Extremity Sarcoma Research Articles

Feasibility of tomotherapy for postoperative irradiation of lower extremity sarcomas.

To evaluate the effectiveness of helical tomotherapy-based image-guided radiotherapy (IGRT) following surgery for lower extremity sarcoma. A retrospective review of three patients undergoing postoperative irradiation with tomotherapy for lower extremity sarcoma was conducted. Planning target volume (PTV) coverage, acute side effects, long-term complications and functional results were assessed. Tomotherapy allows adequate coverage of the PTV without an excessive radiation dose to the normal adjacent structures. Radiotherapy side effects were acceptable with no treatment breaks. All patients were disease free with no complications and no impairment of their daily activity at the last follow-up. IGRT delivered by tomotherapy may be ideally suited for sarcoma of the extremities because of its ability to achieve a high radiation dose along with excellent normal tissue sparing. Further prospective studies should be conducted to confirm this hypothesis.

A service evaluation of on-line image-guided radiotherapy to lower extremity sarcoma: Investigating the workload implications of a 3 mm action level for image assessment and correction prior to delivery

IntroductionAlthough all systematic and random positional setup errors can be corrected for in entirety during on-line image-guided radiotherapy, the use of a specified action level, below which no correction occurs, is also an option. The following service evaluation aimed to investigate the use of this 3 mm action level for on-line image assessment and correction (online, systematic set-up error and weekly evaluation) for lower extremity sarcoma, and understand the impact on imaging frequency and patient positioning error within one cancer centre. MethodsAll patients were immobilised using a thermoplastic shell attached to a plastic base and an individual moulded footrest. A retrospective analysis of 30 patients was performed. Patient setup and correctional data derived from cone beam CT analysis was retrieved. The timing, frequency and magnitude of corrections were evaluated. The population systematic and random error was derived. Results20% of patients had no systematic corrections over the duration of treatment, and 47% had one. The maximum number of systematic corrections per course of radiotherapy was 4, which occurred for 2 patients. 34% of episodes occurred within the first 5 fractions. All patients had at least one observed translational error during their treatment greater than 0.3 cm, and 80% of patients had at least one observed translational error during their treatment greater than 0.5 cm. The population systematic error was 0.14 cm, 0.10 cm, 0.14 cm and random error was 0.27 cm, 0.22 cm, 0.23 cm in the lateral, caudocranial and anteroposterial directions. The required Planning Target Volume margin for the study population was 0.55 cm, 0.41 cm and 0.50 cm in the lateral, caudocranial and anteroposterial directions. ConclusionThe 3 mm action level for image assessment and correction prior to delivery reduced the imaging burden and focussed intervention on patients that exhibited greater positional variability. This strategy could be an efficient deployment of departmental resources if full daily correction of positional setup error is not possible.

Current treatment landscape and emerging management options for extremity sarcoma

Malignant tumors of extremity are mostly of mesenchymal origin and arise from bone or extraskeletal soft tissue. Combination chemotherapy has greatly increased the survival of non-metastatic localized osteosarcoma and Ewing's sarcoma; however, there is conflicting evidence regarding the role of neoadjuvant and adjuvant chemotherapy in soft tissue sarcoma due to the rarity and heterogeneous population. Despite intensive multimodal therapy and valiant efforts, most of the patients with relapsed and metastatic sarcoma will succumb to their disease. Molecular studies like next-generation sequencing have revealed various targetable biomarkers which can be further explored in the therapeutic landscape with specific targeted therapies. We reviewed all ongoing and completed clinical trials involving chemotherapy, targeted therapy, and immunotherapy valid for patients with extremity sarcoma. We present the current viable therapeutic options for such a cohort of patients in routine clinical practice.

Retrospective Analysis of Spectrum of Presentation and Treatment Outcome in Extremity Sarcomas: A Single-Centre Experience.

