Lifelong Imaging Surveillance is Indicated for Patients with Primary Retroperitoneal Liposarcoma.

BACKGROUND: Surveillance imaging of patients with retroperitoneal liposarcoma (RP-LPS) after surgical resection is based on a projected risk of locoregional and distant recurrence. The duration of surveillance is not well defined because the natural history of RP-LPS after treatment is poorly understood. This study evaluated the long-term risk of recurrence and disease-specific survival (DSS) for a cohort of patients with at least 10 years of progression-free survival (10yr-PFS) from their primary resection. METHODS: The prospective University of California, Los Angeles (UCLA) Sarcoma Database identified RP-LPS patients with 10yr-PFS after initial resection. The patients in the 10yr-PFS cohort were subsequently evaluated for recurrence and DSS. The time intervals start at date of initial surgical resection. Cox proportional hazards models were used to determine factors associated with recurrence and DSS. RESULTS: From 1972 to 2010, 76 patients with RP-LPS had at least 10 years of follow-up evaluation. Of these 76 patients, 39 (51%) demonstrated 10yr-PFS. The median follow-up period was 15 years (range 10-33 years). Among the 10yr-PFS patients, 49% (19/39) experienced a recurrence at least 10 years after surgery. Of those who experienced recurrence, 42% (8/19) died of disease. Neither long-term recurrence nor DSS were significantly associated with age, sex, tumor size, LPS subtype, surgical margin, or perioperative treatment with radiation or chemotherapy. CONCLUSION: Patients who have primary RP-LPS treated with surgical resection ± multimodality therapy face a long-term risk of recurrence and disease-specific death unacknowledged by current surveillance imaging guidelines. Among the patients with 10yr-PFS, 49% experienced a recurrence, and 42% of those died of disease. These findings suggest a need for lifelong surveillance imaging for patients with RP-LPS.

The combination of gemcitabine and nab-paclitaxel as a novel effective treatment strategy for undifferentiated soft-tissue sarcoma in a patient-derived orthotopic xenograft (PDOX) nude-mouse model.

Undifferentiated/unclassified soft-tissue sarcomas (USTS) is recalcitrant neoplasms that is usually treated with doxorubicin (DOX)-containing regimens as first-line therapy. Nanoparticle albumin-bound paclitaxel (nab-PTX) is a nanotechnology-based drug and is widely used in pancreatic cancer in combination with gemcitabine (GEM). The major goal of the present study was to determine the efficacy of nab-PTX in combination with GEM, compared to conventional drugs such as docetaxel (DOC), GEM combined with DOC, or first-line drug DOX on a USTS not-otherwise specified (USTS/NOS) from a striated muscle implanted in the right biceps femoris muscle of nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. USTS PDOX models were randomized into six groups: untreated control; DOX; DOC; nab-PTX; GEM combined with DOC; and GEM combined with nab-PTX. Tumor size and body weight were measured. Tumor growth was inhibited to the greatest extent by GEM combined with nab-PTX. Tumors treated with GEM combined with nab-PTX had the most necrosis. Body weight of the treated mice was not significantly different from the untreated controls. The present study demonstrates the power of the PDOX model to identify a novel effective treatment strategy of the combination of GEM and nab-PTX for recalcitrant soft-tissue sarcomas. These results suggest that combination of GEM and nab-PTX could be a promising therapeutic strategy for USTS.

Oral Recombinant Methioninase Combined with Caffeine and Doxorubicin Induced Regression of a Doxorubicin-resistant Synovial Sarcoma in a PDOX Mouse Model.

BACKGROUND/AIM: Synovial sarcoma (SS) is a recalcitrant neoplasm with low chemosensitivity. We recently reported that recombinant methioninase (rMETase) inhibited SS growth in a patient-derived orthotopic xenograft (PDOX) mouse model and was more effective when administered in combination with the first-line drug doxorubicin (DOX). Caffeine enhances the efficacy of anticancer drugs by overcoming drug-induced cell-cycle arrest and increasing subsequent apoptosis. Here, we determined the efficacy of oral recombinant methioninase (o-rMETase) in combined with caffeine on an SS-PDOX model. MATERIALS AND METHODS: Mice bearing SS-PDOX tumors were randomized into four treatment groups of six: Untreated control; o-rMETase alone; o-rMETase with caffeine; DOX plus o-rMETase with caffeine. Tumor size and body weight were measured during the treatment and plasma L-methionine (MET) levels were measured at the end of treatment. RESULTS: All treatments significantly inhibited SS-PDOX tumor growth. Combining caffeine with o-rMETase was more effective than o-rMETase alone. DOX combined with o-rMETase and caffeine led to regression of SS-PDOX. Plasma MET levels were reduced with o-rMETase treatment. CONCLUSION: These results suggest that combining o-rMETase and caffeine along with first-line chemotherapy can be highly effective for SS and has clinical potential for this recalcitrant disease.

