Use of Vacuum-Assisted Closure to Reduce the Likelihood of Wound Complications After Limb-Sparing Resection of Pediatric Primary Bone Sarcomas of the Femur.

BACKGROUND: Limb-sparing surgery is the standard of care for primary bone tumors. However, such procedures are associated with high rates of wound complications, specifically in lower-extremity surgeries. Therefore, identifying and implementing interventions to minimize the likelihood of wound complications after limb-sparing resection of the lower extremity is crucial. METHODS: Patients who underwent limb-sparing osteosarcoma or Ewing sarcoma resection during a 7-year period at a single institution were retrospectively reviewed. Data were collected on 39 patients who underwent limb-sparing resection of the femur. Patient demographics, tumor characteristics, and perioperative and postoperative data were extracted and analyzed. Patients who underwent resection before April 2017 received conventional postoperative incision dressings. Starting in April 2017, patients received vacuum-assisted closure (VAC) with the 3 M™ Prevena VAC system after surgical closure. Eighteen patients received conventional postoperative incision dressing, and 21 received incisional wound VAC. A wound complication was defined as any Clavien-Dindo classification greater than 0 within a 28-day postoperative period. RESULTS: Patients who received postoperative incisional wound VAC had lower rates of wound complications than those who received conventional incision dressings (14% vs. 50%; p = 0.035). Additionally, patients in whom wound complications developed had a longer average hospital stay than those without wound complications (5 days vs. 4 days; p = 0.029). CONCLUSIONS: Wound complications prolong the hospital stay and can delay adjuvant chemotherapy for bone tumors. The use of postoperative incisional wound VAC is associated with less likelihood of wound complications and should be considered in any high-risk surgical closure. LEVEL OF EVIDENCE: Level III Treatment Study.

Radiation therapy dose escalation achieves high rates of local control with tolerable toxicity profile in pediatric and young adult patients with Ewing sarcoma.

BACKGROUND: Local control for patients with Ewing sarcoma (EWS) who present with large tumors are suboptimal when treated with standard radiation therapy (RT) doses of 54-55.8 Gy. The purpose of this study is to determine local control and toxicity of dose-escalated RT for tumors ≥8 cm (greatest diameter at diagnosis) in pediatric and young adult patients with EWS. METHODS: Eligible patients ≤30 years old with newly diagnosed EWS ≥8 cm treated with definitive conformal or intensity modulated photon, or proton radiation therapy techniques were included. All patients in the study received dose-escalated RT doses. Outcomes included overall survival (OS), event-free survival (EFS), local failure rates, and toxicity. RESULTS: Thirty-two patients were included, 20 patients presented with metastatic disease and 12 patients with localized disease. The median RT dose was 64.8 Gy (range, 59.4-69.4 Gy) with variability of doses to protect normal surrounding tissues. All patients received systemic chemotherapy. The 5-year OS and EFS for the cohort was 64.2% and 42%, respectively. The 5-year cumulative incidence of local failure was 6.6%. There were two combined local and distant failures with no isolated local failures. Twenty-nine patients experienced short term toxicity, 90% of those being radiation dermatitis. Twenty-seven patients experienced long-term toxicity, with only one experiencing grade 4 toxicity, a secondary malignancy after therapy. CONCLUSION: This study demonstrates that definitive RT for pediatric and young adult patients with EWS ≥8 cm provides high rates of local control, while maintaining a tolerable toxicity profile.

Reconstruction of Bony Defects With Motorized Intramedullary Nails After Tumor Resection.

Motorized intramedullary lengthening nails allow for transport of a bone segment for limb lengthening, deformity correction, healing of nonunion, and intercalary distraction osteogenesis. Resection of tumors involving the bone can result in substantial defects that require reconstruction. Use of these nails allows for a biologic reconstruction with the incorporation of allograft or by distraction osteogenesis. Limb lengthening after an internal hemipelvectomy where the hip joint is resected can be performed to improve gait, decrease pain, and prevent the need for a custom shoe or shoe lift. Using these nails in compression aids the incorporation of intercalary allografts and prevents stress shielding and stress risers within the graft when compared with plating. It also allows for a subsequent lengthening of the limb using the same implant. Plate-assisted bone segment transport or the use of a bone transport nail allows for a true biologic reconstruction of an intercalary defect using distraction osteogenesis. These implants provide the orthopaedic oncologist with more options for reconstruction and the potential to improve the function and outcomes of their patients.

