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Purpose: The purpose of this study is to investigate local control (LC), survival outcomes, and associated prognostic factors for patients with malignant peripheral nerve sheath tumors (MPNSTs) treated with combined surgery and radiation therapy (RT)., Methods: We reviewed the medical records of 71 consecutive patients treated with surgery and RT for localized MPNST between 1965 and 2012. Preoperative RT was used to treat 23 patients (32%) to a median dose of 50 Gy (range, 50 to 60 Gy), whereas 48 (68%) received postoperative RT to a median dose of 64 Gy (range, 45 to 70 Gy)., Results: Median follow-up for living patients was 118 months (range, 21 to 512 mo). The 5-year LC, distant metastatic free survival, and disease-specific survival rates were 84%, 62%, and 66%, respectively. To identify predictors of outcome, several multivariate models were constructed: (1) positive/uncertain surgical margin status was the only factor adversely associated local relapse at 5 years (28% vs. 5% for negative margins; P=0.02; hazard ratios 5.92; 95% confidence interval, 1.3-27.4). (2) No factors were significantly associated with distant metastatic free survival. Of the 35 patients (49%) who sustained disease relapse, only 3 were ultimately salvaged. Only 2 patients had grade 2 late toxicities (necrosis, fibrosis) based on Common Terminology Criteria for Adverse Events version 4.03 criteria, and 1 patient had grade 1 edema., Conclusions: Combination therapy with surgery and RT provides favorable LC. Distant recurrences, however, continue to be challenging with limited salvage success at the time of relapse.

Purpose: To report survival outcomes and local control in patients with solitary fibrous tumors (SFT) treated using surgery and radiation therapy (RT)., Methods: We reviewed the medical records of 31 consecutive patients definitively treated for SFT with surgery and RT between 1982 and 2012. The median age was 51 years (range, 23 to 88 y) and tumors were evenly distributed between the head and neck (n=9, 29%), trunk (n=10, 32%), and lower extremities (n=9, 29%). The majority of tumors were large (>5 cm) (n=23, 72%). Specimens had a median of 2 mitoses/10 HPF (range, 0 to 8). Nearly half the cases were treated with postoperative RT (n=14, 45%; median dose, 58 Gy) and the other 17 patients (55%) received preoperative RT (median dose, 50 Gy)., Results: Median follow-up time was 59 months (range, 18 to 349 mo). The 5-year rates of local control, overall survival, and distant metastatic-free survival were 100%, 95%, and 92%, respectively. There were no local or nodal relapses and the 10-year complication rate was 6% (n=2)., Conclusions: Treatment of soft tissue SFT using combined surgery and RT results in excellent local control.

Purpose: The purpose of this study was to investigate the incidence of and risk factors associated with femur fracture after combined modality therapy for soft tissue sarcomas (STS) of the proximal lower extremity., Methods and Materials: We reviewed the records of 596 patients with STS of the proximal lower extremity consecutively treated with surgery and radiation therapy (RT) from 1966 to 2012. One hundred ninety-seven patients (33%) received 50 Gy to the entire femur circumference (n = 197, 33%); 265 patients (45%) received perioperative chemotherapy, and during surgery, 155 patients (26%) had bone exposure, whereas 82 patients (14%) had the periosteum stripped. The Kaplan-Meier method was used to estimate actuarial outcome rates, and both Cox regression modeling and competing risk analyses using the method of Fine and Gray were performed., Results: Median follow-up time was 110 months (range, 6-470 months). The actuarial 10-year local control and overall survival rates were 88% (95% confidence interval [CI], 84%-90%) and 62% (95% CI, 57%-66%). Twelve patients had pathologic fractures, which were associated with 50 Gy to the entire bone circumference (P < .001), bone exposure (P < .001), and periosteal stripping during surgery (P < .001) and use of perioperative chemotherapy (P = .04). Using a competing risk model, bone exposure (P = .001; sub-hazard ratio [SHR], 9.13; 95% CI, 2.5-33.0), periosteal stripping (P < .001; SHR, 13.03; 95% CI, 4.0-43.0), and perioperative chemotherapy (P = .03; SHR, 4.03; 95% CI, 1.1-14.4) were significantly associated with fracture. The actuarial 10-year fracture rate was 2% (95% CI, 1%-3%) when the 50-Gy isodose line encompassed the entire bone circumference without the other risk factors, whereas it increased to 37% (95% CI, 12%-45%) when all 4 treatment-related factors were present., Conclusions: Although femur fractures are rare, a component from each of the 3 therapeutic modalities contributes to the overall risk, and a multidisciplinary approach to mitigating fracture risk is needed. Although avoiding circumferential bone coverage with the 50-Gy isodose line may be a valuable dosimetric parameter, more rigorous dosimetric studies are required., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with aggressive surgery and radiation therapy (RT) for retroperitoneal sarcomas (RPS)., Methods and Materials: We reviewed the medical records of 121 consecutive patients treated for RPS with surgery and RT between 1965 and 2012. The most common histology was liposarcoma (n = 42; 35%). The median follow-up was 100 months (range: 20-467 months). Eighty-six patients (71%) were treated for initial presentation of RPS, and 35 patients (29%) presented with and were treated for RPS recurrence. RT was preoperative in 88 patients (73%; median dose: 50.4 Gy) and postoperative in 33 patients (27%; median dose: 55 Gy)., Results: Five-year local control and overall survival rates were 56% and 57%, respectively. Two factors were associated with higher risk of any intra-abdominal recurrence at 5 years: positive or uncertain margins (58% vs 30% for negative margins, P < .001; hazard ratio [HR]: 2.7; 95% confidence interval [CI]: 1.6-4.8) and disease recurrence after previous resection (76% vs 31% for de novo RPS, P < .001; HR: 4.4; 95% CI: 2.5-7.5). The 10-year complication rate was 5%, and RT-related complications were associated with postoperative RT (P < .001) and RT dose of ≥ 60 Gy (P < .001)., Conclusions: Intra-abdominal RPS recurrence continues to be a significant challenge despite the use of aggressive surgery and radiation therapy. Given the complications associated with postoperative radiation therapy, we recommend that preoperative radiation therapy is the preferred strategy when combined modality therapy is recommended., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with limb-sparing surgery and radiation therapy (RT) for soft tissue sarcomas (STS) of the hands and feet., Methods and Materials: We reviewed the medical records of 85 consecutive patients treated for STS of the hands (n=38, 45%) and feet (n=47, 55%) between 1966 and 2012. The median age was 41 years (range, 10-82 years of age). Sixty-seven patients (79%) received postoperative RT after resection of their tumor (median dose, 60 Gy; range, 45-70 Gy). The remaining 18 patients (21%) were treated with preoperative RT followed by tumor resection (median dose, 50 Gy; range, 50-64 Gy)., Results: Median follow-up was 140 months (range, 24-442 months). Five-year local control, overall survival, and disease-specific survival rates were 86%, 89%, and 89%, respectively. Positive or uncertain surgical margin status was the only factor adversely associated with local recurrence (19% vs 6% for negative margins, P=.046) but this lost significance on multivariate analysis when adjusting for RT dose ≥64 Gy. Of the 12 patients who had local relapses, 6 (50%) were salvaged, and only 2 of those required salvage amputation. Five patients had grade ≥3 late RT sequelae, with 2 patients (2%) having moderate limitations of limb function and 3 patients (4%) having severe limitations requiring procedures for skin ulceration., Conclusions: Limb-sparing surgery combined with RT provides excellent local control outcomes for sarcomas arising in the hands or feet. In patients who have local recurrence, salvage without amputation is possible. The excellent cancer control outcomes observed, considering the minimal impact on limb function, support use of combined modality, limb-sparing local therapy for STS arising in the hands or feet., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: In the current study, the authors sought to evaluate outcomes, specifically with respect to adjuvant radiotherapy (RT), for patients with desmoplastic melanoma., Methods: The records of 130 consecutive patients who presented between 1985 and 2009 with nonmetastatic desmoplastic melanoma and were treated curatively with either surgery alone (59 patients; 45%) or surgery and postoperative RT (71 patients; 55%) were retrospectively reviewed. Ages ranged from 21 years to 97 years (median age, 66 years). The location of the primary tumor was in the head and neck region in 62% of patients. Only 5 patients (4%) had lymph node involvement at the time of presentation., Results: The median follow-up was 6.6 years (range, 11 months-24 years). Overall survival rates at 5 years and 10 years were 69% and 53%, respectively. Disease-specific survival rates were 84% and 80%, respectively, at 5 years and 10 years. The actuarial rate of local recurrence was 17% at 5 years and beyond. Of the patients who underwent surgery without receiving postoperative RT, 14 (24%) experienced local recurrence. Of the 71 patients treated with surgery and postoperative RT, 5 (7%) experienced local recurrence. In a Cox multivariate regression model, improved local control was significantly associated with the receipt of postoperative RT (P= .009)., Conclusions: Surgery followed by postoperative RT appears to provide superior local control compared with surgery alone for patients with desmoplastic melanoma., (© 2013 American Cancer Society.)

