Reirradiation in Conservative Salvage of Recurrent Soft-tissue Sarcoma: An Analysis of Treatment Efficacy and Toxicities.

OBJECTIVE: Compared with radical resection alone, perioperative radiation therapy (RT) combined with neurovascular preserving surgery is the standard for the management of virgin soft-tissue sarcomas. Yet, the optimal management of a local recurrence remains unclear. We report outcomes of patients with locally recurrent soft-tissue sarcoma treated with resection and reirradiation at the University of Florida. MATERIALS AND METHODS: We reviewed the records of patients treated with primary conservative surgery and radiation for soft-tissue sarcoma followed by salvage resection and reirradiation for a local recurrence at our institution. RESULTS: We analyzed 23 patients treated between 1976 and 2014 (median follow-up, 46 mo). Tumor sites included: proximal extremity, 11 patients; trunk, 6; distal extremity, 5; and head and neck, 1. All patients had conservative gross total resection of their recurrent tumor, without amputation. For reirradiation, 16 patients received external-beam RT alone, 6 received external-beam RT and brachytherapy, and 1 received brachytherapy alone. Two patients received chemotherapy. After retreatment, the 5-year overall survival, cause-specific survival, local control, and distant control rates were 39%, 42%, 46%, and 60%, respectively. Ten patients experienced local recurrences, 1 experienced regional recurrence, and 9 developed distant metastases. Retreatment-related complications ranged from delayed wound healing to limb amputation; 8 patients required amputation. Only 3 patients remained disease-free at last follow-up. No statistically significant associations were found between treatment factors (eg, RT dose) and local control. CONCLUSIONS: Achieving local control of recurrent soft-tissue sarcoma is challenging. Treatment with reoperation and reirradiation can lead to debilitating complications affecting function and quality of life.

Function Preservation After Conservative Resection and Radiotherapy for Soft-tissue Sarcoma of the Distal Extremity: Utility and Application of the Toronto Extremity Salvage Score (TESS).

OBJECTIVE: To evaluate outcomes after conservative resection and radiotherapy (RT) for soft-tissue sarcoma (STS) of the distal extremity, with assessment of functional quality of life using the validated Toronto Extremity Salvage Score (TESS) questionnaire and Common Terminology Criteria for Adverse Events (CTCAE), v4.0. METHODS: Thirty-three patients with STS involving the hand/wrist (N=18) or foot/ankle (N=15) complex received adjuvant RT with conservative resection and were evaluated for local tumor control, survival, toxicities, and preservation of objective functional ability. Eight patients were treated with preoperative RT (median dose, 50.4 Gy) and 25 with postoperative RT (median dose, 61.8 Gy). Median follow-up was 11.5 years. Functional outcomes were measured using TESS; patients with amputations were excluded from the TESS analysis. Adverse events related to gait, limb edema, skin infection, wound complication, and wound dehiscence were assessed using the CTCAE. RESULTS: The 5- and 10-year local control rates were both 90%. The 10-year cause-specific, absolute, and distant metastasis-free survival rates were 97%, 87%, and 84%, respectively. Three patients had an amputation for reasons other than local recurrence or treatment complications and underwent amputation for patient preference. One third of the subjects (11/33 patients) were able to complete the TESS questionnaire; scores ranged from 88 to 100 (mean, 98.2). CTCAEv4 acute adverse events occurred in 2 cases: 1 patient had a grade 3 skin infection and 1 had a grade 2 wound complication of dehiscence. CONCLUSIONS: For management of distal extremity STS, the combination of adjuvant RT and conservative surgery achieves excellent local control and overall survival with few adverse events. In addition, through application of the TESS survey instrument, we have demonstrated that this treatment plan achieves robust functional preservation objectively and quantifiably.

Radiation therapy for hemangioendothelioma: the university of Florida experience.

