Management Of Soft Tissue Sarcomas Research Articles

Optically-tracked handheld fluorescence imaging platform for monitoring skin response in the management of soft tissue sarcoma.

Standard clinical management of extremity soft tissue sarcomas includes surgery with radiation therapy. Wound complications (WCs) arising from treatment may occur due to bacterial infection and tissue breakdown. The ability to detect changes in these parameters during treatment may lead to earlier interventions that mitigate WCs. We describe the use of a new system composed of an autofluorescence imaging device and an optical three-dimensional tracking system to detect and coregister the presence of bacteria with radiation doses. The imaging device visualized erythema using white light and detected bacterial autofluorescence using 405-nm excitation light. Its position was tracked relative to the patient using IR reflective spheres and registration to the computed tomography coordinates. Image coregistration software was developed to spatially overlay radiation treatment plans and dose distributions on the white light and autofluorescence images of the surgical site. We describe the technology, its use in the operating room, and standard operating procedures, as well as demonstrate technical feasibility and safety intraoperatively. This new clinical tool may help identify patients at greater risk of developing WCs and investigate correlations between radiation dose, skin response, and changes in bacterial load as biomarkers associated with WCs.

(i) Management of soft tissue sarcoma

Abstract Soft tissue sarcomas (STS) are rare malignant connective tissue tumours. A multi-disciplinary approach is required to manage such tumours. This article reviews the diagnosis and management of STSs.

Timelines for multidsiciplinary limb soft tissue sarcoma management.

e17549 Background: Treatment timelines are an important metric in health services delivery. In rare tumors such as limb soft tissue sarcomas (STS’s) expert multidisciplinary management is very indi...

The Effect of Smoking and Major Vein Resection on Post-therapy Lymphedema in Soft Tissue Sarcomas Treated With Neoadjuvant Radiation and Limb-salvage Surgery

Neoadjuvant therapy with radiation +/- chemotherapy is an accepted management for soft tissue sarcomas (STS). The incidence of post-therapy lymphedema is around 30%. The purpose of this study was to identify variables that predict for post-therapy lymphedema. From 2000 to 2010, 132 patients with STS were treated with neoadjuvant radiation +/- chemotherapy followed by resection. Patient variables and treatment outcomes were reviewed. Presence of lymphedema was determined by the treating physician. The Fisher exact test was used for univariate analysis and logistic regression was used for multivariate analysis. Median follow-up was 3.1 years. Of the lower extremity STS, major veins were sacrificed in 34% of patients. Lymphedema occurred in 22.4% of patients. Smoking negatively predicted for lymphedema on univariate analysis (P=0.007), and sacrifice of a major vein was associated with an increased risk of lymphedema (P=0.02). On multivariate analysis, smoking (P=0.02, odds ratio 0.31) negatively predicted for and sacrifice of a major vein (P=0.03, odds ratio 2.7) positively predicted for lymphedema. There may be an association between smoking and decrease post-therapy lymphedema. Also, patients who undergo resection of a major vein seem to be more prone to post-therapy lymphedema.

Chimiothérapie adjuvante des sarcomes des tissus mous de l'adulte

The main progress in the management of soft tissue sarcomas have been obtained in the field of local control. Although the main evolutive, vital, risk of these diseases is metastatic dissemination, efficacy of adjuvant chemotherapy remains a controversial issue. Thus, adjuvant chemotherapy cannot be considered as a standard for any situation. The last results of clinical trials, meta-analysis and population studies are presented and discussed in this article. New therapeutic strategies are to bedeveloped to prevent metastases in soft tissue sarcomas. This needs a better understanding of the biology of those tumors, of metastases risk factors and of the determinants of systemic therapies efficacy in these tumors.

Modern surgical techniques for management of soft tissue sarcomas involving the spine: outcomes and complications.

Several types of soft tissue sarcomas may locally extend to the spine. The best therapeutic strategy for such lesions strongly depends on the histological diagnosis. In this article the authors provide an up-to-date review of current guidelines regarding the management of soft tissue sarcomas involving the spine. Special attention is given to outcomes and complications of modern surgical series in order to highlight current challenges in the management of such lesions.

