Selective combination of modalities in soft tissue sarcomas: limb salvage and survival

One hundred fifty-two consecutive patients with soft tissue sarcomas were operated in the period 1977 through 1985. Eighty-seven patients with minimum resection margin of 2 cm or greater had no further local therapy, whereas 65 patients with minimum margin less than 2 cm had adjuvant postoperative radiation. Of 121 patients with extremity sarcomas, only 5 (4%) were managed with amputation. The overall 5-year survival rate is 58%, and for patients with extremity tumors, 67%. The 5-year local recurrence rate in extremity sarcomas was 10% for patients with minimum surgical margins 2 cm or greater and no further local therapy, and 6% for those with lesser surgical margins and adjuvant postoperative radiation. With selective combination of modalities limb salvage can now be practiced in 96% of the patients with acceptable local control and survival rates.     

Feasibility of limb salvage and survival in soft tissue sarcomas

One hundred nine consecutive patients with soft tissue sarcomas were treated in the period 1977 through 1983. Of 85 patients with extremity sarcomas, only 3 patients (4%) were managed with amputation, whereas in the previous decade, 40% of such patients were treated with amputation in our institute. The current 5-year survival rate is 63%; in the previous decade it was 45%. In the current series, for extremity locations, patients with minimum surgical margins of 2 cm or greater and no further local therapy had a 5-year local recurrence rate of 17%, whereas those with minimum surgical margins of less than 2 cm and who were treated with adjuvant postoperative radiation had a local recurrence rate of 7%. In the previous period, the local recurrence rate was 30% after wide resection and 66.6% after local excision. With a combination of modalities, limb salvage can be practiced currently in the majority of patients with extremity soft tissue sarcomas without any adverse effect on recurrence rates and survival.     

Limb salvage in soft tissue sarcomas with selective combination of modalities

One hundred and seventy-one consecutive patients with soft tissue sarcomas were treated in the period 1977-1986. Of 144 patients with extremity sarcomas, only eight (6%) were managed with amputation. The overall estimated 5-year survival rate is 64%, and that for patients with extremity tumors is 71%. The 5-year local recurrence rate in extremity sarcomas was 6% for patients with minimum surgical margins 2 cm or greater and no further local therapy, and 6% for those with narrower surgical margins and adjuvant postoperative radiation; 80 patients (56%) were in the former group and 64 (44%) in the latter. With a selective combination of modalities, limb salvage can now be practiced in 94% of the patients with acceptable local control and survival rates.     

Randomized study of systemic chemotherapy following complete excision of nonosseous sarcomas

Between June 1975 and April 1981, 61 of the 177 eligible patients whose nonosseous sarcomas of extremity or trunk origin had been completely excised primarily or after local recurrences agreed to participate in a randomized study of adjuvant chemotherapy. Dermatofibrosarcoma, lymphomas, myeloma, Kaposi's sarcoma, and embryonal rhabdomyosarcoma were excluded as were patients with significant second primary cancers and those who received either preoperative or postoperative radiation therapy. After stratification by anatomic status of disease, site of origin, and histologic grade, a random one half of the 61 participants began alternating courses of vincristine/cyclophosphamide/dactinomycin, and vincristine/doxorubicin/dacarbazine at six-week intervals for one year. The control group was evaluated at six-week intervals without adjuvant chemotherapy, but these patients were offered this chemotherapy later if they had progressive disease excised. Although 30% of the 61 patients experienced local recurrence of disease within the first five years after randomization, and only 54% were continuously disease free for five or more years, 82% were surviving at five years (Kaplan-Meier calculations) with a median follow-up of 64.3 months. Partial suppression of distant metastasis by adjuvant chemotherapy was apparent in the overall study, in the extremity tumor category, and in the subgroup of patients who had received limb-sparing surgery; however, no survival advantage for chemotherapy-treated patients was demonstrated. The 30 adjuvant chemotherapy-treated patients received a total of three thoracotomies as compared with 17 salvage thoracotomies for the 31 control patients; however, salvage surgery for local recurrences has been similar in the two groups. Recent improvement in the survival of patients with soft-tissue sarcomas is not necessarily a result of adjuvant chemotherapy or radiation therapy.     