OBJECTIVES: The benefit of radiotherapy (RT) for unresectable hemangioendotheliomas or patients with a high risk of local recurrence is unclear. This single-institution report describes the long-term effectiveness of RT for hemangioendothelioma. METHODS: From 1976 to 2009, 14 patients with nonmetastatic hemangioendothelioma were treated with RT at our institution. Median patient age was 45 years (range, 20 to 71 y). Nine patients had hemangioendothelioma of the extremities and 5 had spinal tumors. Eleven tumors originated from bone. Most tumors (n=12) were ≤5 cm in diameter. Nine patients had multifocal tumors. Four patients underwent surgery and postoperative RT, whereas 10 had RT alone. All 4 operative patients had microscopic negative margins. Median RT dose was 52.2 Gy (range, 45 to 60 Gy) for RT alone and 62.2 Gy (range, 60 to 64.8 Gy) for postoperative patients. Seven patients received 1.5-2 Gy once daily and 7 patients received 1.2 Gy twice daily. The median follow-up was 10.3 years (range, 0.1 to 28.0 y). RESULTS: The 10-year local control, cause-specific survival, and overall survival rates were 100%, 86%, and 73%, respectively. Two patients experienced a distant metastasis and died within 3 months of starting definitive RT. Three patients died of intercurrent illness at a median of 10.5 years after treatment. Nine patients had no evidence of disease at most recent follow-up. No patients experienced greater than grade 1 acute or late toxicity from RT. CONCLUSIONS: With no local recurrences and minimal risk of toxicity, our data suggest that RT can effectively manage this disease and radical surgery compromising function or cosmesis may be safely avoided with moderate-dose RT.

Radiotherapy in the management of giant cell tumor of bone.

OBJECTIVES: To evaluate the long-term treatment outcomes for patients with giant cell tumor of bone (GCTB) treated with radiotherapy with or without surgical resection. METHODS: This retrospective review includes 34 patients with GCTB treated with megavoltage radiotherapy between January 1973 and January 2008 at the University of Florida. Patients' ages ranged from 16 to 85 years (median, 29). Tumor sizes ranges from 2.5 to 12 cm (median, 4.8 cm) in the maximum dimension. Twenty-one patients received radiation for gross disease, either de novo (22 patients) or recurrent (12 patients). Thirteen patients were treated with postoperative radiation after gross total resection. The median dose was 45 Gy in both the definitive and adjuvant settings. RESULTS: The median follow-up was 16.8 years. The 5- and 10-year local-control (LC) rates were 85% and 81%, respectively. Six patients developed an isolated local recurrence (2/13 treated postoperatively and 4/21 who were treated for gross disease). All 6 patients who developed a local recurrence were successfully salvaged with surgery; therefore, the ultimate LC rate was 100%. Both the 5- and 10-year freedom from distant metastasis rates were 91%. Three patients developed lung metastases, including 1 patient who experienced GCTB transformation into a high-grade sarcoma. The 5- and 10-year progression-free survival rates were both 78%. CONCLUSIONS: Moderate-dose radiotherapy for GCTB provides a long-term LC >80%, justifying its role as an alternative to morbid surgery.

Long-term treatment outcomes for patients with synovial sarcoma: a 40-year experience at the University of Florida.

OBJECTIVES: The objective of the study was to evaluate our long-term outcomes and prognostic factors for patients treated for localized synovial sarcoma. METHODS: We retrospectively reviewed the medical records of 92 patients treated for nonmetastatic synovial sarcoma at the University of Florida from 1967 to 2007. Most patients were treated with limb-sparing surgery and radiation (63%), 27% received surgery alone and 10% received radiation only as definitive treatment. Among patients treated with surgery and radiation, 69% received preoperative radiation and 31% received postoperative radiation. RESULTS: Median follow-up of living patients was 12.5 years. Overall survival rates at 5 and 10 years were 61% and 56%, respectively. Progression-free survival rates were 56% and 53%, respectively. Local control (LC) rates at 5 and 10 years were 90% and 88%, respectively. Freedom from distant metastasis rates were 57% at 5 years and 55% at 10 years. The severe complication (requiring surgery) rate was 13%. Size >5 cm predicted worse overall survival, progression-free survival, and freedom from distant metastasis, but not LC. No other prognostic factor was significant on multivariate analysis. CONCLUSIONS: Selectively adding radiotherapy to surgery results in excellent LC for these patients. However, distant metastasis remains the principal factor limiting survival and seems directly related to primary tumor size at presentation.

External-beam radiotherapy for pediatric and young adult desmoid tumors.

