Intra-arterial adriamycin, conventionally fractionated radiotherapy and conservative surgery for soft tissue sarcomas.

Thirteen patients with soft tissue sarcomas were treated with a combination of intra-arterial Adriamycin, conventionally fractionated radiotherapy (2 Gy per day), and conservative surgery (trimodal therapy). Severe acute complications occurred in 10 patients: 3 brachial artery thromboses, 6 delayed wound healing, 4 wound infections, and 3 cases of necrosis of the skin plus subcutaneous tissues. Three patients have developed local recurrence. Five patients are alive, 4 of whom are disease-free, and the median follow up time of surviving patients is 56 months. One has significant impairment of limb function due to joint ankylosis. An additional 2 patients were treated with intra-arterial Adriamycin and conservative surgery for local recurrence after previous surgery and radiotherapy; both died of subsequent metastatic disease, one having a further local recurrence. One patient with multifocal angiosarcoma was treated with intra-arterial Adriamycin and radiotherapy but no surgery, and is alive free of disease 49 months later. The combination of radiotherapy and intra-arterial Adriamycin with surgery resulted in significant acute toxicity. This small study has not demonstrated any improvement in local control compared with that expected with conservative surgery and radiotherapy alone.

High dose hyperfractionated radiotherapy in the treatment of extremity soft tissue sarcomas.

A hyperfractionated radiotherapy schedule has been evaluated in the treatment of 29 adults with limb or limb girdle soft tissue sarcomas. The objective was to increase the total administered dose and possibly improve local control, without increasing late normal tissue damage. Twice daily 1.25 Gy fractions (with a minimum interval of 6 h) have been given over 5 to 6 weeks to 12 patients pre-operatively, 10 post-operatively and 7 palliatively. Five patients received 62.5 Gy in 5 weeks pre-operatively and 3 palliatively. Nineteen of the remaining 21 patients received 75 Gy in 6 weeks with a field size reduction after 5 weeks. Sixteen of 29 tumours were situated in the thigh and only 2 were in the upper limb. Twenty were of high grade. The mean tumour size of those treated radically was 13.1 cm (range 5 to 40 cm). Sixteen patients (76%) given 75 Gy developed moderate or severe skin erythema maximal at 5 weeks. Despite the large field sizes used (mean phase one of 34.5 cm, and phase two of 22.8 cm) only 2 patients failed to complete the planned treatment because of the severity of these reactions. Two other patients developed partial wound breakdowns after the end of treatment--both healing spontaneously. Fourteen patients developed an area of moist desquamation--11 mild, 2 moderate and one severe. There have been four late wound breakdowns requiring surgical intervention; all have since healed well. The median follow up is short at 556 days. Ten of 19 evaluable patients have developed moderate/severe induration, 5/19 mild and 4/19 none.(ABSTRACT TRUNCATED AT 250 WORDS)

The vascularity of cutaneous melanoma: a quantitative histological study of lesions 0.85-1.25 mm in thickness.

The vascularity of 107 primary cutaneous melanomas has been characterized by morphometric histological analysis. The lesions selected for study were of thickness 0.85-1.25 mm and the aim was to evaluate the prognostic significance of tumour vascularity. Two groups of patients were identified; 86 with no evidence of recurrence after a minimum follow-up period of 5 years and 21 with locoregional recurrence and/or metastasis. The lectin Ulex europaeus type I was used for endothelial cell staining of tissue sections and morphometric analysis was performed to derive the vascular length, surface and volume density from independent measurements of tumour, adjacent dermis and the junctional zone between tumour and underlying tissue. A wide range of values was obtained for each parameter with increased vascularity always found at the tumour base compared with the tumour as a whole. In relation to the adjacent normal dermis, vascularity was generally found to be higher at the tumour base but either higher or lower in the tumour overall. Tumour recurrence could not be predicted by any of the derived vascular parameters either independently or together with other histological and clinical features. This study suggests that tumour vascularity is of no prognostic significance in melanoma of the above thickness range. The highly variable extent of tumour vascularity was not correlated with other clinical or histological parameters, but may have implications for the delivery of pharmaceutical agents used for diagnosis or therapy.

