Use of positron emission tomography in localized extremity soft tissue sarcoma treated with neoadjuvant chemotherapy

BACKGROUND: Patients with high-grade soft tissue sarcomas are at high risk of developing local disease recurrence and metastatic disease. [F-18]-fluorodeoxy-D-glucose (FDG) positron emission tomography (PET) scans are hypothesized to detect histopathologic response to therapy and to predict risk of tumor progression in patients with various malignancies. Serial FDG-PET scans were taken to determine the correlation between FDG uptake and patient outcomes in patients receiving multimodality treatment of extremity sarcomas. METHODS: Forty-six patients with high-grade localized sarcomas were studied. The maximum standardized uptake values (SUVmax) of tumors were measured before receipt of neoadjuvant chemotherapy and again before surgery. Resected specimens were examined for residual viable tumor. Patients were followed up at least annually for evidence of local and distant recurrence of disease and survival. RESULTS: Patients with a baseline tumor SUVmax >/= 6 and < 40% decrease in FDG uptake were at high risk of systemic disease recurrence estimated to be 90% at 4 years from the time of initial diagnosis. Patients whose tumors had a >/= 40% decline in the SUVmax in response to chemotherapy were at a significantly lower risk of recurrent disease and death after complete resection and adjuvant radiotherapy. CONCLUSIONS: The FDG-PET scan was found to be a useful method with which to predict the outcomes of patients with high-grade extremity soft tissue sarcomas treated with chemotherapy. The pretreatment tumor SUVmax and change in SUVmax after neoadjuvant chemotherapy independently identified patients at high risk of tumor recurrence. The FDG-PET scan showed promise as a tool to identify the patients with sarcoma who are most likely to benefit from chemotherapy.     

The influence of anatomic location on outcome in patients with soft tissue sarcoma of the extremity

BACKGROUND: The anatomic location of an extremity soft tissue sarcoma may influence the patient's presentation, management, and local and systemic recurrence rates. The objective of this study was to compare the presentation, management, and outcome of patients with soft tissue sarcomas of the upper extremity and the lower extremity. METHODS: Prospectively collected data from patients who underwent limb-sparing surgery for extremity soft tissue sarcoma between January, 1986 and April, 1997 were analyzed. Local recurrence free rates and metastasis free rates were calculated using the method of Kaplan and Meier. Univariate and multivariate analyses of potential predictive factors were evaluated with the log-rank test and the Cox proportional hazards model. RESULTS: Of 480 eligible patients, 48 patients (10.0%) had a local recurrence, and 131 patients (27.3%) developed distant metastasis. The median follow-up of survivors was 4.8 years (range, 0.1-12.9 years). Patients with upper extremity tumors had smaller lesions (6.0 cm vs. 9.3 cm; P < 0.001), more often underwent unplanned excision before referral (89 patients [64.0%] vs. 160 patients [46.9%]; P < 0.001), and less often received radiotherapy (98 patients [70.5%] vs. 289 patients [84.8%]; P < 0.001). The 5-year local recurrence free rate was 82% for patients with sarcomas of the upper extremity and 93% for patients with sarcomas of the lower extremity (P = 0.002). The 5-year metastasis free rate was 82% for patients with sarcomas of the upper extremity and 69% for patients with sarcomas of the lower extremity (P = 0.013). CONCLUSIONS: Local recurrence was more frequent in patients who had sarcomas of the upper extremity compared with patients who had sarcomas of the lower extremity. Factors that contributed to this difference included histologic type, the use of radiotherapy, and local anatomy. Metastasis was more frequent among patients with sarcomas of the lower extremity, because those tumors tended to be large and deeper compared with upper extremity tumors.     