Long-term Outcomes With Ifosfamide-based Hypofractionated Preoperative Chemoradiotherapy for Extremity Soft Tissue Sarcomas.

OBJECTIVES: The objective of this study was to analyze outcomes for patients with soft tissue sarcoma of the extremities using neoadjuvant ifosfamide-based chemotherapy and hypofractionated reduced dose radiotherapy, followed by limb-sparing surgery. MATERIALS AND METHODS: An Institutional Review Board (IRB)-approved retrospective review of patients treated at a single institution between 1990 and 2013 was performed. In total, 116 patients were identified who received neoadjuvant ifosfamide-based chemotherapy and 28 Gy in 8 fractions of preoperative radiation (equivalent dose in 2 Gray fractions, 31.5 Gy [α/ß 10] 36.4 Gy [α/ß 3]) followed by limb-sparing surgery. Local recurrence (LR), distant failure (DF), and overall survival (OS) were calculated. Univariate and multivariate analysis for LR, DF, and OS were performed using Cox analysis. Statistical significance was set at a P<0.05. RESULTS: Median follow-up was 5.9 years (range, 0.3 to 24 y). Actuarial LR at 3/6 years was 11%/17%, DF at 3/6 years was 25%/35%, and OS at 3/6 years was 82%/67%. On multivariate analysis, only a positive surgical margin was significantly correlated with worse local control (P=0.005; hazard ratio [HR], 18.33; 95% confidence interval (CI), 2.41-139.34). Age over 60 years (P=0.03; HR, 2.34; 95% CI, 1.10-4.98) and tumor size over 10 cm compared with tumor size ≤5 cm (P=0.03; HR, 3.32; 95% CI, 1.15-9.61) were associated with worse OS. CONCLUSIONS: Soft tissue extremity sarcoma patients treated using reduced dose hypofractionated preoperative radiotherapy in combination with ifosfamide-based chemotherapy shows acceptable local control and warrants further investigation.

Predictors of Local Recurrence in Patients With Myxofibrosarcoma.

OBJECTIVES: Myxofibrosarcoma (MFS) is reported to have a higher risk of local recurrence (LR) following definitive surgical excision relative to other soft tissue sarcomas. We reviewed our clinical experience treating MFS to investigate predictors of LR. MATERIALS AND METHODS: We retrospectively reviewed treatment outcomes for MFS patients treated at our institution between 1999 and 2015. A total of 52 patients were identified. Median age was 65 years (range, 21 to 86 y). Site of disease was: upper extremity (27%), lower extremity (46%), trunk (15%), pelvic (8%), and head and neck (4%). Patients had low, intermediate, high-grade, and unknown grade in: 23%, 8%, 67%, and 2% of tumors, respectively. Tumors were categorized as ≤5 cm (35%), >5 cm (56%), or unknown size (9%). In total, 71% received radiotherapy: 19% preoperative, 50% postoperative, and 2% both. All patients underwent surgery. Margins were negative in 71%, close/positive in 21%, and unknown in 8%. In total, 27% of patients received chemotherapy. Univariate Cox regression analysis was utilized to determine associations between clinical and treatment factors with LR. RESULTS: Median follow-up time was 2.9 years (range, 0.4 to 14.3 y). The 3-year actuarial LR, distant metastasis, and overall survival were: 31%, 15%, and 87%, respectively. Predictors of LR were patient age greater than or equal to the median of 65 years (hazard ratio, 13.46, 95% confidence interval, 1.71-106.18, P=0.013), and having close/positive tumor margins (hazard ratio, 3.4, 95% confidence interval, 1-11.53, P=0.049). CONCLUSIONS: In this institutional series of MFS older age and positive/close margins were significantly associated with a higher risk of LR.

