malignancy, superficial or deep in) are recommended for extensive tumor resection, <5cm tumors do not require preoperative radiation, and postoperative margins >3cm, and radiation therapy is not necessary.
In stage II-III cases (highly malignant), extensive surgical resection can be performed directly. If the tumor is located in the joint area and it is difficult to ensure the cutting edge, preoperative or postoperative radiotherapy can be performed. For low-grade malignant sarcoma, chemotherapy is often insensitive.
Adjuvant therapy for resectable tumors.
Whether to perform adjuvant therapy after surgery often depends on whether the surgical resection is adequate and whether the pathologist determines whether there is still tumor residue in the cut margin. Superficial and small to medium sized tumors with negative cut margins do not require further adjuvant therapy, while radiotherapy is required if the tumor is adjacent to important blood vessels and nerve structures and is at high risk of recurrence. If the specimen has positive margins, it is recommended that additional surgery should be performed again. The principle of additional surgery should be completed within one month, if more than three months, other treatment methods are appropriate. Supplementary radiotherapy may also be considered if surgery in certain areas is difficult to complete radically, or if clean margins cannot be guaranteed and there are residuals under the microscope.
The dose of preoperative radiotherapy can be up to 50Gy, and for certain areas with residual tumor, high dose iridium 192 or intra-particle irradiation can be used. If the tumor is found to be adjacent to blood vessels and nerves during surgery, and it is difficult to ensure the incisional margin, silver clips should be placed around to mark the tumor for postoperative radiotherapy, and tubes can also be placed intraoperatively, arranged according to the Paris system, with a distance of 1 cm, requiring straightness, and high-dose iridium 192 internal irradiation within a few days after surgery, with a tumor dose of 12-16 Gy. The postoperative radiotherapy tumor bed dose is 45-50 Gy. The dose can be increased by 10-20Gy depending on the margin.
Certain highly malignant sarcomas often require adriamycin-based chemotherapy, (Ewing’s sarcoma, rhabdomyosarcoma, osteosarcoma, etc.) Chemotherapy can also be administered in combination with isocyclophosphamide and adriamycin, but strong chemotherapy sometimes does not increase survival rates and brings about side effects. Chemotherapy can be applied in highly malignant cases with risk of recurrence and metastasis and in good systemic status. Currently, preoperative arterial interventional chemotherapy can shrink the tumor and facilitate surgical resection, and can be applied in certain larger tumors.
In cases where surgical resection is difficult, preoperative application of adriamycin, isocyclophosphamide chemotherapy or preoperative radiotherapy is recommended to create the opportunity for re-surgical resection, and then surgical resection of the tumor if the treatment is effective, and postoperative continuation of chemotherapy or supplemental radiotherapy can be considered. At present, it is believed that combined radiotherapy and chemotherapy can achieve the purpose of local control of tumor, and for certain isocyclophosphamide and adriamycin resistant patients, Jianzhi can be tried.
In the past year, the sarcoma comprehensive treatment group has applied sequential regimens for the treatment of Ewing sarcoma family tumors, which are now being used clinically.
Follow up.
Stage I cases are followed up and reviewed in 3-6 months for 3 years, including ultrasound, routine physical examination, X-ray chest radiograph, which can be examined once in 6-12 months, and CT and MRI are applied as appropriate.
For highly malignant and recurrence risk cases, it is recommended to have a physical examination every 3-4 months for three years after treatment, and to review ultrasound every 6 months for the next two years, and to implement CT or MRI annually. within 10 years, recurrence is generally less likely, but long-term follow-up is still required, including regular X-ray chest films, ultrasound or CT, etc.
Treatment of recurrent or metastatic cases.
For some smaller metastases without symptoms (e.g. small pulmonary nodules), observation and follow-up are possible, but for symptomatic cases, chemotherapy, radiotherapy or palliative surgical treatment are required, mainly based on the patient’s symptoms, and systemic condition.
If the metastatic lesion is located in a single organ, metastasectomy, cryosurgery, thoracic and laparoscopic means can also be considered to accomplish this.
Retroperitoneal sarcoma.
Retroperitoneal sarcoma includes malignant and benign lesions. It is still debated whether to biopsy retroperitoneal sarcoma, but if preoperative radiotherapy or chemotherapy is required to clarify the histological pattern, CT and MRI examinations are necessary.
Primary tumor treatment.
If the primary tumor is less than 5 cm and there are no adhesions in the surrounding tissues and organs, it can often be resected and no further radiotherapy or chemotherapy is needed after surgery. If the tumor is larger and highly malignant, postoperative supplemental radiotherapy is recommended.
