High-dose planned adaptive helical tomotherapy for cutaneous angiosarcoma of the scalp.

PURPOSE: The purpose of this study was to investigate the feasibility and effectiveness of high-dose planned adaptive intensity-modulated radiation therapy (IMRT) with helical tomotherapy (HT) for cutaneous angiosarcoma (cAS) of the scalp. METHODS: This retrospective cross-sectional included a total of 12 consecutive patients with cAS of the scalp who underwent high-dose planned adaptive IMRT with HT. Prescribed doses were 72.5-74 Gy in 35-37 fractions for the gross tumor volume plus a 1-2 mm margin (PTV1), 58-60 Gy in 29-30 fractions for the clinical target volume plus a 2-3 mm margin (PTV2), and 46 Gy in 23 fractions for the clinical target volume plus a 5-15 mm margin (PTV3) over periods of 7.5, 6 and 4.5 weeks, respectively. RESULTS: The estimated 1­year and 2­year overall survival rate were 65.6% and 27.3%, respectively, and the local progression-free survival at 2 years was 74.1%. All local recurrences were either in or marginal to the PTV2 or PTV3. No local recurrence was observed in the PTV1. All patients tolerated the treatment without grade 3 or higher adverse events during the radiotherapy period. No late adverse events were observed during the follow-up period. CONCLUSION: Planned adaptive high-dose IMRT with HT has the potential to improve local control rate without increasing adverse events.

Treatment of radiation-associated angiosarcoma.

PURPOSE OF REVIEW: Radiation-associated angiosarcoma is a cutaneous aggressive tumor that is very rare and it represents a specific entity poorly studied in literature. It requires new therapeutic opportunity. RECENT FINDINGS: The complete surgical resection with negative margins is the mainstay treatment of localized treatment, even though it is difficult to reach in case of diffuse cutaneous infiltration. Adjuvant re-irradiation may improve local control with no benefit demonstrated on survival. Many systemic treatments can be efficient not only in metastatic setting but also in neoadjuvant setting in case of diffuse presentation. These treatments have never been compared to each other; the most efficient regimen remains to be determined, and a high heterogeneity of treatment is observed, even between sarcoma reference centers. SUMMARY: Immune therapy represents the most promising treatment under development. At the time of building clinical trial to assess the efficacy of immune therapy, the lack of randomized studies prevents the identification of a strong and consensual reference arm treatment. Given the rarity of the disease, only international collaborative clinical trials may have a chance to include enough patients to draw any conclusion and so will have to counteract the heterogeneity of management.

Clinical significance of local control of primary tumour in definitive radiotherapy for scalp angiosarcomas.

INTRODUCTION: Scalp angiosarcoma is a rare and aggressive cancer. Definitive radiotherapy is a treatment option for localised scalp angiosarcoma patients. Although definitive surgical resection reportedly prolongs overall survival (OS), whether initial local treatment effect affects OS when definitive radiotherapy is administered is unclear. Therefore, this study analysed whether local recurrence within 6 months of irradiation correlates with OS and cancer-specific survival (CSS). Furthermore, how local control affects patients' quality of life was investigated. MATERIALS AND METHODS: Thirty-one localised scalp angiosarcoma patients who had received definitive radiotherapy at our institution between October 2010 and July 2021 were analysed retrospectively. The most commonly used dose fractionation was 70 Gy in 35 fractions (83.9%). Local recurrence within 6 months of radiotherapy and other clinical factors were examined in univariate and subsequent multivariate analyses for correlation with OS and CSS. RESULTS: The median follow-up period was 16 months (range, 6-45 months). Local recurrence was detected in 16 patients (51.6%), 12 of whom had recurrence within 6 months. In multivariate analyses, the presence of local recurrence within 6 months of radiotherapy was significantly associated with OS and CSS (p = 0.003, 0.0001, respectively). Ten of the 16 patients with local recurrence had severe symptoms such as bleeding, pain, difficulty opening the eye and malodour. CONCLUSIONS: The initial local treatment effect was significantly associated with OS and CSS after definitive radiotherapy. Furthermore, local recurrence after radiotherapy resulted in a variety of symptoms, including bleeding and pain, which reduced the patient's quality of life.