Long-term outcomes of cement in cement technique for revision endoprosthesis surgery.

BACKGROUND AND OBJECTIVE: Cemented endoprosthetic reconstruction after resection of primary bone sarcomas has been a standard-of-care option for decades. With increased patient survival, the incidence of failed endoprostheses requiring revision surgery has increased. Revision of cemented endoprotheses by cementing into the existing cement mantle (CiC) is technically demanding. METHODS: This is a retrospective review of our endoprosthesis database of 512 consecutive cemented endoprosthetic reconstructions performed for oncologic diagnoses between 1980 and 2014. A total of 54 implants (mean patient age 32 years, range 13-81) were revised with a CiC technique. Outcomes evaluated were prosthesis survival, revision surgery categorized according to the Henderson Failure Mode Classification, complications, and functional scores. RESULTS: Fifteen-year Kaplan-Meier survival rate was 34% for initial revision and 39% for subsequent revision implants. Mean revised Musculoskeletal Tumor Society (MSTS) Score was 27 at latest follow-up. Infection rate was 2%, 9%, and 13% for primary endoprostheses, initial revisions, and subsequent revisions, respectively. Limb salvage rate was 87%. CONCLUSIONS: At long-term follow up, endoprostheses revised with the CiC technique showed consistent 15-year survival from initial (34%) to subsequent (39%) revision. Despite a relatively high failure rate, these results are encouraging and demonstrate that this is a conservative, repeatable technique.

Endoprosthetic reconstruction after resection of musculoskeletal tumors.

In the literature, long-term survival of endoprosthetic reconstruction varies widely. Few long-term reports analyze both anatomical and disease-specific implant and patient survival. We retrospectively reviewed the results of 489 patients who underwent resection of musculoskeletal tumor and reconstruction using an endoprosthetic device between December 1980 and August 2009. Implants were considered to have failed if the cemented components were revised for any reason, or the major body segment was removed for any reason. Implant survival, limb survival, and patient survival were determined using the Kaplan-Meier method. Sixty-one (12.5%) of the 489 cases were revised at a mean follow-up of 6.6 years (range, 1 month to 27.3 years). Kaplan-Meier analysis revealed overall implant survival of 23.1% at 27 years (95% CI, 5.0% to 100.0%). At 15 years, modular implants outperformed older custom designs (90.8% and 59.6% survival, respectively; P < .05). Complications that led to failure of the limb-salvage effort included local recurrence (21 cases), infection (11), positive surgical margins (3), and intractable pain (1). Thirty-six amputations (7.4%) were performed. There were no cases of amputation performed as a direct outcome of mechanical failure. Endoprosthetic implants provide a reliable, durable method of reconstruction after resection of musculoskeletal tumors.

Outcome prediction in primary resected retroperitoneal soft tissue sarcoma: histology-specific overall survival and disease-free survival nomograms built on major sarcoma center data sets.

PURPOSE: Integration of numerous prognostic variables not included in the conventional staging of retroperitoneal soft tissue sarcomas (RPS) is essential in providing effective treatment. The purpose of this study was to build a specific nomogram for predicting postoperative overall survival (OS) and disease-free survival (DFS) in patients with primary RPS. PATIENTS AND METHODS: Data registered in three institutional prospective sarcoma databases were used. We included patients with primary localized RPS resected between 1999 and 2009. Univariate (Kaplan and Meier plots) and multivariate (Cox model) analyses were carried out. The a priori chosen prognostic covariates were age, tumor size, grade, histologic subtype, multifocality, quality of surgery, and radiation therapy. External validation was performed by applying the nomograms to the patients of an external cohort. The model's discriminative ability was estimated by means of the bootstrap-corrected Harrell C statistic. RESULTS: In all, 523 patients were identified at the three institutions (developing set). At a median follow-up of 45 months (interquartile range, 22 to 72 months), 171 deaths were recorded. Five- and 7-year OS rates were 56.8% (95% CI, 51.4% to 62.6%) and 46.7% (95% CI, 39.9% to 54.6%. Two hundred twenty-one patients had disease recurrence. Five- and 7-year DFS rates were 39.4% (95% CI, 34.5% to 45.0%) and 35.7% (95% CI, 30.3% to 42.1%). The validation set consisted of 135 patients who were identified at the fourth institution for external validation. The bootstrap-corrected Harrell C statistics for OS and DFS were 0.74 and 0.71 in the developing set and 0.68 and 0.69 in the validating set. CONCLUSION: These nomograms accurately predict OS and DFS. They should be used for patient counseling in clinical practice and stratification in clinical trials.