A randomized prospective trial using postoperative adjuvant chemotherapy (adriamycin) in high-grade extremity soft-tissue sarcoma

From March 1981 to December 1984 119 patients with primary grade III extremity soft-tissue sarcoma were randomized postoperatively to single agent Adriamycin (57) or to control, no adjuvant chemotherapy (62). Adjuvant therapy was begun within 6 weeks of surgery, and consisted of Adriamycin 90 mg/m2 given over 2 days, once a month for 5 months. All patients had received preoperative intraarterial Adriamycin, radiation therapy (1,750 cGy) and subsequent surgical excision. At a median follow-up of 28 months there was no difference between the two groups in overall survival (Adriamycin = 84%, control = 80%), local tumor recurrence, or in the disease-free survival (Adriamycin = 58%, control = 54%). This study indicates that the use of single-agent Adriamycin as postoperative adjuvant chemotherapy has no significant clinical benefit in patients with high-grade extremity soft-tissue sarcoma treated with preoperative Adriamycin, radiation, and surgical excision. Although the Adriamycin postoperative adjuvant chemotherapy did not significantly benefit the experimental group relative to the control group, both groups of patients had an improved disease-free and overall survival rate compared to historical controls.     

Treatment and local control of primary extremity soft tissue sarcomas.

BACKGROUND AND OBJECTIVES: Modern series of adult extremity soft tissue sarcomas utilize combinations of modalities in all patients. Remaining questions: 1) is it necessary to strive for wide margins in the multimodality era; 2) to use adjuvant therapy in every high-grade sarcoma? 3) Does previous partial or marginal resection seriously interfere with the definitive resection? METHODS: In a retrospective review of 194 extremity soft tissue sarcomas (1977-1994), limb preservation was possible in 181/194 (93%) of cases. Patients with narrow margins received adjuvant radiation. Some patients were referred after partial (n = 39) or "complete" (n = 63) excision. RESULTS: Local recurrence was observed in 181/141 (13%) of patients treated with wide or compartmental resection, and in 10 of 42 (24%) of those treated with conservative resection plus radiation (P = 0.14). The 5-year survival rate for grade III, >/=5-cm sarcomas was not significantly different (P = 0.82) with adjuvant (46%) or without (48%) adjuvant systemic chemotherapy. Five-year survival varied (P = 0.0001) according to grade. Patients referred with partial, or "complete" (63%, 38/63, had residual tumor at reoperation) excision had a local recurrence rate of 8% and 6%, and 5-year survival rates of 75% and 84%, respectively. CONCLUSIONS: 1) It is important to strive for wide margins even when adjuvant radiation is intended. 2) When a wide margin is possible, adjuvant radiation may not be necessary. 3) Adjuvant systemic chemotherapy may be considered for high-grade tumors, preferably within a prospective protocol. 4) A partial or "complete" excision of the tumor before referral to a tertiary center does not appear to compromise the limb preservation, local control, or survival rates of these patients.     

Adjuvant therapy for sarcomas.

Adjuvant therapy is currently established in the treatment of osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma. Of the 12 reported randomized studies of adjuvant chemotherapy for soft tissue sarcoma, only 2 show a significant overall survival advantage for chemotherapy (the most important endpoint). In three randomized trials, the survival of the observation arm exceeds that of the chemotherapy arm. In two additional studies, subset analyses currently indicate a significant DFS advantage for adjuvant chemotherapy in extremity lesions, but no significant improvement in survival. Although initial NCI reports showed significantly prolonged survival for the subset of chemotherapy-treated extremity primaries, survival on longer follow-up is no longer significantly different. In the subset analysis of retroperitoneal sarcomas in the same NCI study, the survival of the control group is superior to the treatment group. Doxorubicin associated cardiotoxicity has occurred in about 10% of treated patients, occasionally contributing to treatment-related deaths. Based on these data, adjuvant chemotherapy should be considered investigational for adult soft-tissue sarcomas of any primary site. Future randomized trials should include patients at high risk for metastases (large, high-grade lesions) with a reasonable likelihood of local control by radical resection, or resection with uninvolved margins and subsequent radiotherapy. Low-grade sarcomas are currently cured by surgical resection in 80% of cases, and thus should not be included in adjuvant trials.     