Neoadjuvant radiation for cutaneous and soft tissue angiosarcoma.

BACKGROUND AND OBJECTIVES: Neoadjuvant radiation (NRT) is frequently utilized in soft tissue sarcomas to increase local control. Its utility in cutaneous and soft tissue angiosarcoma remains poorly defined. METHODS: This retrospective cohort study was performed using the National Cancer Database (2004-2016) evaluating patients with clinically localized, surgically resected angiosarcomas. Factors associated with receipt of NRT in the overall cohort and margin positivity in treatment naïve patients were identified by univariate and multivariable logistic regression analyses. Survival was assessed using Kaplan-Meier analysis. RESULTS: Of 597 patients, 27 (4.5%) received NRT. Increasing age (odds ratio [OR] 0.95, p = 0.025), tumor size more than or equal to 5 cm (OR 3.16, p = 0.02), and extremity tumor location (OR 3.99, p = 0.04) were associated with receipt of NRT. All patients who received NRT achieved an R0 resection (p = 0.03) compared with 17.9% of patients without NRT. Factors associated with risk of margin positivity included tumor size more than or equal to 5 cm (OR 1.85, p = 0.01), and head/neck location (OR 2.24, p = 0.006). NRT was not significantly associated with improved survival (p = 0.21). CONCLUSIONS: NRT improves rates of R0 resection but is infrequently utilized in cutaneous and soft tissue angiosarcoma. Increased usage of NRT, particularly for patients with lesions more than or equal to 5 cm, or head and neck location, may help achieve complete resections.

MYC-Nonamplified Secondary Lymphatic-Type Angiosarcoma With Prominent Lymphocytic Infiltrate Following Radiation Therapy for Myxoid Liposarcoma.

ABSTRACT: Cutaneous angiosarcomas (AS) are uncommon and morphologically heterogeneous. Recently, a distinctive lymphatic-type AS with prominent lymphocytic infiltrate has been observed. Although conventional AS typically bear poor prognosis, lymphatic-type AS with prominent lymphocytic infiltrate and pseudolymphomatous AS show prolonged survival with rare extracutaneous spread. We describe a unique case of AS in a 55-year-old woman who received surgical resection and radiation therapy for her prior myxoid liposarcoma. She developed a suspected recurrence 15 years later. Microscopically, the lesion showed an infiltration of the reticular dermis by irregular interanastamosing vascular spaces lined by atypical endothelial cells with nuclear "hobnailing" and hyperchromasia. A prominent intratumoral and peritumoral lymphocytic infiltrate obscuring the tumor cells was also present. The tumor cells were diffusely positive for endothelial cell markers, including D2-40. Notably, there was no evidence of MYC gene amplification by FISH. Additional NGS-based molecular analysis demonstrated no significant genetic mutations. The patient is alive with a history of two local recurrences, but no evidence of metastasis. We present this case to raise awareness of MYC-nonamplified secondary lymphatic-type AS with prominent lymphocytic infiltrate (pseudolymphomatous AS) and to discuss its differential diagnosis.

Radiation-associated Angiosarcoma Mimicking Fallopian Tube High-grade Serous Carcinoma in a Woman With De Novo Li-Fraumeni Syndrome.

We present a case study of a woman with history of rectal adenocarcinoma, and a new diagnosis of radiation-associated angiosarcoma mimicking fallopian tube high-grade serous carcinoma who was subsequently found to have de novo Li-Fraumeni syndrome. Our objective is to highlight angiosarcoma as a potential pitfall in the diagnosis of high-grade serous carcinoma.

