Functional connectome fingerprinting using shallow feedforward neural networks.

Although individual subjects can be identified with high accuracy using correlation matrices computed from resting-state functional MRI (rsfMRI) data, the performance significantly degrades as the scan duration is decreased. Recurrent neural networks can achieve high accuracy with short-duration (72 s) data segments but are designed to use temporal features not present in the correlation matrices. Here we show that shallow feedforward neural networks that rely solely on the information in rsfMRI correlation matrices can achieve state-of-the-art identification accuracies ([Formula: see text]) with data segments as short as 20 s and across a range of input data size combinations when the total number of data points (number of regions × number of time points) is on the order of [Formula: see text].

Recovery of spatially varying acoustical properties via automated partial differential equation identification.

Observable dynamics, such as waves propagating on a surface, are generally governed by partial differential equations (PDEs), which are determined by the physical properties of the propagation media. The spatial variations of these properties lead to spatially dependent PDEs. It is useful in many fields to recover the variations from the observations of dynamical behaviors on the material. A method is proposed to form a map of the physical properties' spatial variations for a material via data-driven spatially dependent PDE identification and applied to recover acoustical properties (viscosity, attenuation, and phase speeds) for propagating waves. The proposed data-driven PDE identification scheme is based on ℓ1-norm minimization. It does not require any PDE term that is assumed active from the prior knowledge and is the first approach that is capable of identifying spatially dependent PDEs from measurements of phenomena. In addition, the method is efficient as a result of its non-iterative nature and can be robust against noise if used with an integration transformation technique. It is demonstrated in multiple experimental settings, including real laser measurements of a vibrating aluminum plate. Codes and data are available online at https://tinyurl.com/4wza8vxs.

A Sparse Conjugate Gradient Adaptive Filter.

In this letter, we propose a novel conjugate gradient (CG) adaptive filtering algorithm for online estimation of system responses that admit sparsity. Specifically, the Sparsity-promoting Conjugate Gradient (SCG) algorithm is developed based on iterative reweighting methods popular in the sparse signal recovery area. We propose an affine scaling transformation strategy within the reweighting framework, leading to an algorithm that allows the usage of a zero sparsity regularization coefficient. This enables SCG to leverage the sparsity of the system response if it already exists, while not compromising the optimization process. Simulation results show that SCG demonstrates improved convergence and steady-state properties over existing methods.

Nuisance effects and the limitations of nuisance regression in dynamic functional connectivity fMRI.

In resting-state fMRI, dynamic functional connectivity (DFC) measures are used to characterize temporal changes in the brain's intrinsic functional connectivity. A widely used approach for DFC estimation is the computation of the sliding window correlation between blood oxygenation level dependent (BOLD) signals from different brain regions. Although the source of temporal fluctuations in DFC estimates remains largely unknown, there is growing evidence that they may reflect dynamic shifts between functional brain networks. At the same time, recent findings suggest that DFC estimates might be prone to the influence of nuisance factors such as the physiological modulation of the BOLD signal. Therefore, nuisance regression is used in many DFC studies to regress out the effects of nuisance terms prior to the computation of DFC estimates. In this work we examined the relationship between seed-specific sliding window correlation-based DFC estimates and nuisance factors. We found that DFC estimates were significantly correlated with temporal fluctuations in the magnitude (norm) of various nuisance regressors. Strong correlations between the DFC estimates and nuisance regressor norms were found even when the underlying correlations between the nuisance and fMRI time courses were relatively small. We then show that nuisance regression does not necessarily eliminate the relationship between DFC estimates and nuisance norms, with significant correlations observed between the DFC estimates and nuisance norms even after nuisance regression. We present theoretical bounds on the difference between DFC estimates obtained before and after nuisance regression and relate these bounds to limitations in the efficacy of nuisance regression with regards to DFC estimates.

Single dose Intravenous Tranexamic acid may not be adequate to reduce blood loss and blood transfusion requirement in patients undergoing single stage bilateral total knee arthroplasty.