Purpose: To evaluate outcomes of conservative surgery and radiation therapy (RT) treatment in patients with dermatofibrosarcoma protuberans., Methods and Materials: We retrospectively reviewed the medical records of 53 consecutive dermatofibrosarcoma protuberans patients treated with surgery and preoperative or postoperative radiation therapy between 1972 and 2010. Median tumor size was 4 cm (range, 1-25 cm). Seven patients (13%) were treated with preoperative RT (50-50.4 Gy) and 46 patients (87%) with postoperative RT (60-66 Gy). Of the 46 patients receiving postoperative radiation, 3 (7%) had gross disease, 14 (30%) positive margins, 26 (57%) negative margins, and 3 (7%) uncertain margin status. Radiation dose ranged from 50 to 66 Gy (median dose, 60 Gy)., Results: At a median follow-up time of 6.5 years (range, 0.5 months-23.5 years), 2 patients (4%) had disease recurrence, and 3 patients (6%) had died. Actuarial overall survival was 98% at both 5 and 10 years. Local control was 98% and 93% at 5 and 10 years, respectively. Disease-free survival was 98% and 93% at 5 and 10 years, respectively. The presence of fibrosarcomatous change was not associated with increased risk of local or distant relapse (P=.43). One of the patients with a local recurrence had gross residual disease at the time of RT and despite RT to 65 Gy developed both an in-field recurrence and a nodal and distant recurrence 3 months after RT. The other patient with local recurrence was found to have in-field recurrence 10 years after initial treatment. Thirteen percent of patients had an RT complication at 5 and 10 years, and 9% had a moderate or severe complication at 5 and 10 years., Conclusions: Dermatofibrosarcoma protuberans is a radioresponsive disease with excellent local control after conservative surgery and radiation therapy. Adjuvant RT should be considered for patients with large or recurrent tumors or when attempts at wide surgical margins would result in significant morbidity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Trabectedin and thioglitazones have been documented to induce adipocytic maturation in myxoid liposarcoma; we have noted this in our experience as well. Intriguingly, we have also encountered this same phenomenon in myxoid liposarcomas exposed to various combinations of neoadjuvant doxorubicin and ifosfamide systemic chemotherapy with preoperative radiation, where the pathological effects have been less characterized. We examined the histological changes, including adipocytic maturation, associated with this treatment in patients with myxoid liposarcoma and evaluated for prognostic significance., Methods: Twenty-two patients were identified with histologically confirmed myxoid liposarcomas (9 with variable hypercellular areas) who were treated with neoadjuvant doxorubicin (75-90 mg/m2/continous infusion over 72h every 3 week) and ifosfamide (2.5 g/m2 daily x 4 every 3 weeks) for 4-6 cycles. Twenty-one patients received pre-operative radiation including 5 with concurrent gemcitabine. Pre- and post-treatment MRI studies were compared for changes in tumor area, fat content and contrast uptake, with the latter two estimated as: none, <25%, 25-49% and >50%. Post-treatment specimens were evaluated for hyalinization, necrosis and adipocytic maturation. Clinical follow-up was obtained., Results: Median age was 45 (26-72) years with a median tumor size of 11 (2-18) cm. All occurred in the lower extremities except for one case in the neck. As is common in myxoid liposarcoma, all had extensive treatment changes (>90%) with extensive hyalinization (n = 16; >90%) or prominent adipocytic maturation (n = 6; >50%) including 2 cases composed almost entirely of mature-appearing adipose tissue. Variable necrosis was identified (5-30%). MRI revealed a decrease in tumor area in all but one tumor (median, 65%), an increase in fat content in 7 tumors (n = 2, >50%;n = 2, 25-50%;n = 3,<25%), and a decrease in contrast enhancement in most tumors (n = 5, >50%; n = 9, 25-49%; n = 7, <25%). Median follow-up was 57 (12-96) months with 17 alive with no disease/metastases, 3 alive with disease and 2 dead of disease. Six patients developed metastases with median interval of 26 (22-51) months post resection. Four of 6 tumors with increased adipocytic maturation >50% on histology had increased fat detected by MRI (>25%). All 6 are alive but 2 developed metastases. In the remaining patients, 4 developed metastases with 14 alive and 2 dead of disease., Conclusion: Myxoid liposarcoma exposed to neoadjuvant doxorubicin and ifosfamide and pre-operative radiation can have prominent adipocytic maturation similar to trabectedin treatment. Myxoid liposarcomas exhibit extensive treatment changes with prominent hyalinization being the most common histological change. Despite this, patients develop metastases regardless of adipocytic maturation. While of unclear significance, no patient with fatty maturation died of disease.

Purpose: The aim of this study was to assess preoperative biopsy utilization for patients with soft tissue sarcoma (STS) of ≥5 cm in size and whether or not preoperative biopsy was associated with fewer surgical procedures to adequately treat these tumors., Methods: We identified 899 patients from the Surveillance, Epidemiology, and End Results-Medicare database with a diagnosis of STS and who underwent surgical resection of their tumors between 1992 and 2006. We used diagnosis and procedure codes from claims data to identify which patients had a biopsy performed and the corresponding number of surgical procedures for each patient. Multivariate logistic regression analyses were carried out to assess the influence of patient, tumor, and sociodemographic characteristics on performance of biopsy and the likelihood of multiple STS operations., Results: Only 40.6% of patients with tumors of ≥5 cm in size underwent biopsy as part of initial management of their STS. In multivariate analysis, biopsy utilization varied significantly by sex, tumor size, grade, and geographic region. After adjusting for patient, tumor, and sociodemographic characteristics, receipt of a biopsy was the only factor significantly associated with reduced likelihood of multiple STS operations (odds ratio=0.34, 95% confidence interval, 0.24-0.49)., Conclusion: Preoperative biopsy utilization among Medicare beneficiaries undergoing surgery for STS of ≥5 cm in size is low. Performance of a biopsy for patients with soft tissue tumors of ≥5 cm in size is associated with a decreased likelihood of a patient undergoing multiple surgeries for treatment of STS.

Background: Anorectal melanoma is a rare disease with a poor prognosis. Because survival is determined by distant failure, many centers have adopted sphincter-sparing excision for primary tumor control. However, this approach is associated with high rates of local failure (∼50%). In this study, the authors report their 20-year experience with sphincter-sparing excision combined with radiation therapy (RT) for the treatment of localized anorectal melanoma., Methods: The authors reviewed the records of 54 patients with localized anorectal melanoma who were treated at the University of Texas MD Anderson Cancer Center from 1989 to 2008. All patients underwent definitive local excision with or without sentinel lymph node biopsy or lymph node dissection. RT (25-36 grays in 5-6 fractions) was delivered to extended fields that targeted the primary site and draining pelvic/inguinal lymphatics in 39 patients and to limited fields that targeted only the primary site in 15 patients., Results: The 5-year rates of local control (LC), lymph node control (NC), and sphincter preservation were 82%, 88%, and 96%, respectively. However, because of the high rate of distant metastasis, the overall survival (OS) rate at 5 years was only 30%. Although there were no significant differences in LC, NC, or OS based on RT field extent, patients who received extended-field RT had higher rates of lymphedema than patients who received limited-field RT., Conclusions: The current results indicated that combined sphincter-sparing local excision and RT is a well tolerated approach that provides effective LC for patients with anorectal melanoma. Inclusion of the inguinal lymph node basins in the RT fields did not improve outcomes and was associated with an increased risk of lymphedema., (Copyright © 2011 American Cancer Society.)

Background: The aim of the present analysis was to retrospectively evaluate outcomes in patients with cutaneous angiosarcoma of the face/scalp treated curatively with surgery, radiation therapy (RT), or a combination of surgery and RT., Methods: In all, 70 patients with nonmetastatic angiosarcoma underwent surgery, RT, or combined-modality therapy. Of these, 20 patients (29%) were treated with surgery alone, 27 patients (39%) with RT alone, and 23 patients (33%) with combined-modality therapy; 44 patients received chemotherapy, either neoadjuvantly or adjuvantly or both., Results: Median follow-up was 2.1 years. The overall survival (OS) rate was 43% at 5 years, and disease-specific survival (DSS) was 46% at 5 years. Tumor size > 5 cm and satellitosis were prognostic for inferior OS and DSS. Combined-modality therapy (vs surgery alone or RT alone) was associated with improved OS, DSS, and local control., Conclusions: Primary local therapy with combined-modality therapy was associated with improved local control, OS, and DSS for patients with angiosarcoma of the face/scalp., (Copyright © 2010 Wiley Periodicals, Inc.)