Surgical management of soft tissue sarcomas: Extremity sarcomas

Wide surgical resection is the recommended treatment for extremity soft tissue sarcomas. Chemotherapy and/or radiotherapy may improve local control, but with marginal effect on overall survival. Advanced reconstructive techniques and multidisciplinary care, including plastic surgery, may allow a higher rate of limb salvage. This report focuses on surgical and reconstructive aspects in the multimodality care of extremity sarcomas.

Can OP-1 stimulate union in a rat model of pathological fracture post treatment for soft tissue sarcoma?

The goal of soft tissue sarcoma management in the extremities is limb preservation, often combining surgery and external beam radiation. In patients who have undergone this therapy in the thigh, pathologic fracture is a serious, late complication. Non-union rates of 80-90% persist. No reliable biologic solution exists. A rat model combining one 18 Gy dose of radiation and diaphyseal periosteal excision reliably generates atrophic non-union of femoral fractures. We hypothesized that augmentation with OP-1 would increase union rate. Female Sprague-Dawley retired breeder rats were randomized to Control, Disease (external beam radiotherapy and periosteal stripping), Control + OP-1 (80 µg) and Disease + OP-1 groups. Animals underwent prophylactic fixation and controlled left femur fracture. Twenty-eight, 35, and 42 days post-fracture were end-points. Femora were analyzed using MicroCT, Back Scattered Electron Microscopy, and Histomorphometry. We observed a 2% union rate in the Disease groups (±OP-1 treatment). The union rate in Control groups was 97%. MicroCT demonstrated a lack of callus volume in Disease groups. Heterotopic ossification was observed in some OP-1 treated animals. The ineffectiveness of OP-1 in stimulating fracture union in this model suggests the endogenous repair mechanism has been compromised beyond the capabilities of osteoinductive biologics.

Surgical Management of Soft Tissue Sarcomas of the Extremities

The operative treatment of soft tissue sarcomas (STSs) requires extensive planning involving a multidisciplinary approach. The diagnosis is established through imaging and subsequent biopsy, which must be performed without contaminating surrounding tissues in ways that might complicate the definitive resection. Many factors related to both the patient and the sarcoma must be carefully evaluated to determine the most appropriate form of adjuvant treatment and the feasibility of limb salvage. Finally, patients should be counseled preoperatively regarding functional expectations. This article discusses the techniques and considerations that are essential to optimizing both oncologic outcome and patient satisfaction in the management of soft tissue sarcomas.

Experience of Interstitial Permanent I125 Brachytherapy for Extremity Soft Tissue Sarcomas

AimsSoft tissue sarcomas are uncommon, but relatively aggressive tumours. Although surgical resection remains the primary therapeutic modality for all localised tumours, brachytherapy combined with function-preserving excision is a popular treatment for extremity soft tissue sarcomas. The objective of this study was to evaluate the effect of interstitial permanent brachytherapy using I125 seeds in patients undergoing the combined modality in the management of soft tissue sarcomas at our institution. Materials and methodsBetween January 2007 and January 2012, 110 adult patients aged 18–86 years (median = 44 years) with extremity soft tissue sarcomas and who underwent interstitial permanent brachytherapy as part of the local treatment were included in this study. Treatment included wide local excision of the tumour and brachytherapy using a permanent I125 implantation. Complications were assessed in terms of wound complication and peripheral nerve damage. ResultsAfter a median follow-up of 43.7 months, the local control, disease-free survival and overall survival for the entire cohort studied were 74, 54 and 77%, respectively. The actual rates of wound complications requiring reoperation and nerve damage were 4.5 and 1.8%, respectively. ConclusionsWe conclude that interstitial permanent brachytherapy with I125 after function-preserving surgery results in a satisfactory outcome in patients with extremity soft tissue sarcomas and the complication rate is low.