Introduction The most common site for soft tissue sarcoma is extremity. As complete surgical resection is possible in majority, outcome of this subset is relatively better. There is paucity of data regarding extremity soft tissue sarcoma (STS) from sub-Himalayan and hilly geographical regions. Materials and Methods Retrospective analysis was done for extremity STS visiting the study center over a period of 5 years. Data were collected and analyzed for demography, disease characteristics, treatment modalities, and outcome. Result Extremity STS constituted 32.8% of all STS enlisted. Most common subtype noted was pleomorphic STS. Metastatic disease at presentation was noted among 7/43 cases with lung being the most common metastasis site. Wide local excision was done in 37 cases while amputation was required in 5 cases. Adjuvant radiotherapy was given in 27 cases while 18 cases received adjuvant chemotherapy. At median follow-up of 47 months, the overall survival and event-free survival were noted as 47.64% and 41.49%, respectively. Conclusion This study depicts single-center experience of extremity STS. The population analyzed was from sub-Himalayan region with significant lost to follow-up. Pooling of data from different centers has been advocated to derive conclusive results.

Myxofibrosarcoma and Undifferentiated Pleomorphic Sarcoma

Both myxofibrosarcoma and undifferentiated pleomorphic sarcoma (UPS) are sarcomas that primarily occur in the extremities of older patients. UPS (previously known as malignant fibrous histiocytoma) is now considered a diagnosis of exclusion, representing a group of high-grade, heterogeneous tumors with no clear line differentiation and characterized by high rates of distant metastases. Myxofibrosarcoma (formerly myxoid variant of malignant fibrous histiocytoma) is a distinct histologic entity that is largely distinguished from UPS by its myxoid stroma and curvilinear vascular pattern. Myxofibrosarcoma tends to have a locally infiltrative behavior that can often be seen as T2 hyperintense “tails” on magnetic resonance imaging. Local recurrence rates can be as high as 61% and are independent of grade. Unlike other sarcomas, it is recommended that tumors be excised with at least a 2 cm margin around both clinically and radiographically evident tumor. Low-grade tumors do not tend to metastasize but can recur as high-grade tumors with increased metastatic potential. Surgery is the mainstay of treatment for localized disease. For high-grade tumors, this may require complex plastics and vascular reconstruction. Selecting cases for multimodality therapy, including radiation and chemotherapy, should be done on a case-by-case basis after review by a multidisciplinary sarcoma team with particular attention to a patient’s risk of local recurrence and distant metastases. Further studies into histology-specific therapeutic targets will help inform future clinical trials. This review contains 4 figures, 4 tables and 54 references Key words: chemotherapy, distant metastases, extremity sarcoma, local recurrence, malignant fibrous histiocytoma, myxofibrosarcoma, radiation, sarcoma, surgical margins, T2 hyperintense tails, undifferentiated pleomorphic sarcoma

Myxofibrosarcoma and Undifferentiated Pleomorphic Sarcoma

Both myxofibrosarcoma and undifferentiated pleomorphic sarcoma (UPS) are sarcomas that primarily occur in the extremities of older patients. UPS (previously known as malignant fibrous histiocytoma) is now considered a diagnosis of exclusion, representing a group of high-grade, heterogeneous tumors with no clear line differentiation and characterized by high rates of distant metastases. Myxofibrosarcoma (formerly myxoid variant of malignant fibrous histiocytoma) is a distinct histologic entity that is largely distinguished from UPS by its myxoid stroma and curvilinear vascular pattern. Myxofibrosarcoma tends to have a locally infiltrative behavior that can often be seen as T2 hyperintense “tails” on magnetic resonance imaging. Local recurrence rates can be as high as 61% and are independent of grade. Unlike other sarcomas, it is recommended that tumors be excised with at least a 2 cm margin around both clinically and radiographically evident tumor. Low-grade tumors do not tend to metastasize but can recur as high-grade tumors with increased metastatic potential. Surgery is the mainstay of treatment for localized disease. For high-grade tumors, this may require complex plastics and vascular reconstruction. Selecting cases for multimodality therapy, including radiation and chemotherapy, should be done on a case-by-case basis after review by a multidisciplinary sarcoma team with particular attention to a patient’s risk of local recurrence and distant metastases. Further studies into histology-specific therapeutic targets will help inform future clinical trials. This review contains 4 figures, 4 tables and 54 references Key words: chemotherapy, distant metastases, extremity sarcoma, local recurrence, malignant fibrous histiocytoma, myxofibrosarcoma, radiation, sarcoma, surgical margins, T2 hyperintense tails, undifferentiated pleomorphic sarcoma