Background: The aim of this study was to evaluate the role of regional nodal radiation therapy (RT) for patients with bilateral cervical nodal metastases from melanoma., Methods: Between 1998 and 2008, 16 patients with bilateral cervical metastases without distant metastases were treated with postoperative RT (30 Gy in 5 fractions delivered twice weekly)., Results: Median follow-up was 5 months (range, 1-34 months). Median survival was 9 months (95% confidence interval [CI], 0-23 months). Overall survival was 68%, 50%, and 27% at 6, 12, and 24 months, respectively. Regional nodal control was 74% and 64% at 6 and 12 months, respectively. Rates of development of distant metastasis were 60%, 70%, and 90% at 6, 12, and 18 months, respectively. The actuarial rate of RT-related complications was 49% at 12 months., Conclusion: The limited life expectancy of patients observed with this disease combined with the high rate of RT-related complications argue against the routine use of adjuvant RT for regional nodal disease in this setting., ((c) 2009 Wiley Periodicals, Inc. Head Neck, 2010.)

Background: The current study was performed to evaluate outcomes in patients with osteosarcoma of the head and neck (OHN) who were treated with surgery with or without radiotherapy (RT)., Methods: Between 1960 and 2007, 119 patients with OHN underwent macroscopic total resection with or without RT. The median age of the patients was 33 years (range, 7-77 years). Of these 119 patients 92 (77%) underwent surgery alone whereas 27 (23%) patients were treated with combined modality treatment (CMT) comprised of surgery and RT (median dose, 60 Gray [Gy]; range, 50-66 Gy)., Results: The median follow-up was 5.8 years. Overall survival (OS) rates at 5 years and 10 years were 63% and 55%, respectively. Corresponding disease-specific survival (DSS) rates were 67% and 61%, respectively. Stratified analysis by resection margin status demonstrated that CMT compared with surgery alone improved OS (80% vs 31%; P = .02) and DSS (80% vs 35%; P = .02) for patients with positive/uncertain resection margins. Multivariate analysis indicated that CMT for patients with positive/uncertain resection margins improved OS (P < .0001). A total of 44 (37%) patients experienced local disease recurrence (LR) and 25 (21%) developed distant metastases (DM). There was no difference noted with regard to DSS if disease recurrence was isolated (LR vs DM: 26% vs 29%, respectively, at 5 years; P = .48) The use of CMT versus surgery alone improved local control (LC) (75% vs 24%; P = .006) for patients with positive/uncertain resection margins. The rate of surgical complications was 28% at 5 years. The rates of RT-associated complications were 40% and 47% at 5 years and 10 years, respectively., Conclusions: The results of the current study indicated that RT in addition to surgery improves OS, DSS, and LC for patients with OHN who have positive/uncertain resection margins.

The role of radiotherapy for nodal metastases from malignant melanoma is controversial. In patients with features that indicate high risk of recurrence of nodal disease, adjuvant irradiation lowers recurrence rates. High-risk features include extranodal spread of melanoma, more than two positive lymph nodes, large nodal size, or recurrent disease in previously dissected nodal basin. Data from randomised trials that confirm a benefit of adjuvant radiotherapy in patients with nodal disease at high risk of recurrence are unavailable. However, the use of adjuvant radiotherapy for high-risk nodal disease is increasingly widespread. Recurrence rates and risk of complications differ with anatomic location of the nodal basin involved, and treatment decisions should be made accordingly. Whether to use hypofractionated radiotherapy or conventional fractionation regimens for adjuvant irradiation to nodal basins is also a matter of debate. Hypofractionation is the accepted approach when radiotherapy is recommended. Technical issues have to be considered when hypofractionated regimens are given because survival might be long and the potential for normal tissue toxicity is high. Overall survival remains poor for patients with macroscopic nodal metastases from malignant melanoma. Until advances in systemic treatment are available, regional nodal control is an important endpoint for patients with this disease.

Purpose: To compare treatment-related outcomes and toxicity for patients with axillary lymph node metastases from malignant melanoma treated with postoperative radiation therapy (RT) to either the axilla only or both the axilla and supraclavicular fossa (extended field [EF])., Methods and Materials: The medical records of 200 consecutive patients treated with postoperative RT for axillary lymph node metastases from malignant melanoma were retrospectively reviewed. All patients received postoperative hypofractionated RT for high-risk features; 95 patients (48%) received RT to the axilla only and 105 patients (52%) to the EF., Results: At a median follow-up of 59 months, 111 patients (56%) had sustained relapse, and 99 patients (50%) had died. The 5-year overall survival, disease-free survival, and distant metastasis-free survival rates were 51%, 43%, and 46%, respectively. The 5-year axillary control rate was 88%. There was no difference in axillary control rates on the basis of the treated field (89% for axilla only vs. 86% for EF; p = 0.4). Forty-seven patients (24%) developed treatment-related complications. On both univariate and multivariate analyses, only treatment with EF irradiation was significantly associated with increased treatment-related complications., Conclusions: Adjuvant hypofractionated RT to the axilla only for metastatic malignant melanoma with high-risk features is an effective method to control axillary disease. Limiting the radiation field to the axilla only produced equivalent axillary control rates to EF and resulted in lower treatment-related complication rates.

Background: The objective of the current study was to analyze the potential treatment-related mortality in long-term survivors of soft-tissue sarcoma (STS) treated with radiotherapy (RT) and conservation surgery., Methods: Between 1960 and 2000, 629 of 1089 patients treated with conservation surgery and RT for nonmetastatic STS at the University of Texas M. D. Anderson Cancer Center never developed disease recurrence. Long-term survival and causes of death were evaluated using the person-years method to determine the standardized mortality ratio (SMR). SMRs were calculated for death from all causes, cancer, and cardiac disease using standard U.S. data., Results: The median follow-up was 13.2 years. The 10-year, 20-year, and 30-year actuarial survival rates were 88%, 69%, and 52%, respectively. The overall all-case mortality was 1.14 (95% confidence interval [95% CI], 0.98-1.33). The all-cause mortality exceeded that expected for female patients with an SMR of 1.48 (95% CI, 1.15-1.88), patients aged

Purpose: To evaluate long-term outcomes in patients with desmoid fibromatosis treated with radiation therapy (RT), with or without surgery., Methods and Materials: Between 1965 and 2005, 115 patients with desmoid tumors were treated with RT at our institution. The median age was 29 years (range, 8-73 years). Of the patients, 41 (36%) received RT alone (median dose, 56 Gy) for gross disease, and 74 (64%) received combined-modality treatment (CMT) consisting of a combination of surgery and RT (median dose, 50.4 Gy)., Results: Median follow-up was 10.1 years. Local control (LC) rates at 5 and 10 years were 75% and 74%, respectively. On univariate analysis, LC was significantly influenced by tumor size (< or =5 cm vs. 5-10 cm vs. >10 cm) (p = 0.02) and age (< or = 30 vs. >30 years) (p = 0.02). There was no significant difference in LC for patients treated with RT alone for gross disease vs. CMT. For patients treated with CMT, only tumor size significantly influenced LC (p = 0.02). Patients with positive margins after surgery did not have poorer LC than those with negative margins (p = 0.38). Radiation-related complications occurred in 20 (17%) of patients and were associated with dose >56 Gy (p = 0.001), age < or =30 years (p = 0.009), and receipt of RT alone vs. CMT (p = 0.01)., Conclusions: Desmoid tumors are effectively controlled with RT administered either as an adjuvant to surgery when resection margins are positive or alone for gross disease when surgical resection is not feasible. Doses >56 Gy may not be necessary to control gross disease and are associated with high rates of radiation-related complications.

Purpose: To evaluate the local control rates and patterns of metastatic relapse in patients with localized myxoid liposarcoma treated with conservation surgery and radiotherapy (RT)., Patients and Methods: Between 1960 and 2003, 127 patients with non-metastatic myxoid liposarcoma were treated with conservation surgery and RT at our institution. The median patient age was 39 years (range, 14-79 years). Of the 127 patients, 46% underwent preoperative RT (median dose, 50 Gy) and 54% underwent postoperative RT (median dose, 60 Gy). Also, 28% received doxorubicin-based chemotherapy as a part of their treatment., Results: The median follow-up was 9.1 years. The overall survival rate at 5 and 10 years was 87% and 79%, respectively. The corresponding disease-free survival rates were 81% and 73%. The local control rate at > or =5 years was 97%. The actuarial rate of distant metastases at 5 and 10 years was 15% and 24%, respectively. Of the 27 patients who developed distant metastases, 48% did so in the retroperitoneum, 22% in other extrapulmonary soft tissues, 22% in the lung, 15% in bone, and 4% in the liver., Conclusion: The results of our study have shown that RT and conservation surgery for localized myxoid liposarcoma provide excellent local control. Distant metastatic relapse tended to occur in the retroperitoneum and other nonpulmonary soft tissues. Therefore, staging and surveillance imaging should include the abdomen and pelvis, as well as the thorax, for patients with localized myxoid liposarcoma.