Brachytherapy and function-saving resection of soft tissue sarcoma arising in the limb

The treatment of soft tissue sarcoma of the limb by function-saving resection and brachytherapy (BRT) was systematically studied from 1975 to 1990 at the Memorial Sloan-Kettering Cancer Center, using iridium-192 temporary tumor-bed implants. Initial experiences showed an 88% local control rate in 33 patients who had locally advanced sarcomas, many of which would have required treatment by amputation. The technique also controlled 70% of tumors that abutted or invaded a major neurovascular bundle that was dissected out and preserved. A prospective randomized study (BRT vs no BRT) confirmed the highly significant efficacy of BRT in preventing local recurrence. This salutary effect is mainly seen in high-grade tumors. Major complications of wound healing occurred in the earlier years of this experience. Adoption of improved techniques of surgical wound repair, standardization of radiation dose planning, and in particular, postponing the loading of radiation sources until after the fifth postoperative day has reduced the rate of serious wound complications, to a level not significantly different from that seen after surgical resection alone. These results rival those currently achieved in centers experienced in external beam therapy of soft tissue sarcomas, and offer the advantage of completion of treatment in one relatively short hospital stay.     

Function preserving surgery of limb sarcomas: history and improvements]

In the seventies, limb-sparing surgery and radiation therapy appeared capable of successfully treating the great majority of adult patients with soft tissue sarcomas of the extremities. No survival benefit could be demonstrated in the patients selected for amputation. Microscopically positive surgical margins are related to a greater risk of local recurrence, whereas overall survival is compromised by high grade and large tumor size. Presurgery multidisciplinary discussion, management in reference center and management within cancer network independently predict conformity to the clinical practice guidelines. Reoperation should be a planned part of definitive management whenever the initial surgical procedure was done without a histologic diagnosis or was not planned to be a wide excision. Soft tissue flap reconstruction facilitates therapy for patients with locally advanced tumors so that patients with larger tumors can undergo resection, limiting complications and limb sacrifice. Vascular reconstruction is a feasible option in case of involvement of major vessels. Isolated limb perfusion (ILP) with TNF and chemotherapy is an efficient limb-sparing neoadjuvant therapy for locally advanced limb soft tissue sarcomas. Efficacy and safety of low-dose TNFalpha could greatly facilitate ILP procedures in the near future.     

A new limb salvage surgery in cases of high-grade soft tissue sarcoma using photodynamic surgery, followed by photo- and radiodynamic therapy with acridine orange

BACKGROUND: To maintain excellent limb function after tumor resection in patients with high-grade malignant sarcomas, we developed and established a new surgical adjuvant therapy using acridine orange (AO) after intra-lesional or marginal resection while sparing normal tissues of major nerves, vessels or bones adjacent to the tumor. METHOD: Our AO therapy procedure was combined with photodynamic surgery (PDS), photodynamic therapy (PDT) and radiodynamic therapy (RDT). In this study, 26 patients with primary high-grade soft tissue sarcomas were treated with AO therapy. RESULT: Results showed a low local recurrence rate (7.7%) and good local recurrence-free rate (88%) after AO therapy. Limb function of all patients was maintained at 100% of ISOLS criteria. CONCLUSION: Based on these results, we concluded that AO therapy is useful for local control after margin-positive tumor resection and for preserving excellent limb function in patients with high-grade soft tissue sarcomas.     

Limb salvage surgery in combination with brachytherapy and external beam radiation for high-grade soft tissue sarcomas

While combined treatment of high-grade soft tissue sarcoma with resection and radiotherapy has become an accepted standard, outlines of treatment algorithms remain a matter of debate. Our institutional practice foresees wide surgical resection with adjuvant brachytherapy and external beam radiation. It was the purpose of this study to determine long-term outcome, prognostic factors for local and systemic recurrence and morbidity in patients with high-grade soft tissue sarcomas of the extremities, who were subjected to this regimen.     

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.     