BACKGROUND: To report long-term outcomes following radiotherapy for desmoid tumors in children and young adults and identify variables impacting local-regional control and treatment complications. PROCEDURE: From 1978 to 2008, 30 patients <30 years old were treated with radiotherapy for a pathologically confirmed desmoid tumor. The median age at radiotherapy was 23.7 years old (range, 10.3-29.9). Fifteen patients underwent definitive radiotherapy, 14 received radiotherapy after gross total resection, and 1 received preoperative radiotherapy. Sixteen patients received 1.8 Gy once daily and 14 received 1.2 Gy twice daily. Variables analyzed for prognostic value included gender, age at diagnosis, primary or recurrent presentation, age at radiotherapy, tumor site, tumor size, extent of resection, fractionation schedule, and radiotherapy dose. RESULTS: The actuarial 15-year overall survival and local-regional control rates were 96% and 55%, respectively. Local-regional control in patients <18 years old at the time of radiotherapy was 20% versus 63% in those 18-30 years old (P = 0.08). Local-regional control rates for tumors receiving ≥ 55 Gy and < 55 Gy were 79% and 30%, respectively (P = 0.02). No other factors had a statistically significant association with local-regional control by univariate analysis. Twelve of 30 patients experienced grade 3-4 complications, including pathologic fractures, impaired range of motion, pain, and in-field skin cancers. CONCLUSIONS: The role of radiotherapy in managing young patients with desmoid tumors remains unclear. Younger patient age is associated with inferior local-regional control following RT. In children and young adults, doses ≥55 Gy were associated with improved tumor control, but also lead to increased risk of complications.

Anesthesia-related maternal mortality in the United States: 1979-2002.

OBJECTIVE: To examine 12 years of anesthesia-related maternal deaths from 1991 to 2002 and compare them with data from 1979 to 1990, to estimate trends in anesthesia-related maternal mortality over time, and to compare the risks of general and regional anesthesia during cesarean delivery. METHODS: The authors reviewed anesthesia-related maternal deaths that occurred from 1991 to 2002. Type of anesthesia involved, mode of delivery, and cause of death were determined. Pregnancy-related mortality ratios, defined as pregnancy-related deaths due to anesthesia per million live births were calculated. Case fatality rates were estimated by applying a national estimate of the proportion of regional and general anesthetics to the national cesarean delivery rate. RESULTS: Eighty-six pregnancy-related deaths were associated with complications of anesthesia, or 1.6% of total pregnancy-related deaths. Pregnancy-related mortality ratios for deaths related to anesthesia is 1.2 per million live births for 1991-2002, a decrease of 59% from 1979-1990. Deaths mostly occurred among younger women, but the percentage of deaths among women aged 35-39 years increased substantially. Delivery method could not be determined in 14%, but the remaining 86% were undergoing cesarean delivery. Case-fatality rates for general anesthesia were 16.8 per million in 1991-1996 and 6.5 per million in 1997-2002, and for regional anesthesia were 2.5 and 3.8 per million, respectively. The resulting risk ratio between the two techniques for 1997-2002 was 1.7 (confidence interval 0.6-4.6, P=.2). CONCLUSION: Anesthetic-related maternal mortality decreased nearly 60% when data from 1979-1990 were compared with data from 1991-2002. Although case-fatality rates for general anesthesia are falling, rates for regional anesthesia are rising. LEVEL OF EVIDENCE: II.

Perioperative analgesia for forequarter amputation in a child: a dual paravertebral approach.

We describe the management of postoperative pain for a 10-year-old girl who underwent forequarter amputation for osteosarcoma of the left humerus. Because the brachial plexus itself was divided and resected during surgery, and the main body part innervated by the nerves from this plexus (the entire upper limb including the scapula and clavicle) was removed, providing analgesia via a brachial plexus block alone would probably not have provided adequate coverage. Because the tissue not resected with this surgery was innervated via the cervical and brachial plexuses and some upper thoracic nerve roots, we elected to combine a perioperative high continuous cervical paravertebral block at the C5 level with a continuous thoracic paravertebral block at the T2 level for postoperative analgesia. Our patient experienced excellent postoperative analgesia and required no narcotics during the immediate postoperative period.

Percutaneous radionuclide ablation of axial aneurysmal bone cysts.

