The role of adjuvant radiotherapy in the local management of desmoplastic melanoma.

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.

Sphincter-sparing local excision and hypofractionated radiation therapy for anorectal melanoma: a 20-year experience.

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.

Adjuvant radiation therapy for high-risk nodal metastases from cutaneous melanoma.

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.

Long-term outcomes for desmoid tumors treated with radiation therapy.

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.

Excellent local control rates and distinctive patterns of failure in myxoid liposarcoma treated with conservation surgery and radiotherapy.

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.

Malignant Peripheral Nerve Sheath Tumors: A Single Institution's Experience Using Combined Surgery and Radiation Therapy.

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.

Soft Tissue Solitary Fibrous Tumor: Combined Surgery and Radiation Therapy Results in Excellent Local Control.

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.

Management of locally recurrent soft-tissue sarcoma after prior surgery and radiation therapy.

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.

Long-term outcomes for synovial sarcoma treated with conservation surgery and radiotherapy.

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.

Retroperitoneal soft tissue sarcoma: an analysis of radiation and surgical treatment.

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.

Combined-modality therapy for patients with regional nodal metastases from melanoma.

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.

Treatment-related fractures after combined modality therapy for soft tissue sarcomas of the proximal lower extremity: Can the risk be mitigated?

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.

Mortality after cure of testicular seminoma.

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.

Sphincter-sparing local excision and adjuvant radiation for anal-rectal melanoma.

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.

Phase I trial of preoperative concurrent doxorubicin and radiation therapy, surgical resection, and intraoperative electron-beam radiation therapy for patients with localized retroperitoneal sarcoma.

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.

Extraosseous osteosarcoma: response to treatment and long-term outcome.

PURPOSE: To evaluate the clinicopathologic features of extraosseous osteosarcoma (EOO), a rare soft tissue form of osteosarcoma, and to examine its response to multimodality therapy. PATIENTS AND METHODS: The medical records of all patients with EOO evaluated at The University of Texas M.D. Anderson Cancer Center between 1960 and 1999 were reviewed for clinicopathologic factors, treatment, and outcome. RESULTS: Sixty consecutive patients with EOO were identified, including 38 patients with localized (American Joint Committee on Cancer stages I to III) disease. The majority of patients presented with T2 tumors (n = 35, 58%), and 90% of tumors were located beneath the investing fascia. Twenty-seven patients with measurable and assessable disease were treated with doxorubicin-based chemotherapy (median doxorubicin starting dose, 75 mg/m(2); median number of cycles, four). The overall response rate was 19%, with two complete and three partial responses; one (6%) of 18 doxorubicin-treated patients who underwent subsequent surgery had a pathologic complete response. For the subset of 30 patients with localized disease treated at M.D. Anderson, the 5-year actuarial local recurrence-free, distant recurrence-free, event-free, and disease-specific survival rates were 82% (95% confidence interval [CI], 70% to 98%), 64% (95% CI, 43% to 93%), 47% (95% CI, 30% to 70%), and 46% (95% CI, 26% to 80%), respectively. CONCLUSION: EOO should be considered clinically and therapeutically distinct from osseous osteosarcoma. Radiographic response rates and pathologic complete response rates to doxorubicin-based systemic therapy are low.

Phase I trial of preoperative doxorubicin-based concurrent chemoradiation and surgical resection for localized extremity and body wall soft tissue sarcomas.

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.

Ki-67 staining is an independent correlate of biochemical failure in prostate cancer treated with radiotherapy.

PURPOSE: To determine the significance of Ki-67/MIB1 staining as a marker of patient outcome for prostate cancer patients treated with radiotherapy. EXPERIMENTAL DESIGN: Pretreatment archival prostate biopsy tumor tissue was available from 106 stage T1-T4 prostate cancer patients treated with external beam radiotherapy between 1987 and 1993 at M. D. Anderson Cancer Center. Diagnosis was made from prostate needle biopsy in 64 cases and from transurethral resection of the prostate (TURP) in 42 cases. All patients had a pretreatment prostate-specific antigen (PSA), and no patient had evidence of metastasis. Immunohistochemical staining for MIB1 was used to determine the percentage of Ki-67-positive tumor cells, the Ki-67 labeling index (Ki67-LI). Biochemical failure after radiotherapy was defined as three rises in PSA on follow-up. Median follow-up was 62 months. RESULTS: The mean and median Ki67-LI for the entire cohort was 3.2 and 2.3. The mean and median Ki67-LIs for those diagnosed by needle biopsy were 3.2 and 2.3, and by TURP were 3.1 and 2.4. For all patients, mean Ki67-LI levels were significantly higher with stage T3/T4 disease, Gleason 7-10 disease, and in those that developed treatment failure. Similar relationships were observed when the Ki67-LI was dichotomized into low (< or =3.5%) and high (>3.5%) groups. Actuarial freedom from biochemical failure (bNED) when Ki67-LI was low and high was 76 and 33% at 5 years (P < 0.0001, log rank). Similar statistically significant differences were observed when the TURP and needle biopsy groups were analyzed separately. Cox proportional hazards regression showed that dichotomized Ki67-LI was an independent correlate of bNED, along with pretreatment PSA, Gleason score, and clinical stage. CONCLUSIONS: The Ki67-LI obtained from pretreatment prostate cancer tissue is a strong independent predictor of failure after radiotherapy using biochemical criteria. This prognostic factor was equally valuable for patients diagnosed by TURP or needle biopsy.

Combined Limb-Sparing Surgery and Radiation Therapy to Treat Sarcomas of the Hands and Feet: Long-Term Cancer Outcomes and Morbidity.

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.

Combined Modality Management of Retroperitoneal Sarcomas: A Single-Institution Series of 121 Patients.

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.