Periosteal margin in soft-tissue sarcoma

BACKGROUND: Soft-tissue sarcomas frequently rest in contact with bone. The purpose of the study was to evaluate the risk of local recurrence for sarcomas adjacent to bone and to determine whether the periosteum provides an adequate margin of resection. METHODS: Fifty patients with soft-tissue sarcomas abutting bone were treated at a single institution between 1990 and 2004. All patients had high-grade, T2 (>5 cm), nonmetastatic disease in the lower extremity. Bone contact was verified by preoperative magnetic resonance imaging (MRI) and/or computed tomography (CT) scans. Forty-three of 50 patients received preoperative radiation with a mean dose of 50 Gy. In 11 cases a composite resection of bone and soft tissue was performed. In 39 cases the excision involved only soft tissue. RESULTS: True bone invasion was verified by histopathologic examination in 3 of 50 cases (6%). Local recurrence in the soft tissues developed in 8 of 50 (16%) patients. In no case did the recurrence involve destruction of cortical bone or erosion into bone. The recurrent tumor resided against the region of previous bone contact in 1 of 8 cases. There was no statistically significant difference in local recurrence between patients who had composite bone resection and patients who had soft-tissue resection only (P = .87). CONCLUSIONS: Relatively few sarcomas are able to penetrate cortical bone. Composite bone and soft-tissue resections are indicated primarily for frank bone invasion. In the absence of this, the periosteum is an adequate surgical margin for sarcomas treated with wide excision and radiation.     

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.     

单中心高度恶性软组织肉瘤的诊疗经验

背景与目的：高度恶性软组织肉瘤是一类转移率高、预后差的恶性肿瘤。该研究总结单中心高度恶性软组织肉瘤的治疗经验,以指导制定这类肿瘤患者的个体化治疗方案。方法：对2000年7月—2014年7月在北京大学人民医院骨与软组织治疗中心接受手术及辅助治疗的473例高度恶性软组织肉瘤患者的临床资料进行回顾性分析,随访这些患者复发、转移及生存情况,分析影响预后的因素。结果：共有400例（84.6%）患者接受了保肢治疗。103例患者出现局部复发,148例患者出现肺、骨等远处转移,419例（88.6%）患者接受广泛性切除。370例患者接受术后化疗,153例患者接受局部放疗。平均随访时间为46.9个月（8.0~127.0个月）。随访期间114例患者死亡。3、5及10年总生存率分别为82.6%、69.0%及58.7%。统计学分析显示,肿瘤的组织学类型、辅助化疗及转移情况是影响患者预后的危险因素。结论：对高风险的肿瘤患者应进行积极的辅助治疗,包括通过化疗降低转移风险和局部放疗降低复发率,以期提高这些患者的生存率。     

Sarcomas of the head and neck

With the exception of pediatric RMS, soft tissue sarcomas only rarely arise in the head and neck region. Soft tissue sarcomas include a diverse array of histologic types because of the variety of mesenchymal tissues from which they originate. The combination of infrequent occurrence, varied pathologic features, and the many potential sites of presentation makes these tumors a challenge for the head and neck oncologist and underscore the need for review by a pathologist experienced with soft tissue tumors. Classification schemes that group sarcomas according to grade have been helpful in providing prognostic information. Although local control of the primary tumor is critical to successful treatment of both high- and low-grade lesions, the high rate of distant metastases in high-grade tumors supports the role of combined modality therapy. Compared with other types of head and neck neoplasms, such as squamous cell carcinoma, soft tissue sarcomas have low rates of regional metastases. Surgery generally has been recommended as the primary method of treatment for achieving local control, except in those high-grade tumors arising in sites not amenable to resection. Exceptions to this principle include RMSs of the orbit, paranasal sinuses, and masticator space in children; these are usually treated with radiotherapy and combined multiagent chemotherapy, thereby avoiding the functional and cosmetic impact of surgery. Also, extensive angiosarcomas of the scalp should be treated with multimodality therapy combining surgery and wide-field radiation therapy in an attempt to achieve local control. Adjuvant radiotherapy is generally recommended for high-grade sarcomas, large tumors, close or positive surgical margins, and certain histologic variants. Systemic chemotherapy is recommended for those tumors with a significant risk of distant metastases. Increasingly, neoadjuvant chemotherapy is being used to determine responsiveness to chemotherapy, which can help physicians select patients who may benefit from systemic postoperative therapy. Traditional predictors of treatment failure for soft tissue sarcomas include larger tumor size, high-grade histology, and positive surgical margins. The advent of more advanced reconstructive techniques, including free tissue transfer, has made more aggressive surgical resection of these tumors possible. Nevertheless, a considerable number of ancillary support staff are critical to the patient's postoperative rehabilitation and eventual return to a satisfactory level of function and quality of life. In the future, the discovery of the molecular pathogenesis of specific tumor types, such as the cytogenetic findings in synovial sarcoma, will improve physicians' prognostic abilities and selection of patients who are most likely to benefit from emerging adjuvant therapies.     