Purpose: To evaluate prognostic factors and treatment outcomes in patients with localized synovial sarcoma treated with conservation surgery and radiotherapy (RT)., Methods and Materials: Between 1960 and 2003, 150 patients with nonmetastatic synovial sarcoma were treated with conservation surgery and RT. The majority of patients (81%) were aged >20 years. Sixty-eight percent received postoperative RT, and 32% received preoperative RT. Forty-eight percent received adjuvant chemotherapy., Results: Median follow-up was 13.2 years. Overall survival (OS) rates at 5, 10, and 15 years were 76%, 57%, and 51%, respectively. Corresponding disease-free survival (DFS) rates were 59%, 52%, and 52%, respectively. Tumor size >5 cm predicted worse OS, DFS, disease-specific survival (DSS), and higher rate of distant metastases (DM). Age >20 years predicted worse DFS and DSS but not OS. Local control (LC) was 82% at 10 years. Positive or unknown resection margins predicted inferior LC rates. Forty-four percent developed DM by 10 years. Only 1% developed nodal metastases. Analysis of outcomes by treatment decade showed no significant differences with respect to LC and DM rates., Conclusions: Synovial sarcoma is adequately controlled at the primary site by conservation surgery and RT. Elective nodal irradiation is not indicated. Rates of development of DM and subsequent death from disease remain high, with no significant improvement in outcomes for this disease in the past four decades.

Purpose: The aim of this study was to evaluate outcome and treatment toxicity after wide local re-excision (WLE), with or without additional radiation therapy, for patients with isolated first local recurrence of soft-tissue sarcoma arising within a previously irradiated field., Methods: A retrospective review was performed of 62 consecutive patients. All patients underwent prior resection and external beam radiation. For recurrent disease, 25 patients were treated with WLE alone, and 37 patients were treated with WLE and additional radiation (45- 64 Gy). In 33 patients, the radiation was delivered via an afterloaded brachytherapy, single-plane implant., Results: The 5-year disease specific and distant metastasis-free survival rates were 65% and 73%, respectively. Local control (LC) at 5 years was 51%, and on multivariate analysis, a positive surgical resection margin (p< 0.001) was associated with a lower rate of LC. Reirradiation was not associated with improved LC; however complications requiring outpatient or surgical management were more common in patients who had undergone reirradiation (80% vs. 17%, p < 0.001). Amputation was also more common in the subgroup of patients who underwent extremity reirradiation (35% with radiation vs. 11% without, p = 0.05), although only one amputation was performed to resolve a treatment complication., Conclusion: Conservative surgery alone results in LC in a minority of patients who have failed locally after previous excision and external beam radiation. Although selection biases and small patient numbers confound the analysis, local treatment intensification with additional radiation does not clearly improve outcome after surgical excision alone, and is associated with an increase in complications.

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., ((c) 2007 American Cancer Society.)

Purpose: To evaluate the clinical outcomes of patients with localized retroperitoneal soft tissue sarcoma (STS) treated with complete surgical resection and radiation., Methods and Materials: The medical records of 83 patients were reviewed retrospectively. Sixty patients presented with primary disease and the remaining 23 had recurrence after previous surgical resection., Results: With a median follow-up of 47 months, the actuarial overall disease-specific survival (DSS), distant metastasis-free survival, and local control (LC) rates were 44%, 67%, and 40%, respectively. Of the 38 patients dying of disease, local disease progression was the sole site of recurrence for 16 patients and was a component of progression for another 11 patients. Multivariate analysis indicated that histologic grade was associated with the 5-year rates of DSS (low-grade, 92%; intermediate-grade, 51%; and high-grade, 41%, p = 0.006). Multivariate analysis also indicated an inferior 5-year LC rate for patients presenting with recurrent disease, positive or uncertain resection margins, and age greater than 65 years. The data did not suggest an improved local control with higher doses of external-beam radiation (EBRT) or with the specific use of intraoperative radiotherapy (IORT). Radiation-related complications (10% at 5 years) developed in 5 patients; all had received their EBRT postoperatively., Conclusions: Although preoperative radiation therapy and aggressive surgical resection is well tolerated in patients, local disease progression continues to be a significant component of disease death. In this small cohort of patients, the use of higher doses of EBRT or IORT did not result in clinically apparent improvements in outcomes.

Background: Correlations between various patient, tumor, and treatment characteristics and complications in patients undergoing combined modality treatment for primary lower extremity soft-tissue sarcomas were investigated., Methods: Using the M. D. Anderson Radiation Oncology database, the records of the subset of patients treated with combined radiation and limb-sparing surgery for primary lower extremity soft-tissue sarcomas were retrospectively reviewed from the years 1960 to 2003., Results: In all, 412 patients were identified. With a median follow-up of 9.3 years, there were a total of 113 (27%) acute wound complications and 41 (13% at 20 years) chronic radiation-related limb complications. Preoperative radiation and tumor sizes >5 cm were associated with an increased risk of acute wound complications (34% preoperative vs. 16% postoperative, P < .001; and 31% >5 cm vs. 17% < or =5 cm, P = .005). At 20 years the radiation-related complication rate was higher in patients with a groin or thigh tumor location (16% vs. 4% other; P = .008), prior acute wound complications (20% vs. 10% no surgical complication), and a radiation dose > or =60 grays (Gy) (18% vs. 9% for dose < 60 Gy; P = .04). Five fractures occurred, resulting in a crude overall fracture rate of 1.2%., Conclusions: Patients treated with preoperative radiation for larger tumors are more likely to have acute surgical wound complications. Acute wound complications followed by postoperative radiation are associated with chronic radiation-related limb problems, as are higher radiation dose and proximal tumor location. The fracture rate is so low that prophylactic fixation is not warranted.

Background: Major wound complications (MWCs) are frequent after preoperative radiotherapy (RT) for extremity soft-tissue sarcoma (STS). We examined the rate of MWCs at a single institution with readily available reconstructive surgery., Methods: The medical records of consecutively treated extremity STS patients treated with preoperative external-beam RT and surgical resection from June 1996 through February 2003 were reviewed. Patients underwent RT (median 50 Gy), followed by resection 4-8 weeks later. Patients believed to be at higher risk for MWC underwent wound closure by the reconstructive surgery service (RSS). MWCs included secondary operation, invasive procedure, hospital readmission, or persistent deep packing or dressing changes., Results: A total of 173 patients underwent preoperative RT. Median age was 54 years; 51% were female; 80% had lower extremity STS. Wound closure was performed by the primary surgeon in 91 cases (53%). The RSS performed wound closure in the remaining 82 patients (47%). One or more MWCs occurred in 55 patients (32%). Wound complications were more likely in patients with lower extremity (49/138, 36%) than upper extremity (6/35, 17%) STS (P = 0.03). Among patients with lower-risk wounds closed by the primary surgical team, 29 (32%) experienced MWC, whereas in the higher-risk patients closed by the RSS, MWC occurred in 26 (32%)., Conclusions: MWCs are frequent after preoperative RT and occur more commonly in patients with lower extremity tumors. The MWC rate observed in a single-institution setting was comparable to that observed in the preoperative therapy arm of a multicenter Canadian trial. Patients believed to be at higher risk for MWCs undergoing RSS closure have MWC rates comparable to those with lower-risk wounds closed by the primary team.

Purpose: To evaluate the outcome and patterns of failure for patients with nodal metastases from melanoma treated with combined-modality therapy., Methods and Materials: Between 1983 and 2003, 466 patients with nodal metastases from melanoma were managed with lymphadenectomy and radiation, with or without systemic therapy. Surgery was a therapeutic procedure for clinically apparent nodal disease in 434 patients (regionally advanced nodal disease). Adjuvant radiation was generally delivered with a hypofractionated regimen. Adjuvant systemic therapy was delivered to 154 patients., Results: With a median follow-up of 4.2 years, 252 patients relapsed and 203 patients died of progressive disease. The actuarial 5-year disease-specific, disease-free, and distant metastasis-free survival rates were 49%, 42%, and 44%, respectively. By multivariate analysis, increasing number of involved lymph nodes and primary ulceration were associated with an inferior 5-year actuarial disease-specific and distant metastasis-free survival. Also, the number of involved lymph nodes was associated with the development of brain metastases, whereas thickness was associated with lung metastases, and primary ulceration was associated with liver metastases. The actuarial 5-year regional (in-basin) control rate for all patients was 89%, and on multivariate analysis there were no patient or disease characteristics associated with inferior regional control. The risk of lymphedema was highest for those patients with groin lymph node metastases., Conclusions: Although regional nodal disease can be satisfactorily controlled with lymphadenectomy and radiation, the risk of distant metastases and melanoma death remains high. A management approach to these patients that accounts for the competing risks of distant metastases, regional failure, and long-term toxicity is needed.

