The term ‘soft tissue’ describes the extraskeletal connective tissue that accounts for more than 50 per cent of body weight and includes muscle, tendon, fat, fascia, and synovium. The soft tissues arise embryologically from the mesenchyme. Although soft tissue tumours are all thought to arise from primitive mesodermal tissue, they vary widely in their histological appearance and in the mature tissue type that they resemble. By convention, tumours arising in the peripheral nerves are also grouped with soft tissue tumours, as their presentation and treatment are similar.

Benign soft tissue tumours such as lipoma or benign fatty tumour closely resemble specific normal adult tissues. They exhibit little tendency to local invasion, rarely recur after local excision, and do not metastasize. Malignant soft tissue tumours are termed sarcomas (from the Greek ‘sarkoma’, meaning fleshy growth), while malignant tumours arising from epithelial tissues are termed carcinomas. Exceptions to this generalization are tumours arising from the endothelium of blood or lymphatic vessels, or the mesothelial lining of body cavities, which are grouped with soft tissue tumours. A classification has been developed by Enzinger using the principle of similarity of histological appearance to normal tissues (Table 1) 431. Occupying a middle ground between sarcomas and benign neoplasms is a group of locally aggressive tumours such as desmoid tumours, aggressive fibromatoses, atypical lipomas, and aggressive neurofibromas. These do not metastasize and are not called sarcomas, but require more comprehensive treatment than do other benign soft tissue tumours.

Benign tumours of soft tissue are far more common than sarcomas, outnumbering them by about 100:1 in biopsy series. As many lipomas and haemangiomas are never submitted for biopsy examination, the actual ratio is probably considerably higher. Considering the volume of tissue from which sarcomas may arise they are rare, with an annual age-adjusted incidence of about 2:100000. Just over 5000 soft tissue sarcomas are diagnosed annually in the United States, accounting for 0.7 per cent of newly diagnosed invasive cancers (excluding squamous and basal cell carcinoma of the skin). In children under 15 years of age they account for over 6 per cent of all cancers.

The pathogenesis of most soft tissue tumours is poorly understood. Genetic factors are associated with certain benign tumours: about 5 per cent of lipomas and angiolipomas are multiple and familial. Soft tissue sarcomas have no established genetic predisposition, but occur with increased frequency in patients with genetically transmitted conditions such as intestinal polyposis, Gardner's syndrome, and basal cell naevus syndrome. Patients with von Recklinghausen's disease have a 15 per cent chance of developing a soft tissue sarcoma. Chemical carcinogens have been implicated in anecdotal reports but no link has been established. Exposure to dioxin, phenoxyacetic acid, or to agent orange have not been shown to have an association with development of sarcomas in case-control studies. Although trauma is often incidental to the discovery of a soft tissue tumour by a patient, no evidence exists of any link between the two. Anecdotal reports of sarcoma occurring in association with foreign bodies such as bullets and shrapnel pieces exist, but prospective studies of large numbers of patients with metallic or Silastic implants have not shown any associated tumour development. There is an increased incidence of lymphangiosarcoma in lymphoedematous extremities, first described in women's arms following radical mastectomy (Steward–Treves' syndrome).

Radiation exposure is associated with a later incidence of sarcoma estimated at between 2 and 4/1000 patients after 10 years. Although any type of soft tissue sarcoma can arise, malignant fibrous histiocytoma, extraskeletal osteosarcoma, and fibrosarcoma are most common. Oncogenic viruses remain an area of research, but no clear association with sarcoma has been established. Kaposi's sarcoma is common in patients with acquired immunodeficiency syndrome (AIDS). This event may represent an association with the human immunodeficiency virus alone or in common with another agent, or with the action of a different causative agent in immunosuppressed hosts. Most soft tissue tumours arise in individuals in whom no predisposing factor can be identified.