Barriers to rehabilitation of patients with extremity sarcomas

The treatment of most extremity bone or soft tissue sarcomas involves either limb salvage surgery with adjuvant chemoradiation therapy or amputation. The rehabilitation of patients with extremity sarcomas is challenging, and the approach differs depending on the choice of surgical procedure as well as potential-associated medical complications. Early, interdisciplinary rehabilitation involvement is helpful in lessening the impact of expected impairments and disability. There is a lack of evidence examining specific rehabilitation interventions in this patient population. Functional outcomes and quality of life studies suggest overall similar findings between limb salvage patients and amputees, but with differences in various subscales. Rehabilitation interventions are therefore individualized; based on the assessment of medical limitations, functional goals and expectations, and modification of environmental factors. Overcoming medical and oncologic barriers to rehabilitation; as well as psychological, structural, cultural, political, and economic barriers; can serve to lessen the degree of disability.     

How much is a leg worth following radical tumor resection in bone sarcomas? Literature review

Bone sarcomas of the lower extremities are rare malignancies occurring mostly amongst adolescents and young adults. Necessarily, the therapy conducted in sarcoma centers is multimodal and multidisciplinary. In certain cases, in a metastasis free situation with adequate therapy, an overall survival rate of 90% can be achieved. Two principal surgical procedures exit for the local control of the malignancy: 1. Limb salvage with biological with/or endoprosthetic reconstruction; and, 2. amputation with restoration of the function with exoprosthesis or endo-exoprosthesis. Currently, limb salvage procedures are performed in up to 95% of cases. In contrast, amputation is performed when the disease has reached an advanced stage or limb salvage has failed. Both of the surgical options have their risks and possible complications.According to the literature, there should be no significant difference between limb salvage and amputation with respect to long-term overall survival, overall quality of life, psycho-socio-economic outcomes, or patient satisfaction. An important advantage of limb salvage is greater everyday functionality.With the expanded indication of limb salvage and great survival rates, the cases of late complications in patients expecting to maintain their own leg continues to increase.In some cases, it requires multiple interventions, ranging from minor up to the most complex revisions, to maintain the functionality of the extremity. Despite the great costs, personal effort, and the possible complications, limb salvage could be a suitable method to achieve functionally beneficial outcomes and patient satisfaction in bone sarcomas of the lower extremities over the long-term even in cases involving complications.     

Soft tissue sarcomas of the lower extremity: surgical treatment and outcome.

AIMS: The aims of this retrospective follow-up study were to evaluate the justification for limb-saving multi-disciplinary treatment of soft tissue sarcomas (STS) and to report the results achieved by our treatment protocol. Local control was studied, with emphasis on tumour depth, operation margin and need for post-operative radiotherapy. METHODS: We examined 130 patients with STS in the lower limb referred to the multi-disciplinary group of Helsinki University Central Hospital. For the survival analysis 106 patients with local disease remained. The goal of treatment was to preserve a functional limb. Wide excision was attempted. If the margin was less than 2.5 cm, post-operative radiotherapy (RT) was delivered to all except 20 patients. RESULTS: Ninety-two per cent of the patients were treated by limb salvage. The success rate of free flaps was 16 out of 18. The 5-year disease-specific overall survival was 76%, metastasis-free survival 72% and local control 79%. Prognostic factors for local recurrence were extracompartmental site and large size; for development of metastases high grade, extracompartmental site and large size; for decreased disease-specific overall survival high grade, large size and advanced age. Local control of intramuscular tumours (n=6) was 100%, subcutaneous tumours (n=38) 94% and tumours penetrating the deep or muscle fascia and those locating extracompartmentally (n=62) 67%. CONCLUSIONS: Limb salvage in patients with STS is possible with an acceptable outcome by selective combination of treatment modalities. Modern plastic surgical methods with free tissue transfers are successful and often needed. Subcutaneous and intramuscular tumours have good local control. The outcome is poorest for tumours penetrating the deep or muscle fascia and for those located extracompartmentally, and patients with such tumours might be a target for adjuvant therapy. Treatment should be coordinated by multidisciplinary teams.     