Background: Although patients with inguinal or pelvic lymph node (LN) metastases from melanoma may develop regional recurrence after dissection, the role of adjuvant radiotherapy remains controversial., Methods: The medical records of 40 patients with inguinal and/or pelvic lymph node metastases from melanoma were reviewed retrospectively. Indications for adjuvant radiotherapy included the following nodal characteristics: extracapsular extension, LNs > or =3 cm in diameter, > or =4 involved LNs, and LN recurrence after prior nodal surgery. Thirty-seven of 40 patients underwent formal LN dissection. Three patients had only local excision of gross disease for recurrence after prior dissection. All patients received radiation to a median dose of 30 Gy at six Gy/fraction delivered twice weekly., Results: With a median follow-up time of 22.5 months, the 3-year actuarial distant metastasis-free and overall survival rates were 35% and 38%, respectively. The 3-year regional control rate was 74%. Univariate analyses of patient, tumor, and treatment characteristics failed to reveal any association with distant metastasis-free survival, overall survival, or regional control. Regional failures occurred in nine patients; seven of these were isolated dermal failures within the field of irradiation. Only two patients (5%) had LN basin recurrences; one of these patients also developed dermal recurrence. Fifteen of 40 patients developed lymphedema; in seven of these, lymphedema was present before initiation of radiation therapy., Conclusions: Radiation may prevent recurrence of nodal disease in patients at high risk for regional failure, but in-field dermal recurrences may sometimes occur (8 of 40, 20%). Treatment-related lymphedema and death from metastatic melanoma were common.

Purpose: The primary objective of this phase I trial was to define the maximum-tolerated dose of continuous-infusion doxorubicin administered with standard preoperative radiation for patients with localized, potentially resectable soft tissue sarcomas of the extremities or body wall., Patients and Methods: Twenty-seven patients with radiographically resectable intermediate- or high-grade soft tissue sarcomas were treated. Preoperative external-beam radiation was administered in 25 2-Gy fractions (total dose, 50 Gy). Concurrent continuous-infusion doxorubicin was administered by an initial bolus (4 mg/m(2)) and subsequent 4-day continuous infusion (12.5, 15.0, 17.5, or 20.0 mg/m(2)/wk). Radiographic restaging was performed 4 to 7 weeks after chemoradiation, and patients with localized disease underwent surgical resection., Results: Chemoradiation was completed as an outpatient procedure in 25 patients (93%). The maximum-tolerated dose of continuous-infusion doxorubicin combined with standard preoperative radiation was 17.5 mg/m(2)/wk; at this dose level, seven (30%) of 23 patients had grade 3 dermatologic toxicity. Macroscopically complete resection (R0 or R1) was performed in all 26 patients who underwent surgery. Among 22 patients who were treated with doxorubicin 17.5/mg/m(2)/wk with concurrent radiation and subsequent surgery, 11 patients (50%) had 90% or greater tumor necrosis, including two patients who had complete pathologic responses., Conclusion: Preoperative doxorubicin-based chemoradiation appears safe and feasible. The maximum-tolerated dose of continuous-infusion doxorubicin with standard preoperative radiation was 17.5 mg/m(2)/wk. Pathologic response rates with this regimen are encouraging.

Purpose: To evaluate the clinical significance of the interval between surgery and postoperative radiotherapy (RT) for patients with soft tissue sarcoma., Methods and Materials: The records of 799 patients who underwent postoperative RT for soft tissue sarcoma between 1960 and 2000 were retrospectively reviewed. Univariate and multivariate analyses were used to evaluate the potential impact of the timing of postoperative RT on the rate of local control (LC)., Results: The actuarial overall LC rate was 79% at 10 years and 78% at 15 years. Univariate analysis indicated that the factors associated with an inferior 10-year LC rate were positive resection margins (p <0.0001); treatment for recurrent disease (p <0.0001); primary location in the head and neck or deep trunk (p <0.0001); age >64 years (p <0.0001); histopathologic subtype of malignant fibrous histiocytoma, neurogenic sarcoma, or epithelioid sarcoma (p = 0.01); tumor size >10 cm (p = 0.02); postoperative radiation dose <64 Gy (p = 0.03); and high histologic grade (p = 0.05). On multivariate analysis, all these factors remained statistically significant, except for high histologic grade and large size. A delay between surgery and the start of RT of >30 days was associated with a decreased 10-year LC rate, but this association was not statistically significant (76% vs. 83%, p = 0.07). The potential association between RT delay and inferior LC could be explained by an imbalance in the distribution of other prognostic factors., Conclusion: The interval between surgery and RT did not significantly impact the 10-year LC rate. These findings indicate that an RT delay should not be viewed as an independent adverse factor for LC and that treatment intensification may not be necessary for patients in whom a treatment delay has already occurred.

Purpose: To determine the incidence of potentially treatment-related mortality in long-term survivors of testicular seminoma treated by orchiectomy and radiation therapy (XRT)., Patients and Methods: From all 477 men with stage I or II testicular seminoma treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX) with post-orchiectomy megavoltage XRT between 1951 and 1999, 453 never sustained relapse of their disease. Long-term survival for these 453 men was evaluated with the person-years method to determine the standardized mortality ratio (SMR). SMRs were calculated for all causes of death, cardiac deaths, and cancer deaths using standard US data for males., Results: After a median follow-up of 13.3 years, the 10-, 20-, 30-, and 40-year actuarial survival rates were 93%, 79%, 59%, and 26%, respectively. The all-cause SMR over the entire observation interval was 1.59 (99% CI, 1.21 to 2.04). The SMR was not excessive for the first 15 years of follow-up: SMR, 1.30 (95% CI, 0.93 to 1.77); but beyond 15 years the SMR was 1.85 (99% CI, 1.30 to 2.55). The overall cardiac-specific SMR was 1.61 (95% CI, 1.21 to 2.24). The cardiac SMR was significantly elevated only beyond 15 years (P <.01). The overall cancer-specific SMR was 1.91 (99% CI, 1.14 to 2.98). The cancer SMR was also significant only after 15 years of follow-up (P <.01). An increased mortality was evident in patients treated with and without mediastinal XRT., Conclusion: Long-term survivors of seminoma treated with post-orchiectomy XRT are at significant excess risk of death as a result of cardiac disease or second cancer. Management strategies that minimize these risks but maintain the excellent hitherto observed cure rates need to be actively pursued.

Purpose: To document the prognostic factors for survival of patients with soft-tissue sarcoma sustaining a first relapse after definitive treatment., Methods and Materials: The clinicopathologic features, relapse patterns, and disease-specific survival rates for 402 consecutive patients sustaining a first relapse of sarcoma after combined surgery and radiotherapy were retrospectively reviewed. Factors affecting disease-specific survival after relapse were evaluated with univariate and multivariate techniques., Results: The median follow-up after relapse was 6.8 years. The overall disease-specific survival rate was 25%, 19%, and 16% at 5, 10, and 15 years, respectively, after the first relapse. The median survival duration was 21 months. Patients with an isolated local recurrence had a 5- and 10-year disease-specific survival rate of 48% and 46%, respectively, and those with an initial metastatic relapse had a disease-specific survival rate of 16% and 10%, respectively (p < 0.001). For isolated local recurrences, the independent determinants of survival were (favorable feature first) the primary tumor site (extremity and superficial trunk vs. head and neck and deep trunk); tumor grade (low and intermediate vs. high); time to recurrence (>12 vs. 5 cm). Although the development of subsequent metastasis was the major cause of death, a significant fraction of patients died of uncontrolled primary tumor. For patients presenting with metastasis as the first relapse, the time to metastasis was the major determinant of survival (>12 vs. < or =12 months). Long-term salvage was largely confined to patients who could and did undergo resection of relapsed disease, either local or metastatic., Conclusion: On the whole, patients whose sarcoma relapses fare poorly. However, select subgroups are potentially salvageable. Patients with an isolated local recurrence at sites other than the head and neck and deep trunk have a reasonable prospect for satisfactory outcome. Surgical resection of recurrences and metastases appears to play a major role in potential salvage.

Objectives: To assess patient-reported prostate cancer-specific quality of life 2 and 3 years after radiotherapy to the prostate in a randomized dose-escalation trial of 70 versus 78 Gy conducted from 1993 to 1998., Methods: Two years after completing radiotherapy, a questionnaire that assessed bladder, rectal, and sexual function was sent to 301 patients in the study. Three years after treatment, a second questionnaire was sent to the 175 patients with adequate follow-up., Results: Three years after radiotherapy, urinary incontinence was reported by 35% of patients, but only 6% required the use of a pad or other protective device. Patients reported increased leakage with a full bladder (urge incontinence) between the 2 and 3-year questionnaires (42% versus 50%; P = 0.03). At 3 years, 33% of patients reported rectal bleeding compared with 47% at 2 years (P = 0.006). Patients in the 78-Gy arm reported more frequent bowel movements at 3 years and less change in bowel function at 2 years than patients in the 70-Gy arm. Before radiotherapy, 84% of patients reported erections adequate for intercourse at least a few times during the previous year. After 2 and 3 years, this had decreased to 49% and 41%, respectively (P <0.02)., Conclusions: By patient-reported questionnaire, 78 Gy produced an increase in bowel movement frequency and no increase in bladder or sexual side effects at 3 years compared with 70 Gy. Comparing the results 2 and 3 years after radiotherapy, the symptoms of rectal bleeding had improved, erectile function had decreased, and urinary urge incontinence had increased.

