Limb-sparing therapy of extremity soft tissue sarcomas: treatment outcome and long-term functional results.

The purpose of this study is to assess the long-term success rate and functional results of limb-sparing therapy in a group of 156 patients with soft tissue sarcomas of the extremities in the Netherlands Cancer Institute, treated according to a standard protocol of surgery and radiotherapy, if indicated. The patients (79 females and 77 males) were treated between 1977 and 1983 by an intended wide local excision with a margin of at least 2 cm. Postoperative radiotherapy was applied in 117 patients; 26 patients had surgery only, including 13 patients who had to be treated by amputation. The total dose was 60 Gy, with 40 Gy to a large volume and a boost of 20 Gy to the tumour bed at 2 Gy per fraction, five fractions per week. Most sarcomas were located in the proximal part of the lower extremity (51%). The group comprised 50 liposarcomas, 47 malignant fibrous hystiocystoma (MFH) and 59 other histologies; 69 (44%) had high-grade tumours. Three treatment groups with limb-sparing treatment were defined: group I (n = 26) patients who had a complete excision receiving no further treatment, group II (n = 64) with narrow surgical margins and radiotherapy and group III (n = 53) with incomplete resection and radiotherapy. The 10-year actuarial overall survival and local control rate for all patients was 63 and 81%, respectively. Multivariate analysis showed that histological grade (P < 0.0001), age (P = 0.0005) and location deep to the fascia (P = 0.0008) were independent prognostic factors for survival, while local control was predicted by grade (P = 0.0014) and treatment group (p = 0.028). Patients with surgery only (group I) had 81% 5-year local control as compared to 92% with radiotherapy after narrow surgery (group II) and 74% with incomplete surgery and radiotherapy (group III). Limb preservation when attempted was achieved in 90% of the patients. After limb-sparing treatment, 7% had severe impairment of mobility, 3% had lymph oedema and 16% marked fibrosis. Fractures in the irradiated bone occurred in 6% of the patients. The combination of limited surgery followed by radiotherapy resulted in a high local control rate with good functional results. Ultimately limb sparing treatment was successful in 83% of all patients with extremity sarcomas.

A randomised phase II study on neo-adjuvant chemotherapy for 'high-risk' adult soft-tissue sarcoma.

The aim of this study was to examine the strategy, feasibility and outcome of neo-adjuvant chemotherapy, with doxorubicin and ifosfamide, in adult patients with 'high-risk' soft-tissue sarcomas. Patients with 'high-risk' soft-tissue sarcomas, defined as tumours > or =8 cm of any grade, or grade II/III tumours <8 cm, or grade II/III locally recurrent tumours, or grade II/III tumours with inadequate surgery performed in the previous 6 weeks and therefore requiring further surgery, were randomised between either surgery alone or three cycles of 3-weekly doxorubicin 50 mg/m(2) intravenous (i.v.) bolus and ifosfamide 5 g/m(2) (24 h infusion) before surgery. The type of surgery had to be planned at randomisation. Tumours were to be amenable to surgery by amputation, compartmental resection, wide or marginal excision. If chemotherapy was given, surgery had to be performed within 21 days after the last chemotherapy. Patients received postoperative radiotherapy in cases of marginal surgery, microscopically incomplete resection and no further possibility for surgery, and in cases of surgery because of local recurrence. 150 patients were entered into the study and 134 were eligible, 67 in each arm. The most frequent side-effects of chemotherapy were alopecia, nausea and vomiting (95%), and leucocytopenia (32%). One patient died of neutropenic fever after the first cycle of chemotherapy. Chemotherapy did not interfere with planned surgery and did not affect postoperative wound healing. Limb-salvage was achieved in 88%, amputation was necessary in 12% (all according to the plan at randomisation). The trial was closed after completion of phase II, since accrual was too slow to justify expanding the study into the scheduled phase III study. At a median follow-up of 7.3 years, the 5 year disease-free survival is estimated at 52% for the no chemotherapy and 56% for the chemotherapy arm (standard error: 7%) (P=0.3548). The 5 year overall survival for both arms is 64 and 65%, respectively (standard error 7%) (P=0.2204). Neo-adjuvant-chemotherapy with doxorubicin and ifosfamide at these doses and with this schedule was feasible and did not compromise subsequent treatment, surgery with or without radiotherapy. Although not powered to draw definitive conclusions on benefit, but with an at least 7 year median follow-up, the results render it less likely that major survival benefits will be achieved with this type of chemotherapy.

Epithelioid sarcoma.