Lipomas are among the most common benign tumours. They are usually subcutaneous, not tethered or fixed to the underlying fascia, multilobulated, and vary greatly in size. Angiolipomas contain many small vessels and are usually tender or painful. Their major significance is their confusion with liposarcomas. They should be biopsied or removed when evidently growing, when larger than 5 cm, or if symptomatic. Large lipomas, or those tethered to fascia or deep to the fascia should be biopsied, as recommended for liposarcomas.

Neurofibromas and neurilemmomas both arise from Schwann cells. Simple excision is curative, but when they arise in nerves of clinical significance, every effort should be made to preserve the affected nerve. Multiple neurofibromas are seen in patients with von Recklinghausen's disease and are too numerous to be removed: 10 to 15 per cent of these patients will develop neurogenic sarcomas. Neurofibromas should be removed when they undergo rapid enlargement or if they become painful, as well as for cosmetic reasons.

Dermatofibromas, also called sclerosing haemangiomas, occur in the skin and have a very characteristic appearance. They are usually about 1 cm in diameter and do not tend to grow. Excision is curative when desired. Myxomas and mesenchymomas present as soft tissue tumours; the diagnosis is made histologically. They are almost always cured by simple excision. Mesotheliomas arise in the pleura, pericardium, or peritoneum. They project but do not infiltrate and are usually cured by excision.

Haemangiomas are vascular neoplasms that are usually present at birth in the head and neck area, but they can be anywhere. Most congenital haemangiomas regress spontaneously by the age of 5 years, even if they grow rapidly during the first months of life. It is extremely rare for such lesions to compromise vital structures, but low dose radiation to a very focused field may be used to treat this situation. Haemangiomas of extremities may not regress, and can result in limb enlargement. Such patients are often best treated by angiographic embolization, or sometimes by surgical de-arterialization. The haemangioma may involve bone, and surgery too near the tumour may be accompanied by severe or even fatal haemorrhage. Lymphangiomas are similar tumours which can be surgically excised. Conservative management of both of these tumour types allows preservation of function and achieves a favourable cosmetic result.

Ganglions are fibrous walled cysts, most commonly seen on the dorsal surface of the wrist. They result from an excrescence of synovial tissue and are filled with synovial fluid. Simple excision is usually curative. They are easily confused with giant cell tumours of the tendon sheath, which are also most commonly seen in the wrist or hand and are also treated by simple excision.

Leiomyomas most commonly arise from the smooth muscle of the uterus and gastrointestinal tract. Leiomyoblastomas are similar to leiomyomas, but tend to grow large and to develop areas of haemorrhage and cystic degeneration. Both are treated by simple excision.

Nodular fasciitis has been often mistaken for a fibrosarcoma. These tumours usually occur in the superficial or deep fascia and grow rapidly when they first appear. In weeks to months they reach 3 to 5 cm and then usually stop growing. They are generally eliminated by simple excision.

Desmoid tumours or aggressive fibromatosis can arise from any fascial tissue. These lesions are remarkable for their infiltrative nature and fall into two groups. Abdominal desmoid tumours arise from the muscular wall of the abdomen, often in association with abdominal incisions, and are especially common in postpartum women, in whom they may be related to hormonal changes and surgical trauma. If resected to clear margins they seldom recur. Extra-abdominal desmoid tumours behave more aggressively. They are common about the shoulder or within an extremity, where they infiltrate diffusely. Although these tumours do not metastasize, they cause local destruction of function. Surgical resection short of amputation is often impossible, but wide resection is the preferred treatment when it can be accomplished with minimal morbidity. Resection to close margins or to positive margins is generally followed by recurrence. Irradiation is effective in controlling desmoid tumours if 60 Gy can be delivered. The hormonal milieu may affect desmoid tumours, and treatment with progesterone, tamoxifen, indomethacin, and ascorbic acid have all been reported to induce remissions. These therapies are associated with minimal toxicity and deserve further study, but they usually fail to produce a response.