Purpose: To evaluate the outcomes of patients with giant cell tumor of bone (GCTB) treated with radiotherapy (RT) with or without surgical resection., Methods and Materials: We performed a retrospective review of the records from 25 consecutive patients with pathologically confirmed GCTB who had undergone RT between 1956 and 2000., Results: Patients ranged in age from 11 to 69 years (median 32); 16 were female and 9 were male. The anatomic distribution of lesions was as follows: cervical spine, 3; temporal bone, 1; thoracic or lumbar spine, 9; sacrum, 8; ilium, 1, and humerus, radius, and thumb metacarpal, 1 each. Tumors ranged in size from 2 to 20 cm (median 9.5) at their maximal dimension. Thirteen patients had been referred for RT for primary GCTB and 12 had been referred with locally recurrent disease after having undergone one or more other treatments. Fourteen patients had undergone RT for gross disease, and the remaining 11 had been treated with RT after gross total resection. In 10 of these 11 patients, the treatment margins were positive or uncertain. Radiation doses ranged from 25 to 65 Gy (median 46). At a median follow-up of 8.8 years (range 0.67-34), 7 patients had developed isolated local recurrence, 2 had developed isolated distant recurrence, and 3 had developed both. The actuarial 5-year overall and disease-free survival rate was 91% and 58%, respectively, and the actuarial 5-year local control and distant metastasis-free survival rate was 62% and 81%, respectively. Univariate analysis suggested that treatment for recurrent disease correlated with a lower disease-free survival rate (83% vs. 33%, p = 0.06), distant metastasis-free survival rate (100% vs. 64%, p = 0.08), and local control rate (83% vs. 42%, p = 0.08) at 5 years. Of the 12 cases of recurrence, 7 were ultimately successfully treated with additional salvage therapy. In 4 of these patients, salvage therapy included interferon-alpha 2b., Conclusion: RT should be considered an adjuvant to surgery or as alternative therapy in cases of GCTB that are unresectable or in which excision would result in substantial functional deficits. When RT is used as primary therapy, the rate of local control seems to be satisfactory. In heavily pretreated patients, however, RT delivered as it was in this series can result in poor local control, and alternative therapies should be considered.

Purpose: The primary objective of this phase I trial was to define the maximum-tolerated dose of external-beam radiation with concurrent fixed-dose continuous-infusion doxorubicin followed by surgical resection and electron-beam intraoperative radiation therapy (EB-IORT) for patients with localized, potentially resectable retroperitoneal sarcomas (RPS)., Patients and Methods: Thirty-five patients with radiographically resectable primary or recurrent intermediate- or high-grade RPS were treated. Doxorubicin was administered each week for 4 or 5 weeks as an initial bolus (4 mg/m2) followed by a 4-day continuous infusion (4 mg/m2/d). Concurrent radiation therapy was administered in escalating doses of 18.0, 30.6, 36.0, 41.4, 46.8, or 50.4 Gy in 1.8-Gy fractions. Radiographic restaging was performed 4 to 8 weeks after chemoradiation, and patients with localized disease underwent surgical resection with EB-IORT (15 Gy)., Results: Chemoradiation was completed as outpatient therapy in 31 patients (89%); four patients required hospital admission during chemoradiation or in the postchemoradiation preoperative period. At the highest radiation dose of 50.4 Gy, two (18%) of 11 patients had grade 3 or 4 nausea. Twenty-nine patients (83%) underwent laparotomy; six patients had interval disease progression and did not undergo surgery. Grossly complete resection (R0 or R1) was performed in 26 (90%) of 29 patients who had surgery. EB-IORT was feasible and successfully administered to 22 patients who had R0 or R1 resections., Conclusion: Preoperative chemoradiation, surgical resection, and EB-IORT are feasible for patients with RPS. Preoperative external-beam radiation can be administered to a total dose of 50.4 Gy with continuous-infusion doxorubicin.

Purpose: For soft tissue sarcoma, adjuvant postoperative radiotherapy improves the local control rate over surgery alone. However, the issue of a dose-control relationship is controversial and was addressed in this study., Methods and Materials: We retrospectively reviewed the records of 775 consecutive patients who received postoperative external beam radiotherapy and used univariate and multivariate analysis to determine whether a dose-control relationship exists for the whole group and for specific high-risk subgroups., Results: With a median follow-up of 12.3 years, overall local control rates were 82%, 80%, and 79% at 5, 10, and 15 years. Factors adverse for local control were positive resection margins; tumor location in the head and neck and deep trunk; presentation with locally recurrent disease; patient age >64 years; histopathologic subtype of malignant fibrous histiocytoma, neurogenic sarcoma or epithelioid sarcoma; and tumor size >10 cm. In multivariate analysis, radiation dose > or = 64 Gy vs. <64 Gy independently correlated with improved local control. Significant interactions were noted between increased effectiveness of a higher dose and presentation with locally recurrent disease, with head and neck and deep trunk tumor sites, and with positive or uncertain resection margins such that local control was specifically improved under these circumstances with doses on the order of 64-68 Gy compared with doses on the order of 60 Gy. Higher dose, however, did not completely abrogate the adverse effect of positive margins., Conclusion: After gross total resection, soft tissue sarcoma with features predictive of a higher than average local recurrence rate benefited from doses of 64-68 Gy compared with 60 Gy.

Purpose: Radiation (XRT) is a proven component in the treatment of soft tissue sarcoma. However, there is little evidence regarding the relative effectiveness of preoperative vs. postoperative XRT. This retrospective study addresses the relative effectiveness of disease control by these two treatment sequences., Methods and Materials: A total of 517 patients (246 treated with postoperative XRT, and 271 treated with preoperative XRT) with nonmetastatic sarcoma were evaluated for disease outcome and late complications using univariate and multivariate techniques., Results: With a median follow-up of 6 years, overall local control was 81% and 78% at 5 and 10 years, respectively. Although local control appeared superior with preoperative XRT (83% at 10 years) compared with postoperative XRT (72%), multivariate analysis revealed that this difference could be entirely explained by the unequal distribution of prognostic factors between the two groups, and there was no evidence that treatment sequence independently determined local control. There were no differences in nodal or metastatic relapse between the two treatments, and disease-specific survival was not significantly different. There was a slightly higher incidence of late XRT-related complications among those treated with postoperative XRT (10-year incidence of 9% vs. 5%, p = 0.03)., Conclusions: This study found no evidence for differences in disease outcome attributable to the use of either pre- or postoperative XRT. There was a slight increase in long-term complications with postoperative XRT, likely due to the higher doses used in this sequence.

Soft-tissue sarcomas are a rare and heterogeneous group of diseases with variable biology and pattern of metastases. These characteristics make it challenging to conduct large, randomized studies that could be used to generate evidence-based guidelines for unique subsets. Much of the data summarized here therefore represents standard practice based on the consensus of a group of experienced specialists and retrospective analysis of large databases. A surveillance guideline should be based on known prognostic factors, outcomes in individual subsets, and patterns of recurrence. It has to be practical and relatively cost-effective. The major goals of such an algorithm for soft-tissue sarcomas would be early identification of potentially curable recurrences, identification of therapy-related complications, and patient reassurance.

Background: Patients with localized soft tissue sarcoma (STS) who present to specialist centers after undergoing apparent macroscopic total resection often have a significant incidence of residual tumor and may benefit from reresection of the tumor bed. The potential benefits of such reresection have not been documented adequately., Methods: The clinicopathologic features and disease outcome for 666 consecutive patients with localized STS who presented after undergoing apparent macroscopic total tumor resection were analyzed to elucidate the relative merits of reresection. Actuarial univariate and multivariate methods were used to compare disease outcome of patients who presented with positive or uncertain microscopic resection margins according to whether they underwent reresection. All patients received adjuvant radiation therapy., Results: Two hundred and ninety-five patients underwent reresection of their tumor bed, and residual tumor was found in 136 patients (46%), including macroscopic tumor in 73 patients (28%). Final resection margins among patients who underwent reresection were negative in 257 patients (87%), positive in 35 patients (12%), and uncertain in 3 patients (1%). Patients who did not undergo reresection had final margins that were negative in 117 patients (32%), positive in 47 patients (13%), and uncertain in 207 patients (56%). Local control rates at 5 years, 10 years, and 15 years for patients who underwent reresection were 85%, 85%, and 82%, respectively; for patients who did not undergo reresection, the respective local control rates were 78%, 73%, and 73% (P = 0.03). Reresection remained a significant determinant of local control when other prognostic factors were incorporated into a multivariate proportional hazards regression analysis. A similar beneficial effect of reresection was found for metastasis free survival and disease specific survival., Conclusions: Patients with localized STS who were referred to a specialist center after undergoing apparent macroscopic total resection of their tumor had a high incidence of residual tumor in their tumor bed and benefited from undergoing reresection, even if radiation was administered routinely., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11367)