Simultaneous bilateral total knee arthroplasty (TKA) causes increased blood loss and increases the risk of venous thromboembolism. Tranexamic acid (TXA) is commonly used to minimize blood loss and transfusion requirements. However, the optimal regimen of TXA in single stage bilateral TKA is still not defined. In this retrospective study, 35 patients who received TXA and 31 patients who did not receive TXA were evaluated for blood loss and transfusion requirement. Both the groups were comparable in terms of age, sex, body mass index and preoperative haemoglobin (Hb) and haematocrit (Hct). There was no significant difference in the change in Hb levels (2.42 ± 1.28 vs 2.44 ± 1.31 ; p=0.95) and Hct (1.37 ± 0.96 vs 1.62 ± 0.98, p=0.22) between the groups. There were no significant differences between the study and control groups in the intraoperative blood loss (163.71 vs 165.32 ml, p=0.92), drain output (621.71 vs 695.65 ml, p=0.65) and total blood loss (785.0 vs 860.97, p=0.40). There was no significant difference in allogeneic blood transfusion between the groups (62.85% received blood in the study group vs 58.06% in the control group, p>0.05). Single intraoperative dose of TXA may not be adequate to reduce blood loss and blood transfusion requirement in bilateral TKA.

The role of routine imaging in pediatric cutaneous melanoma.

BACKGROUND: Optimal imaging for children with pediatric malignant melanoma (MM) is unknown. METHODS: We reviewed clinical and imaging findings of patients with American Joint Commission on Cancer (AJCC) stage IIC-IV MM treated on our institutional MEL06 trial. All patients had baseline brain magnetic resonance imaging/computed tomography (MRI/CT), positron emission tomography/computed tomography (PET/CT), CT chest, abdomen, and pelvis (CTCAP). Patients on stratum A (PEG-interferon, where PEG is pegylated; AJCC IIC, IIIA, IIIB; n = 16) had imaging every 6 months; stratum B1 (PEG-interferon and temozolomide; unresectable measurable disease, metastatic, or recurrent; n = 2) had PET/CT scans every 2 months and brain imaging studies every 4 months; stratum B2 patients (PEG-interferon and temozolomide; unresectable nonmeasurable, metastatic, or recurrent, n = 3) had imaging every 4 months. Off-therapy imaging was done every 6 months for 3 years. RESULTS: There were 21 patients (11 females, 11 spitzoid, median age 14 years, head/neck [6], trunk [7], extremities [8]). Patients with spitzoid melanoma underwent 236 imaging studies in total (86 PET/CT, 81 CTCAP, 11 CT chest, 10 CT brain, 48 MRI brain) at a median cost per patient of $32,718. Thirteen studies (5.8%) had findings that led to two biopsies (one positive). For conventional MM, 162 studies (61 PET/CT, 57 CTCAP, 8 CT chest, 7 CT brain, and 29 MRI brain) were performed with a median cost per patient of $23,420. Twenty (14%) had findings leading to six biopsies (four positive). At 6.3 years (range 0.4-9.2), 17 patients remain disease-free. CONCLUSION: Children with spitzoid melanoma require minimal imaging at diagnosis and follow-up. Patients with conventional MM should be imaged according to adult guidelines.

Impact of ovarian transposition before pelvic irradiation on ovarian function among long-term survivors of childhood Hodgkin lymphoma: A report from the St. Jude Lifetime Cohort Study.

BACKGROUND: We reviewed the effect of ovarian transposition (OT) on ovarian function among long-term survivors of childhood Hodgkin lymphoma (HL) treated with pelvic radiotherapy. PROCEDURE: Female participants (age 18+ years) with HL in the St. Jude Lifetime Cohort Study (SJLIFE) were clinically evaluated for premature ovarian insufficiency (POI) 10 or more years after pelvic radiotherapy. Reproductive history including age at menopause and pregnancy/live births was available on all patients. RESULTS: Of 127 eligible females with HL, 90 (80%) participated in SJLIFE, including 49 who underwent OT before pelvic radiotherapy. Median age at STLIFE evaluation was 38 years (range 25-60). In a multiple regression adjusted for age at diagnosis, pelvic radiotherapy doses > 1,500 cGy (hazard ratio [HR] = 25.2, 95% confidence interval [CI] = 3.1-207.3; P = 0.0027) and cumulative cyclophosphamide equivalent doses of alkylating agents > 12,000 mg/m2 (HR = 11.2, 95% CI = 3.4-36.8; P < 0.0001) were significantly associated with POI. There was no significant association between OT and occurrence of POI (HR = 0.6, 95% CI = 0.2-1.9; P = 0.41). CONCLUSIONS: OT did not appear to modify risk of POI in this historic cohort of long-term survivors of HL treated with gonadotoxic therapy. Modern fertility preservation modalities, such as mature oocyte cryopreservation, should be offered to at-risk patients whenever feasible.

Empirical Bayes based relative impulse response estimation.