Atypical lipomas and atypical fibrous histiocytomas are generally located deep in the soft tissue or muscle; they appear atypical histologically and although they do not metastasize they tend to recur locally after resection, particularly if wide margins are not achieved.

Dermatofibrosarcoma protuberans arises insidiously in the skin or subcutaneous tissue. These tumours do not metastasize, even when multiply recurrent, but they behave locally as though malignant. It is important to achieve control at the time of first resection, with generous (at least 2 cm) margins to minimize the risk of further recurrence. Half of all patients treated with simple excision and more limited margins will suffer recurrence; amputation may be required and death may result. Radiation therapy as a supplement to conservative resection appears beneficial but has not been subject to controlled trial. Radiation has been used in place of very radical resection in some patients with a favourable result.

Soft tissue sarcomas can arise in any part of the body and usually present as a painless lump. When they arise in the retroperitoneum or deep in the thigh or buttock they may be quite large before they are first noticed; on the foot or wrist very small masses may be apparent. The larger the soft tissue mass, the more likely it is to be a sarcoma, and this diagnosis should be considered for any mass that is at or below the level of the deep fascia. Progressive growth increases the probability that the tumour will prove malignant. Careful physical examination will give the dimensions of the palpable tumour and provide information about the infiltrative nature of its borders, fixation to normal structures, and involvement of skin, muscle, bone, major blood vessels, or nerves. The insidious feature of soft tissue sarcomas is their ‘benign’ presentation that too frequently induces a false sense of security in both patient and physician.

A biopsy specimen of any putative sarcoma should be obtained: the technique used is of great importance. Fine-needle aspiration cytology will often yield a diagnosis of malignancy, but the classification and grading of a sarcoma cannot reliably be performed from cytology alone. A core-needle biopsy allows examination of a thin core of tissue and permits recurrent sarcoma to be recognized. Sample size is limited, however, and this hinders the accuracy of diagnosis and grading of soft tissue sarcomas. Incisional biopsy is the technique of choice for all but the smallest tumours. The excision of any tumour greater than 3 cm in diameter contaminates the environs with nests of tumour cells that may be carried for some distance along tissue planes by dissecting haematomas, and creates a need for more radical therapy than would otherwise have been needed.

The correct placement of a biopsy incision is also of far greater importance in the management of soft tissue sarcomas than is the case for most other tumours. The biopsy should be performed by a surgeon who is prepared to treat the tumour if it proves to be a sarcoma, and who can place the biopsy incision where it does not compromise the planned treatment. Biopsy incisions should be oriented longitudinally in the extremities, and over the direction of underlying muscle, placed for inclusion in possible later resection of skin. General anaesthesia is preferable to local anaesthesia since these tumours are usually at the level of or beneath the deep fascia. Attempts to obtain biopsy samples at this depth under local anaesthesia are often limited by the patient's discomfort, and therefore produce inadequate samples of tissue. Cautery should not be applied until the specimen has been removed, to avoid heat artefacts. Meticulous haemostasis and closure in multiple layers to avoid haematoma formation is beneficial. Inappropriate biopsy techniques contributed to diminished quality of care in a high proportion of sarcoma patients studied by the Musculoskeletal Tumor Society. Classification and grading of soft tissue tumours should be reviewed by subspecialty pathologists when treatment decisions will relate to the histological type or grade: proper management of soft tissue sarcomas depends upon accuracy in classification and grading, which in turn depend upon representative well-stained slides interpreted by one with considerable interest and experience in sarcomas.

The first aspect of TNM staging is the evaluation of the tumour itself (T). In addition to physical examination, radiological studies are essential. CT and MRI imaging have revolutionized the local staging of sarcomas, and the comparative value of the two techniques is still a subject of study. Depending on location, arteriography can be helpful in planning resection close to major vessels, but the routine use of arteriography, along with soft tissue films and nuclear scans, has been replaced by MRI or CT. The size of sarcomas, measured as the longest axis diameter, carries independent prognostic information for risk of distant metastasis (Table 2) 432.