Clinical outcomes of intraoperative radiation therapy for extremity sarcomas

Purpose. Radiation of extremity lesions, a key component of limb-sparing therapy, presents particular challenges, with significant risks of toxicities. We sought to explore the efficacy of intraoperative radiation therapy (IORT) in the treatment of soft tissue sarcomas of the extremities. Patients. Between 1995 and 2001, 17 patients received IORT for soft tissue sarcomas of the extremities. Indications for IORT included recurrent tumors in a previously radiated field or tumors adjacent to critical structures. Results. Gross total resections were achieved in all 17 patients. Two patients experienced locoregional relapses, six patients recurred at metastatic sites, and one patient died without recurrence. Thirty-six month estimates for locoregional control, disease free survival, and overall survival were 86%, 50%, and 78%, respectively. IORT was extremely well tolerated, with no toxicities referable to IORT. Conclusions. For patients with soft tissue sarcomas of the extremities, IORT used as a boost to EBRT provides excellent local control, with limited acute toxicities.     

The Role of Radiation Therapy in the Treatment of Sarcoma of Soft Tissue

The treatment of sarcomas of soft tissue has evolved considerably over the years. Initially, as these tumors were often pseudoencapsulated, it was thought that a local excision might be adequate in producing local tumor control. As it was shown that there was a high incidence of local recurrence after local excision alone, surgeons began to treat these tumors with more aggressive resections. Thus, many surgeons began performing amputations at the joint above the tumor in order to maximize local control. Radiation therapy was seldom used as these tumors were thought to be radioresistant. However, over the last 20 years it has become apparent that sarcomas of soft tissue are not radioresistant, and microscopic disease can be controlled in a high percentage of patients with the use of high-dose radiation. Even bulky tumor masses can occasionally be controlled with radiation alone. Thus, there has been a gradual change in treatment policy so that many patients are now treated with the combination of a local resection and radiation therapy. This approach utilizes the ability of the surgical resection to remove the gross tumor and radiation therapy to eradicate microscopic tumor extensions.     

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.     

Amputation for extremity soft tissue sarcoma does not increase overall survival: A retrospective cohort study

To determine if amputation increases survival when compared to limb salvage surgery in patients with a soft tissue sarcoma (STS) of the extremity when there is often a misconception among physicians and patients that ablative surgery eliminates local recurrence and increases overall survival. This retrospective cohort study assessed 278 patients with STS and compared 18 patients who had undergone amputations for soft tissue sarcomas of the extremities to a comparative cohort of 260 patients who underwent limb salvage surgery during the same time period. Our limb salvage surgery (LSS) rate was 94% overall for soft tissue sarcomas with a median follow-up of 3.1 years. Patients undergoing amputations either had tumors that involved a critical neurovascular bundle (in particular nerve rather than vessel resection was more responsible for a decision toward ablation), or underlying bone or had neoplasms whose large size would require such an enormous resection that a functional limb would not remain. In comparing prognostic effects, mainly death due to sarcoma, distant metastasis and local recurrence, it was found that there was no statistically significant difference between patients undergoing amputation to those undergoing limb salvage surgery (p > 0.05). While amputations do not increase overall survival in soft tissue sarcomas of the extremity as compared to LSS, they are still a valuable option in a surgeon's arsenal. In particular, amputations can provide improved local control and symptomatic treatment in patients who might not be candidates for limb salvage surgery.     