Long-term results (>25 years) of a randomized, prospective clinical trial evaluating chemotherapy in patients with high-grade, operable osteosarcoma.

BACKGROUND: The authors present the long-term follow-up (>25 years) data from 1 of the original prospective, randomized trials that compared adjuvant chemotherapy with expectant management in patients with high-grade, localized osteosarcoma. In addition, the value of pathologic necrosis induced by a single cycle of neoadjuvant chemotherapy was analyzed as a predictive marker of disease-free and overall survival. METHODS: Fifty-nine patients with high-grade, localized osteosarcoma were enrolled in a prospective trial that was performed between 1981 and 1984 at the University of California-Los Angeles (UCLA). Patients were randomized to receive either adjuvant chemotherapy or observation after surgical resection. Long-term outcomes, follow-up, and pathologic review of all available histologic sections were performed. RESULTS: The 25-year disease-free survival rate was 28% for patients who received adjuvant chemotherapy compared with 15% for the untreated patients (P = .02). The overall survival rate at 25 years was also significantly higher for treated patients versus untreated patients (38% vs 15%; P = .02). Tumor necrosis >90% after a single round of chemotherapy was a statistically significant predictor of overall survival and disease-free survival for patients who received adjuvant therapy (164 months vs 65 months [P = .04] and 141 months vs 14 months [P < .01], respectively). CONCLUSIONS: Patients with high-grade, localized osteosarcoma who received adjuvant chemotherapy after undergoing definitive surgical resection had a statistically significant benefit in disease-free and overall survival that was maintained through 25 years. Tumor necrosis after just 1 cycle of neoadjuvant chemotherapy and radiation was predictive of overall survival and disease-free survival in patients who received adjuvant chemotherapy.

Inferior vena cava resection and reconstruction for retroperitoneal tumor excision.

OBJECTIVE: This study reviews the results of en bloc resection of the inferior vena cava (IVC) for malignant tumor excision and reconstruction. METHODS: A prospective database was reviewed. IVC resection was categorized as suprarenal, perirenal, infrarenal, or extensive (>one segment resected). Repairs were divided into primary, patch, or circumferential. Tumor type, perioperative morbidity, mortality, and graft patency were recorded. RESULTS: Between 1990 and 2011, 47 patients (21 women; mean age, 56; range, 35-89 years) underwent IVC resection for en bloc tumor excision. Sarcomas were most common (36 [77%]: 30 primary IVC). Eleven patients had primary IVC repair, nine patch repair (two autogenous), and 27 had circumferential replacement with a polytetrafluoroethylene ringed graft. Extensive IVC reconstruction in 18 patients included the entire IVC, with renal (RV) and hepatic vein reimplantation in eight; suprarenal and perirenal in six (seven RVs reimplanted); and infrarenal and perirenal in four (four RVs reimplanted). Nine single-segment IVC replacements were infrarenal. Morbidity was 10.6%: one each with bowel obstruction, chyle leak, renal failure with complete recovery (left RV reimplant, right nephrectomy), reoperation for bleeding, and IVC graft thrombosis. Morbidity did not differ by type of reconstruction. There was no mortality. Follow-up ranged from 1.5 to 216 months (18 years) with a mean of 3.5 years. Computed tomography or duplex scans were available in 28 of 47 patients and in 15 of 27 patients in group 3 at a mean follow-up of 36 and 20 months, respectively. One IVC graft thrombosis was documented at 10 months after chemotherapy/sepsis. Tumor recurrence caused three graft stenoses. Cumulative 5-year patency in group 3 was 80% (imaging) and 92% (clinical). Lower extremity edema was universally avoided. Cumulative 5-year survival for the series was 45% ± 8.5%. Mean long-term survival was 5.8 ± 0.56 years (range, 4 months-17 years), with a significant difference between primary or patch (mean, 6.5 years) and circumferential or extensive repair (mean, 4.2 years; P < .005). Cumulative (47% vs 52%) and mean (3.1 vs 3.6 years; P > .12) survival was similar between patients with single-segment and extensive IVC resection and replacement. CONCLUSIONS: IVC resection and reconstruction for en bloc tumor excision is safe, even when extensive repairs are necessary. Replacement of the IVC with prosthetic graft avoids extremity venous complications and likely contributes to quality of survival. Survival depends on tumor behavior and degree of IVC involvement, where primary and patch repair has a better prognosis than circumferential resection.