In a 9-year period we treated 11 patients with an epithelioid sarcoma. Most patients were young adults. The tumour affected mainly the distal upper extremity (hand and fingers: four patients; wrist and forearm: three patients); one patient had an epithelioid sarcoma of the knee. Trunk localizations were seen in two patients and one patient presented with a vulva localization. Treatment consisted of surgery, regional isolation perfusion with doxorubicin (Adriamycin) or melphalan, radiation therapy, systemic chemotherapy or a combination of these modalities. Radical surgery in eight patients resulted in only two local recurrences. Locoregional metastases occurred in five patients. In five patients a therapeutic lymph node dissection was performed, in all instances followed by extensive recurrent disease. Distant metastases were seen in seven patients and mainly affected the skeleton (6x) and the lungs (4x); in the majority of cases these metastases occurred within a year after excision of the primary. Remissions following regional or systemic chemotherapy were not observed. At the time of analysis seven patients had died as a result of their epithelioid sarcoma; two patients were still alive with tumour 18 and 27 months after diagnosis. Only two patients remained tumour free for 17 and 65 months respectively following radical surgery, postoperative radiation therapy and (in one case) adjuvant chemotherapy. It is concluded that epithelioid sarcoma is a rare but exceedingly aggressive tumour. Since early diagnosis can only be auspicious, familiarity with the clinical features is of great importance.

Regional lymph node metastases in patients with soft tissue sarcomas of the extremities, what are the therapeutic consequences?

In the period 1977-1983, 183 adult patients with soft tissue sarcomas of the extremities were treated in the Netherlands Cancer Institute. One hundred and seventy-one patients had initially operable tumors. Fifteen patients (8.2%) developed regional lymph node metastases (RLNM) during the course of their disease. Only two patients (1.2%) developed RLNM as first site of tumor recurrence. The incidence of RLNM varied according to the histological subtypes: liposarcoma: 1/64, fibrosarcoma: 1/12, tendosynovial sarcoma: 5/24, unclassifiable sarcoma: 3/8. The outcome in patients with RLNM was invariably fatal. In all cases with RNLM distant metastases were present either at the time RLNM were found or shortly afterwards (median 4 months). Based on this experience we now consider RLNM in soft tissue sarcoma an expression of systemic tumor spread, which should be treated as such. We find no indication for elective lymph node dissection as part of the initial treatment of soft tissue sarcoma of any histological subtype. Therapeutic lymph node dissection might be indicated as part of the palliative management.

Dermatofibrosarcoma protuberans: treatment and prognosis.

Dermatofibrosarcoma protuberans (DFSP) is a rare tumor of the skin with a strong tendency to recur locally. Nineteen cases of DFSP are presented. In eight of them a total of 20 local recurrences occurred, in five after irradical and in three after 'narrow' excisions. After wide excision (greater than 2 cm) for primary or wide re-excision for recurrent tumor, all patients remained free of tumor with a mean follow-up of 13.2 years (range 2-28 years). An extensive literature review revealed 913 cases of DFSP. The overall recurrence rate is about 50%; after adequate wide excision, 13%. Recurrent tumor is safely treated by wide re-excision and the recurrence rate is then 12%. Regional and distant recurrences are infrequent. Eleven cases (1%) were reported to have regional lymph node metastases and 37 (4%, 17 of whom were histologically confirmed) distant metastases, principally in the lung. The prognosis after appearance of regional or distant recurrence is bad. The role of radiotherapy in the management of this tumor is unclear. Primary or recurrent DFSP is best treated by surgical excision with a minimal margin of 2- preferably 3-cm of surrounding skin including the underlying fascia. Elective lymph node dissection is not advised.

Surgical repair of radiation damage of the rectum: a systematic approach to a difficult problem.

Twenty-three patients with serious irradiation damage of the rectum underwent surgical treatment. Patients were classified according to the level of the lesion and the presence of stenosis. Patients with high lesions (Type I) (n = 5), were treated by resection with end to end anastomosis. Patients with low lesions, with stenosis (Type II) (n = 6), were treated by resection with descending colon flap repair. Patients with low lesions, without stenosis (Type III) (n = 7) were treated by gracilis muscle repair. The remaining patients (n = 5) with miscellaneous, often complex problems (Type IV) were treated by a variety of techniques. Results in Type I, II, and III patients were encouraging with 80% of the reconstructed patients obtaining normal faecal continence.

Surgical intervention for complications caused by late radiation damage of the small bowel: a retrospective analysis.

We studied the records of 46 patients who had been operated on between 1974 and 1990 in The Netherlands Cancer Institute because of complications due to late radiation damage of the small bowel. Data were collected on preoperative history, surgical intervention, postoperative complications and survival. By means of Cox's proportional hazards regression analysis we sought to identify factors that contribute to complication-risk and survival. The following factors led to an increase in complication-risk: hypoalbuminemia, more than one laparotomy prior to irradiation and a short interval (< 12 months) between irradiation and surgical intervention. The following factors related to a poorer survival: incomplete resection of the primary tumor and a short interval (< 12 months) between irradiation and surgical intervention. The type of surgical intervention did not have cumulative prognostic value in relation to complication-risk or survival. As patients undergoing resections differed considerably from patients undergoing bypass-procedures, no conclusions could be drawn about the superiority of one technique over the other. We think that both types of intervention have their own field of indication.