OBJECTIVE: The purpose of our study was to retrospectively examine the efficacy of intralesional injection of 32P chromic phosphate, a beta-emitting colloidal radiopharmaceutical, in the treatment of aneurysmal bone cysts of the axial skeleton. Five patients with large aneurysmal bone cysts were managed with injection of 32P chromic phosphate into their tumors under CT guidance. With only a single minor complication, all lesions were observed to ossify on follow-up CT, with an average follow up of 2 years. CONCLUSION: CT-guided injection of axial aneurysmal bone cysts with 32P chromic phosphate leads to excellent local lesion control. In addition, the morbidity associated with this procedure is lower than that associated with surgical or other nonsurgical treatments.

Effectiveness and morbidity associated with reirradiation in conservative salvage management of recurrent soft-tissue sarcoma.

PURPOSE: The management of isolated local recurrence of soft-tissue sarcoma is therapeutically complex, and functional conservative management is preferable to radical or amputative salvage surgery. This study reviews the University of Florida experience using conservative resection and reirradiation to manage isolated local recurrences of soft-tissue sarcoma. METHODS AND MATERIALS: Between 1976 and 2005, a total of 14 patients who underwent primary conservative resection and irradiation developed isolated local recurrence and were managed with salvage conservative resection and reirradiation. Of the patients treated, 3 had tumors of the distal extremity, 8 had tumors of the proximal extremity, and 3 had tumors of the trunk. At the time of recurrence, 64% of tumors were greater than 5 cm and 79% were high grade. In combination with gross total resection, 13 of 14 patients received external beam radiotherapy with or without brachytherapy, and 1 patient was treated with brachytherapy alone. Two patients received chemotherapy. RESULTS: The median follow-up was 30 months, and no living patients were lost during follow-up. From retreatment, the 5-year actuarial overall survival, cause-specific survival, and local control rates were 40%, 40%, and 18% respectively. There was a 50% incidence of serious complication requiring either reoperation or leading to permanent functional impairment. Of the 14 patients, only 1 has remained disease free and without significant complications. No treatment factors, including achieving wide surgical margins or delivering higher radiation dosages, seemed to confer an advantage in local control. CONCLUSIONS: Salvage therapy for management of locally recurrent soft-tissue sarcoma is challenging, and the effects of reoperation and reirradiation can be severe.

Long-term clinical and functional outcomes after treatment for localized Ewing's tumor of the lower extremity.

PURPOSE: Retrospective review describing the 35-year University of Florida experience with Ewing's tumors of the lower extremity. PATIENTS AND METHODS: Fifty-three patients were treated between 1971 and 2006. Thirty patients were treated with radiotherapy (RT) alone and 23 patients were treated with surgery +/- RT. Larger tumors and tumors of the femur were treated more often with definitive RT. Median potential follow-up was 19.2 years. Functional outcome was assessed using the Toronto Extremity Salvage Score (TESS). RESULTS: Before 1985, 24% of patients were treated with surgery; since then, the rate has increased to 61%. The 15-year actuarial overall survival (OS), cause-specific survival (CSS), freedom from relapse, and limb preservation rates were 68% vs. 47% (p = 0.21), 73% vs. 47% (p = 0.13), 73% vs. 40% (p = 0.03), and 43% vs. 40% (p = 0.52), respectively, for patients treated with surgery +/- RT vs. RT alone. Excluding 8 patients who underwent amputation or rotationplasty, the 15-year actuarial local control rate was 100% for the surgery +/- RT group and 68% for the definitive RT group (p = 0.03). The ranges of the TESS for surgery +/- RT vs. RT alone were 70-100 (mean, 94) and 97-100 (mean, 99), respectively. Twenty-six percent (6/23) of patients had complications related to surgery requiring amputation or reoperation. CONCLUSIONS: Overall survival and CSS were not statistically compromised, but we observed an increased risk of relapse and local failure in patients treated with RT alone, thereby justifying a transition toward primary surgical management in suitable patients. However, despite an adverse risk profile, patients treated with RT alone had similar long-term amputation-free survival and demonstrated comparable functional outcomes. Poor results observed in Ewing's of the femur mandate innovative surgical and RT strategies.