Focal myositis, a benign inflammatory pseudotumour: CT appearances.

Focal myositis is a rare benign pseudotumour of skeletal muscle, of unknown cause. Clinically it presents as an enlarging mass within muscle, usually of an extremity, and is often mistaken for a soft tissue neoplasm. The diagnosis is made by biopsy which reveals characteristic histological changes of inflammation, focal degeneration and regeneration, and some evidence of denervation. The CT findings include irregularity and enlargement of the muscles involved, with diffuse, poorly defined fatty infiltration of the muscle planes, but no evidence of an associated mass. We present two cases of focal myositis of the calf, both of which mimicked a soft tissue neoplasm, and in which CT was helpful in determining the nature and extent of the abnormality, for needle biopsy, and follow-up.

Chondrosarcoma of the pelvis: the role of palliative debulking surgery.

Curative resection of pelvic chondrosarcoma is sometimes technically impossible. In such cases, surgical debulking on one or more occasions may provide symptomatic relief. In a series of 12 patients with pelvic chondrosarcoma, three have undergone a single debulking procedure and three two or more such procedures. All six patients obtained symptomatic relief and five remain alive and well at a median of 12 months from surgery. Two patients have no clinical evidence of recurrent disease 21 and 25 months after the last debulking procedure.

Limb function following conservation treatment of adult soft tissue sarcoma.

Quality of life and limb function were studied in 54 patients who were disease-free 2 or more years after limb-conserving treatment for soft tissue sarcoma of the leg or pelvic girdle. Tumours of the thigh predominated (25 patients) and the mean tumour size was 9.9 cm. 41 patients had been treated with a combination of surgery and radiotherapy (29 with conventional and 12 with high dose), 12 with surgery alone and one with irradiation and intra-arterial doxorubicin. Only 15 patients had a normal range of movement in all lower limb joints and only 12 had normal power in all muscle groups; tumours of the lower leg were particularly unfavourable in this respect. Gait was normal in 42 patients but 8 required a walking aid and 4 a joint support. 16 had detectable lymphoedema but only 2 needed to wear compression hosiery. 35 patients still experienced pain at some time but only 6 required analgesia. However, when assessed by questionnaire for locomotion, grooming and home/leisure/vocational activities, 37 patients (68%) reported excellent function, and only 2 had moderate impairment. Function loss was most marked in leisure (25 patients) and vocational (8) activities, but was mild in 66% of cases. Multivariate analysis was carried out to determine the prognostic factors for poor limb function. The results suggested that overall functional score was predominantly determined by gait (P less than 0.001), muscle power or range of movement (P less than 0.001), with increasing age, female sex and the use of radiotherapy poor prognostic factors. Reduced muscle power or range of movement were the major factors determining gait (P less than 0.02) with the use of radiotherapy the significant prognostic factor for both in the conventionally treated group. Doses in excess of 60 Gy resulted in increased fibrosis and a worse functional outcome. Extent of surgery was not an independent prognostic factor for limb function, although univariate analysis suggested an association with range of movement in the conventionally treated group (P less than 0.025). Despite significant objective loss of range of movement and muscle power patients retain excellent limb function and quality of life following limb conserving treatment. For optimal function, radiotherapy should be given with small fractions to a dose not exceeding 60 Gy.

Innervation of the trapezius muscle: a study in patients undergoing neck dissections.

Twenty-four patients with surgical section of the accessory nerve and/or its cervical contribution(s) were examined from 1 to 156 months after surgery, and compared to twenty controls. Thirteen patients had a classical neck dissection; seven had the whole length of the accessory nerve preserved but not the cervical plexus contributions. Four had the upper half of the accessory nerve sectioned, but with preservation of both the lower half and its cervical contributions. Clinical and electrophysiological studies of the three portions of the trapezius suggested the existence of an undescribed motor nerve supply to the trapezius and of a motor input from the cervical plexus contributions via the accessory nerve. The former is also supported by an anatomical study.

Treatment of extremity soft tissue sarcomas with surgery and radiotherapy.