Outcome of Chemotherapy for Adult Soft Tissue Sarcomas in Jos, North Central Nigeria

Background: Soft tissue sarcomas (STS) have a poor response to chemotherapy and reports have documented a 20% response rate. Chemotherapeutic regimens have evolved from the use of multiple drug combinations which were thought to be more efficacious, to high doses of single agent chemotherapy and targeted therapies. Predicting the response to chemotherapy in soft tissue sarcomas is difficult because even tumours of the same class exhibit different patterns of responsiveness to the same drugs. Single agent Adriamycin chemotherapy for soft tissue sarcomas is cheap and reputably gives comparable treatment outcomes to combination therapies. This study was therefore aimed at determining the outcome of management of soft tissue sarcomas with single agent Adriamycin chemotherapy. Patients and Method: This was a prospective analysis of consecutive patients managed for STS with single agent Adriamycin at the Jos University Teaching Hospital from January 2000 to December 2009.Results: A total of 89 adult soft tissue sarcomas were managed in 49 males and 40 females (M: F=1.2:1). The mean age of the study population was 37.4 +/- 12.6 with age range of 18 to 85years.Forty patients (44.9%) could afford chemotherapy with single agent Adriamycin and formed the basis of this study while 49 (53.1%) could not afford chemotherapy. All the tumours were more than 5cm in size at presentation. Rhabdomyosarcoma was seen in 17 patients (42.5%), fibrosarcoma in 14 (35%), liposarcoma and dermatofibrosarcoma 4 (10% ) each and one patient (2.5% ) had synovial sarcoma. Response to chemotherapy was seen in seven patients (17.5%) and this was noticed within six weeks of chemotherapy. Conclusion: Response to chemotherapy with single agent Adriamycin for the treatment of soft tissue sarcomas is very poor and it is difficult to predict which patient will respond to this therapy in our setting. We therefore suggest that all patients with STS on single agent Adriamycin in resource scarce settings should have their treatment discontinued or changed to other chemotherapeutic combinations if there is no response to chemotherapy after six weeks.

Diagnostic power and pitfalls of intraoperative consultation (frozen section) in rhabdomyosarcoma.

Intraoperative consultation plays an important role in the management of soft tissue sarcomas, such as rhabdomyosarcoma. In this study, we aimed to draw attention to the important points during frozen section interpretation, and analyse the accuracy of frozen diagnosis in rhabdomyosarcoma patients. The cases, both diagnosed as rhabdomyosarcoma or followed with a history of rhabdomyosarcoma, and interpreted with intraoperative consultation (frozen section) between 2000 and 2013 were culled from pathology archives. The diagnoses were confirmed by desmin and myogenin, immunohistochemically. The frozen and final diagnoses were noted of 21 biopsy specimens of 19 patients. Sensitivity and specificity of intraoperative consultation were calculated regarding to the major diagnostic discrepancies leading to a change in surgical management of the patient, after exclusion of the cases deferred to paraffin section. Of the evaluated 21 biopsy material, 3 (14%) were misdiagnosed: Of the 2 false negative embryonal rhabdomyosarcoma cases, sample was not representative of the tumor, and there was chemo/radiotherapy induced changes in the other case. In the only false positively diagnosed case with a known history of rhabdomyosarcoma, inflammatory cells were misinterpreted as small round cell neoplasm. In 5 (29%) of 21 biopsies, a frozen diagnosis could not be given, and the diagnosis was deferred. Six cases (29%) were evaluated with cytological squash or imprint preparation; none of the misdiagnosed cases was evaluated with adjunct cytological preparation. Six of 8 misdiagnosed or deferred biopsies showed morphological changes secondary to radiotherapy and/or chemotherapy. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated as 85%, 67%, 92% and 50%, respectively. Intraoperative consultation for rhabdomyosarcoma is a reliable tool with high sensitivity and fair specificity. Cases with treatment effect may lead to diagnostic difficulties, especially false negative results. Understanding the diagnostic algorithm of surgeon may prevent misdiagnosis of frozen specimen. Our results also emphasize the diagnostic role of intraoperative cytology as an adjunct to frozen section.