The evaluation of regional lymph nodes (N) is confined to physical examination. Much is made of the rarity of regional nodal metastases in patients with soft tissue sarcoma, averaging 3.9 per cent in 12 series comprising more than 2500 patients. A review of 323 patients with clinical M0 sarcomas treated at the Massachusetts General Hospital identified 19 (5.9 per cent) with regional lymph node involvement. The incidence varied with stage, being 0 per cent, 2 per cent, and 12 per cent in Grades I, II, and III, respectively. Four of five patients with epithelioid sarcomas had regional node disease: any palpable regional lymph nodes in a patient with Grade III sarcoma should be viewed with suspicion.

The search for metastases (M) in soft tissue sarcomas is focused on the lungs. Although sarcomas of the retroperitoneum commonly metastasize to the liver, the lung is easily the most common site of distant metastasis from other sites. CT scans of the chest are consequently an essential part of initial staging of sarcoma patients.

Unlike most other solid tumours, where classification by stage is based upon TNM alone, grade (G) is the dominant factor in assigning the stage of soft tissue sarcomas and is most closely related to prognosis (Fig. 1) 1498. Grade I sarcomas (well differentiated) are less likely to recur locally or to exhibit distant metastasis than are Grade III sarcomas (poorly differentiated). The grade of the tumour is based on the presence of necrosis, the number of mitotic figures per 10 high power fields, cellularity, and the extent of stroma. The grade of the tumour is more predictive of clinical course than the histological classification and also subject to less interobserver variation. The pathological grade is combined with the TNM classification to assign a stage to soft tissue sarcomas (Table 3) 433.

Although the stage incorporating tumour grade is more predictive of clinical course than is the histological classification of soft tissue sarcomas, some unique features exist based on the tissue subtype. However, even among pathologists with particular experience and expertise in soft tissue sarcomas, there is often discordance of histological classification. Although striated muscle comprises more than one-third of human body mass, rhabdomyosarcomas are rare, although they are the most common soft tissue sarcomas in children under 15 years of age. These are managed best by a combination of treatments, chosen according to the location of the tumour. When all gross tumour can be resected with minimal morbidity, resection followed by adjuvant chemotherapy affords excellent control, radiation therapy being reserved for close margins. Over one-third of childhood rhabdomyosarcomas originate in the head and neck, where removal of biopsy specimens is followed by primary irradiation and adjuvant chemotherapy. Such combined therapy has improved the 3-year survival rate of children from about 20 per cent in the early 1960s to more than 70 per cent now. Survival ranges from 88 per cent for patients with localized disease to 32 per cent for children who have metastatic disease present at the time of diagnosis.

Liposarcoma is a malignant fatty tumour and may be multicentric. It is not known whether this is true multicentricity or whether these other foci represent metastases to other fatty tissue sites. Liposarcomas are frequently large, arising in the proximal extremity, trunk, or retroperitoneum. Many tumours exceeding 23 kg (50 pounds) in weight have been reported; one weighing 125 kg (275 pounds) has been reported. They may regress quite dramatically following radiotherapy, but well-differentiated liposarcomas may be aggressive locally and recur many times before presenting with metastases. Pleomorphic and lipoblastic liposarcomas tend to be of higher grade and to exhibit distant metastases.

Malignant fibrous histiocytoma is the most frequent classification applied to soft tissue sarcomas, and encompasses many tumours that would have been classified as fibrosarcomas or pleomorphic rhabdomyosarcomas in the past. It implies a high-grade sarcoma that lacks specific features of differentiation. The disease is currently thought to be derived from fibroblasts rather than the histiocyte that gave the tumour its name. Although classified as a soft tissue sarcoma, malignant fibrous histiocytomas may arise from bone and a variety of other tissues. Fibrosarcoma was once the most common soft tissue sarcoma: when studying older series one should remember that most fibrosarcomas would now be classified as malignant fibrous histiocytomas or other types.