Radical chest wall resection and hyperfractionated accelerated radiotherapy for radiation-associated angiosarcoma of the breast: A safe and effective treatment strategy.

Radiation-associated angiosarcomas (RAS) of the breast are vascular tumors arising in a previous radiation field for primary breast cancer. They occur rarely but confer a high probability of local recurrence (LR) and poor prognosis. A wide range of treatment strategies exists due to limited evidence, and although resection is the definitive treatment, LR rates remain high. It has been suggested hyperfractionated accelerated radiotherapy (HART) has the potential to prevent LR. The sarcoma group at the Juravinski Cancer Centre (JCC) reports our experience of nine patients treated with radical resection and adjuvant HART. This is one of the largest reported cohorts we are aware of to receive this treatment. The JCC pathologic data base was reviewed between the year 2006-2015 for patients with RAS. Patients who received radical surgery and immediate HART were eligible. Patients underwent radical chest wall resection and en bloc mastectomy. Radiotherapy was then delivered to 4500 cGy in 45 fractions three times daily using parallel opposed photon beams and electron patching, or volumetric modulated arc therapy. Primary outcome was recurrence-free survival in months, and records were reviewed for descriptive reports of toxicity. We compared our results to other institutions experience with surgery alone or other adjuvant therapies. Median follow-up was 19 months (range 3-41 months). One of nine patients developed LR and developed metastasis, one died of other causes, and seven are alive with no recurrent disease. There were seven reports of mild skin toxicity during treatment. One patient developed chronic wound healing complications which eventually resolved and one patient developed asymptomatic radiation osteitis of a rib. On the basis of our experience at the JCC, we recommend treatment with radical chest wall resection and adjuvant HART to prevent recurrence in RAS patients. As demonstrated in our patients, the large normal tissue volume irradiated is tolerable with in combination with small fraction sizes, and no major toxicities were seen. Further investigation into adjuvant therapy regimens and prospective studies are required to reach consensus on optimal treatment for this disease.

A Patient With Submerged Sinonasal Angiosarcoma After Resection of Underlying Organizing Hematoma.

A 30-year-old female patient with facial pain diagnosed as organizing hematoma of maxillary sinus by biopsy and imaging studies, and subsequently tumor was resected via an endoscope-assisted midfacial degloving approach. The tumor was histopathologically confirmed as organizing hematoma. In 3-week follow-up, asymptomatic emerging mass was observed at the same site, and needed a revision endoscopic resection. On pathologic examination, a low-grade angiosarcoma was identified, not organizing hematoma. After postoperative radiotherapy, she has been a status of no evidence of disease. This report emphasizes that complete and delicate resection of sinonasal tumor should be made to prevent recurrence and submerged malignant potential.

Development of RET mutant cutaneous angiosarcoma during BRAF inhibitor therapy.

Treatment with BRAF inhibitors may lead to paradoxical mitogen-activated protein kinase (MAPK) pathway activation and accelerated tumorigenesis in cells with preexisting oncogenic hits. This phenomenon manifests clinically in the development of squamous cell carcinomas (SCCs) and keratoacanthomas (KAs) in patients treated with BRAF inhibitors. Cases of extracutaneous malignancies associated with BRAF inhibitors have also been reported. We present a case of a patient who developed a cutaneous angiosarcoma 6 months after initiation of vemurafenib therapy. Next-generation sequencing (NGS) revealed a mutation in RET, which lies upstream of the MAPK pathway. This case highlights that treatment with BRAF inhibitors may promote the accelerated growth of secondary malignancies. Physician awareness of the spectrum of secondary malignancies associated with BRAF inhibitor treatment will support their early detection and treatment.

[A Case of Angiosarcoma of the Breast Following Breast-Conserving Surgery with Radiotherapy for Breast Cancer].