Surgical Management of Extremity and Truncal Sarcoma

Soft tissue sarcomas are a heterogeneous group of neoplasms that arise throughout the body, but most commonly in the extremity and trunk. A multidisciplinary treatment approach has resulted in local control rates exceeding 90% and 5-year survival rates exceeding 70%. For patients with localized soft tissue sarcoma, limb-sparing surgical resection is the mainstay of therapy, with radiation therapy and chemotherapy used as adjuncts to reduce local and distant recurrences. Amputation is reserved for patients with primary or recurrent tumors that cannot be grossly resected with a limb-sparing procedure and preservation of function, which should occur in less than 5% of patients. Most patients who die of soft tissue sarcoma die of metastatic disease, which becomes evident within 2 to 3 years of initial diagnosis in 80% of cases, highlighting the need for improved systemic therapy options and optimal treatment at the time of diagnosis. This review contains 13 figures, 4 tables and 53 references Key words: amputation, multimodality, radiation therapy, soft tissue sarcoma, staging, surgery, treatment, wide resection

Surgical Management of Extremity and Truncal Sarcoma

Soft tissue sarcomas are a heterogeneous group of neoplasms that arise throughout the body, but most commonly in the extremity and trunk. A multidisciplinary treatment approach has resulted in local control rates exceeding 90% and 5-year survival rates exceeding 70%. For patients with localized soft tissue sarcoma, limb-sparing surgical resection is the mainstay of therapy, with radiation therapy and chemotherapy used as adjuncts to reduce local and distant recurrences. Amputation is reserved for patients with primary or recurrent tumors that cannot be grossly resected with a limb-sparing procedure and preservation of function, which should occur in less than 5% of patients. Most patients who die of soft tissue sarcoma die of metastatic disease, which becomes evident within 2 to 3 years of initial diagnosis in 80% of cases, highlighting the need for improved systemic therapy options and optimal treatment at the time of diagnosis. This review contains 13 figures, 4 tables and 53 references Key words: amputation, multimodality, radiation therapy, soft tissue sarcoma, staging, surgery, treatment, wide resection

Adjuvant Radiation for Tissue Extremity and Truncal Sarcomas

In this review, we cover the clinical use of radiation therapy in the treatment of soft tissue extremity and truncal sarcomas. After a brief overview of the seminal trials establishing the efficacy of radiation therapy as a component of limb-preserving therapy, we cover current indications for use and discuss when radiation therapy can be withheld without compromising oncologic outcomes. Controversies in treatment sequencing with surgery are fleshed out with pros and cons for both pre- and postoperative treatment. Finally, different modalities of radiation therapy are discussed and common toxicities are covered. This review contains 3 figures, 1 table and 41 references Key words: brachytherapy, limb preservation, neoadjuvant therapy, radiation therapy, soft tissue sarcoma

Adjuvant Radiation for Tissue Extremity and Truncal Sarcomas

In this review, we cover the clinical use of radiation therapy in the treatment of soft tissue extremity and truncal sarcomas. After a brief overview of the seminal trials establishing the efficacy of radiation therapy as a component of limb-preserving therapy, we cover current indications for use and discuss when radiation therapy can be withheld without compromising oncologic outcomes. Controversies in treatment sequencing with surgery are fleshed out with pros and cons for both pre- and postoperative treatment. Finally, different modalities of radiation therapy are discussed and common toxicities are covered. This review contains 3 figures, 1 table and 41 references Key words: brachytherapy, limb preservation, neoadjuvant therapy, radiation therapy, soft tissue sarcoma