Leiomyosarcomas arise from or resemble smooth muscle cells; they can arise from the walls of blood vessels at any site in the body. When they arise in the wall of the gut, their behaviour correlates with the number of mitoses in 50 high-power fields. For other soft tissue sarcomas the number of mitoses in 10 fields is used in determining the grade of the tumour. Synovial sarcomas arise most commonly in the lower extremities, in a muscle away from a joint. Histological glandularity is an important prognostic feature: tumours with over 50 per cent glandularity and less than 15 mitoses/10 high power fields are unlikely to prove fatal if properly treated.

Neurofibrosarcomas (also called malignant schwannomas and malignant neurilemmomas) originate from or resemble neural sheath tissue. They frequently arise in patients with von Recklinghausen's disease, about 15 per cent of whom will develop sarcomas. Epithelioid sarcomas usually arise in the extremity, where they often spread to areas of skin, fatty tissue, and bone. Whether this represents multicentricity or a pattern of metastasis is not known. They metastasize to regional lymph nodes twice as often as to the lungs. Some surgeons advocate elective dissection of regional draining lymph node groups, and any palpably enlarged node should certainly be biopsied. Surgical margins should be more generous for epithelioid sarcomas than for most other soft tissue sarcomas. Alveolar soft part sarcomas are rare, even for sarcomas, and have no benign counterpart. In adults the tumour usually affects an extremity, while in children it is usually a head and neck tumour. Protracted but ultimately fatal progression is a common clinical course.

Angiosarcomas account for only 1 to 2 per cent of soft tissue sarcomas, but these are usually high-grade and behave aggressively. Lymphangiosarcoma arising in an oedematous extremity is often diffuse and radical amputation is typically required for its control. Many of these tumours arise in the skin and subcutaneous tissues, in contrast to the deep-tissue location of most soft tissue sarcomas. Half of all angiosarcomas arise in the head and neck: these are particularly aggressive, often progress, and are unresponsive to treatment. Any attempt to resect them should be preceded by examination of numerous biopsy specimens from the anticipated resection margin, permanent section histology being used to plan the resection. Evidence of microscopic tumour is often present 6 to 8 cm from the apparent tumour border on permanent sections, even though it was not apparent on frozen sections.

For many years Kaposi's sarcoma was a rare sarcoma seen in elderly Jewish men in Europe or the United States of America. It was clinically characterized as multiple pigmented sarcoma nodules, usually beginning on the legs as red nodules and slowly spreading. The condition was rather indolent and could be excised or treated by irradiation. Later, it was recognized as a common neoplasm in certain areas of Africa, where it behaved more aggressively but was sensitive to combination cytotoxic chemotherapy. A third presentation of Kaposi's sarcoma was reported in transplant patients who were receiving immunotherapy. Although it affects well under 1 per cent of transplant recipients, such patients have a 200-fold increase in risk.

Since 1981 Kaposi's sarcoma has presented in epidemic form in patients with AIDS. Its clinical presentation and behaviour is similar to that seen in immunosuppressed transplant recipients. Kaposi's sarcoma is not seen in transfusion-related AIDS and is uncommon in drug abuse-associated AIDS, but it occurs in nearly half of male homosexuals with AIDS. The epidemic form of Kaposi's sarcoma presents with smaller lesions, usually on the chest, arms, head, and neck. It frequently involves the mucosa of mouth and anus and half of affected patients have visceral lesions by the time of diagnosis. These are usually asymptomatic, although gastrointestinal tract lesions may bleed.