Background: Prognostic factors for patients with soft-tissue sarcoma who are treated with conservative surgery and radiation are documented poorly., Methods: The clinicopathologic features and disease outcome for 1225 patients with localized sarcoma who were treated with conservative surgery and radiation were reviewed retrospectively. Actuarial univariate and multivariate statistical methods were used to determine significant prognostic factors for local control, metastatic recurrence, and disease specific survival., Results: The median follow-up of surviving patients was 9.5 years. The respective local control rates at 5 years, 10 years, and 15 years were 83%, 80%, and 79%. Factors predictive of local recurrence were positive or uncertain resection margins; tumors located in the head and neck and the deep trunk; presentation with local recurrence; patient age > 64 years; malignant fibrous histiocytoma, neurogenic sarcoma. or epithelioid sarcoma histopathology; tumor measuring > 10 cm in greatest dimension; and high pathologic grade. Freedom from metastasis at 5 years, 10 years, and 15 years was 71%, 68%, and 66%, respectively. Factors that were predictive of metastatic recurrence were high tumor grade; large tumor size (> 5 cm); and leiomyosarcoma, rhabdomyosarcoma, synovial sarcoma, or epithelioid sarcoma. The respective disease specific survival rates at 5 years, 10 years, and 15 years were 73%, 68%, and 65%. Adverse factors for disease specific survival were high tumor grade; large tumor size (> 5 cm); tumors located in the head and neck and deep trunk; rhabdomyosarcoma, epithelioid sarcoma, or clear cell sarcoma; patient age > 64 years; and positive or uncertain resection margins., Conclusions: Soft-tissue sarcoma comprises a heterogeneous group of diseases. Prognostic factors for local recurrence, metastatic recurrence, lymph node recurrence, disease free survival, and disease specific survival are different, and optimal treatment strategies need to take this complexity into account., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11365)

Purpose: To evaluate whether disease outcome for localized soft-tissue sarcoma (STS) excised before referral to a specialist center and there re-resected was influenced by the timing of radiation therapy (XRT)-before or after re-resection., Materials and Methods: Two hundred ninety-five consecutive patients with localized grossly excised STS were retrospectively evaluated for local control, freedom from metastasis, disease-free survival, and disease-specific survival, according to whether they had XRT before (121) or after (174) re-resection of their tumor bed. Univariate and multivariate statistical techniques were employed., Results: At re-resection, residual STS was found in 159 patients (54%), including gross tumor in 73 (25%). The incidence of residual disease was lower in those receiving preoperative XRT (median dose 50 Gy) (36%) than in those having postoperative RT (median dose 60 Gy) (54%) (p = 0.024). With a median follow-up of 9.1 years, the local control rates for all patients at 5, 10, and 15 years were 86%, 84%, and 81%, respectively, and there were no differences between the two XRT sequences. In multivariate regression, there was no evidence that XRT sequence influenced local control, metastatic control, disease-free survival, or disease-specific survival. There was a trend toward fewer XRT-related late complications with preoperative XRT, but this was not significant, and the incidence of complications was low (5% at 15 years)., Conclusions: Patients who present after total but oncologically inadequate excision of STS can receive approximately 50 Gy before re-resection or approximately 60 Gy after re-resection, with approximately equivalent, satisfactory local control and overall disease outcome. Decisions as to the most appropriate treatment sequence for any individual patient can be made regardless of considerations as to the effectiveness of one sequence compared with the other.

Background: The risk of regional disease recurrence after surgery alone for lymph node metastases from melanoma is well documented. The role of adjuvant irradiation remains controversial., Methods: The medical records of 160 patients with cervical lymph node metastases from melanoma were reviewed retrospectively. Of these, 148 (93%) presented with clinically palpable lymph node metastases. All patients underwent surgery and radiation to a median dose of 30 grays (Gy) at 6 Gy per fraction delivered twice weekly. Surgical resection was either a selective neck dissection in 90 patients or local excision of the lymph node metastasis in 35 patients. Only 35 patients underwent a radical, modified radical, or functional neck dissection., Results: At a median follow-up of 78 months, the actuarial local, regional, and locoregional control rates at 10 years were 94%, 94%, and 91%, respectively. Univariate analysis of patient, tumor, and treatment characteristics failed to reveal any association with the subsequent rate of local or regional control. The actuarial disease-specific (DSS), disease-free, and distant metastasis-free survival (DMFS) rates at 10 years were 48%, 42%, and 43%, respectively. Univariate and multivariate analyses revealed that patients with four or more involved lymph nodes had a significantly worse DSS and DMFS. Nine patients developed a treatment-related complication requiring medical management, resulting in a 5-year actuarial complication-free survival rate of 90%., Conclusions: Adjuvant radiotherapy resulted in a 10-year regional control rate of 94%. Complications for all patients were rare and manageable when they did occur. The authors recommend adjuvant irradiation for patients with extracapsular extension, lymph nodes measuring 3 cm in size or larger, the involvement of multiple lymph nodes, recurrent disease, or any patient having undergone a selective therapeutic neck dissection., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11243)

Sarcomas are relatively uncommon tumors of mesenchymal origin. They may arise anywhere within the musculoskeletal system and are typically classified by clinical behavior into benign, borderline, or malignant. This article focuses primarily on the role of radiation for malignant soft tissue sarcoma and selected borderline tumors.

Background: Abnormal expression of key proteins of the apoptotic pathway has been associated with poor prognosis, although there have been few studies of these correlations in patients with prostate carcinoma who are treated with radiotherapy. The current study examined the association between expression levels of Ki-67, bcl-2, bax, and bcl-x in pretreatment biopsy specimens and patient outcome after definitive radiotherapy alone., Methods: Archival pretreatment prostate biopsy tumor tissue was retrieved from 106 patients with Stage T1-T3 prostate carcinoma who were treated at the University of Texas M. D. Anderson Cancer Center with external beam radiotherapy between 1987 and 1993. Expression levels of Ki-67 (MIB-1 staining; n = 106 patients), bcl-2 (n = 77 patients), bax (n = 70 patients), and bcl-x (both long and short splice variants; n = 72 patients) were determined by immunohistochemical staining. The Ki-67 labeling index (Ki67-LI) was available for all patients and was derived from the percentage of Ki-67 positive cells. Biochemical failure after radiotherapy was defined as three consecutive rises in prostate specific antigen level on follow-up. The median follow-up was 62 months., Results: High Ki67-LI (> 3.5%) expression was observed in 33% of patients, overexpression of bcl-2 was observed in 16% of patients, altered bax expression was observed in 23% of patients, and altered bcl-x expression was observed in 53% of patients. There was no correlation found between the biomarkers. Kaplan-Meier survival estimates of freedom from biochemical failure (bNED) and the log-rank test revealed significantly lower rates in association with high Ki67-LI, positive bcl-2, and altered bax staining. No correlation was observed between bcl-x staining and bNED. Cox proportional hazards multivariate analysis confirmed that bcl-2 and bax were independent of pretreatment PSA level, Gleason score, disease stage, and Ki67-LI in predicting bNED., Conclusions: Abnormalities in the expression levels of bcl-2 and bax were associated with increased failure after patients were treated for prostate carcinoma with external beam radiotherapy. These biomarkers appeared to be useful in categorizing patient risk further, beyond Ki-67 staining and conventional clinical prognostic factors., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11230)

Purpose: To evaluate the outcome and toxicity of a sphincter-sparing treatment strategy in the management of patients with anal-rectal melanoma., Patients and Methods: Between 1989 and 2000, 23 patients with invasive anal-rectal melanoma were managed with sphincter-sparing surgical resection and adjuvant radiation. Surgery consisted of primary local excision, as well as dissection for patients with documented regional nodal disease. Adjuvant radiation was delivered using a hypofractionated regimen of 30 Gy in five fractions over 2.5 weeks. Adjuvant systemic therapy was delivered to nine patients: cytotoxic chemotherapy in seven and immunotherapy in two., Results: After a median follow-up of 32 months, 15 patients had relapsed and 15 patients had died. The actuarial 5-year overall, disease-specific, disease-free, and distant metastasis-free survival rates were 31%, 36%, 37%, and 35%, respectively. The actuarial 5-year local and regional nodal control rates were 74% and 84%, respectively. No patient had locoregional failure as the sole site of failure and no patient required salvage abdominoperineal resection (APR). By univariate analysis, patients with nodal disease at presentation had a decreased actuarial 5-year disease-specific (0% v 45%, P =.004), disease-free (0% v 45%, P <.001), and distant metastasis-free survival (0% v 42%, P <.001). The actuarial complication-free survival rate was 71%. Two patients developed mild scrotal edema (grade 1), and four patients developed moderate proctitis requiring prolonged medical management (grade 2)., Conclusion: Sphincter-sparing local excision and adjuvant radiation is well tolerated and can effectively control local-regional disease while avoiding the functional morbidity of APR.