Evaluation of well-differentiated/de-differentiated liposarcomas by high-resolution oligonucleotide array-based comparative genomic hybridization.

Well-differentiated/de-differentiated liposarcomas (WDLS/DDLS) encompass an intriguing disease model in which a temporal intersection occurs between the malignant transformation of mesenchymal cells and the process of adipogenesis. Deciphering the molecular events that trigger and are characteristic of the intersection of these oncogenic and normal processes is critical to affect the often morbid and lethal consequences of malignant tumors of fat. High-resolution genome-wide oligonucleotide array-based comparative genomic hybridization (aCGH) with matched gene expression analyses was performed on seven lipomas, one hibernoma, and 38 WD and DDLS to define and compare the genomic events associated with these tumors. WD and DDLS had complex karyotypes. On average, WDLS had 11.1 and DDLS had 22.7 chromosomal copy number aberrations. All of the liposarcomas had 12q13-q15 amplifications with varying peaks at CDK4 (12q14.1), HMGA2 (12q14.3), and MDM2 (12q15); 24% of the DDLS and no WDLS had 1p32.2 (JUN) amplifications; 33% WDLS and 35% DDLS had 1q24.3 amplifications involving DNM3 and miR-214/miR-199a2; 24% of the liposarcomas had 6q23-q24 amplifications (including MAP3K5). Amplifications in GLI1 (12q13.3), JUN, and MAP3K5 (6q23.3) were mutually exclusive and occurred predominately in the DDLS. 6q amplifications occurred primarily in retroperitoneal tumors and females represented the majority of those patients who developed fatty tumors prior to the age of 50 years old. This detailed genetic mapping provides insight into the heterogeneity of WD and DDLS and the chromosomal and genetic abnormalities that are present in and distinguish these mesenchymal malignancies.

Evaluation of neoadjuvant therapy and histopathologic response in primary, high-grade retroperitoneal sarcomas using the sarcoma nomogram.

BACKGROUND: Patients with primary high-grade retroperitoneal soft tissue sarcomas have a 5-year disease-specific survival (DSS) of <40%. The impact of neoadjuvant therapy on histopathologic response and DSS are unknown. METHODS: From 1987 to 2007, 55 patients with primary high-grade retroperitoneal sarcoma received neoadjuvant therapy. All patients underwent surgical resection, and response was assessed histopathologically. Patients with >or=95% pathologic necrosis were classified as responders. Clinicopathologic variables were analyzed for association with DSS. Observed DSS was then compared with the Memorial Sloan-Kettering Cancer Center Sarcoma Nomogram predicted DSS. RESULTS: The median tumor size was 15 cm, and the median follow-up time for survivors was 68 months. The 5-year DSS for all 55 patients was 47% and did not significantly differ from the 37% predicted by the sarcoma nomogram for such patients (P=.44). Fourteen (25%) of the patients had >or=95% pathologic necrosis and were defined as responders; 41 (75%) were nonresponders. The 5-year DSS for responders was 83%. This was significantly better than the 5-year DSS of 34% for nonresponders (P=.002) and the 39% predicted by the sarcoma nomogram for responders (P=.018). The 34% 5-year DSS for nonresponders did not significantly differ from the 35% predicted by the sarcoma nomogram (P=.51). CONCLUSIONS: Neoadjuvant therapy was not associated with an overall improvement in DSS in patients with primary high-grade retroperitoneal sarcoma compared with the sarcoma nomogram prediction. Histopathologic response to neoadjuvant therapy was associated with a significantly improved DSS compared with nonresponders and with the sarcoma nomogram prediction for such patients.