The true meaning of complete resection in retroperitoneal sarcoma accounts for only 50%, mainly because the tumor is adjacent to the surrounding organs and blood vessels, and it is difficult to achieve extensive resection similar to limb. Well-differentiated tumors do not require intraoperative biopsy and are directly resected in a single pass (e.g., low-grade malignant liposarcoma). Debulking operation is also one of the methods of palliative resection.
Unresected tumors are mainly due to the involvement of surrounding vital organs, blood vessels and nerves, and are prone to death by resection, therefore, biopsy is required in such cases, followed by radiotherapy and chemotherapy. Palliative surgery is only used for symptomatic patients to enhance nutrition and to observe asymptomatic patients to survive with tumor. Unresectable sarcoma can be resected again after chemoradiotherapy. In case of unresectable sarcoma with distant metastasis, only chemotherapy, such as adriamycin, azulenamidine, and Kenze, can be relied on.
Follow up.
After successful resection of low-grade malignant sarcoma, chest X-ray, abdominal and pelvic CT examinations are required every 3-6 months for 2-3 years, and similar review cycles as above for those with incomplete resection or failure to resect.
After successful complete resection of highly malignant sarcoma, further follow-up is required, with chest X-ray and CT every 3-4 months for 3 years, and then every 6 months for another 2 years.
Those with incomplete resection are also reviewed at the same time.
Treatment procedure.
Necessary items in the gastrointestinal mesenchymal tumor diagnostic and treatment procedures include history and physical examination (H&P), CT-enhanced scan and/or magnetic resonance imaging (MRI) of the abdominal pelvis, chest x-ray, and endoscopy when indicated. The need for pathological biopsy should be based on the clinician’s level of suspicion of other malignancies. It is recommended that biopsy specimens should be diagnosed by an experienced pathologist and that immunohistochemical staining for CD117 antigen (the kit detects the KIT kinase receptor, which is a characteristic marker for GIST) should be performed on pathology specimens, as the application of selective kinase inhibitors (i.e., imatinib mesylate, Gleevec) in patients with inoperable resectable or metastatic GIST, treated is likely to produce a positive therapeutic response and clinical benefit after
Initial therapy.
For the vast majority of patients with GIST, imatinib mesylate may provide long-term clinical benefit and objective antitumor effects. A phase II clinical trial demonstrated exceptionally high patient survival rates with imatinib mesylate for treatment of inoperable and/or metastatic GIST. An objective treatment response was also observed in more than 50% of patients. The previous view was that tumors such as GIST are insensitive to all conventional chemotherapy regimens and should be differentially diagnosed from GIST, which can present with epithelial-like changes and thus are often misdiagnosed as poorly differentiated cancerous lesions, so the specific histopathological features of GIST mentioned above should be taken into account. In the case of GIST, surgery is the decisive treatment option if the lesion is easily resectable and does not cause severe functional impairment. If the tumor cannot be resected (or if resection of the tumor would cause severe postoperative functional deficits in the patient) or in patients with metastatic GIST, treatment with imatinib mesylate should be chosen before surgical treatment. Surgery may be considered if the tumor is bleeding or if the tumor is only a focal metastasis. Surgery is also indicated if the GIST responds to imatinib mesylate treatment and the tumor shrinks to the point where it can be surgically removed. At this point, lifelong treatment with imatinib mesylate may be required for patients with metastatic GIST. It should be noted that if the patient’s disease is stable and there is no objective evidence of disease progression, the therapeutic dose of imatinib mesylate should not be increased, but should be maintained at the original dose of imatinib mesylate treatment. If the tumor does not decrease in size, an increase in the therapeutic dose of Imatinib mesylate is not recommended as long as the disease is stable. If the tumor progresses, the therapeutic dose of imatinib mesylate can be increased if the patient can tolerate it. After complete tumor resection, if it is a high-risk recurrent patient (tumor 5 > cm intraoperative tumor rupture, bleeding necrosis, small intestine tumor, multiple tumors in the abdominal cavity) can be considered to take Imatinib 400 mg/day, human for one year, liver metastases are treated according to different situations, recurrent cases should be given Imatinib treatment or reoperation.
It is also reasonable to apply Imatinib mesylate for trial treatment in GIST patients with negative CD117 staining, but close evaluation and follow-up should be performed.
Follow-up monitoring.
Each patient, regardless of initial status at the time of presentation and regardless of the treatment received, should receive a comprehensive history and physical examination every 3-6 months for 5 years, with a change to annual review thereafter. Similarly, abdominal CT should be reviewed every 3-6 months for 3-5 years after treatment, and then annually. For patients with metastatic and non-surgically resectable tumors under active treatment, the frequency of follow-up should be increased if a change in treatment regimen is anticipated (e.g., every 3-6 months to maintain lifetime follow-up.)