Epidemic Kaposi's sarcoma has its own staging system which is based on extent of disease and modified by A and B subtypes, which refer to systemic symptoms. Minimal tumour without B symptoms, which include weight loss, fever, or ongoing infection, is either observed, or treated with &agr;-interferon; if B symptoms are present single agent chemotherapy is generally used, typically with the vinca alkaloids. More extensive tumour is generally treated with interferon or chemotherapy in the absence of B symptoms; in patients with B symptoms or rapid growth of tumour more intensive chemotherapy with doxorubicin and/or etoposide is suggested. Irradiation is directed toward symptomatic or disfiguring tumour nodules. A response to interferon therapy is largely seen in those without B symptoms. Although patients often respond to chemotherapy, these are commonly partial responses and of limited duration.

Although treatment is determined by the specific diagnosis and the stage of the soft tissue sarcoma, the goal is to eliminate both the primary tumour and any metastatic disease. Basic local control may be accomplished by surgical resection. In the first half of the twentieth century this was most commonly attempted by resection of all apparent tumour, often to margins reported to be free by pathological evaluation. Subsequent review of patients so treated reported local failure rates ranging from 50 per cent to over 90 per cent (Table 4) 434, and inapparent tumour obviously extended well beyond visible disease. Wider excisions with more generous margins improved the local failure rate to just less than 50 per cent. In the 1950s and 1960s the widespread acceptance of radical surgery, particularly radical amputations for extremity sarcoma, lowered the rate of local failure to between 12 and 20 per cent. In patients for whom surgery is the only available treatment, the lessons of this era are still appropriate. Local control of soft tissue sarcoma requires resection with a generous margin of seemingly normal tissue. For low-grade sarcomas (other than epithelioid) this may be as little as 1 cm of clean margin; for high-grade sarcomas 4 cm in the closest dimension is required. For tumours in the centre of a muscle compartment, this goal can be accomplished by removal of the entire compartment from origin to insertion, which clearly causes appreciable functional and cosmetic morbidity. Many soft tissue sarcomas arise in less convenient locations, near a joint or between two muscle compartments. One recent analysis found that only 30 per cent of soft tissue sarcomas of the extremities occurred in deep intracompartmental locations, and only one-half of these could be treated by compartment resection or primary myectomy. Treatment of such lesions of the extremity by surgery alone requires amputation. For high-grade sarcomas of the foot a below-knee amputation would be required: an above-knee amputation is needed to achieve local control of such tumours affecting the ankle or lower leg. For tumours of the mid to distal thigh hip disarticulation suffices, but proximal sarcomas of high grade near the hip require hindquarter amputation or hemipelvectomy. The latter may be modified according to the location of the primary tumour. If the iliac wing can be spared, rehabilitation to ambulation with a prosthesis is aided. Similar procedures exist for high- grade sarcomas of the upper extremity, up through interscapulothoracic or forequarter amputation for sarcomas of the proximal arm and distal shoulder. This involves removal of both clavicle and scapula and can be modified to encompass adjacent or attached ribs for more proximal tumours of lower grade. Resection of sarcomas should not be limited to standard procedures, but should be tailored to the biology and location of the individual tumour.

Although such radical surgical procedures greatly affect the patient, they are often well tolerated: many patients demonstrate great resilience and resourcefulness in dealing with the loss of a major body part and the attendant disability and cosmetic defect. Physical therapy, rehabilitation, the availability of sophisticated prostheses, and psychosocial support are all essential parts of caring for the patient faced with such ablative surgery.

Radiation therapy has been used in attempts to achieve local control of soft tissue sarcomas. Although effective control was sometimes achieved, shrinkage of the tumour was followed all too often by progression. These events led to the concept that soft tissue sarcomas were ‘radioresistant’. The use of high-dose radiation increased the rate of tumour control, but the attendant morbidity also increased. Local control rates, even following aggressive irradiation, are generally inferior to those achieved by surgery alone. Consequently, radiation alone should be reserved for patients whose tumours cannot be resected because of size or location, for those who are medically unfit for surgery, or those who refuse surgical management. As mentioned above, desmoid tumours, although they are not true sarcomas, are well managed by radiation therapy alone.