Cemented endoprosthetic reconstruction of the proximal tibia: how long do they last?

BACKGROUND: The few available studies documenting the long-term survival of cemented proximal tibial endoprostheses for musculoskeletal tumors do not differentiate between stem designs or patient diagnosis. There is wide variation in survival rates reported, possibly a result of this heterogeneity in patient population and implant design. QUESTIONS/PURPOSES: We therefore asked: (1) How long do proximal tibial endoprostheses last? (2) What is the typical long-term functional result after proximal tibial replacement? And (3) what are the short- and long-term complications associated with endoprosthetic reconstruction of the proximal tibia, particularly with respect to the soft tissue reconstruction? PATIENTS AND METHODS: We retrospectively reviewed 52 patients with 52 proximal tibial endoprosthetic reconstructions for a tumor-related diagnosis. Kaplan-Meier survivorship analysis was performed using revision of the stemmed components for any reason as an endpoint for implants, and death due to disease progression for patients. Function was assessed using the MSTS scoring system. The minimum followup was 1 month (mean, 96 months: range, 1-284 months; median, 69 months). RESULTS: Using revision of the stemmed components for any reason as an end point, overall prosthesis survival at 5, 10, 15, and 20 years was 94%, 86%, 66%, and 37%, respectively. The 29 modular implants demonstrated a trend toward improved survival compared to the 23 custom-designed components, with a 15-year survivorship of 88% versus 63%. The mean postoperative Musculoskeletal Tumor Society score at most recent followup was 82% of normal function (mean raw score, 24.6; range, 4-29). CONCLUSIONS: Cemented endoprosthetic reconstruction of the proximal tibia provides a reliable method of reconstruction following tumor resection.

Cemented distal femoral endoprostheses for musculoskeletal tumor: improved survival of modular versus custom implants.

BACKGROUND: Advocates of newer implant designs cite high rates of aseptic loosening and failure as reasons to abandon traditional cemented endoprosthetic reconstruction of the distal femur. QUESTIONS/PURPOSES: We asked whether newer, modular distal femoral components had improved survivorship compared with older, custom-casted designs. PATIENTS AND METHODS: We retrospectively reviewed 254 patients who underwent distal femoral endoprosthetic reconstruction. We excluded two patients with cementless implants, 27 with expandable prostheses, and 39 who had a nontumor diagnosis. This left 186 patients: 101 with older custom implants and 85 with contemporary modular implants. The minimum followup was 1 month (mean, 96.0 months; range, 1-336 months). The tumor was classified as Stage IIA/IIB in 122 patients, Stage IA/IB or benign in 43, and Stage III or metastatic in 21. RESULTS: Kaplan-Meier analysis revealed overall 10-, 20-, and 25-year implant survival rates of 77%, 58%, and 50%, respectively, using revision of the stemmed components as an end point. The 85 modular components had a greater 15-year survivorship than the 101 custom-designed implants: 93.7% versus 51.7%, respectively. Thirty-five stemmed components (18.8%) were revised for aseptic loosening in 22 patients, implant fatigue fracture in 10, infection in two, and local recurrence in one. CONCLUSIONS: Cemented modular rotating-hinge distal femoral endoprostheses demonstrated improved survivorship compared with custom-casted implants during this three-decade experience. Patients with low-grade disease and long-term survivors of high-grade localized disease should expect at least one or more revision procedures in their lifetime. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

The Friedman-Eilber resection arthroplasty of the pelvis.

UNLABELLED: It has been argued that internal hemipelvectomy without reconstruction of the pelvic ring leads to poor ambulation and inferior patient acceptance. To determine the accuracy of this contention, we posed the following questions: First, how effectively does a typical patient ambulate following this procedure? Second, what is the typical functional capacity of a patient following internal hemipelvectomy? In the spring of 2006, we obtained video documentation of eight patients who had undergone resection arthroplasty of the hemipelvis seen in our clinic during routine clinical followup. The minimum followup in 2006 was 1.1 years (mean, 8.2 years; range, 1.1-22.7 years); at the time of last followup in 2008 the minimum followup was 2.9 years (mean, 9.8 years; range, 2.9-24.5 years). At last followup seven of the eight patients were without pain, and were able to walk without supports. The remaining patient used narcotic medication and a cane or crutch only occasionally. The mean MSTS score at the time of most recent followup was 73.3% of normal (range 53.3-80.0%; mean raw score was 22.0; range 16-24). All eight patients ultimately returned to gainful employment. These observations demonstrate independent painless ambulation and acceptable function is possible following resection arthroplasty of the hemipelvis. LEVEL OF EVIDENCE: Level IV, case series. See Guidelines for Authors for a complete description of levels of evidence.