Actualisation de la stratégie thérapeutique locorégionale dans les sarcomes des tissus mous et les tumeurs desmoïdes des membres

The treatment of soft tissue sarcomas of limbs should be discussed within an experienced multimodality team. Surgical resection remains the cornerstone of therapy for localized disease and achieves a five years overall survival around 75% and a local recurrence rate as low as 10% in the best series. In complex cases, neo-adjuvant treatments may be used such as systemic chemotherapy, isolated limb perfusion, or radiotherapy to achieve an optimal conservative approach. Molecular genetics of sarcomas and quality of margins are essential to guide diagnosis and therapeutic selection. In case of marginal or incomplete resection, a new enlarged surgical resection should always be discussed before administration of any adjuvant treatments. Many retrospective studies and two randomized studies (one of adjuvant brachytherapy and one of external beam radiotherapy) have shown that adjuvant radiotherapy after complete surgery significantly reduces the risk of local recurrence in extremity soft tissue sarcomas. A randomized study has compared pre- to postoperative radiotherapy. The results in terms of local control are similar in both arms. The risk of surgical complications is higher in the preoperative arm and the risk of late sequelae is higher in the postoperative arm. A randomized study within the French sarcoma group is ongoing evaluating the omission of postoperative radiotherapy in favourable cases. Presently, the role of systematic first-line invasive treatment (including surgery and/or radiotherapy) of desmoids is debated. It is becoming evident that up to 50% of patients with desmoids benefit from a front-line non-aggressive policy, because growth arrest is a common feature of this disease. Additional study of the molecular determinants of desmoid behaviour is needed to guide treatment.     

Sarcomas of soft tissue and bone

Sarcomas arise primarily from mesenchymal structures at any site in the body, even within visceral stroma and neurovascular bundles. Sarcomas have been associated with prior radiation therapy, toxic exposures, and genetic conditions and soft tissue sarcomas have been distinguished from bone sarcomas. For localized soft tissue sarcoma, tumor grade is the most important prognostic variable. Low-grade tumors are generally cured by wide surgical excision, but there is a significant rate of both local recurrence and development of distant metastasis in high-grade lesions. The treatment of soft tissue sarcoma histologic subtypes is generally similar grade-for-grade, with the exception of rhabomyosarcoma, Kaposi's sarcoma, and mesothelioma. Tumor location strongly influences resectability. Radiation therapy has been used successfully in conjunction with conservative surgery to improve local control rates for soft tissue sarcomas, particularly in extremity lesions. Currently, adjuvant chemotherapy remains unproven for most adult soft tissue sarcomas, but is established in the treatment of rhabdomyosarcomas, osteosarcomas, and Ewing's sarcomas.     

Adjuvant therapy for extremity sarcomas

Opinion statement Extremity soft tissue sarcomas (STS) represent a rare, heterogeneous malignancy. Surgery is the primary treatment for patients with no evidence of metastatic disease, and for small low-grade superficial tumors in which adequate margins can be obtained, it may be the only therapy indicated. For large, deep tumors or tumors that are close to important neurovascular structures or bone, the addition of radiotherapy to resection has improved local control and increased limb salvage without affecting overall survival. Adjuvant chemotherapy has been an issue of considerable debate. Because 50% of patients with high-risk tumors will develop metastatic disease, effective systemic treatment with chemotherapy is needed. Unfortunately, studies have shown minimal improvement in overall survival when chemotherapy is added to the local treatment of high-risk extremity STS. More recently, a few trials of neoadjuvant chemotherapy consisting of mesna, doxorubicin, ifosfamide, and dacarbazine and high-dose doxorubicin and ifosfamide have shown some early promising results, but at the price of increased toxicity. Targeted therapy has shown some of its best results with gastrointestinal stromal tumors, but so far there has been little success in treating extremity STS. At this time, high-dose adjuvant or neoadjuvant chemotherapy should be given in the setting of a clinical trial to patients with high-risk tumors who can tolerate a potentially toxic chemotherapeutic regimen. The goal of these trials should be to assess new combination therapies, possibly including targeted therapies, for the management of large highgrade, high-risk soft tissue sarcomas.     