Functional Outcomes for Children, Adolescents, and Young Adults with Osteonecrosis following Hip Core Decompression.

Background: Patients with pediatric leukemia and sickle cell disease are at risk for developing osteonecrosis (ON), a disease that can result in pain, loss of function, and disability. Hip core decompression surgery is an option aimed to prevent femoral head collapse and avoid future arthroplasty. Objective: Describe functional outcomes and gait quality among a young population with hip ON before and after hip core decompression. Methods: Study included participants with hip ON secondary to treatment for hematologic malignancy or sickle cell disease, between 8 and 29 years old, requiring hip core decompression surgery. At one-year follow-up, 13 participants (9 male, median age 17 years) completed the Functional Mobility Assessment (FMA), range of motion, and GAITRite® testing. Results: Participants demonstrated improved mobility and endurance on the FMA at 1-year post-operatively compared to pre-operatively, with higher scores for time on the Timed Up and Go (mean FMA score = 2.92 [SD = 1.32] vs. 2.07 [SD = 1.70]), time on the Timed Up and Down Stairs (3.69 [0.85] vs. 2.92 [1.66]), and 9-Minute Walk Test scores for distance walked (2.69 [0.63] vs. 2.23 [0.93]) and heart rate (4.54 [0.66] vs. 3.31 [1.38]). GAITRite® analysis also showed improvements in many gait parameters at one-year follow-up. Limitations: Cancer treatment complications other than ON could have contributed to results, not all eligible participants agreed to participate, and follow-up was only one year. Conclusions: Young patients with hip ON demonstrated improvements in functional mobility, endurance, and gait quality one year following hip core decompression.

Total Hip Arthroplasty in Adolescents and Young Adults for Management of Advanced Corticosteroid-Induced Osteonecrosis Secondary to Treatment for Hematologic Malignancies.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a potentially severe toxicity associated with glucocorticoid treatment for pediatric hematologic malignancy. We examined clinical outcomes of THA in adolescents and young adults treated for hematologic malignancies who developed advanced ONFH. METHODS: In a single-institution cohort, we retrospectively reviewed medical records and imaging for perioperative complications, reoperations, functional assessment at last follow-up, and radiological outcomes. Twenty-seven patients (41 hips) underwent THA (bilateral in 14 patients). There were 11 males. Median (interquartile range [IQR]) age at primary diagnosis was 14.9 years [1.8-18.9]. The median (IQR) age at THA was 19.8 years [14.6-30.3]. Mean (range) post-THA follow-up was 111.5 months (65.4-165.8). RESULTS: Perioperative complications included one intraoperative calcar fracture that was secured with a cerclage wire and one posterior hip dislocation that occurred 6 days postoperatively, requiring closed reduction. One hip required a revision 21.1 months post-THA due to a fractured ceramic liner. The radiographic review was available for 38 of 41 hips and demonstrated none with loosening, subsidence, or osteolysis; nine developed periacetabular stress shielding. Incidence of stress shielding was associated with increased postoperative pain (P = .0130). There was a significant functional improvement in range of motion (ROM), pain, use of supports, participation in school, work, and sports, and use of pain medication from preoperative to postoperative clinical visits (P < .001). DISCUSSION: Total hip arthroplasty in adolescents and young adults offers symptomatic and functional improvement in patients with ONFH. We found it to be safe with low perioperative complication rates even in patients undergoing active treatment for malignancy. LEVEL OF EVIDENCE: Level IV, case series study. See Instructions for authors for a complete description of levels of evidence.

Team approach: Management of osteonecrosis in children with acute lymphoblastic leukemia.