We report a case of angiosarcoma of the breast following breast-conserving surgerywith radiotherapyfor breast cancer. The patient was 82-year-old woman, developed induration and eruption in the bilateral breast more than 8 years after the initial operation for breast cancer. The induration was diagnosed as angiosarcoma based on skin-biopsyand vacuum-assisted biopsy. The patient received simple mastectomy, and has been become recurrent condition about one month after simple mastectomy. We operated partial excision for recurrence tumor. She is still alive after rearly 1 year of past operation. There are no established therapies for angiosarcoma of the breast following breast-conserving surgerywith radiotherapyfor breast cancer. Although radiotherapy-induced sarcoma is rare, earlydetection of the tumor in the irradiation area is important, as radiotherapyis often performed for the breast cancer patients. This interesting case of angiosarcoma of the breast after breast-conserving surgeryfor breast cancer is reported.

Intraoral angiosarcoma: treatment with a brachytherapy prosthesis.

Angiosarcomas are rare, malignant neoplasms of vascular origin that account for less than 1% of all soft tissue tumors. Angiosarcomas of the oral cavity are especially rare, and brachytherapy may be prescribed as a localized treatment to manage these malignancies. Intraoral brachytherapy requires collaboration between the radiation oncologist and a dental professional for the fabrication of the brachytherapy delivery prosthesis. This clinical report describes an intraoral angiosarcoma and the fabrication of an intraoral brachytherapy prosthesis to manage this malignancy.

Radiation therapy for angiosarcoma of the scalp: treatment outcomes of total scalp irradiation with X-rays and electrons.

BACKGROUND AND PURPOSE: Wide surgical excision is the standard treatment for angiosarcoma of the scalp, but many patients are inoperable. Therefore, we investigated the outcome of radiation therapy for angiosarcoma of the scalp. PATIENTS AND METHODS: Seventeen patients with angiosarcoma of the scalp underwent radiation therapy with total scalp irradiation. Four patients had cervical lymph node metastases, but none had distant metastases. A median initial dose of 50 Gy in 25 fractions was delivered to the entire scalp. Subsequently, local radiation boost to the tumor sites achieved a median total dose of 70 Gy in 35 fractions. RESULTS: Fourteen of the 17 patients developed recurrences during the median follow-up period of 14 months after radiation therapy; 7 had recurrences in the scalp, including primary tumor progression in 2 patients and new disease in 5, and 12 patients developed distant metastases. The primary progression-free, scalp relapse-free, and distant metastasis-free rates were 86, 67, and 38 % at 1 year and 86, 38, and 16 % at 3 years, respectively. Thirteen patients died; the overall and cause-specific survival rates were both 73 % at 1 year and 23 and 44 % at 3 years, respectively. The median survival time was 16 months. There were no therapy-related toxicities ≥ grade 3. CONCLUSION: Total scalp irradiation is safe and effective for local tumor control, but a dose of ≤ 50 Gy in conventional fractions may be insufficient to eradicate microscopic tumors. For gross tumors, a total dose of 70 Gy, and > 70 Gy for tumors with deep invasion, is recommended.

Chemoradiotherapy with taxane is superior to conventional surgery and radiotherapy in the management of cutaneous angiosarcoma: a multicentre, retrospective study.