Extremity preservation by combined modality therapy in sarcomas of the hand and foot: an analysis of local control, disease free survival and functional result

A primary tumor arising in the hand or foot represents an uncommon presentation for patients with Ewing's sarcoma (ES) or soft tissue sarcoma (STS). While there exists considerable literature on the treatment of extremity sarcomas, very little deals specifically with lesions of the hand or foot. It remains controversial whether these lesions can be successfully treated with combined modality therapy which preserves the extremity and maintains function. From 1972 to 1979, 10 patients with sarcomas arising in the hand or foot were treated with combined modality therapy at the National Cancer Institute. Seven patients with ES of bone received local irradiation to 5000 rad and combination chemotherapy following an incisional biopsy. Three patients with STS received a gross tumor excision and local irradiation to 6000 rad. One STS patient also received combination chemotherapy. Local control was achieved in nine patients (90%) with a follow-up of 30-119 months (median 56 months). These patients have complete or almost complete function of the treated extremity. Nine patients are alive with five patients remaining disease-free following the initial combined modality treatment. Two patients with Ewing's sarcoma relapsed (1 patient with both local and distant failure) at 26 and 58 months and were again rendered disease-free with surgery, total body irradiation and further chemotherapy. One patient relapsed for a second time, being disease-free from the first relapse for 30 months. We conclude that for selected patients with sarcomas arising in the hand or foot, combined modality therapy which leaves the extremity intact results in excellent local tumor control and preserves function. Careful treatment planning is an essential aspect of successful radiation therapy of a hand or foot primary. Our treatment recommendations are outlined. This approach is a viable alternative to amputation in these patients.     

Adjuvant Radiation Therapy of Retroperitoneal Sarcoma: The Role of Intraoperative Radiotherapy (IORT)

Purpose. The purpose is to review the natural history, the clinicopathological prognostic factors, and the role of adjuvant radiation therapy with particular attention to the limited but favorable experience with IORT.Methods. Retroperitoneal sarcomas present a continuing therapeutic challenge to the oncologist. In contrast to sarcomas of the extremity and superficial trunk in which complete resection plus radiation therapy results in excellent local control, sarcomas of the retroperitoneum are difficult to resect and even if completely resected, demonstrate high rates of local relapse, the primary pattern of failure. Due to the proximity of normal organs, the delivery of therapeutic doses of adjuvant external beam radiation therapy is problematic.To deliver adequate doses (>60 Gy) of external beam to most patients would result in unacceptable toxicity. The therapeutic dilemma is unfortunate and better strategies are needed. One attractive approach has been to incorporate intraoperative radiation therapy (IORT) with maximal resection and external beam radiation. Results and Discussion. A number of institutions have explored this approach with encouraging preliminary results.     

Surgical considerations for management of distal extremity soft tissue sarcomas

PURPOSE OF REVIEW: This review focuses on the surgical management of soft tissue sarcomas of the hands and the feet. With recent advances in limb salvage surgery and radiotherapy delivery, local control of soft tissue sarcoma in the extremity has become optimized, and the associated functional results of this treatment have taken on extreme importance. Techniques to limit the amount of normal tissue resected and to reconstruct the resulting defects are critical to the final functional result. RECENT FINDINGS: Several features of soft tissue sarcoma unique to the hand and foot have been reported. Certain histologic subtypes of soft tissue sarcoma have been noted to arise preferentially in the hand and the foot, such as epithelioid sarcoma, clear cell sarcoma, and synovial sarcoma. Patients with hand and foot sarcomas have been described as having improved overall survival, but this is likely a result of the smaller size of tumors arising in these locations. Reconstruction of bone defects using various techniques, vascular reconstruction, tendon transfers, and soft tissue reconstruction using regional flaps in the hand and free flaps in the foot have resulted in good functional outcomes. Amputation and early prosthetic fitting still have a role in management of some soft tissue sarcomas, most frequently in the foot. SUMMARY: Limb salvage remains the standard of care for extremity soft tissue sarcomas. Given the fact that patients have good oncologic and functional outcomes with limb salvage in tumors in the hand and foot, surgical oncologists should have this goal for each patient.     