With current treatments for acute lymphoblastic leukemia (ALL), the overall prognosis for survival is favorable. Increasing emphasis is placed on recognizing and managing the long-term consequences of ALL and its treatment, particularly involving osteonecrosis. Early osteonecrosis diagnosis and management may improve outcomes and is best accomplished through coordinated teams that may include hematologic oncologists, radiologists, orthopedic surgeons, physical therapists, and the patient and their family. Magnetic resonance imaging is the "gold standard" for diagnosis of early-stage and/or multifocal osteonecrosis. Treatments for osteonecrosis in ALL patients are risk stratified and may include observation, corticosteroid or chemotherapy adjustment, and pharmaceutical or surgical approaches.

Whole-joint magnetic resonance imaging to assess osteonecrosis in pediatric patients with acute lymphoblastic lymphoma.

BACKGROUND: Osteonecrosis is a debilitating complication in children and adolescents with acute lymphoblastic leukemia or acute lymphoblastic lymphoma (LLy). An objective screening test to identify patients at risk for symptomatic, extensive joint involvement will help manage osteonecrosis. METHODS: We performed a prospective, longitudinal pilot study with whole-joint magnetic resonance imaging (MRI) of shoulders, elbows, hips, knees, ankles, and hindfeet to evaluate the incidence and timing of osteonecrosis involving multiple joints in 15 patients with LLy aged 9-21 years at diagnosis. RESULTS: Osteonecrosis affecting ≥30% of the epiphysis occurred in eight of 15 patients, with a high prevalence in hips (12 of 26 examined [46%]) and knees (10 of 26 [38%]) post reinduction I and in shoulders (seven of 20 [35%]) post reinduction II. Most osteonecrotic hips and knees with ≥30% epiphyseal involvement became symptomatic and/or underwent surgery (100% and 82%, respectively). All eight patients with ≥30% epiphyseal involvement had multijoint involvement. Seven of these patients had hip or knee osteonecrosis by the end of remission induction, and only these patients developed osteonecrosis that became symptomatic and/or underwent surgery in their hips, knees, shoulders, ankles, and/or feet; all of these joints were associated with epiphyseal abnormalities on post reinduction I imaging. CONCLUSIONS: MRI screening in adolescent patients with LLy revealed osteonecrosis in multiple joints. Initial screening with hip and knee MRI at the end of induction may identify susceptible patients who could benefit from referrals to subspecialties, more extensive follow-up imaging of other joints, and early medical and surgical interventions.

Long-Term Functional Outcomes Among Childhood Survivors of Cancer Who Have a History of Osteonecrosis.

BACKGROUND: Glucocorticoids used to treat childhood leukemia and lymphoma can result in osteonecrosis, leading to physical dysfunction and pain. Improving survival rates warrants research into long-term outcomes among this population. OBJECTIVE: The objective of this study was to compare the physical function and quality of life (QOL) of survivors of childhood cancer who had an osteonecrosis history with that of survivors who had no osteonecrosis history and with that of people who were healthy (controls). DESIGN: This was a cross-sectional study. METHODS: This study included St Jude Lifetime Cohort Study participants who were ≥ 10 years from the diagnosis of childhood leukemia or lymphoma and ≥ 18 years old; 135 had osteonecrosis (52.5% men; mean age = 27.7 [SD = 6.08] years) and 1560 had no osteonecrosis history (52.4% men; mean age = 33.3 [SD = 8.54] years). This study also included 272 people who were from the community and who were healthy (community controls) (47.7% men; mean age = 35.1 [SD = 10.46] years). The participants completed functional assessments and questionnaires about QOL. RESULTS: Survivors with osteonecrosis scored lower than other survivors and controls for dorsiflexion strength (mean score = 16.50 [SD = 7.91] vs 24.17 [SD = 8.61] N·m/kg) and scored lower than controls for flexibility with the sit-and-reach test (20.61 [SD = 9.70] vs 23.96 [SD = 10.73] cm), function on the Physical Performance Test (mean score = 22.73 [SD = 2.05] vs 23.58 [SD = 0.88]), and mobility on the Timed "Up & Go" Test (5.66 [SD = 2.25] vs 5.12 [SD = 1.28] seconds). Survivors with hip osteonecrosis requiring surgery scored lower than survivors without osteonecrosis for dorsiflexion strength (13.75 [SD = 8.82] vs 18.48 [SD = 9.04] N·m/kg), flexibility (15.79 [SD = 8.93] vs 20.37 [SD = 10.14] cm), and endurance on the 6-minute walk test (523.50 [SD = 103.00] vs 572.10 [SD = 102.40] m). LIMITATIONS: Because some eligible survivors declined to participate, possible selection bias was a limitation of this study. CONCLUSIONS: Survivors of childhood leukemia and lymphoma with and without osteonecrosis demonstrated impaired physical performance and reported reduced QOL compared with controls, with those requiring surgery for osteonecrosis most at risk for impairments. It may be beneficial to provide strengthening, flexibility, and endurance interventions for patients who have pediatric cancer and osteonecrosis for long-term function.