Management of Locally Recurrent Sarcoma in the Extremity

Extremity sarcomas are a heterogeneous group of malignant tumors with a varied propensity for local recurrence. This review focuses on factors associated with local recurrence and survival, diagnostic workup, management, outcomes, and surveillance. Local recurrence is more common in patients with previous local recurrence, positive margins, high-grade histology, and deep tumors. In the absence of metastases, the mainstay of treatment is limb-sparing surgery, with radiation to improve local control. Modalities such as brachytherapy or proton therapy may be valuable in the setting of previous irradiation. Systemic chemotherapy is typically limited to the treatment of distant disease, although chemotherapy can be delivered locally via limb perfusion or infusion for locally advanced or recurrent disease. Amputation is used if local control cannot be achieved while preserving adequate limb function or as a palliative option for pain, bleeding, or fungating tumors. Prognostic factors associated with poor survival include tumors that recur with high-grade histology, with a large size (> 5 cm), or within a short interval (< 16 months). Reports of 5-year overall survival in patients with locally recurrent sarcomas vary from 36 to 65%. Surveillance includes physical examination, cross-sectional imaging, and chest x-ray. Genetic profiling and intratumoral injections provide novel therapeutic targets. This review contains 1 figure, 4 tables and 40 references. Key words: chemotherapy, hyperthermic isolated limb perfusion, intratumoral injection, isolated limb perfusion, local recurrence, margin status, radiation, soft tissue sarcoma, wide local excision

Management of Locally Recurrent Sarcoma in the Extremity

Extremity sarcomas are a heterogeneous group of malignant tumors with a varied propensity for local recurrence. This review focuses on factors associated with local recurrence and survival, diagnostic workup, management, outcomes, and surveillance. Local recurrence is more common in patients with previous local recurrence, positive margins, high-grade histology, and deep tumors. In the absence of metastases, the mainstay of treatment is limb-sparing surgery, with radiation to improve local control. Modalities such as brachytherapy or proton therapy may be valuable in the setting of previous irradiation. Systemic chemotherapy is typically limited to the treatment of distant disease, although chemotherapy can be delivered locally via limb perfusion or infusion for locally advanced or recurrent disease. Amputation is used if local control cannot be achieved while preserving adequate limb function or as a palliative option for pain, bleeding, or fungating tumors. Prognostic factors associated with poor survival include tumors that recur with high-grade histology, with a large size (> 5 cm), or within a short interval (< 16 months). Reports of 5-year overall survival in patients with locally recurrent sarcomas vary from 36 to 65%. Surveillance includes physical examination, cross-sectional imaging, and chest x-ray. Genetic profiling and intratumoral injections provide novel therapeutic targets. This review contains 1 figure, 4 tables and 40 references. Key words: chemotherapy, hyperthermic isolated limb perfusion, intratumoral injection, isolated limb perfusion, local recurrence, margin status, radiation, soft tissue sarcoma, wide local excision

Amputation for Extremity Sarcoma: Contemporary Indications and Outcomes.

Amputation for localized extremity sarcoma (ES), once the primary therapy, is now rarely performed. We reviewed our experience to determine why patients with sarcoma still undergo immediate or delayed amputation, identify differences based on amputation timing, and evaluate outcomes. Records of patients with primary, nonmetastatic ES who underwent amputation at our institution from 2001 to 2011 were reviewed. Univariate analysis was performed, and survival outcomes were calculated. We categorized 54 patients into three cohorts: primary amputation (A1, n=18, 33%), secondary amputation after prior limb-sparing surgery (A2, n=22, 41%), and hand and foot sarcomas (HF, n=14, 26%). Median age at amputation was 54years (range 18-88years). Common indications for amputation (>40%) were loss of function, bone involvement, multiple compartment involvement, and large tumor size (A1); proximal location, joint involvement, neurovascular compromise, multiple compartment involvement, multifocal or fungating tumor, loss of function, and large tumor size (A2); and joint involvement and prior unplanned surgery (HF). There was no difference in disease-specific survival (DSS) (p=0.19) or metastasis-free survival (MFS) (p=0.31) between early (A1) and delayed (A2) amputation. Compared with cohorts A1/A2, HF patients had longer overall survival (OS) (p=0.04). Indications for amputation for extremity sarcoma vary between those who undergo primary amputation, delayed amputation, and amputation for hand or foot sarcoma. Amputations chosen judiciously are associated with excellent disease control and survival. For patients who ultimately need amputation, timing (early vs. delayed) does not affect survival.

