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03 Special Surgical Considerations
Revised 4 January 2012
1) Retroperitoneal Soft Tissue Sarcomas (RSTS)
- RSTS are uncommon lesions constituting less than 10% of all soft tissue sarcomas.
- The majority of retroperitoneal soft tissue tumours are malignant.
- They tend to present late in their course as they can grow silently for many years. Presenting symptoms may be vague abdominal pain or abdominal protrusion or intestinal complaints due to massive tumour size. They may also be detected unexpectedly at the time of laparotomy.
- General management is as described in the general sections on musculoskeletal and soft tissue sarcomas. Core biopsy should be used for tissue diagnosis after all investigations are completed. Because of the location of these lesions, it is usually not possible to excise the biopsy tract.
- Early referral for consultation is extremely important.
- Surgical excision, with clear margins, gives the best chance of cure. This often requires the en bloc removal of adjacent organs, most commonly the kidney, adrenal, small bowel and colon. As for musculoskeletal and non-retroperitoneal soft tissue sarcomas, "shell-out" procedures should be avoided as they leave microscopically positive margins. Mobilizing adjacent organs off the tumour is equivalent to "shelling-out" the tumour.
- Patients found, unexpectedly, at the time of a laparotomy, to have a retroperitoneal tumour should not undergo incisional biopsy. This contaminates the peritoneal cavity and substantially decreases the cure rate. Core biopsy (Tru-cut needle) may be acceptable if hemostasis can be assured and contamination of the peritoneal cavity avoided. Tissues should not be mobilized to expose the tumour for biopsy purposes.
- Recurrent retroperitoneal tumours may be suitable for re-excision. Re-operative surgery is generally considered palliative and should be offered for symptom control. Cures following re-excision of lesions that were not treated with primary wide local excision have been reported. Prolonged palliation can be achieved for low grade tumours.
A. Intra-abdominal Sarcomas
- Complete excision is essential if cure is to be achieved. Unlike for retroperitoneal tumours, preoperative tissue diagnosis is not recommended for intra-abdominal masses because of the risk of peritoneal dissemination.
- For lesions arising from the stomach or rectum, diagnosis via endoscopic ultrasound is an option, particularly in cases where simple surgical resection is not feasible (proximal gastric tumours, low rectal tumours, metastatic tumours).
- Nodal clearance is not essential, as dissemination tends to be by direct, intra-coelomic or hematogenous spread rather than by lymphatic spread.
- Adjuvant therapies are not indicated.
- Palliative radiotherapy may be of benefit in managing unresectable disease where bleeding or pain is problematic.
B. Gastrointestinal Stromal Tumours (GIST)
- 85% of tumours previously called leiomyosarcomas of gastrointestinal tract are now known to be gastrointestinal stromal tumours (GIST's). The incidence is 14.5/106/year or about 50 cases per year in BC.
- These tumors have staining characteristics similar to the cells responsible for peristalsis - the interstitial cells of Cajal. These cells stain for KIT, a receptor tyrosine kinase (RTK), which helps to distinguish them from smooth muscle cell tumors, true leiomyosarcomas. Targeting KIT with Imatinib has revolutionized the treatment of advanced GIST.
- Most patients have an exon-11 mutation of KIT (85-90%) especially primary lesions in the stomach. The second most common mutation is exon-9, more commonly found in small bowel GIST. Platelet-derived factor alpha (PDGFRA) mutations occur in about 5% cases. This is a RTK in the same family as KIT and is blocked by Imatinib.
- Mutation analysis is recommended at the time metastasis are diagnosed, or in the case of small bowel tumours, at the time of diagnosis. Requisition form
Instructions to requesting physician:
- fill out patient demographics, requesting physician name and date of request
- fill out originating hospital, date of procedure, and pathology number
- fax BOTH pages of the request form directly to the originating hospital pathology department
- FAX the request form to Cancer Genetics Laboratory at 604.877.6038
- It is difficult to determine the malignant potential of these tumours. The most important considerations are mitotic index, size and non-gastric location of primary (likely related to Exon-9 mutation not being common in gastric GIST).