BACKGROUND: The prognosis of cutaneous angiosarcoma (CAS), especially for patients with tumours > 5 cm has been reported to be dismal, even after conventional surgery and radiotherapy (S + RT). OBJECTIVES: To demonstrate the efficacy of chemoradiotherapy with taxane (T + RT) and maintenance chemotherapy. METHODS: We retrospectively reviewed 16 patients with CAS treated with T + RT and 12 patients treated with S + RT. None had distant metastasis. Tumour sites included the scalp (n = 25) and limbs (n = 3). The chemotherapy regimens used in T + RT were monthly docetaxel (n = 10), biweekly docetaxel (n = 1), weekly docetaxel (n = 5) and weekly paclitaxel (n = 1). The median radiation dose was 70 Gy. Nine patients receiving T + RT continued chemotherapy as maintenance therapy (monthly docetaxel in nine patients and monthly paclitaxel in two patients) and four patients receiving S + RT received adjuvant chemotherapy (weekly docetaxel). RESULTS: The response ratio of T + RT was 94% (14 complete remission and one partial remission). The 5-year overall survival (OS) rate of patients receiving T + RT was statistically higher than those receiving conventional S + RT (56% and 8%, respectively; P < 0·01). Moreover, patients who received T + RT with maintenance chemotherapy showed a significant improvement in OS than those receiving T + RT alone (P < 0·01). There was a strong trend for relapse-free survival, but it was not significant (P = 0·07). These data indicate that maintenance chemotherapy is crucial for long-term survival after T + RT. CONCLUSIONS: From these results, we suggest that T + RT followed by maintenance chemotherapy is a plausible method for managing CAS, especially large tumours that are difficult to manage with S + RT alone.

Angiosarcoma after breast-conserving therapy: long-term disease control and late effects with hyperfractionated accelerated re-irradiation (HART).

BACKGROUND: Secondary angiosarcoma is a malignant cancer that develops in approximately 1% of patients treated with breast-conserving therapy (BCT) for primary breast cancer. Most treatments for secondary angiosarcoma have been unsuccessful and no consensus has been reached on what is the best therapeutic strategy. We report long-term outcomes of patients with secondary angiosarcoma treated with hyperfractionated and accelerated re-irradiation (HART). MATERIAL AND METHODS: We retrospectively reviewed the medical records of, and established direct contact with, 14 consecutive patients with secondary angiosarcoma after BCT with axillary lymph node dissection who were treated at our institution with HART with or without surgery from November 1997 to March 2006. With HART, patients received three radiation therapy treatments each day, with a minimum interfraction interval of four hours, five days a week, at 1 Gy per fraction, to total doses of 45 Gy, 60 Gy, and 75 Gy for areas with a moderate risk for subclinical disease, a high risk for subclinical disease, and gross disease, respectively. The minimum follow-up for these patients was six years. RESULTS: Median survival was 7.0 years (range 0.4-14.7 years), with five- and 10-year overall survival rates of 79% [95% confidence interval (CI), 51-93%] and 63% (95% CI 37-84%), respectively, and five- and 10-year cause-specific survival rates of 79% (95% CI 51-93%) and 71% (95% CI 44-89%), respectively. Toxicity was minimal. CONCLUSION: Our long-term study provides evidence that patients with secondary angiosarcoma after BCT can frequently be cured. Patients treated with HART have higher overall survival, progression-free survival, and cause-specific survival rates than patients who receive only surgery, conventional radiation therapy, or chemotherapy. HART is well tolerated.

A simpler method for total scalp irradiation: the multijaw-size concave arc technique.

The lateral electron-photon technique (LEPT) and intensity-modulated radiation therapy (IMRT) are commonly used for total scalp irradiation. However, the treatment planning and irradiation are laborious and time-consuming. We herein present the multijaw-size concave arc technique (MCAT) as a total scalp irradiation method that overcomes these problems. CT datasets for eight patients previously treated for angiosarcoma of the scalp were replanned using MCAT, LEPT, and IMRT. The MCAT was designed with a dynamic conformal arc for the total scalp, with a multileaf collimator to shield the brain. Two additional conformal arcs with a decreased upper-jaw position of the first dynamic conformal arc were used to reduce the cranial hotspots. The prescribed dose was 40 Gy (2 Gy/fraction) to 95% of the planning target volume (PTV, defined as the total scalp plus a 4 mm margin). MCAT was compared with LEPT and IMRT with respect to the PTV dose homogeneity (D5%-95%), underdosage (V < 90%), overdosage (V > 110%), doses to the brain, and the delivery time and monitor units (MUs) for single irradiation. We were able to formulate treatment plans for all three techniques that could deliver the prescription dose in all patients. MCAT was significantly superior to LEPT with respect to PTV dose homogeneity, overdosage, and underdosage, although MCAT was inferior to IMRT with respect to dose homogeneity and overdosage. The mean brain dose and high-dosage volume of all three techniques were low, but IMRT provided larger volume to the brain than did the other two techniques in the low dosage region. In MCAT, the mean delivery time could be reduced by approximately half or more, and the mean MUs could be reduced by at least 100 compared to the other two techniques. MCAT can achieve total scalp irradiation with substantially fewer MUs and a shorter delivery time than LEPT and IMRT.