Favorable outcome after complete resection in elderly soft tissue sarcoma patients: Japanese Musculoskeletal Oncology Group study

The surgical management of soft tissue sarcoma (STS) in elderly patients has only been addressed in a few studies. The objective of the current study was to assess surgical outcomes in patients with STS aged 70 years and older and the association of older age with the survival after complete resection. A retrospective analysis was conducted in 158 elderly patients with localized STS who visited 11 institutions participating in Japanese Musculoskeletal Oncology Group between 1995 and 2006 and were treated by surgical resection. Univariate and multivariate analyses were performed to identify prognostic factors. Median follow-up period was 38 months. Histologically high-grade tumors were detected in 71% of the patients. Wide resection with adequate margins was performed in 66% of the cases. Systemic chemotherapy was performed in only 5 patients. Univariate analysis identified histological grade and gender as statistically significant prognostic factors for sarcoma-specific survival. Multivariate analysis did not identify significant prognostic factors for sarcoma-specific survival, although high grade sarcoma emerged as a potentially significant prognostic factor (P = 0.050). Local recurrence was detected in 19% of the patients. Multivariate analysis of local recurrence-free survival showed that tumor site and surgical margins were statistically significant prognostic factors. Older age was not identified as a prognostic factor for sarcoma-specific survival, which is not consistent with the findings of previous studies showing that older age was associated with decreased sarcoma-specific survival. Complete resection should be indicated and can lead to optimal treatment outcome for properly selected elderly patients.

Influence of Physician Specialty on Treatment Recommendations in the Multidisciplinary Management of Soft Tissue Sarcoma of the Extremities

Although prospective randomized data are available to guide the multidisciplinary management of soft tissue sarcoma (STS) of the extremities, controversy exists regarding adjuvant chemotherapy and radiation therapy. To determine if clinical specialty introduces bias in recommendations for multimodality treatment of STS. Electronic survey. Database of active members of the American Society of Clinical Oncology, the Society of Surgical Oncology, and the Connective Tissue Oncology Society. Members of specialty oncology societies with an active interest in STS. Physician specialty. Survey responses regarding the multidisciplinary management of STS were scored on a 5-point Likert scale and analyzed using analysis of variance. The questionnaire was completed by 320 of 490 potential respondents (65%), including medical (18%), radiation (8%), orthopedic (22%), and surgical oncologists (45%). Respondents concurred on the use of radiation therapy for margins positive for tumor, for high-grade tumors, for improvement in local control, for tumors larger than 10 cm, and for tumors in close proximity to a neurovascular bundle. Respondents diverged on the use of radiation therapy for tumors 5 to 10 cm in size, for low-grade tumors, for radiation-associated STS, and for survival benefit. Only radiation oncologists felt that radiation therapy was underutilized as a treatment modality (mean [SEM] Likert scale score, 2.44 [0.12]; P < .001). There was agreement on the use of chemotherapy for synovial sarcoma, for high-grade tumors, for tumors larger than 10 cm, for patients younger than 50 years of age, and for survival benefit. Medical oncologists were more likely to recommend chemotherapy for margins positive for tumor (mean [SEM] score, 3.12 [0.12]; P = .03) and for improvement in local control (mean [SEM] score, 2.91 [0.12] P = .08). Surgical oncologists placed the least emphasis on chemotherapy in the overall treatment plan (mean [SEM] score, 2.60 [0.07]; P = .001). Specialty bias exists in adjuvant treatment recommendations for STS. This highlights the importance of multidisciplinary STS tumor boards and interdisciplinary care to facilitate consensus decision making for individual patients.

Effects of radiation and surgery on healing of femoral fractures in a rat model

Management of soft tissue sarcoma involves multimodality treatment, including surgery and radiotherapy. Pathologic fracture of the femur after such treatment in the thigh is one serious, late complication and nonunion rates of 80-90% are reported. We hypothesize that the combination of radiotherapy and periosteal stripping (during tumor resection) leads to greater impairment of the fracture repair process than either intervention alone. Female Wistar retired breeder rats were randomized into four treatment groups (control, radiotherapy, surgery, and combination of radiotherapy and surgery) and three end-points (21, 28, and 35 days post-fracture). Designated animals first underwent radiotherapy, followed by surgical stripping of the periosteum 3 weeks later and femoral fracture with fixation after another 3 weeks. Animals were sacrificed and fractures examined using microCT and histomorphometry. Simple transverse or short oblique femoral fractures were produced. By 35 days, control animals formed unions, periosteum-stripped animals formed hypertrophic non-unions and irradiated animals formed atrophic non-unions. Histomorphometry revealed an absence of chondroid and osteoid production in animals undergoing radiotherapy. The relative contribution of periosteal stripping to occurrence of non-union was statistically insignificant. Radiation prior to fracture reliably resulted in atrophic non-union in our model. The contribution of periosteal stripping was negligible.