Relative impulse responses (ReIRs) have several applications in speech enhancement, noise suppression and source localization for multi-channel speech processing in reverberant environments. Estimating the ReIRs can be reduced to a system identification problem. A system identification method using an empirical Bayes framework is proposed and its application for spatial source subtraction in audio signal processing is evaluated. The proposed estimator allows for incorporating prior structure information of the system into the estimation procedure, leading to an improved performance especially in the presence of noise. The estimator utilizes the sparse Bayesian learning algorithm with appropriate priors to characterize both the early reflections and reverberant tails. The mean squared error of the proposed estimator is studied and an extensive experimental study with real-world recordings is conducted to show the efficacy of the proposed approach over other competing approaches.

Rectified Gaussian Scale Mixtures and the Sparse Non-Negative Least Squares Problem.

In this paper, we develop a Bayesian evidence maximization framework to solve the sparse non-negative least squares problem (S-NNLS). We introduce a family of probability densities referred to as the Rectified Gaussian Scale Mixture (R-GSM), to model the sparsity enforcing prior distribution for the signal of interest. The R-GSM prior encompasses a variety of heavy-tailed distributions such as the rectified Laplacian and rectified Student-t distributions with a proper choice of the mixing density. We utilize the hierarchical representation induced by the R-GSM prior and develop an evidence maximization framework based on the Expectation-Maximization (EM) algorithm. Using the EM-based method, we estimate the hyper-parameters and obtain a point estimate for the solution of interest. We refer to this proposed method as rectified Sparse Bayesian Learning (R-SBL). We provide four EM-based R-SBL variants that offer a range of options to trade-off computational complexity to the quality of the E-step computation. These methods include the Markov Chain Monte Carlo EM, linear minimum mean square estimation, approximate message passing and a diagonal approximation. Using numerical experiments, we show that the proposed R-SBL method outperforms existing S-NNLS solvers in terms of both signal and support recovery, and is very robust against the structure of the design matrix.

A unified framework for sparse non-negative least squares using multiplicative updates and the non-negative matrix factorization problem.

We study the sparse non-negative least squares (S-NNLS) problem. S-NNLS occurs naturally in a wide variety of applications where an unknown, non-negative quantity must be recovered from linear measurements. We present a unified framework for S-NNLS based on a rectified power exponential scale mixture prior on the sparse codes. We show that the proposed framework encompasses a large class of S-NNLS algorithms and provide a computationally efficient inference procedure based on multiplicative update rules. Such update rules are convenient for solving large sets of S-NNLS problems simultaneously, which is required in contexts like sparse non-negative matrix factorization (S-NMF). We provide theoretical justification for the proposed approach by showing that the local minima of the objective function being optimized are sparse and the S-NNLS algorithms presented are guaranteed to converge to a set of stationary points of the objective function. We then extend our framework to S-NMF, showing that our framework leads to many well known S-NMF algorithms under specific choices of prior and providing a guarantee that a popular subclass of the proposed algorithms converges to a set of stationary points of the objective function. Finally, we study the performance of the proposed approaches on synthetic and real-world data.

Global signal regression acts as a temporal downweighting process in resting-state fMRI.

In resting-state functional MRI (rsfMRI), the correlation between blood oxygenation level dependent (BOLD) signals across different brain regions is used to estimate the functional connectivity of the brain. This approach has led to the identification of a number of resting-state networks, including the default mode network (DMN) and the task positive network (TPN). Global signal regression (GSR) is a widely used pre-processing step in rsfMRI that has been shown to improve the spatial specificity of the estimated resting-state networks. In GSR, a whole brain average time series, known as the global signal (GS), is regressed out of each voxel time series prior to the computation of the correlations. However, the use of GSR is controversial because it can introduce artifactual negative correlations. For example, it has been argued that anticorrelations observed between the DMN and TPN are primarily an artifact of GSR. Despite the concerns about GSR, there is currently no consensus regarding its use. In this paper, we introduce a new framework for understanding the effects of GSR. In particular, we show that the main effects of GSR can be well approximated as a temporal downweighting process in which the data from time points with relatively large GS magnitudes are greatly attenuated while data from time points with relatively small GS magnitudes are largely unaffected. Furthermore, we show that a limiting case of this downweighting process in which data from time points with large GS magnitudes are censored can also approximate the effects of GSR. In other words, the correlation maps obtained after GSR show a high degree of spatial similarity (including the presence of anticorrelations between the DMN and TPN) with maps obtained using only the uncensored (i.e. retained) time points. Since the data from these retained time points are unaffected by the censoring process, this finding suggests that the observed anticorrelations inherently exist in the data from time points with small GS magnitudes and are not simply an artifact of GSR.