Combined surgery and irradiation was pioneered by Suit and colleagues. Experimental data suggested that radiation at a level of 60 Gy would control microscopic deposits of sarcoma cells, although larger solid sarcomas would have hypoxic areas that might not be eliminated at this dose. However, surgery alone needs to be as radical to achieve local control since microscopic deposits of sarcoma cells extend beyond the primary tumour mass. Radiation, therefore, could be used to eliminate subclinical extensions of disease into the surrounding, normal appearing tissue with surgical resection of gross tumour, sparing adjacent major nerves and vessels.

A clinical example contrasting combined treatment with surgery alone might be a Grade III, 6-cm malignant fibrous histiocytoma arising in the gastrocnemius muscle of the left leg of a 26-year-old woman (G3 T2 N0 M0). Surgical treatment alone (Fig. 2) 1499 would require at least resection of the posterior compartment of the calf. If the posterior compartment were small, or if the tumour was tethered or too close to the deep structures of the leg, amputation above the knee would be required to achieve local control of the sarcoma. Alternatively, preoperative irradiation using a four-field technique that spares the anterior tissues at 2 Gy/day for a total of 45 Gy could be followed by a resection of the tumour with a small envelope of normal tissue 3 to 5 mm thick to ensure that all gross tumour was removed. After would healing is complete a 15- to 20-Gy boost dose of irradiation to the region at highest risk (brachytherapy or particle therapy using electron or proton beams) would be administered for a total dose of 60 to 65 Gy. Such treatment is at least as effective as radical resection or amputation alone in achieving local control of soft tissue sarcomas, and produces minimal cosmetic or functional impairment (Table 4) 434.

Radiation therapy can be added to limited surgery for control of soft tissue sarcomas either pre- or postoperatively. A strong theoretical case can be made for delivering the radiation prior to the tumour resection (Fig. 3) 1500. First, the volume of tumour subjected to irradiation may be limited to those tissues at risk by virtue of the biology of the sarcoma and its anatomical location, while post-resection radiation must include all tissue planes that may have been contaminated by the surgical procedure, drain tracts, or haematoma-borne clumps of viable tumour cells. This option generally requires a larger radiation field. Secondly, radiation therapy can begin immediately, while postoperative radiotherapy is delayed for a week or even longer, depending on the rate of wound healing. It may be delayed for several weeks by persisting seromas. Thirdly, after irradiation the tumour commonly regresses in size and develops a plane of peritumour oedema that marks the borders of infiltrative sarcomas quite well. Regression allows defined resections to be performed, sparing the majority of normal tissue in the region. The well-oxygenated tumour at the periphery of the sarcoma is most likely to be sterilized, increasing the distance between the dissection and the location of any viable tumour, which tends to be near the centre of the tumour mass in relatively hypoxic regions of the sarcoma. This plan further diminishes the likelihood of tumour implantation at the time of conservative resection.

Pre- and postoperative irradiation have not been compared in a prospective, randomized trial. In a single institution's experience (Table 5) 435 preoperative irradiation was administered. Patients with smaller tumours of lower grade were more likely to have undergone resection prior to referral, often with the expectation that the tumour was benign. Many of the tumours were not resectable at the time of referral. Although there was no apparent difference in outcome for the smaller tumours, larger tumours showed better local control following preoperative radiation therapy.

When irradiation is added to resection, the surgical procedure is directed toward the removal of all gross tumour with a sufficient margin of normal tissue to allow confirmation of complete excision—a gross margin of 5 to 10 mm. The resection should not be performed with a cautery knife because evaluation of surgical margins cannot be accurately performed. The surface of the specimen should be painted with India ink by the surgeon or pathologist to facilitate evaluation of the resection margins. Attention is then focused on elimination of dead space and prevention of haematomas or seromas. When a large potential dead space exists at the conclusion of the resection, it is best filled with a transposed muscle flap. If the tissues are sufficiently mobile to fall together without the need for transposed tissue, suction drains alone may suffice. The area should be immobilized, particularly if it is in an extremity, and suction drains should be left in place until the threat of seroma formation is past. Early mobilization and drain removal accounts for many wound complications in this setting. Poor healing is most common where irradiated tissues are very thin, such as about the knee, or in areas of abundant fat, such as the buttock or proximal thigh. In the latter setting fat necrosis following radiation and surgery can lead to late wound breakdown requiring revision. When breakdown occurs it is often best managed by coverage with a myocutaneous flap.