Multidisciplinary Management of Soft Tissue Sarcoma

Soft tissue sarcoma is a rare malignancy, with approximately 11,000 cases per year encountered in the United States. It is primarily encountered in adults but can affect patients of any age. There are many histologic subtypes and the malignancy can be low or high grade. Appropriate staging work up includes a physical exam, advanced imaging, and a carefully planned biopsy. This information is then used to guide the discussion of definitive treatment of the tumor which typically involves surgical resection with a negative margin in addition to neoadjuvant or adjuvant external beam radiation. Advances in imaging and radiation therapy have made limb salvage surgery the standard of care, with local control rates greater than 90% in most modern series. Currently, the role of chemotherapy is not well defined and this treatment is typically reserved for patients with metastatic or recurrent disease and for certain histologic subtypes. The goal of this paper is to review the current state of the art in multidisciplinary management of soft tissue sarcoma.

The Significance of Close but Negative Excision Margin for Treatment of Soft-Tissue Sarcoma

Wide excision is the major recommendation for management of soft-tissue sarcomas. Pathologic reports of postexcision sarcomas revealed very close (within 2 mm) but clear excision margins. This investigation was a retrospective study to determine whether wide reexcision plus radiotherapy (R/T), or R/T only, yielded better outcomes. We evaluated our soft-tissue sarcoma cases who had received wide excision in the past 15 years. The surgical margin conditions (negative, positive, or close margins) and pathologic status were evaluated. The different management modalities for each condition were also evaluated individually and discussed. There were 73 cases from 1995 to 2010 in our section who had received wide excision. The overall recurrence rate was 24.6%. In cases with margin positive, the recurrence rate was 20% (2/8) after quick reexcision. However, the recurrence rate was 56% in patients who received R/T but without quick reexcision. In cases with close resection margins (<2 mm) with no reexcision but R/T, the recurrence rate was 45%, and all of them had a high-grade malignancy sarcoma. The other nonrecurrence cases (55%) had low-grade malignancy or well-differentiated sarcoma.In summary, in cases with positive margin sarcoma, quick reexcision plus R/T was suggested and the recurrence rate was relatively low. In soft-tissue sarcoma cases with close margin, we believe quick reexcision plus R/T is necessary, especial in high-grade, poor differentiated soft-tissue sarcomas.

Simple Guidelines for Efficient Referral of Soft-Tissue Sarcomas

Optimal treatment of soft-tissue sarcoma requires multidisciplinary management at a sarcoma center. However, these rare tumors are often misinterpreted as benign and many are inadequately treated outside a sarcoma center, with an increased risk of local recurrence that often requires further extensive surgical treatment. To improve referral and centralization of soft-tissue sarcoma management in the southern Sweden health care region, an open-access outpatient clinic at our sarcoma center and simple referral guidelines have been established for the past thirty years. The guidelines call for referral of all deep-seated soft-tissue tumors and of all ≥5-cm superficial tumors before open biopsy or surgery. We evaluated adherence to these guidelines and characterized referral patterns. We also studied the consequences of our strategy with regard to the relative numbers of benign and malignant diagnoses among referred patients. Adherence to guidelines, referral pathways, and time to referral to the sarcoma center were analyzed in a population-based series of 100 consecutive patients with soft-tissue sarcoma in the extremities or trunk wall. We also analyzed diagnosis and management of benign and malignant tumors in a second cohort consisting of 464 consecutive patients referred to the sarcoma center because of a soft-tissue tumor. Ninety-seven of the 100 patients with soft-tissue sarcoma were referred to the sarcoma center. All fifty-eight of the deep-seated soft-tissue sarcomas and twenty-eight of the forty-two superficial tumors were referred before open biopsy or surgery. Three-quarters of the patients with soft-tissue sarcoma first presented to a general practitioner. One-quarter of these patients were directly referred to the sarcoma center, which cut the referral time in half compared with patients initially referred to a local hospital. One-quarter of all patients referred to the outpatient clinic were diagnosed with a malignancy, with the majority of the malignancies being soft-tissue sarcoma. Our simple referral guidelines and open-access outpatient clinic resulted in nearly complete referral of patients with soft-tissue sarcoma to the sarcoma center. The "excess work" associated with referral of benign tumors according to our strategy was limited to the diagnosis of three benign tumors for each malignant tumor. We consider this surplus evaluation of benign tumors acceptable and probably necessary to achieve a high referral rate of soft-tissue sarcoma before initial surgery. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