Purpose: A positive biopsy after external beam radiotherapy in patients free of any evidence of treatment failure is not synonymous with eventual recurrence. Although biopsy positivity is a predictor of outcome, the utility of biopsy status as a surrogate end point, the effect of radiation dose on biopsy status, and the interrelationships of these associations to prostate-specific antigen (PSA) nadir level are not well-defined. These issues were investigated in a cohort of men with Stage T1-T3 prostate cancer who were randomized to receive between 70 Gy and 78 Gy and were prospectively biopsied at about 2 years after the completion of radiotherapy (RT)., Methods and Materials: Of the 301 assessable patients in the trial, 168 underwent planned sextant or greater prostate post-RT biopsies in the absence of biochemical or clinical failure; this group constituted the study cohort. Of the 168 patients, 87 were in the 70-Gy arm and 81 in the 78-Gy arm. Biopsies were classified into four groups: negative (no tumor), atypical/suspicious cells (not diagnostic of carcinoma), carcinoma with treatment effect (CaTxEffect), and carcinoma without treatment effect (CaNoTxEffect). Any diagnosis of carcinoma in the specimen was classified as biopsy positive. Freedom from failure (FFF) included biochemical failure and/or clinical failure. Kaplan-Meier curves were calculated from the completion of RT. For those alive in the study cohort, the median follow-up was 65 months., Results: The rate of biopsy without tumor was 42%; with atypical cells, it was 28%, with CaTxEffect 21%, and with CaNoTxEffect 9%. The overall biopsy positivity rate (CaTxEffect + CaNoTxEffect) was 30%; 28% in the 70-Gy group and 32% in the 78-Gy group (p = 0.52). The distribution of PSA nadir levels was 73% 0.5-1.0, 5% >1.0-2.0, and 1% >2.0 ng/mL. Significantly more patients randomized to 78 Gy had a PSA nadir of 2.0 ng/mL., Conclusion: For patients free of treatment failure at the time of prostate biopsy 2 years after RT, the prognosis of no tumor cells was the same as that of atypical/suspicious cells and CaTxEffect was the same as CaNoTxEffect. The biopsy positivity rate was not altered by dose, suggesting that most of the outcome differences between the 70-Gy and 78-Gy groups were due to events occurring before prostate biopsy at 2 years and/or were not entirely dependent on biopsy status. Biopsy status is a strong prognostic factor, but, as an early end point, it may be misleading. PSA nadir appears to have little clinical value in patients treated to doses of >/=70 Gy who are failure free 2 years after RT.

A number of retrospective and randomized trials have studied the effect of external-beam radiation therapy (EBRT) plus androgen deprivation therapy (ADT) on locally advanced/high-risk prostate cancer. Of 6 published randomized trials that have compared EBRT plus ADT with EBRT alone, 2 have shown a highly significant overall survival benefit for EBRT plus ADT, and 2 have demonstrated an advantage for the combination in patient subsets based on Gleason score. The results from the positive trials of EBRT plus ADT versus EBRT alone, as well as a recent report of a comparison of short-term (6 months) ADT plus EBRT versus long-term (>6 months) ADT plus EBRT, suggest that short-term ADT plus EBRT preferentially lengthens the survival of patients with Gleason score 2 to 6 disease, whereas for Gleason score 8 to 10 disease, prolongation of survival requires long-term ADT plus EBRT. These data are far from clear-cut because there are factors that confound interpretation of the subgroup analyses. Retrospective data on patients with positive lymph node status support the assertion that EBRT plus ADT prolongs survival to a greater degree than either treatment given individually. The weight of the available investigations on the survival effect of EBRT plus ADT supports its use on a routine basis for patients with high-risk prostate cancer. The results with long-term ADT are much more convincing than short-term ADT, and, as a consequence, 2 to 3 years are recommended.

Background: Soft tissue sarcomas of the hand and foot present unique management challenges. The purpose of the current study study was to determine oncologic outcome, particularly with respect to factors affecting local recurrence, distant recurrence, and disease-specific survival., Methods: A retrospective study was performed on 115 patients with soft tissue sarcomas of the hand or foot who were evaluated, treated, and followed at the authors' institution between 1980 and 1998. The medical records and radiographs were reviewed. Kaplan-Meier analysis was used to assess patient survival., Results: Most patients (95%) were referred after previous surgery. The majority of tumors (75%) were T1 lesions (less than 5 cm), and most tumors (81%) were high grade. Patients who were treated by definitive, wide re-excision (n = 43) had a 10 year local recurrence-free survival of 88%, which was significantly better than the corresponding rate of 58% for patients who did not have re-excision (n = 40, P = 0.05). Radiation improved local control in patients who did not undergo re-excision (n = 17, P = 0.02). However, radiation did not improve local control in patients who had definitive re-excision with negative margins (n = 13, P = 0.51). The disease-specific survival at 5 and 10 years was 76% and 65%, respectively, for patients who presented with localized disease. Disease-specific patient survival was significantly worse for patients who had regional or distant metastasis. Radical amputation as initial surgical treatment did not decrease the likelihood of regional metastasis and did not improve disease-specific patient survival. The presence of distant metastasis at presentation was an independent predictor of local recurrence., Conclusion: Limb sparing treatment is possible in many patients with soft tissue sarcomas of the hand and foot. Re-excision to achieve microscopically negative surgical margins is an effective method of achieving a high rate of local control in appropriately selected patients who present after unplanned excision of the primary tumor. There does not appear to be a survival benefit to immediate radical amputation, which should be reserved for cases where surgical excision or re-excision with adequate margins cannot be performed without sacrifice of functionally significant neurovascular or osseous structures., (Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10750)

Purpose: A randomized radiotherapy dose escalation trial was undertaken between 1993 and 1998 to compare the efficacy of 70 vs. 78 Gy in controlling prostate cancer., Methods and Materials: A total of 305 Stage T1-T3 patients were entered into the trial and, of these, 301 with a median follow-up of 60 months, were assessable. Of the 301 patients, 150 were in the 70 Gy arm and 151 were in the 78 Gy arm. The primary end point was freedom from failure (FFF), including biochemical failure, which was defined as 3 rises in the prostate-specific antigen (PSA) level. Kaplan-Meier survival analyses were calculated from the completion of radiotherapy. The log-rank test was used to compare the groups. Cox proportional hazard regression analysis was used to examine the independence of study randomization in multivariate analysis., Results: There was an even distribution of patients by randomization arm and stage, Gleason score, and pretreatment PSA level. The FFF rates for the 70- and 78 Gy arms at 6 years were 64% and 70%, respectively (p = 0.03). Dose escalation to 78 Gy preferentially benefited those with a pretreatment PSA >10 ng/mL; the FFF rate was 62% for the 78 Gy arm vs. 43% for those who received 70 Gy (p = 0.01). For patients with a pretreatment PSA 10 ng/mL who were treated to 78 Gy (98% vs. 88% at 6 years, p = 0.056). Rectal side effects were also significantly greater in the 78 Gy group. Grade 2 or higher toxicity rates at 6 years were 12% and 26% for the 70 Gy and 78 Gy arms, respectively (p = 0.001). Grade 2 or higher bladder complications were similar at 10%. For patients in the 78 Gy arm, Grade 2 or higher rectal toxicity correlated highly with the proportion of the rectum treated to >70 Gy., Conclusion: An increase of 8 Gy resulted in a highly significant improvement in FFF for patients at intermediate-to-high risk, although the rectal reactions were also increased. Dose escalation techniques that limit the rectal volume that receives >or=70 Gy to <25% should be used.

Background: Childhood rhabdomyosarcoma (RMS) has a relatively good prognosis. Outcome for adults with this disease is poorly documented due to its rarity., Methods: The clinicopathologic features, treatment methods, and disease outcome were reviewed retrospectively for 82 adults with locoregional RMS treated between 1960 and 1998. Patients with distant metastasis at diagnosis were excluded. Actuarial univariate and multivariate statistical methods were used to evaluate outcome., Results: Patient ages ranged from 17 to 84 years (median, 27 years). Histologic subtypes were embryonal (34%), pleomorphic (43%), and alveolar (23%). Anatomic sites of origin were head and neck (52%), trunk (26%), and extremity (7%). Tumor size was 5 cm or smaller in 51% of patients. Regional lymph node metastasis was present in 33% of patients at presentation. Treatment consisted of radiation alone in 11%, radiation and surgery in 18%, radiation and chemotherapy in 34%, and all three modalities in 37%. With a median follow-up of 10.5 years, the 10-year actuarial disease-free and overall survival rates were 41% and 40%, respectively. The 10-year actuarial local, lymph node, and metastatic control rates were 75%, 82%, and 53%, respectively. The major determinant of metastatic control and survival was primary tumor size (< or = 5 vs. > 5 cm). Local control was satisfactory (10-year rate of 87%) for sites other than parameningeal (50% at 10 years). Patients whose disease responded to chemotherapy had a significantly better metastasis free period (72% at 10 years) than those whose disease failed to respond (19% at 10 years)., Conclusions: Adult RMS is a highly malignant tumor with a significant incidence of metastatic recurrence. Continuing investigation of new and potentially more effective chemotherapy is crucial. Local control is satisfactory for sites other than parameningeal where new radiation technologies such as intensity-modulated therapy may be necessary to safely deliver adequate doses., (Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10669)