Concepts in limb-sparing treatment of adult soft tissue sarcomas

Pretreatment assessment of patients with soft tissue sarcomas of the extremities requires careful attention to a biopsy approach that will establish the precise diagnosis and will not compromise the subsequent definitive operative procedure. Also, staging procedures are required to evaluate the status of both local and distant sites. Limb-sparing surgery for high grade extremity soft tissue sarcomas is a feasible and appropriate approach in approximately 90% of patients with such lesions. Wide gross surgical margins around the sarcoma are the optimal operative approach. Circumstantial evidence is convincing that local treatment failure can be reduced by adjuvant regional radiation treatment when surgical margins are narrow, and end results appear to be equal to those obtained by more extensive surgical resection alone. Adjuvant radiation following operation with optimal gross surgical margins has not been established as adding benefit. Although some groups treating soft tissue sarcomas do use intraarterial chemotherapy in conjunction with these other modalities, there is, as yet, no convincing evidence that this aspect of the multimodality treatment adds to local and/or systemic disease control. The efficacy of adjuvant systemic chemotherapy for high grade soft tissue sarcomas remains to be established within the context of prospective clinical trials.     

Adjuvant chemotherapy in 2011 for patients with soft-tissue sarcoma

The mainstay of treatment for adults with soft-tissue sarcomas is wide surgical excision. Half of all patients with adequate local control of high-grade sarcomas develop distant metastases and, despite additional treatment, ultimately die from their disease. This daunting reality has resulted in a three-decade research effort to assess the efficacy of adjuvant therapy for adult soft-tissue sarcomas. The multitude of histopathological subtypes, each with its own biology and clinical behavior, and the rarity of adult soft-tissue sarcomas as a whole greatly complicate such an assessment. This Perspectives article examines data that support or refute the use of adjuvant chemotherapy in the treatment of soft-tissue sarcomas.     

Place and technical aspects of external beam radiation therapy in the treatment of adult soft tissue sarcomas]

In soft tissue sarcoma, surgical resection remains the cornerstone of therapy for localized disease. Quality of margins is very important to evaluate. In case of marginal or incomplete resection, a new enlarged surgical resection should always be discussed before administration of any adjuvant treatments. Many retrospective studies and 2 randomized studies (one of adjuvant brachytherapy and one of external beam radiotherapy) have shown that adjuvant radiotherapy after complete surgery reduces significantly the risk of local recurrence in extremity soft tissue sarcomas. Combination of surgery and pre- or postoperative radiotherapy has therefore become the standard treatment with a local recurrence rate 相似文献   

Treatment-induced pathologic necrosis: a predictor of local recurrence and survival in patients receiving neoadjuvant therapy for high-grade extremity soft tissue sarcomas.

PURPOSE: To determine whether treatment-induced pathologic necrosis correlates with local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. PATIENTS AND METHODS: Four hundred ninety-six patients with intermediate- to high-grade extremity soft tissue sarcomas received protocol neoadjuvant therapy. All patients underwent surgical resection after neoadjuvant therapy and had pathologic assessment of tumor necrosis in the resected specimens. RESULTS: The 5- and 10-year local recurrence rates for patients with > or = 95% pathologic necrosis were significantly lower (6% and 11%, respectively) than the local recurrence rates for patients with less than 95% pathologic necrosis (17% and 23%, respectively). The 5- and 10-year survival rates for the patients with > or = 95% pathologic necrosis were significantly higher (80% and 71%, respectively) than the survival rates for the patients with less than 95% pathologic necrosis (62% and 55%, respectively). Patients with less than 95% pathologic necrosis were 2.51 times more likely to develop a local recurrence and 1.86 times more likely to die of their disease as compared with patients with > or = 95% pathologic necrosis. The percentage of patients who achieved > or /= 95% pathologic necrosis increased to 48% with the addition of ifosfamide as compared with 13% of the patients in all the other protocols combined. CONCLUSION: Treatment-induced pathologic necrosis is an independent predictor of both local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. A complete pathologic response (> or = 95% pathologic necrosis) correlated with a significantly lower rate of local recurrence and improved overall survival.