A recently published nomogram (Gold, Lancet Oncology 2009) assesses risk of recurrence based on those factors. The sarcoma systemic team are assigning risk categories using that nomogram as follows:
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RFS 5 yrs |
Nomogram PTS |
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Very low risk |
More than 90% |
32 or less |
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Low risk |
39 – 89% |
33 to 79 |
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High risk |
Less than 39% |
80 + |
- Complete excision is essential if cure is to be achieved.
- In some situations neoadjuvant (preoperative) Imatinib at standard dosing may be considered. The decision to continue with postoperative therapy and its duration would be dependent on initial size, mitoses and intraoperative findings.
- Nodal clearance is not essential, as dissemination tends to be by direct, intra-coelomic or hematogenous spread rather than by lymphatic spread.
- Management patients with newly diagnosed operable non-metastatic GIST by risk category above:
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Very low risk |
Discharge – no recommended routine follow-up testing |
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Low risk |
We recommend clinical evaluation, CBC, LFT’s, creatinine and CT scan at 6 months interval X 1yr; then yearly X 4 years.
These patients can be discharged if adequate follow-up care available in the community. |
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High risk |
Adjuvant Imatinib 400 mg PO Daily (SAAJGI) X 3 yrs for all high risk patients (Joensuu J Clin Oncol 29: 2011 (suppl; abstr LBA1). Protocol code SAAJGI. No CAP required. Class 2 drug application required outside BCCA. http://www.bccancer.bc.ca/NR/rdonlyres/D2AED198-E2C7-4DBB-9490-7B6A332610C4/54957/Class2form_1Jan2012.pdf.
Eligibility: Newly diagnosed non-metastatic high risk GIST patients, those on adjuvant program now and those who completed 1-yr adjuvant on or after 01 June 2011.
Follow-up per SAAJGI Protocol then clinical evaluation, CBC, LFT’s, creatinine and CT scan at 6 months interval X 2yr – follow-up thereafter at oncologist’s discretion.
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Adjuvant Imatinib -The ACOSOG study Z9001showed that adjuvant Imatinib (400 mg dose daily for 1 year) was beneficial, especially for subjects with tumours 10cm or greater who have a relapse rate of 50% at 1 year and 75% by 2 years vs 5% and 25% for the Imatinib treated groups. As yet overall survival improvement has not yet been seen. At ASCO 2011, Joensuu reported on the Finnish group’s randomized adjuvant study for high risk patients with resected GIST comparing taking standard dose Imatinib for 1-year versus 3-years. At a median follow-up of 4.5 years, there was significant relapse-free and overall survival benefit for the 3-year arm (Joensuu, J Clin Oncol 29: 2011 (suppl; abstr LBA1)). At this time the BCCA protocol SAAJGI is for 1 year and a PEC submission has been made for a 3-year program.
- Treatment of advanced disease
- Combination chemotherapy for advanced disease is of limited value; about 0-5% of patients have a response.
- Imatinib (Gleevec, Glivec, STI571) inhibits autophosphorylation of the c-KIT receptor tyrosine kinase causing approximately a 55% response rate (complete or partial responses) and a 88% clinical benefit rate (includes all patients whose disease is smaller or stable) for patients with advanced disease. Median survival after Imatinib is 4.9 years compared with 8 – 10 months in the pre-Imatinib era. Standard dosing is 400 mg orally daily (SAAVGI). Patients with known exon-9 mutations may benefit from double dose Imatinib (800 mg daily) (SAAVGIDD).
- Patients initially responding to 400 mg dose of Imatinib may respond to double dose as first therapy on progression.
- After progression on double dose Imatinib, second line Sunitinib (SAAVGS) (class II) is generally recommended. Improved progression-free survival and overall survival has been observed.
- There is no standard third line therapy. Sorafenib or Nilotinib may be available on compassionate release.
- There is no GIST study open in BC at this time.
- Palliative radiotherapy may be of benefit in managing unresectable disease where bleeding or pain is problematic.
3) Phyllodes Tumor of Breast – Low or High Grade (Cystosarcoma Phyllodes – benign or malignant)
4) Dermatofibrosarcoma Protuberans (DFSP):
- Malignant tumor which is locally aggressive but has low metastatic potential.
- Requires very wide local excision to eradicate
- Moh's surgery may be an option.
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