下肢恶性骨肿瘤切除假体置换的软组织重建

目的 研究下肢恶性骨肿瘤切除、人工假体置换后软组织重建的方法和效果。方法 为32例接受瘤段切除、人工假体置换保肢手术的下肢恶性骨肿瘤患者施行各种形式的软组织重建手术。其中病变位于近侧股骨、远侧股骨、近侧胫骨者分别为6例、19例和7例；骨肉瘤28例，软骨肉瘤3例，恶性纤维组织细胞瘤1例。根据病变所在不同部位施行不同形式的软组织重建。结果 32例平均随访36．2个月（22-40个月）。3例局部复发，4例死亡。参照Enneking评分标准，28例关节功能优良。结论 正确的软组织重建手术，保证了关节功能，减少了肿瘤局部复发和切口并发症。软组织重建手术在下肢恶性骨肿瘤切除、假体置换后具有重要意义。     

Results of isolated regional perfusion in the treatment of malignant soft tissue tumors of the extremities

High-grade soft tissue sarcomas of the extremities continue to pose problems of local disease control and deaths from distant metastases. Between 1969 and 1976, eight patients with primary and six with recurrent high-grade soft tissue sarcomas of the extremities were treated by isolated regional perfusion with cytostatics and local excision. None received systemic adjuvant chemotherapy or external-beam radiotherapy. During the follow-up (median, 13 years) five patients (36%) developed distant metastases. One was cured after resection of a pulmonary metastasis. In one other patient (7%) recurrent local disease was diagnosed after 48 months; he was cured after resection of the local lesion followed by postoperative external beam radiotherapy. The actuarial 5-year and 10-year survival was 69%. Treatment caused no cardiovascular complications and there was no postoperative mortality.     

INTRABEAM术中放疗在软组织肿瘤保肢治疗中的应用（附4例报告）

目的 探讨外科手术联合INTRABEAM术中放疗在软组织肉瘤保肢治疗中的临床疗效。方法 回顾性分析2020年7月到2021年10月收治的4例肢体软组织肉瘤患者,接受保肢手术联合INTRABEAM术中放疗治疗,手术过程顺利,无麻醉及手术意外发生。结果 4例患者均接受随访,时间从6~22月不等。1例术后2月局部复发,患者拒绝截肢,行化疗及靶向治疗;1例术后10月发生肺转移,行手术切除;1例复发患者肢体功能差,余3例患者肢体功能正常。结论 外科手术联合INTRABEAM术中放疗可以在保留肢体功能的同时提高局部控制率,提高了患者的生存质量。     

Prospective randomized evaluation of adjuvant chemotherapy in adults with soft tissue sarcomas of the extremities

Sixty-five patients with high-grade soft tissue sarcomas of the extremities were treated in a prospective randomized trial evaluating the efficacy of adjuvant chemotherapy with doxorubicin, cyclophosphamide, and high-dose methotrexate. Local therapy was administered using either amputation or wide local resection plus radiation therapy and the chemotherapy was begun in the immediate postoperative period. Actuarial analysis with median follow-up of 653 days revealed an advantage in continuous disease-free and overall survival in the patient group receiving chemotherapy (P = 0.0008 and P = 0.04, respectively, one-sided Mantel-Haenszel test). The continuous disease-free survival at three years is 92% in the chemotherapy group compared to 60% in the no chemotherapy group. Overall survival is 95% and 74% in these two patient groups. Fifty-eight percent of patients had limb-sparing surgery plus radiation therapy and 42% underwent amputation. In both treatment subgroups analyzed separately, chemotherapy resulted in an improvement in disease-free survival compared to randomized controls not receiving chemotherapy (P = 0.006 and P = 0.04 for groups receiving amputation and limb sparing, respectively). There were no local failures in the patients receiving chemotherapy and two local failures in the no chemotherapy group. The results of this trial confirm the historically controlled pilot trial performed in 26 patients between 1975 and 1977. A current update of the patients in the pilot trial, with a minimum four-year follow-up, reveals an improvement in disease-free and overall survival due to chemotherapy (P less than 0.002). Analysis of the previous pilot trial indicates that only few recurrences are seen beyond three years. Thus, it appears that adjuvant chemotherapy should be a part of the treatment adult patients with soft tissue sarcomas of the extremities.     

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.