A phase II trial evaluating the feasibility of adding bevacizumab to standard osteosarcoma therapy.

Increased vascular endothelial growth factor (VEGF) expression in osteosarcoma correlates with a poor outcome. We conducted a phase II trial to evaluate the feasibility and efficacy of combining bevacizumab, a monoclonal antibody against VEGF, with methotrexate, doxorubicin and cisplatin (MAP) in patients with localized osteosarcoma. Eligible patients received two courses of MAP chemotherapy before definitive surgery at week 10. Bevacizumab (15 mg/kg) was administered 3 days before starting chemotherapy then on day 1 of weeks 3 and 5 of chemotherapy. After surgery, patients received MAP for a total of 29 weeks; bevacizumab was added every 2 or 3 weeks on day 1 of chemotherapy at least 5 weeks after surgery. Group sequential monitoring rules were used to monitor for unacceptable bevacizumab-related targeted toxicity (grade 4 hypertension, proteinuria or bleeding, grade 3 or 4 thrombosis/embolism, and grade 2-4 major wound complications). Thirty-one patients (median age 12.8 years) with localized osteosarcoma were enrolled. No unacceptable targeted toxicities were observed except for wound complications (9 minor and 6 major), which occurred in 15 patients; none required removal of prosthetic hardware or amputation. The estimated 4-year event-free survival (EFS) rate and overall survival rate were 57.5 ± 10.0% and 83.4 ± 7.8%, respectively. Eight (28%) of 29 evaluable patients had good histologic response (<5% viable tumor) to preoperative chemotherapy. The addition of bevacizumab to MAP for localized osteosarcoma is feasible but frequent wound complications are encountered. The observed histologic response and EFS do not support further evaluation of bevacizumab in osteosarcoma.

Prospective study of neuropathic pain after definitive surgery for extremity osteosarcoma in a pediatric population.

BACKGROUND: Neuropathic pain (NP) after definitive surgery for extremity osteosarcoma (OS) has not been previously characterized. This study prospectively investigates the incidence, duration, and treatment of NP in limb sparing surgery and amputation groups. PROCEDURE: In patients treated for OS on a chemotherapy and definitive surgery (limb sparing vs. amputation) protocol (OS08), we prospectively collected the following data: (i) demographical data (age, sex, race); (ii) NP time of onset and duration; and (iii) dose (starting, maximum) and duration of gabapentin, amitriptyline, and methadone treatment. RESULTS: Thirty-seven patients underwent 38 definitive surgeries: limb sparing (26, 68.4%) or amputations (12, 31.6%). Localization included lower extremity (30, 81%), upper extremity (6, 16%), or pelvis (1, 3%). Thirty patients (81%) developed NP and 26 of them required NP-specific medications (87.7%). The mean [standard deviation (SD)] duration of NP was 6.5 weeks (7.2) (median 4.4, range 0.3-29.9). All 26 patients (27 surgeries) treated with NP medications received gabapentin, either as single therapy (65.4%) (17 patients, 18 surgeries), dual therapy with gabapentin and amitriptyline (five patients), or triple therapy with gabapentin, amitriptyline, and methadone (four patients). The mean starting (maximum) doses of gabapentin, amitriptyline, and methadone (mg/kg/day) were 20.2 (43.8), 0.5 (0.7), and 0.3 (0.3), respectively. The incidence and duration of NP, duration of treatment, and NP-specific dose regimens were similar in the limb sparing and the amputation groups. CONCLUSIONS: NP after definitive surgery for OS is frequently encountered, can persist for a significant time, and NP outcomes are similar in limb sparing and amputation groups.

Pathologic fracture in childhood and adolescent osteosarcoma: A single-institution experience.