The results of treatment with a combination of surgery and radiotherapy of 102 patients with nonmetastatic extremity soft tissue sarcoma are reported. Seventy-nine patients were previously untreated and 23 had locally recurrent disease. Sixty-six tumours were situated in the lower limb and 16 in the limb girdles. Fifty-nine were high grade lesions, and 64 were over 5 cm in length. Surgical clearance was "good" (wide or radical) in only 34 cases. Sixty-eight patients received post-operative irradiation, 23 pre-operative irradiation and 11 both pre- and post-operative radiotherapy. Seventeen patients subsequently developed local recurrence and 9 of these remain disease-free after further surgery. Actuarial 5 year local control and disease-free survival rates for new cases were 87 and 65.4%; and for previously recurrent cases these figures fell to 75 and 54.8%. Following a univariate analysis of patient, tumour, surgical and radiotherapeutic factors only previous local recurrence (p less than 0.1 greater than 0.05) was found to significantly increase the risk of further local relapse. Multivariate analysis found high tumour grade [relative risk (RR) 8.4], tumour size greater than 15 cm (RR 3.66), previous local recurrence (RR 6.47) and proximal site (RR 12.7) to be independent poor risk factors for survival.

Diagnosis of soft tissue tumours by Tru-Cut biopsy.

Tru-Cut biopsies were obtained from 52 consecutive patients referred with soft tissue tumours. Forty-five patients had soft tissue sarcomas; seven had benign soft tissue tumours. Of the biopsies 96 per cent provided adequate material for diagnosis. The histological diagnosis made from the Tru-Cut biopsy was compared with that made from the resected specimen. There were no false positive diagnoses of malignancy. The accuracy of Tru-Cut biopsy was 98 per cent for the diagnosis of malignancy and 94 per cent for the diagnosis of sarcoma. Tumour subtype was correctly specified in 85 per cent of sarcomas and tumour grade in 88 per cent. Tru-Cut biopsy should replace open biopsy as the primary means of diagnosis of soft tissue tumours unless a satisfactory tissue sample cannot be obtained.

Hyperthermic isolated perfusion with melphalan in the treatment of advanced malignant melanoma of the lower limb.

A retrospective study of 91 patients with malignant melanoma treated by lower limb isolated hyperthermic regional perfusion was performed. Objective response in patients with evaluable disease was 78 per cent. The role of perfusion as primary treatment of large melanomas of the foot is confirmed and recommended. Control of locoregional disease and limb salvage remains a valuable and attainable therapeutic goal using this technique.

The influence of local recurrence of extremity soft tissue sarcoma on metastasis and survival.

One hundred seventy-five consecutive patients with soft tissue sarcoma of the limb and limb girdle were studied using univariate and multivariate analysis. The most important factor determining risk of local recurrence was the quality of treatment of the primary tumor, with wide or radical surgery plus radical radiotherapy obtaining the best local control. Tumor size, site, and histologic grade were not predictive of local recurrence. The important tumor variables predicting survival were tumor size at first presentation and histologic grade. Tumors with greater than 10 cm greatest diameter and high-grade tumors carried a poor prognosis. Local recurrence was significantly associated with reduced survival, but only when (correctly) considered as a time-dependent variable in multivariate analysis. Irradiation was also significantly associated with poor survival. Review of the literature indicates that local recurrence is believed to have little influence on survival. Since the relevant randomized controlled trials have been small, the evidence is inconclusive.

Role of compartmental resection for soft tissue sarcoma of the limb and limb girdle.

A total of 143 consecutive operations for soft tissue sarcoma of the extremity, performed by one surgeon over a 5-year period, was studied to determine the place of compartmental excision. The surgical aim was to achieve the nearest to radical surgery compatible with preservation of a functional limb. Of the operations, 73 were for previously untreated primary tumour and 70 for local recurrence. Two tumours arose in areas previously irradiated for other malignancies and 35 recurrences had occurred despite prior radiotherapy; of the 106 remaining cases, adjuvant radiotherapy was used for 79. Adjuvant chemotherapy was used only occasionally and was more often regional than systemic. For the majority of tumours, compartmentectomy was inappropriate or inadequate: 49 were extracompartmental in origin and 48 extended beyond their compartment of origin at the time of surgery. The remaining 46 were confined to one compartment; in only 21 of these 46 operations was a radical compartmental excision performed. Compartmental excision was more likely to be performed when the tumour was centrally located within a compartment, was so large that it replaced most of the muscle group, or was high grade or recurrent (particularly when adjuvant radiotherapy had already been used). The general preference was to combine less-than-radical surgery with adjuvant radiotherapy rather than sacrifice entire muscle groups or adjacent, functionally important, structures such as artery or nerve. This reflects the proven efficacy of radiotherapy in controlling microscopic disease. Overall, compartmental excision was considered appropriate in only 15 per cent of operations.