Clinical outcomes of scalp or face angiosarcoma treatment with intensity-modulated radiotherapy: a multicenter study.

Combined modality therapy, including radiotherapy (RT), is a common treatment for scalp or face angiosarcoma. Although intensity-modulated radiotherapy (IMRT) can deliver homogeneous doses to the scalp or face, clinical data are limited. This multicenter study aimed to evaluate scalp or face angiosarcoma treated with definitive or post-operative IMRT. We retrospectively analyzed data from patients who received IMRT for scalp or face angiosarcoma at three institutions between January 2015 and March 2020. Local control (LC) rate, overall survival (OS), progression-free survival (PFS), recurrence patterns and toxicity were evaluated. Fifteen patients underwent IMRT during the study period. Definitive RT was performed on 10 patients and post-operative RT was performed on 5 patients. The 1-year LC rate was 85.7% (95% confidence interval [CI], 53.9-96.2%). The 1-year OS and PFS rates were 66.7% (95% CI, 37.5-84.6%) and 53.3% (95% CI, 26.3%-74.4%), respectively. Univariate analysis revealed that a clinical target volume over 500 cm3 was associated with poor LC. Distant metastasis was the most common recurrence pattern. All patients experienced Grade 2 or 3 radiation dermatitis, and five patients experienced grade ≥ 3 skin ulceration. One patient who underwent maintenance therapy with pazopanib developed Grade 5 skin ulceration. Fisher's exact test showed that post-operative RT was significantly associated with an increased risk of skin ulceration of grade ≥ 3. These results demonstrate that IMRT is a feasible and effective treatment for scalp or face angiosarcoma, although skin ulceration of grade ≥ 3 is a common adverse event in patients who receive post-operative RT.

Neoadjuvant Reirradiation for Radiation Therapy-Associated Angiosarcoma of the Breast.

PURPOSE: Radiation-associated angiosarcoma of the breast (RAASB) is a rare side effect after breast radiation and has been associated with poor outcomes. At this time, there is no consensus regarding management of RAASB, and the role of reirradiation remains controversial. We present our modern institutional outcomes in managing RAASB with incorporation of neoadjuvant hyperfractionated reirradiation. METHODS AND MATERIALS: Patients identified were treated between 2016 and 2020 with inclusion of any histologically proven RAASB without metastatic disease at diagnosis, while excluding those with a history of radiation therapy outside of the breast/chest wall or other sarcoma histologies. Major wound complications were defined as requiring wound care and/or wound vacuum or return to the operating room for wound repair at any time after surgery. RESULTS: Eight patients were identified, and the median follow-up was 34 months. Median time to RAASB development was 8 years from initial radiation therapy. With respect to RAASB management, all underwent surgery and neoadjuvant reirradiation therapy, and all but 1 patient received taxol-based chemotherapy. At last follow-up, 7 patients remained free of disease, and 1 patient died with distant disease. With respect to acute toxicity after reirradiation, all patients developed at least acute grade 2 toxicities. Five of the 8 patients developed a major wound complication. CONCLUSIONS: Our institutional analysis suggests excellent local control and survival outcomes for RAASB treated with neoadjuvant hyperfractionated reirradiation, surgery, and taxol-based chemotherapy. However, major wound complications represent a major challenge with this approach. Future studies should consider how best to improve the therapeutic ratio while maintaining high rates of local control and survival.

