Aim

While the association of surgery and radiation therapy in high grade Soft Tissue Sarcoma (STS) of extremities is considered the “golden standard”, there is not international agreement regarding type, timing, overall dose of radiation, and size, site and histology of tumours to be irradiated. A similar consideration is about low grade STS. The aim of our paper is critically reconsider our experience, trough a retrospective analysis of 15 years experience. This in order to propose a perspective protocol of treatment of high and low grade STS, in order to minimize the late complication rate.

Neoadjuvant therapy in soft-tissue sarcomas is still a controversial issues regarding indications, patients selection and treatment protocols. In the last fifteen years (1990–2005) at our Institution more than 600 patients affected by soft tissue sarcomas of the limbs and superficial trunk were surgically treated. Among these patients, 49 received preoperative chemotherapy (epirubicin plus ifosfamide, according to Italian Sarcoma Group protocol), associated to preoperative conventional external beam radiationtherapy in 36 cases (73.5%). The histologic types were liposarcoma (30,6%), synovial sarcoma (20,4%), fibrosarcoma (16,3%), pleomorphic sarcoma or malignant fibrous histiocitoma (12,1%), leiomyosarcoma (8,2%), other histotypes (12,1%). Tumor size was 10 cm or larger in 21 cases, 6 to 9 cm in 23 patients and 5 cm or smaller in 5 cases. Neoplasms were high-grade (Broders grade 3 or 4) in all cases but five.

After neoadjuvant treatment we performed a limb-sparing surgical excision of the tumor in 47 patients (96%), while a primary amputation of the limb was necessary in only two cases (4.1%). A vascularized miocutaneous flap was used in 8 cases, and adequate surgical margins were achieved in more than 70% of the cases.

Postoperative chemotherapy was given in 26 cases (53%), postoperative radiotherapy just in 5 (10%). We report the outcome data on these 49 cases, regarding overall survival, local or distant relapse, local and systemic complications, early and long-term limb salvage rate.

According to histologic examination of the resection specimen, average percent of necrosis after neoadjuvant treatment was 70.6% (range 30 – 99%). Wound dehiscence occurred in 6 patients but ultimately healed succesfully in all of them.

At an average follow-up of 23 months (range 3 – 82), 37 patients were continuously disease free (76%), two patients had local recurrence (one amputated), four patients were alive with metastatic disease, five patients had died with disseminated disease (at 4, 19, 28, 37 and 61 months after surgery), one patient had died of unrelated disease.

Due to the inconstant tumor response, neoadjuvant treatment in soft tissue tumors is still a controversial issue. On the basis of data presently available, we think that it can be a useful treatment in high-risk tumors (larger than 5 cm; high grade). In these cases, at a low and acceptable rate of local complications, the conjoined use of preoperative chemotherapy and radiotherapy can help to make a limb-salvage surgery possible and at the same time can maybe reduce the risk of distant metastasis.

In the last fifteen years (1990–2005) at our Institution more than 600 patients affected by soft tissue sarcomas of the limbs and superficial trunk were surgically treated. We investigated the outcome and risk factors in a homogeneous group of 112 patients, affected by high-grade soft tissue sarcomas of the limbs (not metastatic at presentation) and treated with limb-sparing surgery, brachytherapy and conventional postoperative radiation therapy. Postoperative chemotherapy was added in one fourth of the cases.

The histologic types were liposarcoma (21.4%), leiomyosarcoma (19.6%), synovial sarcoma (17.9%), pleomorphic sarcoma or malignant fibrous histiocitoma (14.3%), fibrosarcoma (9.8%), other histotypes (17%).

All the tumors were high-grade (Broders grade 3 or 4). Size of the neoplasm was 10 cm or larger in 8 cases, 6 to 9 cm in 60 patients and 5 cm or smaller in 44 cases.

A limb-sparing surgical excision was performed in all the cases; histologically adequate margins were achieved in 96 cases (85.7 %). In 28 cases a myocutaneous or fasciocutaneous flap was necessary for local reconstruction.