Eilber pioneered the use of intra-arterial doxorubicin followed by limited surgical resection and irradiation for the treatment of extremity sarcomas. This technique allowed excellent local control while sparing the extremity. No direct comparison has been performed between the use of irradiation and limited surgery and this treatment with the addition of intra-arterial chemotherapy. When Eilber compared intravenous (systemic) and intra-arterial routes for doxorubicin administration, the results were equal.

The higher the grade of soft tissue sarcomas, and the greater the size, the higher the risk of metastases. Local control is usually achieved with either radical surgery or radiation and surgery; survival reflects the distant dissemination of sarcoma. Adjuvant chemotherapy to increase survival rates seemed possible.

Cytotoxic chemotherapy offers temporary remission to many patients with advanced, unresectable sarcomas or widespread metastatic disease. A host of combinations of active agents have been evaluated, in both randomized and non-randomized trials. The most active agents include doxorubicin, ifosfamide, and DTIC, and response rates have varied from less than 20 per cent to over 65 per cent in selected series. The proportion of patients achieving a complete clinical remission varies from none to over 20 per cent, but is most commonly 10 to 15 per cent. Some of those achieving complete remission enjoy long-term survival free of disease. Doxorubicin has been the most effective single agent.

These same agents and combinations have been used as adjuvants in an attempt to destroy subclinical metastases in patients with locally controlled high-grade soft tissue sarcomas. Several non-randomized, comparative trials have suggested that this approach confers a survival benefit, but the majority of randomized trials have failed to demonstrate any advantage. One trial that suggested a benefit was performed at the National Cancer Institute, United States. As seen in Table 6 436, survival of the treated patients paralleled that of other studies, but the control group fared less well. The chemotherapy programme used in the NCI trial was quite toxic, and a high proportion of patients developed some degree of cardiac impairment, demonstrable by exercise testing or at rest. It was initially suggested that the benefit seen in this trial might reflect the use of chemotherapeutic agents at the maximum tolerable dose. A subsequent trial performed by the same investigators using lower doses of drugs did not show any survival advantage with the use of higher drug doses. No beneficial adjuvant chemotherapy programme for high-grade soft tissue sarcomas has therefore yet been established.

Patients who have an isolated recurrence or a limited number of pulmonary metastases may be treated by aggressive local or regional therapy; more than one-third of such patients survive for 5 years. Giuliano and associates reported achieving local control in 92 per cent of patients with isolated local recurrence of extremity or truncal soft tissue sarcoma. The actuarial 5-year survival in surgically treated patients was 87 per cent.

Patients with pulmonary metastases from soft tissue sarcoma can be successfully managed by resection. A more favourable prognosis correlates with fewer metastases, a longer interval between treatment of the primary tumour and diagnosis of the pulmonary metastasis, and a longer doubling time, measured from interval chest radiographs. An analysis by Roth et al. confirmed the value of these prognostic factors, but found that no single limit is sufficiently accurate to exclude patients from one attempt at control by resection of pulmonary metastases. Patients who present with recurrent pulmonary metastases following thoracotomy and resection of metastases may be successfully treated by a second procedure. Of 29 patients so treated in the NCI series, there was a 22 per cent 3-year actuarial survival. Because surgical resection of pulmonary metastases has a reasonable expectation of success, patients with high-grade soft tissue sarcomas should be monitored at 6-month intervals for at least 3 years after primary therapy. The use of chest CT scans has been advocated for this follow-up, but there are no data to suggest their superiority to chest radiographs.

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