Sustained activation of the FGF1-MEK-ERK pathway inhibits proliferation, invasion and migration and enhances radiosensitivity in mouse angiosarcoma cells.

Angiosarcoma is a rare refractory soft-tissue tumor with a poor prognosis and is treated by radiotherapy. The fibroblast growth factor 1 (FGF1) mutant, with enhanced thermostability due to several substituted amino acids, inhibits angiosarcoma cell metastasis, yet the mechanism of action is unclear. This study aims to clarify the FGF1 mutant mechanism of action using ISOS-1 mouse angiosarcoma cells. The wild-type FGF1 or FGF1 mutant was added to ISOS-1 cells and cultured, evaluating cell numbers over time. The invasive and migratory capacity of ISOS-1 cells was assessed by transwell analysis. ISOS-1 cell radiosensitivity was assessed by colony formation assay after X-ray irradiation. To examine whether mitogen-activated protein kinase (MEK) inhibitor counteracts the FGF1 mutant effects, a combination of MEK inhibitor and FGF1 mutant was added to ISOS-1 cells and cultured. The FGF1 mutant was observed to inhibit ISOS-1 cell proliferation, invasion and migration by sustained FGF1 signaling activation. A MEK inhibitor suppressed the FGF1 mutant-induced inhibition of proliferation, invasion and migration of ISOS-1 cells. Furthermore, the FGF1 mutant enhanced radiosensitivity of ISOS-1 cells, but MEK inhibition suppressed the increased radiosensitivity. In addition, we found that the FGF1 mutant strongly inhibits actin polymerization, suggesting that actin cytoskeletal dynamics are closely related to ISOS-1 cell radiosensitivity. Overall, this study demonstrated that in ISOS-1 cells, the FGF1 mutant inhibits proliferation, invasion and migration while enhancing radiosensitivity through sustained activation of the MEK-mediated signaling pathway.

Phase 2 study of preoperative image-guided intensity-modulated radiation therapy to reduce wound and combined modality morbidities in lower extremity soft tissue sarcoma.

BACKGROUND: This study sought to determine if preoperative image-guided intensity-modulated radiotherapy (IG-IMRT) can reduce morbidity, including wound complications, by minimizing dose to uninvolved tissues in adults with lower extremity soft tissue sarcoma. METHODS: The primary endpoint was the development of an acute wound complication (WC). IG-IMRT was used to conform volumes to avoid normal tissues (skin flaps for wound closure, bone, or other uninvolved soft tissues). From July 2005 to June 2009, 70 adults were enrolled; 59 were evaluable for the primary endpoint. Median tumor size was 9.5 cm; 55 tumors (93%) were high-grade and 58 (98%) were deep to fascia. RESULTS: Eighteen (30.5%) patients developed WCs. This was not statistically significantly different from the result of the National Cancer Institute of Canada SR2 trial (P = .2); however, primary closure technique was possible more often (55 of 59 patients [93.2%] versus 50 of 70 patients [71.4%]; P = .002), and secondary operations for WCs were somewhat reduced (6 of 18 patients [33%] versus 13 of 30 patients [43%]; P = .55). Moderate edema, skin, subcutaneous, and joint toxicity was present in 6 (11.1%), 1 (1.9%), 5 (9.3%), and 3 (5.6%) patients, respectively, but there were no bone fractures. Four local recurrences (6.8%, none near the flaps) occurred with median follow-up of 49 months. CONCLUSIONS: The 30.5% incidence of WCs was numerically lower than the 43% risk derived from the National Cancer Institute of Canada SR2 trial, but did not reach statistical significance. Preoperative IG-IMRT significantly diminished the need for tissue transfer. RT chronic morbidities and the need for subsequent secondary operations for WCs were lowered, although not significantly, whereas good limb function was maintained.