Genome editing of HBG1 and HBG2 to induce fetal hemoglobin.

Induction of fetal hemoglobin (HbF) via clustered regularly interspaced short palindromic repeats/Cas9-mediated disruption of DNA regulatory elements that repress γ-globin gene (HBG1 and HBG2) expression is a promising therapeutic strategy for sickle cell disease (SCD) and ß-thalassemia, although the optimal technical approaches and limiting toxicities are not yet fully defined. We disrupted an HBG1/HBG2 gene promoter motif that is bound by the transcriptional repressor BCL11A. Electroporation of Cas9 single guide RNA ribonucleoprotein complex into normal and SCD donor CD34+ hematopoietic stem and progenitor cells resulted in high frequencies of on-target mutations and the induction of HbF to potentially therapeutic levels in erythroid progeny generated in vitro and in vivo after transplantation of hematopoietic stem and progenitor cells into nonobese diabetic/severe combined immunodeficiency/Il2rγ-/-/KitW41/W41 immunodeficient mice. On-target editing did not impair CD34+ cell regeneration or differentiation into erythroid, T, B, or myeloid cell lineages at 16 to 17 weeks after xenotransplantation. No off-target mutations were detected by targeted sequencing of candidate sites identified by circularization for in vitro reporting of cleavage effects by sequencing (CIRCLE-seq), an in vitro genome-scale method for detecting Cas9 activity. Engineered Cas9 containing 3 nuclear localization sequences edited human hematopoietic stem and progenitor cells more efficiently and consistently than conventional Cas9 with 2 nuclear localization sequences. Our studies provide novel and essential preclinical evidence supporting the safety, feasibility, and efficacy of a mechanism-based approach to induce HbF for treating hemoglobinopathies.

Curative-intent radiotherapy for pediatric osteosarcoma: The St. Jude experience.

BACKGROUND: Radiation therapy (RT) confers local tumor control and survival advantages in some patients with osteosarcoma, yet pediatric and adolescent and young adult (AYA) population studies are limited. METHODS: Twenty-eight patients treated with curative-intent RT (median dose, 59.4 Gy; range, 40-76 Gy) at our institution from 1990 to 2017 were retrospectively identified. Cumulative incidence (CIN) of local failure (LF) was estimated by Gray's method and overall survival (OS) by the Kaplan-Meier method. Competing-risk regression and Cox proportional hazards models determined predictors of outcome. Toxicity was reported according to CTCAE v4.0. RESULTS: With a median follow-up of 99.1 months in living patients, nine patients (32.1%) developed LF. Estimated CINs of LF with competing risk of death at 5 years for the entire cohort, patients at initial diagnosis (n = 16), and recurrent/refractory patients (n = 12) were 32.7% (95% CI, 16.0-50.5%), 25.0% (95% CI, 7.3-48.0%), and 43.8% (95% CI, 13.6-71.0%), respectively (P = 0.31). Estimated 5-year OS was 42.6% (95% CI, 23.2-62.0%), 54.6% (95% CI, 29.5-79.6%), and 24.3% (95% CI, 0-52.2%), respectively (P = 0.15). No clinicopathologic features were significantly associated with LF, yet lack of chemotherapy or metastasis at the time of RT was independent significant prognostic factors of decreased OS. Eleven patients experienced RT-related morbidity, with two grade 3 toxicities and no grade 4/5 events. CONCLUSIONS: Curative-intent RT in pediatric and AYA patients was well tolerated and achieved a local tumor control rate of 75% in patients with primary disease. Local control rates were similar to those in primarily adult studies, with similar or lower doses.