Report of a symposium on diagnosis and treatment of adult soft tissue sarcomas in the head and neck.

A series of presentations and discussions was held during a symposium on the diagnosis and treatment of adult soft tissue sarcomas in the head and neck (HNSTS). The purpose of this meeting was to define guidelines on diagnosis and treatment of HNSTS. The results of this symposium are summarized and condensed in this report. Recommendations are made for diagnostic strategies and for treatment. Diagnostic efforts in PET scanning and dynamic MRI need to be expanded to detect early recurrences. Firm pathological diagnosis remains the basis for further treatment strategy. Wide surgical excision, if feasible, in combination with radiotherapy is the treatment of choice.

The impact of the CUSA ultrasonic dissection device on major liver resections.

Between 1982 and 1990 major liver resections were carried out in 28 patients, in 14 with the conventional technique, in 14 with the Cavitron ultrasonic surgical aspirator (CUSA) dissection device. The patients in the CUSA group were older and had more often multiple metastases. Peroperative blood loss, duration of operations, postoperative morbidity and mortality, ICU stay and overally hospital stay were all reduced in the CUSA group; for peroperative blood loss (p less than 0.05) and duration of operation (p less than 0.01) the reduction was statistically significant. The use of CUSA has contributed to the increased safety of liver resections.

Early-stage rectal cancer: electrofulguration in comparison to abdominoperineal extirpation or low-anterior resection.

For some small rectal cancers electrofulguration can be an attractive alternative to more extensive surgical procedures. This report is a review of 49 patients who, after careful selection, were considered ideal candidates for curative fulguration in the period 1959-1982. All had rectal adenocarcinomas and were clinically staged as Dukes' A tumors. To put the results of this analysis into perspective, they are compared to the results of those patients (34) who also had early clinical stage rectal adenocarcinomas, but for a variety of reasons underwent abdominoperineal excisions (APE, 11 patients) or low-anterior resections (LAR, 23 patients) instead of fulguration. Postoperative complications after fulguration were minimal, there were no postoperative deaths, and all patients retained anal continence. After APE or LAR there were two postoperative deaths (one myocardial infarction, one ruptured iliac aneurysm); postoperative morbidity was greater. All LAR-treated patients remained continent. Of the patients at risk 55% remained disease-free after fulguration, while 77% remained disease-free after APE or LAR (P = 0.023). This is due to a higher percentage of loco-regional recurrences occurring after fulguration than after APE or LAR (31% vs 9%, respectively, P = 0.021). The percentage of patients with distant metastases in both groups are similar. It seems that electrofulguration of rectal cancers, even in strictly selected patients in a specialized institution, can lead to an unacceptably high percentage of patients with loco-regional recurrences. Nearly all local failures occurred in patients with tumors that measured more than 3 cm in diameter and/or occupied more than one-third of the rectal circumference. Salvage operations for loco-regional failure were performed in 13 patients, 5 of whom are alive with no evidence of disease. Since there seems to be a direct relation between tumor size and the chance of loco-regional recurrence and since salvage operations for local failure are not uniformly successful, electrofulguration for cure must be reserved for the very rare patient with a very small early-stage rectal cancer.

Resectable retroperitoneal soft tissue sarcomas. The effect of extent of resection and postoperative radiation therapy on local tumor control.

BACKGROUND: Soft tissue malignancies of the retroperitoneum are rare. Surgery is commonly considered the first choice of treatment. There is still no consensus concerning the precise value of the extent of surgery and the value of additional treatment modalities. METHODS: From 1973 to 1990, 34 patients were initially treated by surgery for retroperitoneal soft tissue sarcomas at the Netherlands Cancer Institute. In a retrospective study, the prognostic effect of extent of primary surgery and postoperative radiation therapy was examined. RESULTS: Liposarcomas (47%) and leiomyosarcomas (29%) were the histologic types most commonly found. Grade of malignancy was defined as medium to high (II/III) in 44% and as low (I) in 38%. Complete (extended or marginal) resection of the tumor was achieved in 29 patients. After complete resection, the 5-year survival rate and the local recurrence rate were 35% and 63%, respectively. Extended surgery (performed in eight patients) showed a local recurrence rate of 50%. Thirteen patients received high-dose postoperative radiation therapy, which was found to have a significant favorable effect on the recurrence-free interval (P < 0.01). CONCLUSIONS: We conclude that complete (extended) resection followed by high-dose postoperative radiation therapy improves the prognostic outcome of patients with retroperitoneal soft tissue sarcomas.