A review of controversies in the management of soft tissue sarcomas.

Soft tissue sarcomas (STS) constitute a rare and challenging group of solid tumor in the field of oncology. Unlike other malignancies STS can affect a wide variety of anatomical regions in the body with varied histo-pathological variants and clinical outcomes. There are controversies in the diagnosis and management of STS due to rarity and heterogeneity of the disease entity. Due to dedicated research and advances made in the field of imaging, pathology, surgery, radiotherapy and chemotherapy certain controversies were laid to rest and treatment approach to STS could be standardized to a large extent in the recent past. A review of controversies related to STS was performed in this article and an attempt was made to present a balanced view pertaining to these issues.

EP-1557 RADIOTHERAPY OF SOFT-TISSUE SARCOMA OF LOWER EXTREMITY WITH HIGH BONE SPARING WITH RAPIDARC AND PROTONS

Purpose/Objective: To investigate the advanced radiotherapy treatments of soft-tissue sarcoma with adequate target coverage and bone high sparing with volumetric modulated arc therapy (RapidArc) and proton beams. Materials and Methods: Ten patients presenting soft tissue sarcoma of the leg, and treated with RapidArc in author’s institutions were collected for the study. Dose was prescribed to 66.5 Gy in 25 fractions to mean planning target volume (PTV), and significant maximum dose to the bone was limited to 50 Gy. Plans were prepared using RapidArc with flattened 6 MV (6X) and unflattened 10 MV (10FFF) photon beams from a Varian TrueBeam facility, and using proton beams up to 250 MeV. RapidArc photon plans were computed with AAA and Acuros XB in the two options of dose to medium and dose to water. Proton plans were prepared using intensity modulated spot scanned proton beams. Plan evaluation was assessed by dose volume histogram analysis, comparing different dose distributions and different dose calculation algorithms (and dose to medium or to water option). Results: All plans acceptably met the criteria of target coverage (V95%>90-95%) and bone sparing (D1cm3<50 Gy). Better coverage was shown for proton plans with respect to 6X RapidArc photon plans, at 95% of the prescription dose (V95% about 5% higher for protons, p<0.05). Dose was more homogeneously distributed in the proton cases: Standard Deviation 2.3Gy for protons, 3.0-3.3Gy for photons, p<0.05. A small difference tending to be significant was found between 6X and 10FFF plans, in favor of using flattened beams. Bone significant maximum dose objective of 50Gy was met in all cases, photon RapidArc and protons, with no significant differences. The largest difference between proton and photon plans in Bone tissue is reflected in the medium/low doses. Similar results were found for surrounding normal tissue. For Healthy Tissue, the low dose bath is minimized with protons, where the Dose Integral is about halved with respect to all photon plans. Interesting result is the significant (p<<0.01) lower Dose Integral when FFF photon beams are used in place of more conventional flattened beams. Dose to water calculations resulted in bone doses of about 5% higher than for dose to medium calculations. A deep understanding of the two calculation options would lead the user to properly choose between the two modalities of dose to water, or the dose to medium (that better reflects the physical dose to the specific tissue). Conclusions: A substantial equivalence between RapidArc technique for photon beams and proton plans for the management of soft-tissue sarcoma of the lower extremity was here presented, yielding good target coverage to 66.5 Gy prescription, while keeping the maximum significant dose to the bone below the 50 Gy minimizing the risk of bone fractures.