Osteonecrosis of the Shoulders in Pediatric Patients Treated for Leukemia or Lymphoma: Single-Institutional Experience.

BACKGROUND: Osteonecrosis of the hips and knees is an often debilitating adverse event in children treated with glucocorticoids for leukemia and lymphoma but the impact of shoulder involvement has been understudied. Thus, we investigated the severity and functional impairment of shoulder osteonecrosis in a well-characterized population of pediatric patients treated for acute lymphoblastic leukemia or lymphoma. METHODS: We retrospectively reviewed orthopaedic clinic and physical therapy evaluations to determine range of motion (ROM), pain, and impact of magnetic resonance-defined osteonecrosis (ON) on activities of daily living. Adverse events were classified according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.03. RESULTS: We identified 35 patients (22 female), median age at cancer diagnosis 14.2 (range, 4.3 to 19) years; median age at ON diagnosis 16.7 (range, 5.5 to 28) years. Median time to last follow-up from diagnosis of primary malignancy was 6.4 (range, 0 to 12.7) years and from diagnosis of ON was 4.0 (range, 0 to 8.9) years. Twenty-two patients had magnetic resonance evidence of ON; 43 shoulders involved at least 30% of the articular surface of the capital humeral epiphyses.Common Terminology Criteria for Adverse Events mean scores for initial assessments of 55 shoulders (29 patients) showed moderate negative impact of ON on activity of daily living (1.94), decreased ROM limiting athletic activity (0.98), and mild to moderate levels of pain (1.38). Analysis of this group's most recent assessment showed improvement in pain and ON over time, with an average pain grade of 0.58 indicating no pain to mild pain, and 1.37 for ON grade, indicating asymptomatic to mildly symptomatic impact on activities of daily living. We also found minimal worsening average ROM grades (1.11). CONCLUSIONS: Shoulder ON is an underappreciated adverse late effect of therapy in children treated for leukemia/lymphoma which can limit quality of life and functionality. In most cases, pain and disability can be improved with treatment. LEVEL OF EVIDENCE: Level IV-case series.

Role of Amputation in Improving Mobility, Pain Outcomes, and Emotional and Psychological Well-Being in Children With Metastatic Osteosarcoma.

BACKGROUND:: Few studies have analyzed the benefit of limb amputations in children with metastatic osteosarcoma and limited life span. OBJECTIVE:: We studied outcomes of limb amputations in children with metastatic osteosarcoma. DESIGN:: We performed a retrospective review of patients who underwent limb amputations (January 1995-June 2015) and died within 1 year of surgery. SETTING/PARTICIPANTS:: We studied 12 patients with osteosarcoma at a single institution. MEASUREMENTS:: Data on mobility, pain, and emotional and psychological well-being were retrieved from medical records from 1 month before surgery to 6 months after surgery. RESULTS:: Of the 12 patients (7 females and 5 males; median age at surgery 13 years [range, 7-20 years]) meeting study criteria, 3 patients and 9 patients had primary osteosarcoma in upper and lower limbs, respectively. Mobility improved postamputation in 8 bedridden/wheelchair-bound patients. Postamputation, emotional, and psychological well-being improved for 9 patients, 3 patients had persistent psychological and/or emotional symptoms, and no patient experienced signs of regret. Daily mean pain scores were significantly lower at 1 week (median 3 [range, 0-6]; P = .03) and 3 months (median 0 [range, 0-8]; P = .02) postsurgery than at 1 week presurgery (median 5.5 [range, 0-10]). Morphine consumption (mg/kg/d) showed a trend toward higher values at 1 week (median 0.2 [range, 0-7.6]; P = .6) and 3 months (median 0.2 [range, 0-0.5]; P = .3) postsurgery than at 1 week presurgery (median 0.1 [range, 0-0.5]). CONCLUSIONS:: Patients undergoing limb amputations had reduced pain and improved mobility and emotional and psychological well-being. Amputations are likely to benefit children with limited life expectancy.

Nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) in pediatric and young adult patients: Results from a prospective study using limited-margin radiotherapy.