Principles in Reconstruction after Resection of Extremity and Truncal Sarcomas

Reconstruction of sarcoma defects of the trunk or extremity requires detailed understanding of a variety of techniques for wound closure. Advances in reconstruction and oncologic treatment have led to higher rates of limb salvage in patients who would have previously undergone amputation. Such defects often require consideration of the reconstructive ladder, moving from the most simplistic closure to free flaps. As previous surgeries or radiation therapy can create a challenging wound environment with scar and fibrosed tissues, at times the more complex up-front option will be a better long-term solution for a patient following sarcoma resection. A multidisciplinary approach to the initial management, resection, and reconstruction is certainly warranted to attain the best overall outcome for the patient from the oncologic and aesthetic standpoint. This review provides an overview of the reconstructive techniques employed in addressing defects of the trunk and extremities following sarcoma resection. This review contains 20 Figures and 30 References. Key words: abdominal wall reconstruction, chest wall reconstruction, free flap, lower extremity reconstruction, pedicled flap, propeller flap, reconstructive elevator, reconstructive ladder, upper extremity reconstruction

Principles in Reconstruction after Resection of Extremity and Truncal Sarcomas

Reconstruction of sarcoma defects of the trunk or extremity requires detailed understanding of a variety of techniques for wound closure. Advances in reconstruction and oncologic treatment have led to higher rates of limb salvage in patients who would have previously undergone amputation. Such defects often require consideration of the reconstructive ladder, moving from the most simplistic closure to free flaps. As previous surgeries or radiation therapy can create a challenging wound environment with scar and fibrosed tissues, at times the more complex up-front option will be a better long-term solution for a patient following sarcoma resection. A multidisciplinary approach to the initial management, resection, and reconstruction is certainly warranted to attain the best overall outcome for the patient from the oncologic and aesthetic standpoint. This review provides an overview of the reconstructive techniques employed in addressing defects of the trunk and extremities following sarcoma resection. This review contains 20 Figures and 30 References. Key words: abdominal wall reconstruction, chest wall reconstruction, free flap, lower extremity reconstruction, pedicled flap, propeller flap, reconstructive elevator, reconstructive ladder, upper extremity reconstruction

The impact of racial/ethnic disparities on survival for children and adolescents with extremity sarcomas: A population-based study

PurposeThe purpose of this study was to determine whether racial/ethnic disparities exist in disease presentation, treatment, and survival among children and adolescents with extremity sarcoma. MethodsThe Surveillance, Epidemiology, and End Results (SEER) data were analyzed for patients <20years old with soft-tissue extremity sarcomas from 1973 to 2013. Multivariate logistic regression was performed to determine the association between race/ethnicity and disease stage at presentation and likelihood of surgical resection. Overall survival (OS) was evaluated using hazard ratios with 95% confidence intervals. Results1261 cases were identified: 650 (52%) non-Hispanic whites (NHW), 313 (25%) Hispanics, 182 (14%) non-Hispanic blacks (NHB), and 116 (9%) other race/ethnicity. Logistic regression results showed that Hispanics and NHB were 51% and 44%, respectively, less likely to undergo surgical resection compared to NHW (OR=0.49, 95% CI: 0.30–0.80; OR=0.56, 95% CI: 0.32–0.98, respectively). Factors associated with failure to undergo surgical resection included histology, lower extremity site, tumor size, and distant metastases. OS based on race/ethnicity significantly differed using the log-rank test, with NHB having the worst survival (p<0.05). ConclusionsWe conclude that NHB, Hispanics, and other race/ethnicity were less likely to undergo surgical resection for extremity sarcoma. Further work is needed to better characterize and eliminate disparities in the management and outcomes of children with extremity sarcomas. Type of studyPrognosis study. Level of evidenceIV

Pencil Beam Scanning Proton Radiation Therapy Reduces Dose to the Planned Surgical Skin Flap and Uninvolved Bone in Preoperative Radiation Therapy for Soft Tissue Sarcomas of the Lower Extremity