Chemotherapy is associated with improved survival in adult patients with primary extremity synovial sarcoma.

PURPOSE: To determine if ifosfamide-based chemotherapy (IF) offers a survival benefit to adult patients with primary extremity synovial sarcoma. PATIENTS AND METHODS: Prospectively collected patient data from 2 institutions was used to identify all adult patients (>or=16 years) with >or=5 cm, deep, primary, extremity, synovial sarcoma that underwent surgical treatment of cure from 1990 to 2002. A total of 101 patients were identified and the median follow-up for survivors was 58 months. Clinical, pathologic, and treatment variables were analyzed for disease-specific survival (DSS), distant recurrence-free survival (DRFS), and local recurrence-free survival (LRFS). RESULTS: Sixty-eight (67%) patients were treated with IF and 33 (33%) patients received no chemotherapy (NoC) for the primary tumor. The characteristics of the IF-treated patients [median tumor size = 7.2 cm; monophasic n = 46 (68%)] were similar to NoC patients [median tumor size = 7 cm; monophasic n = 23 (70%)]. The 4-year DSS of the IF-treated patients was 88% compared with 67% for the NoC patients (P = 0.01). Smaller size (HR = 0.3 per 5-cm decrease, P < 0.0001) and treatment with IF (HR = 0.3 compared with NoC, P = 0.007) were independently associated with an improved DSS. Treatment with IF was independently associated with an improved DRFS (HR = 0.4, P = 0.03) but not associated with an improved LRFS (P = 0.39). CONCLUSION: Ifosfamide-based chemotherapy was associated with an improved DSS in adult patients with high-risk, primary, extremity, synovial sarcoma and should be considered in the treatment of such patients.

Advances in chemotherapy for patients with extremity soft tissue sarcoma.

Doxorubicin-based chemotherapy does not appear to offer a survival benefit to patients who have high-risk primary extremity soft tissue sarcomas, whereas ifosfamide-based chemotherapy does. This benefit is likely histology- and size-specific. Until a less toxic targeted systemic therapy is developed, treatment with ifosfamide should be strongly considered in patients who have high-risk primary extremity soft tissue sarcomas.

Validation of the postoperative nomogram for 12-year sarcoma-specific mortality.

BACKGROUND: On the basis of a prospectively followed cohort of adult patients with primary soft tissue sarcoma (STS) who were treated at Memorial Sloan-Kettering Cancer Center (MSKCC; New York, NY), a nomogram for predicting sarcoma-specific mortality was developed. Although this nomogram was found to be accurate by internal validation tests, it had not been validated in an external patient cohort, and thus its universal applicability remained unproven. METHODS: Between 1975 and 2002, 1167 adult patients (age > or = 16 years) underwent treatment for primary STS at the University of California-Los Angeles (UCLA; Los Angeles, CA). All patients treated with an ifosfamide-based chemotherapy protocol (n = 238) were excluded from the current analysis. The remaining 929 patients constituted the population on which the validation study was performed. The nomogram validation process comprised two activities. First, the extent of discrimination was quantified using the concordance index. Second, the level of calibration was assessed by grouping patients with respect to their nomogram-predicted mortality probabilities and then comparing group means with observed Kaplan-Meier estimates of disease-specific survival. RESULTS: With median follow-up intervals of 48 months for all patients and 60 months for surviving patients, the 5-year and 10-year disease-specific survival rates were 77% (95% confidence interval [CI], 74-80%) and 71% (95% CI, 67-75%), respectively. Application of the nomogram to the UCLA data set yielded a concordance index of 0.76, and the observed correspondence between predicted and actual outcomes suggested a high level of calibration. CONCLUSIONS: In the current study, the MSKCC Sarcoma Nomogram was found to provide accurate survival predictions when it was applied to an external cohort of patients who were treated at UCLA.