BACKGROUND: Indications for and delivery of adjuvant therapies for pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) have been derived largely from adult studies; therefore, significant concern remains regarding radiation exposure to normal tissue. The authors report long-term treatment outcomes and toxicities for pediatric and young adult patients with high-grade NRSTS who were treated on a prospective trial using limited-margin radiotherapy. METHODS: Sixty-two patients (ages 3-22 years) with predominantly high-grade NRSTS requiring radiation were treated on a phase 2 institutional study of conformal external-beam radiotherapy and/or brachytherapy using a 1.5-cm to 2-cm anatomically constrained margin. The estimated cumulative incidence of local failure, Gray's method estimated cumulative incidence of local failure, Kaplan-Meier method estimated survival, competing-risk regression model determined predictors of disease outcome, and toxicity was reported according to CTCAE v2.0. RESULTS: At a median follow-up of 5.1 years (range, 0.2-10.9 years), 9 patients had experienced local failure. The 5-year overall cumulative incidence of local failure was 14.8% (95% confidence interval [CI], 7.2%-25%), and all but 1 local failure occurred outside the highest-dose irradiation volume. The 5-year Kaplan-Meier estimates for event-free and overall survival were 49.3% (95% CI, 36.3%-61.1%) and 67.9% (95% CI, 54.2%-78.3%), respectively. Multivariable analysis indicated that younger age was the only independent predictor of local recurrence (P = .004). The 5-year cumulative incidence of grade 3 or 4 late toxicity was 15% (95% CI, 7.2%-25.3%). CONCLUSIONS: The delivery of limited-margin radiotherapy using conformal external-beam radiotherapy or brachytherapy provides a high rate of local tumor control without an increase in marginal failures and with acceptable treatment-related morbidity. Cancer 2017;123:4419-29. © 2017 American Cancer Society.

Osteonecrosis is unrelated to hip anatomy in children with acute lymphoblastic leukemia.

Osteonecrosis is a debilitating toxicity associated with acute lymphoblastic leukemia (ALL) treatment. A recent report associated interindividual differences in hip anatomy with the development of idiopathic osteonecrosis in adults. To evaluate the impact of hip anatomy on the development of therapy-related osteonecrosis, we retrospectively evaluated the femoral neck-shaft angle, femoral neck offset, and lateral center-edge angle using x-rays of 18 osteonecrosis cases and 46 control children treated for newly diagnosed ALL on a single protocol. Despite adequate statistical power, we found no association between hip anatomy and osteonecrosis. Investigation of other factors contributing to ALL-associated osteonecrosis is warranted.

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.

Limited Margin Radiation Therapy for Children and Young Adults With Ewing Sarcoma Achieves High Rates of Local Tumor Control.

PURPOSE: To determine the rate of local failure using focal conformal, limited margin radiation therapy (RT) and dose escalation for tumors ≥8 cm (greatest dimension at diagnosis) in children and young adults with Ewing sarcoma (EWS). METHODS AND MATERIALS: Eligible patients with EWS were treated on a phase 2 institutional trial of focal conformal, limited margin RT using conformal or intensity modulated techniques. The treatment volume incorporated a 1-cm constrained margin around the gross tumor. Unresected tumors, <8 cm at diagnosis, received a standard dose of 55.8 Gy and tumors ≥8 cm, an escalated dose to 64.8 Gy. Patients with microscopic residual disease after resection received adjuvant RT to 50.4 Gy. Adjuvant brachytherapy was permitted in selected patients. RESULTS: Forty-five patients were enrolled: 26 with localized and 19 with metastatic disease. Median (range) age, tumor size, and follow-up were 13.0 years (2.9-24.7 years), 9.0 cm (2.4-17.0 cm), and 54.5 months (1.9-122.2 months), respectively. All patients received systemic chemotherapy. The median (range) RT dose for all patients was 56.1 Gy (45-65.5 Gy). Seventeen patients received adjuvant, 16 standard-dose, and 12 escalated-dose RT. Failures included 1 local, 10 distant, and 1 local/distant. The estimated 10-year cumulative incidence of local failure was 4.4% ± 3.1%, with no statistical difference seen between RT treatment groups and no local failures in the escalated-dose RT treatment group. CONCLUSIONS: Treatment with focal conformal, limited margin RT, including dose escalation for larger tumors, provides favorable local tumor control in EWS.