Over 40% of patients treated with preop radiotherapy for soft tissue sarcoma (STS) of the lower extremity develop severe wound complications. Reduced dose to the planned surgical skin flap and uninvolved tissues reduces the rate of severe wound complications. We compared photon and proton treatment planning for target coverage and dose avoidance to the planned surgical skin flap and uninvolved bone and soft tissues for STS of the lower extremity. Plans were generated for 5 patients with deep, lower extremity STS treated with preop radiotherapy. Plans consisted of volumetric arc radiation therapy (VMAT), passively scattered proton radiotherapy (PS) and pencil beam scanning proton radiotherapy (PBS). Target volumes were consistent with guidelines for RTOG 0630. Target volumes and OARs were contoured by a radiation oncologist specializing in sarcoma. Planned surgical flaps were contoured by an orthopedic oncologist. Planning goals were as follows: 1) ensure adequate target volume coverage (CTV D99=100%), 2) achieve dose constraints to the planned surgical skin flap, and 3) avoid uninvolved bone. The prescription dose was 50 Gy in 25 fractions. The average mean dose to the planned surgical flaps was 38.3 Gy RBE (range, 28.1-45.6), 46.1 Gy RBE (range, 38.1-53.1), and 43.4 Gy RBE (range, 33.4-49.1) for the PBS, PS, and VMAT plans, respectively. The mean V30 of the surgical flap with PBS was 69.4% (range, 48.0-87.1%) compared to 86.8% (range, 72.7-98.9%) and 82.8% (range, 55.9-98.4%) with PS and VMAT, respectively. All patients had improved mean flap dose and flap V30 using PBS.Mean uninvolved bone V40 was 6.5% (range, 2.1-10.7%), 22.3% (range, 5.8-43.0%), and 14.6% (range, 2.1-37.8%) using PBS, PS, and VMAT, respectively. Mean bone dose was 17.2 Gy RBE (range 11.8-20.8), 14.4 Gy RBE (range, 4.4-26.1), and 21.7 Gy RBE (range, 13.7-33.3) with PBS, PS, and VMAT plans, respectively. The mean conformality index was 0.91, 0.67, and 0.87 for PBS, PS, and VMAT, respectively. PBS achieved the lowest mean dose and V30 to the planned surgical flap, and the lowest bone V40 compared to PS and VMAT. Further work is necessary to determine if these benefits reduce treatment related side effects.Abstract 3798; Table 1Individual patient dosimetry for each treatment modalityMean dose to flap (Gy RBE)Flap V30 (%)Mean dose to bone (Gy RBE)Bone V40 (%)Pt No.PBSPSVMATPBSPSVMATPBSPSVMATPBSPSVMAT128.138.133.448.072.755.920.89.117.85.214.27.7245.653.149.187.198.992.611.84.414.12.15.82.1342.148.347.174.190.390.519.926.133.310.743.037.8438.346.147.769.784.198.414.520.429.75.429.917.9537.144.839.668.387.976.618.812.113.79.318.77.4 Open table in a new tab

Factors Associated With Acute and Chronic Wound Complications in Patients With Soft-Tissue Sarcoma With Long-Term Follow-Up

Although radiation therapy represents a standard of care in the management of soft tissue sarcoma (STS), it may be associated with acute and chronic wound complications. We performed an analysis to identify the rates of these complications as well as associated factors in a cohort of patients treated with modern radiotherapy and surgical techniques. An institutional review board-approved registry was utilized to identify all adult non-metastatic patients treated for STS at a single institution between 2006 and 2015 with a minimum follow-up of one year. Wound complications were documented as acute within the first 90 days following surgery, and chronic afterward. Factors associated with acute and chronic wound complications were analyzed using binomial logistic regression including interaction terms. A total of 271 patients were identified with a median follow-up of 3.2 years. Lower extremity sarcomas (41.7%) were the most common site followed by the thorax/abdomen (23.6%), and upper extremity (14.4%). The most common histologies were liposarcoma, leiomyosarcoma, and undifferentiated/sarcoma NOS. Overall, 72.7% of cases were > 5 cm and 79.3% were deep tumors. A total of 108 (39.9%) patients received radiation and of these, 43 patients (15.9%) received preoperative radiation therapy, with 79.7% of patients having negative margins. At 5 years, the rates of local recurrence, regional recurrence, distant metastases, and overall survival were 19.4%, 6.8%, 32.3%, and 73.6%, respectively. The rate of acute wound complications was 22.1% (n = 60) with trunk vs. extremity (OR = 0.21, 95% CI = 0.10-0.42, P < 0.0001), radiation (OR = 1.86, 95% CI = 1.04-3.33, P = 0.04), pre-operative therapy (OR = 2.19, 95% CI = 1.08-4.33, P = 0.03) demonstrating an association and a trend noted for reconstruction (OR = 1.97, 95% CI = 0.92-4.07, P = 0.07) on univariate analysis. On multivariate analysis adjusting for reconstruction use and tumor size, extremity tumors were associated with increased acute complications in the absence of RT (OR = 2.95, 95% CI = 1.26-7.40, P = 0.02), and RT further increased this risk (OR for extremity tumors RT vs no RT OR = 1.92, 95% CI = 0.92-3.92, P = 0.07). No association was noted with the use of radiation in non-extremity locations (OR = 0.29, 95% CI = 0.04-1.50, P = 0.17). The rate of chronic wound complications was 3.3% (n = 9) with radiation therapy (OR = 5.58, 95% CI = 1.32-37.94, P = 0.03) associated and a trend noted for trunk vs. extremity location (OR = 0.15, 95% CI = 0.008-0.85, P = 0.08) and acute wound complications (OR = 2.94, 95% CI = 0.71-11.48, P = 0.12). Receipt of radiation therapy was associated with acute and chronic wound complications with treatment site also being a factor. Chronic wound complications may be associated with the development of acute wound complication as well. Future studies may focus on strategies to reduce acute complications as well as evaluating the potential benefits of radiation by treatment site, particularly extremity locations.