PURPOSE: Pathologic fractures occur in 5-10% of pediatric osteosarcoma (OS) cases and have historically been considered a contraindication to limb salvage. Our purpose was to describe the radiographic features of pathologic fracture and examine its impact on local recurrence rates, functional outcomes, and overall survival. METHODS: We retrospectively analyzed patients at our institution from 1990 to 2015 with pathologic fracture at diagnosis or during neoadjuvant chemotherapy. We selected a control group of 50 OS patients of similar age and gender without pathologic fracture from 1990 to 2015. Functional outcomes were scored using Musculoskeletal Tumor Society criteria. Chi-square test was used for comparative analysis of groups. RESULTS: Thirty-six patients with 37 pathologic fractures form the study cohort. Of patients who received surgery, 18 of 34 patients with fracture underwent amputation compared to 8 of 48 patients in the nonfracture group (P = 0.007). Indications for amputation in fracture patients were tumor size (n = 7), neurovascular involvement (n = 6), and tumor progression during neoadjuvant chemotherapy (n = 5). Only one patient (2.9%) in the fracture group who underwent limb salvage suffered local recurrence. Of patients who received neoadjuvant chemotherapy, 25 of 34 fracture patients showed poor histological response compared to 24 of 47 nonfracture patients (P = 0.044). There was no statistically significant difference in overall survival (P = 0.96). Functional outcomes were significantly lower in fracture patients (median = 17.5) than nonfracture patients (median = 24) (P = 0.023). CONCLUSIONS: Radiographic features of pathologic fractures were highly variable in this population. Limb salvage surgery can be performed without increased risk of local recurrence. Patients with pathologic fracture suffer worse functional outcomes but no decrease in overall survival.

Speech quality and stable gain trade-offs in adaptive feedback cancellation for hearing aids.

This paper addresses trade-offs in adaptive feedback cancellation (AFC) for hearing aids. Aggressive AFC for improved added stable gain (ASG) reduces speech quality. In this paper, the hearing-aid speech quality index (HASQI) is used to investigate AFC performance before the system becomes unstable. It is demonstrated that for a desired speech quality, multiple AFC algorithms can be evaluated for their ASG and computational efficiency. An example is presented with HASQI = 0.8, baseline AFC, and two advanced approaches. For the advanced AFCs, ASG gains of 4 and 7 dB were obtained at additional computational complexity of 8% and 11%, respectively.

Gastrostomy Complications in Pediatric Cancer Patients: A Retrospective Single-Institution Review.

BACKGROUND: Complications in pediatric cancer patients after a gastrostomy (GT) placement have not been widely investigated. We aimed to evaluate the complication rate and nature of complications in this specific population. PROCEDURE: Medical records of pediatric cancer patients having a GT placed at our institution from 1998 to 2013 were retrospectively reviewed. Variables analyzed included gender, age, diagnosis, surgical procedure, GT device, duration of GT usage, absolute neutrophil count (ANC) level at surgery, and complications. RESULTS: One hundred seventy-one patients (92 males, 79 females), median age of 6 years (range, 0.2-21), who underwent 181 procedures (110 open, 59 endoscopic, and 12 laparoscopic) were identified. Diagnosis included central nervous system tumor (n = 101), solid tumor (n = 45), and leukemia/lymphoma (n = 25). A GT tube was used in 139 procedures and a GT button in 42. Median ANC level at procedure was 3,300/mm(3) (range, 0-38,988). Median duration of GT usage was 8 months (range, 0.2-142). One hundred seventy-seven complications occurred in 106 patients (61.9%) and were categorized as perioperative (<1 month after surgery, 20.3%) and late (>1 month after surgery, 79.7%). Major complications included 42 (23.7%) GT site infections and four (2.2%) intrabdominal complications. The most common minor complication was granulation tissue (28.8%). Younger age at procedure was associated with complications (P = 0.048) and an open technique was associated with GT site infection (P = 0.003). No statistical significance was observed between complications and gender, diagnosis, GT device, duration of GT usage, and ANC at procedure. CONCLUSIONS: Younger patients were more likely to have complications, and GT site infections were more common after open GT procedures.

Feasibility of Pegylated Interferon in Children and Young Adults With Resected High-Risk Melanoma.