Initial diagnostic management of pediatric bone tumors.

BACKGROUND: Osteosarcoma (OS) and the Ewing sarcoma family of tumors (ESFT) are the most common primary pediatric bone malignancies. We sought to assess the diagnostic accuracy of initial tumor biopsies in patients with OS or ESFT at a pediatric cancer center. METHODS: All biopsies performed at initial presentation of patients with OS or ESFT at our institution from 2003 to 2012 were retrospectively reviewed. Diagnostic accuracy and incidence of complications were correlated with study variables using logistic regression analysis. RESULTS: One hundred forty-two biopsies were performed in 105 patients (median age 13.4years, range: 1.8-23.0), 104 (73.2%) OS and 38 (27.8%) ESFT. Thirty-one (21.8%) were performed on metastatic sites. Eighty-five (76.6%) of 111 primary site biopsies were open procedures, and 26 were percutaneous (23.4%). Primary site biopsies were successful in 94.1% of open and 73.1% of percutaneous procedures. Odds of obtaining a successful diagnostic specimen were 7.8 times higher with open approach (CI: 1.6-36.8). Metastatic site biopsies were successful in 66.7% of percutaneous and 100% of open and thoracoscopic procedures. CONCLUSION: Biopsy of metastatic sites was equal to primary site in obtaining diagnostic material with the added benefit of accurate staging, with few adverse events and high diagnostic yield.

Current Management of Neonatal Soft-tissue Sarcomas and Benign Tumors with Local Aggressiveness.

Neonatal soft-tissue tumors are rare and comprise a heterogeneous group of neoplasms with substantial histological diversity. Treatment options include careful observation, primary surgical resection or medical therapy. Although histologically benign, some neoplasms do exhibit an aggressive local behavior. The most common soft-tissue sarcomas in this age group include rhabdomyosarcoma, fibrosarcoma, malignant rhabdoid tumor and hemangiopericytoma. Prenatal diagnosis on routine ultrasound or in the context of a known predisposition syndrome is increasingly becoming more common. Management of neonatal tumors requires a multidisciplinary team that includes obstetricians, neonatologists, pediatric oncologists, pediatric surgical specialists and psychological support for the family members. Treatment is particularly challenging due to the difficulty in appropriate dosing of chemotherapeutic agents or the limitations of the use of radiation therapy. Although surgical treatment is predominant in this age group, close observation may be appropriate, since spontaneous regression has been reported for certain histological subtypes.

Utility of early screening magnetic resonance imaging for extensive hip osteonecrosis in pediatric patients treated with glucocorticoids.

PURPOSE: Hip osteonecrosis frequently complicates treatment with glucocorticoids. When extensive (affecting ≥ 30% of the epiphyseal surface), 80% of joints collapse within 2 years, so interventions are needed to prevent this outcome. PATIENTS AND METHODS: This prospective cohort magnetic resonance imaging (MRI) screening study included all consecutive children treated for acute lymphoblastic leukemia on a single protocol. Hip MRI was performed at 6.5 and 9 months from diagnosis (early screening) and at completion of chemotherapy (final evaluation) to determine whether screening could identify extensive hip osteonecrosis before symptom development. RESULTS: Of 498 patients, 462 underwent screening MRI. Extensive asymptomatic osteonecrosis was identified by early screening in 26 patients (41 hips); another four patients (seven hips) were detected after the screening period, such that screening sensitivity was 84.1% and specificity was 99.4%. The number of joints screened to detect one lesion was 20.1 joints for all patients, 4.4 joints for patients older than 10 years, and 198 joints for patients ≤ 10 years old (P < .001). Of the 40 extensive lesions in patients older than 10 years, 19 required total hip arthroplasty and none improved. Of eight extensive lesions in younger patients, none required arthroplasty and four improved. CONCLUSION: In patients age 10 years old or younger who require prolonged glucocorticoid therapy, screening for extensive hip osteonecrosis is unnecessary because their risk is low and lesions tend to heal. In children older than 10 years, early screening successfully identifies extensive asymptomatic lesions in patients who would be eligible for studies of interventions to prevent or delay joint collapse.

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.