Limb conservation for soft tissue sarcomas of the shoulder and pelvic girdles.

Fifty-five patients with soft tissue sarcomas of the shoulder and pelvic girdles were treated between 1982 and 1987 with a consistent policy of limb conservation, using a wide variety of excisional and reconstructive surgical techniques and radical radiotherapy. Actuarial 5-year overall survival was 75 per cent for patients with low or intermediate grade tumours, and 38 per cent for those with high grade tumours (log rank test, P less than 0.05). Five-year local recurrence rates were 32 per cent for low or intermediate grade tumours, and 48 per cent for high grade tumours (log rank test, not significant). Multivariate analysis of the following risk factors for overall survival was performed: age, sex, tumour site, diameter, grade, inadequate surgical margins and local recurrence. Age over 55 years and high tumour grade emerged as independent prognostic variables for survival. Forequarter or hindquarter amputations were undertaken in seven of the 55 patients for local recurrence following previous limb-conserving surgery and radiotherapy. Local failure was not always salvaged by major amputation; satisfactory proximal tumour clearance was achieved in only two of seven patients undergoing major amputation; four of the seven patients developed stump recurrence, three of whom died with uncontrolled local disease. Meticulous attention to surgical and radiotherapeutic technique is required to minimize the incidence of local recurrence while maintaining satisfactory limb function.

Surgery in the management of soft tissue sarcoma.

Surgery and radiotherapy are complementary methods of achieving control of primary soft tissue sarcoma. The extent of operation is influenced by adjuvant irradiation which is important in limb conservation surgery where satisfactory margins are not always possible. Modern reconstructive techniques have extended the possibilities of salvage especially in the irradiated limb. Trucut needle biopsy provides an accurate tissue diagnosis in a high proportion of cases.

Structural alterations of the RB1 gene in human soft tissue tumours.

Sixty-nine primary soft tissue tumours were examined for alterations of the RB1 gene which has previously been implicated in the genesis of retinoblastoma. In three tumours loss of both alleles of this gene (homozygous deletion) was detected. Two of these, both leiomyosarcomas, contained a chromosomal breakpoint within the RB1 gene, while in the third tumour, a radiation induced sarcoma, complete deletion was observed. Using a probe that detects a polymorphic locus within the RB1 gene we found loss of only one allele (heterozygous deletion) in 33% of soft tissue sarcomas examined, including two leiomyosarcomas, a malignant peripheral nerve sheath tumour, a rhabdomyosarcoma and a chondrosarcoma. When taken together our results suggest that alterations of the RB1 locus may play an important part in the pathogenesis of soft tissue tumours and particularly in leiomyosarcomas which accounted for four of the eight RB1 alterations observed in this study.

Characterization of the translocation between chromosomes X and 18 in human synovial sarcomas.

Recent studies have identified a specific chromosomal translocation, t(X;18)(p11.2;q11.2), in a high proportion of human synovial sarcomas. As a first step towards characterizing the X;18 translocation we have established a synovial sarcoma cell line. Fusion of this cell line to mouse RAG cells gave rise to somatic cell hybrids that contain the derivative (X) marker chromosome in the absence of other genetic material from chromosomes 18 and X. Southern analysis of DNA from these somatic cell hybrids demonstrated that the human X chromosome markers DXS94, DXS14, DXZ1 and DXS62 were retained. In contrast DXS7, GAPDP1, ARAF1, DXS146 were not consistently present in the hybrids indicating that these markers were on the region of the X chromosome replaced by part of the long arm of chromosome 18 during the generation of the X;18 translocation. The predicted position of the translocation relative to X chromosome markers is DXS7-DXS146-X; 18-DXS14-DXZ1-DXS94.