Neoadjuvant Chemoradiation Compared to Neoadjuvant Radiation Alone in the Management of High-Grade Soft Tissue Extremity Sarcomas

Neoadjuvant Chemoradiation Compared to Neoadjuvant Radiation Alone in the Management of High-Grade Soft Tissue Extremity Sarcomas

Preoperative Intensity-Modulated Radiation Therapy Compared to Three-Dimensional Conformal Radiation Therapy for High Grade Extremity Sarcomas in Children: An Analysis of Children's Oncology Group (COG) Study ARST 0332

One of the potential disadvantages of neoadjuvant chemoradiation therapy for high grade extremity soft tissue sarcomas (STS) is an increased risk of peri-operative wound complications. In adults, studies have demonstrated reduced radiation dose to the skin and subcutaneous soft tissues may decrease the acute wound complication rate and lead to better limb function. Intensity modulated radiotherapy (IMRT) allows delivery of dose to the target volume with the potential advantage of highly conformal therapy to reduce dose to subcutaneous tissues thus limiting dose to the skin. The purpose of this study was to assess tumor coverage and skin dose in pediatric patients treated with IMRT vs. 3D conformal radiation therapy (3D-CRT) on ARST 0332. Of the 551 eligible patients, 200 were enrolled in Arm D of ARST 0332 in which patients <30 years of age were treated with neoadjuvant ifosfamide/doxorubicin chemotherapy and 45 Gy RT, then surgery, and an RT boost based on margins. A total of 121 RT plans of patients were available for review through remote access of the Imaging and Radiation Oncology Core (IROC) Rhode Island database. Of these, 56 RT plans for patients with extremity STS were reviewed to evaluate the dose delivered to the clinical target volume (CTV) and skin (contoured from the surface to a depth of 5 mm). Of the 56 pediatric patients with extremity STS with RT plans available for review, 38 (65%) were treated with 3D-CRT and 18 (32%) with IMRT. There was no difference in distribution of site treated with IMRT vs. 3D-CRT (upper leg: 53% vs. 50%; knee: 16% vs. 17%; lower leg: 11% vs. 17%; lower arm: 11% vs. 17%, IMRT vs. 3D-CRT, respectively) with the exception of 0% vs. 11% of patients treated with IMRT vs. 3D-CRT to the upper arm. There was no difference in CTV volume between groups of patients treated with IMRT (median 1027 cc, range 66-2867 cc) or 3D-CRT (median 647 cc, range 30-4854 cc) (P = 0.920); however, patients treated with IMRT had significantly improved CTV coverage with 100% of the prescription dose compared to those receiving 3D-CRT (median CTV coverage, 95% vs. 87% respectively, P = 0.011). In patients without skin bolus, the percentage of skin receiving 45 Gy or more was significantly lower in patients treated with IMRT compared to 3D-CRT (mean percentage, 3% vs. 8% respectively, P = 0.039). Pre-operative IMRT compared to 3D-CRT may result in improved RT target coverage with reduced dose to the skin. Future studies are important to assess if this lower skin dose translates to reduced wound complications and/or improved limb function.