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Radiation therapy for ISS
Surgical resection of the ISS can facilitate adjunctive therapies by reducing the gross tumour burden; identifying tumour margins; decrease the risk of satellite and skip metastases, eliminate microscopic tumour extension into normal tissue and removing drug- and radiation-resistant cells, circulating immune complexes, and tumour-associated immunosuppressants.44 Furthermore, radiopaque ligation clips can be placed
at surgery to mark the margins of excision and facilitate radiation planning.
Although ISS response to external beam radiation can be unpredictable, it plays an important role in large  xed tumours where CT shows achieving tumour-free margins by surgery alone will be dif cult. Pre-operative radiation will sterilise the reactive zone and surrounding ‘clean’ tissues and so allow for a potentially smaller resection
to be performed and radiation therapy is theoretically more effective in the neoadjuvant setting because an unimpaired vascular supply to the tumour results in tumour cells being better oxygenated, less hypoxic, and more radiosensitive. Post-operative radiation can be used when a curative-intent surgery was unsuccessful and residual tumour disease remains. The orientation
of the scar is an important factor in limiting radiation side-effects– a scar in the midline parallel to the spine will result in minimal dose to the spinal cord as the beams can be targeted from laterally to ‘skyline’ the scar. If the scar runs perpendicular to the spine and extends down over the thoracic wall on both sides, then there is a much greater risk of including the spinal cord within the planned treatment volume. The post-operative treatment is started 10-14 days after surgery when the surgical site has already healed. If radiation is given pre-operatively, the dose is often lower to avoid overly damaging the skin and so reduce the risk of creating a non-healing wound following surgery.
Using pre-operative cobalt 60 in combination with surgery, median time to recurrence was 2.7 years following complete excision and 0.8 years if incompletely excised. Surgery followed by megavoltage radiation gave median survivals of 23-24 months, but time to recurrence and survival were decreased when time to surgery and starting radiation was increased.
Chemotherapy for ISS
Although there are reports using drugs such as doxorubicin, cyclophosphamide, mitoxantrone, and carboplatin to treat cats with ISS, there is little evidence in larger numbers of cats with ISS that adjuvant chemotherapy improves overall survival. Neo-adjuvant doxorubicin in cats with macroscopic ISS has been shown to result in a 40% overall response rate which may allow for increased surgical success. Chemotherapy may delay local recurrence in cats also receiving curative- intent radiation therapy.
Reported rates of local recurrence range from 25-60% after various combinations of surgery, radiation (pre- or post-operative) and chemotherapy. Rates of metastasis range from 5.6% to 22.5%. Pulmonary metastasis is most commonly reported, with other sites including regional lymph nodes, skin, intestine, spleen, epidural and ocular in ltration, or multi-organ involvement.
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