At an average follow-up of six years, 67 patients (59.8%) were continuously disease-free; 8 patients (7.1%) had presented metastatic disease (in one case combined with local relapse) but were alive with no evidence of disease at last follow-up; 3 patients (2.7%) were alive with metastatic disease; 28 patients (25%) had died with disseminated disease; 6 (5.4%) had died of unrelated causes.

Local recurrence occurred in 10 patients (8.9%) requiring an amputation in 2; metastatic disease occurred in 39 patients (34.8%).

Four more patients required an amputation for complications different from recurrence: one early amputation for surgery-related complications and three late amputations for radiation-related complications (two not-healing fractures, one unresolvable wound sloughing).

Wound sloughing occurred in 12 patients (5 surgery-related and 7 radiation-related).

Local control rate, disease-free survival, overall survival and limb salvage rate were examined at 5 and 10 years, aiming also to identify tumor or treatment characteristics with prognostic value for the outcome.

The use of brachytherapy is an important option for achieving a significant boost in radiation within the surgical bed. Combined treatment with limb sparing surgery plus brachytherapy and external beam radiation therapy seems to offer satisfactory results in terms of local control and limb salvage survival. The use of myocutaneous or fasciocutaneous flaps is often useful in this kind of surgery, making possible a limb-sparing procedure with adequate oncological margins. New protocols and randomized studies on chemotherapy need to be introduced to improve systemic control and overall survival.

Liposarcomas (LPS) are the most common soft tissue malignant tumor with a reported annual incidence of 2.5 per million people. The latest histopathologic classification of liposarcomas identifies three main groups: well-differentiated LPS; myxoid-round cell LPS; pleomorphic LPS. Dedifferentiated LPS is considered as a subgroup of well-differentiated LPS where there is an area of transition from a low grade to a high grade non lipogenic lesion (typically MFH or fibrosarcoma). The purpose of the present study was a retrospective review of the data of 146 consecutive patients affected by liposarcoma, with the aim to correlate the outcome of patients with treatment modalities and prognostic factors.

There were 89 males and 57 females with an average age of 54 years (range 16–92). The tumor grading following Broders criteria showed a low grade lesion in 48% of cases and a high grade lesion in 52% of cases. The histologic pattern showed a well differentiated liposarcoma in 25 patients (17%). The most frequent histologic finding was a myxoid liposarcoma in 55 cases (38%) while a round cell component of variable rate was seen in 22 cases (15%). A pleomorphic LPS was observed in 32 cases (22%). Dedifferentiated liposarcoma occurred only in 3 cases (2%). Surgery alone was performed in 31% of cases while chemotherapy (adriamycin and ifosfamide) and/or radiationtherapy were associated in 69% of cases. Brachytherapy was performed in 50 cases. Surgical margins resulted radical in 4 (2.5%) of cases, wide in 89 (61%), marginal in 45 (31%) and intralesional in 8 (5.5%) of cases.

In 10 cases (6.8%) a local recurrence occurred and in 33 cases (22.6%) a metastatic lesion was observed. Local recurrence were treated with surgical excision in 7 cases and with amputation in 3 cases. At an average follow up of 55 months, 68.5% of patients were continuosly disease free, 6.8% were disease free after local recurrence or metastasis excision or both, 4.8% were alive with disease, 14.4% were dead of the disease, 5.5% were dead of other cause. Eleven patients (7%) underwent an amputation, in 5 cases as first surgical procedure, in 3 cases after a local recurrence and in 3 cases for complications of the radiationtherapy. Local control was significantly correlated with the type of surgery at presentation and with surgical margins. Overall survival was significantly correlated with surgical margins, with grading and with the histotype of the tumor.

In the present series of soft tissue liposarcoma the combined treatment allowed limb salvage in 93% of cases (7% of amputations). Virgin lesions at presentation and free surgical margins resulted positive prognostic factors for local control. The histotype of the tumor, grading, and surgical margins resulted significative prognostic factors in survival, with round-cell and pleomorphic and high grade lesions showing the worse prognosis.