BACKGROUND: Pegylated interferon α-2b (IFN α-2b) improves disease-free survival in adults with resected stage III melanoma. We conducted a study to determine the feasibility and safety of incorporating pegylated IFN α-2b as adjuvant therapy in the treatment of children and adolescents with high-risk melanoma. Pharmacokinetic studies of IFN α-2b and neuropsychological and quality of life (OL) assessments were performed. PATIENT AND METHODS: Eligible patients with resected American Joint Committee on Cancer Stage IIC, IIIA, and IIIB cutaneous melanoma received nonpegylated IFN α-2b 20 million units/m(2) /day intravenously 5 days per week for 4 weeks (induction) followed by pegylated IFN α-2b 1 µg/kg/dose weekly subcutaneously (SQ) for 48 weeks (maintenance). RESULTS: Twenty-three patients (15 females, median age 10 years) were enrolled. All patients completed induction therapy; five patients did not complete maintenance therapy either because of recurrent disease (n = 2) or toxicity (n = 3). The most common grade 3 and 4 toxicities of pegylated IFN α-2b were neutropenia (35%) and elevated liver transaminases (17%). The median nonpegylated IFN α-2b AUC0-∞ (5,026 pcg⋅hr/ml) was similar to adults. The median pegylated IFN α-2b exposure (48,480 pcg⋅hr/ml) was greater than the cumulative weekly exposure for nonpegylated IFN α-2b administered SQ three times per week (TIW). Validated measures demonstrated an improvement in QOL scores and no decline in psychological functioning over the course of therapy. CONCLUSIONS: Pegylated IFN α-2b 1 µg/kg/dose SQ weekly as maintenance therapy in children and adolescents with high-risk melanoma is feasible with tolerable toxicity and appears to yield higher exposures than nonpegylated IFN α-2b administered SQ TIW.

Influence of bony resection margins and surgicopathological factors on outcomes in limb-sparing surgery for extremity osteosarcoma.

BACKGROUND: Limb-sparing surgery for osteosarcoma requires taking wide bony resection margins while maximizing preservation of native bone and joint. However, the optimal bony margin and factors associated with recurrence and survival outcomes in these patients are not well established. PROCEDURE: We conducted a retrospective review of outcomes in children and adolescents with newly diagnosed osteosarcoma from 1986 to 2012, where bony resection margins for limb-sparing surgeries were decreased serially from 5 to 1.5 cm. The association between bony margins and other surgicopathological factors with survival and recurrence outcomes was determined. RESULTS: In 181 limb-sparing surgeries in 173 patients, planned and actual bony resection margins were not significantly associated with local recurrence-free survival (LRFS), event-free survival (EFS), and overall survival (OS)-at median 5.8 years follow-up, decreasing planned bony resection margins from 5 to 1.5 cm did not significantly decrease survival outcomes. Multivariable analysis showed that the presence of distant metastases at diagnosis was associated with decreased LRFS, EFS, and OS (P = 0.002, 0.005, and <0.0001, respectively). Post-chemotherapy tumor necrosis ≤90% was associated with decreased EFS and OS (P = 0.001 and 0.022, respectively). Earlier years of treatment and pathologic fractures were associated with decreased OS only (P = 0.018 and 0.008, respectively); previous cancer history and male gender were associated with decreased EFS only (P = 0.043 and 0.023, respectively). CONCLUSION: We did not observe significant increase in adverse survival outcomes with reduction of longitudinal bony resection margins to 1.5 cm. Established prognostic factors, particularly histologic response to chemotherapy and metastases at diagnosis, remain relevant in limb-sparing patients. Pediatr Blood Cancer 2015;62:246-251. © 2014 Wiley Periodicals, Inc.

Management of local recurrence of pediatric osteosarcoma following limb-sparing surgery.

BACKGROUND: The optimal management of locally recurrent pediatric osteosarcoma is not established, especially after prior limb-sparing surgery. We describe our experience in the management of these patients and identify prognostic indicators of post-recurrence survival. METHODS: We conducted a retrospective, single-institution review of patients with locally recurrent osteosarcoma after limb-salvage surgery who were treated between October 1989 and January 2012. The management of each recurrence was evaluated, and patient, disease, and treatment factors were correlated with post-recurrence survival (PRS). RESULTS: Of 200 patients who underwent limb-sparing procedures, 18 (9 %) had biopsy-proven local recurrence. Recurrences occurred in soft tissue in 15 patients (83.3 %). Six patients (33.3 %) were amenable to repeat limb-sparing surgery. Median time to local recurrence was 1.4 (range 0.6-10.4) years. Median PRS was 11.8 months (range 3.7 months-12.1 years). Post-recurrence survival was significantly associated with the length of resection margins and was longer when recurrent tumors were resected with margins of ≥1 cm, compared with subcentimeter or positive margins (P = 0.03). Median PRS was longer in patients who underwent amputations (2.44 years) than those who underwent repeat limb-sparing surgery (0.86 years), and in patients who had distant metastases resected (2.7 years) than those who did not (0.85 years); however, differences were not significant. CONCLUSIONS: Local management of recurrent osteosarcoma in a previously reconstructed limb is highly individualized. A sufficiently wide resection is important for local control of recurrences, independent of the type of surgery. Maintaining control of distant metastases may also contribute to improved survival.