James S. Meyer

Dose-Intensified Compared With Standard Chemotherapy for Nonmetastatic Ewing Sarcoma Family of Tumors: A Children's Oncology Group Study

PURPOSE The Ewing sarcoma family of tumors (ESFT) is a group of malignant tumors of soft tissue and bone sharing a chromosomal translocation affecting the EWS locus. The Intergroup INT-0091 demonstrated the superiority of a regimen of vincristine, cyclophosphamide, doxorubicin (VDC), and dactinomycin alternating with ifosfamide and etoposide (IE) over VDC for patients with nonmetastatic ESFT of bone. The goal of this study was to determine whether a dose-intensified regimen of VDC alternating with IE would further improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue. METHODS Patients with previously untreated, nonmetastatic ESFT of bone or soft tissue were eligible. They were randomly assigned to receive standard doses of VDC/IE over 48 weeks or a dose-intensified regimen of VDC/IE over 30 weeks. RESULTS Four hundred seventy-eight patients met eligibility requirements: 231 patients received the standard regimen; 247 patients received the intensified regimen. The 5-year event-free survival (EFS) and overall survival rates for all eligible patients were 71.1% (95% CI, 67.7% to 75.0%) and 78.6% (95% CI, 74.6% to 82.1%), respectively. There was no significant difference (P = .57) in EFS between patients treated with the standard (5-year EFS, 72.1%; 95% CI, 65.8% to 77.5%) or intensified regimen (5-year EFS, 70.1%; 63.9% to 75%). Patients with soft tissue tumors accounted for 20% of the study population; there was no difference in outcome between patients with soft tissue and bone primary sites. CONCLUSION Dose escalation of alkylating agents as tested in this trial did not improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue.

Anterior Cruciate Ligament Reconstruction in Adolescents with Open Physes

The purpose of this study was to evaluate anterior cruciate ligament reconstructions performed in adolescents with open physes and a skeletal age of at least 14 years. At one center, from 1992 to 1996, 19 adolescents (ages, 11 to 15 years) with open physes and a skeletal age of at least 14 years underwent arthroscopic anterior cruciate ligament reconstruction using an Achilles tendon allograft placed through drill holes across the open physes in both the distal femur and proximal tibia. Fifteen patients returned for reevaluation at an average of 25 months postoperatively (range, 12 to 60 months); the remaining four patients were interviewed by telephone. There were no significant leg-length discrepancies or angular deformities as determined by scanograms and anteroposterior and lateral radiographs of the femur and tibia. The mean Lysholm knee score was 97 (range, 94 to 100) and the mean KT-1000 arthrometer side-to-side difference at 20 pounds of anterior force was 1.7 mm (range, 0.0 to 3.0). All patients were satisfied with the results of surgery, and 16 of 19 patients returned to the same sport they were participating in before the injury. This study demonstrates that anterior cruciate ligament reconstruction using an Achilles tendon allograft is a viable treatment option for skeletally immature patients with a skeletal age of 14 years who have sustained midsubstance tears of the anterior cruciate ligament.

IMAGING OF MUSCULOSKELETAL INFECTIONS

Imaging studies play a critical role in the diagnosis and management of musculoskeletal infections in children. Conventional radiography is usually the first imaging study performed with other imaging modalities as needed. Ultrasound is helpful in detecting joint effusions and fluid collections in the soft tissue and subperiosteal regions, and may guide localization for aspiration or drainage. CT can demonstrate osseous and soft tissue abnormalities and is ideal for detecting gas in soft tissues. Nuclear scintigraphy and MR imaging are valuable because of their high sensitivity. Scintigraphy is particularly useful in identifying multifocal involvement, which is an important consideration in neonatal osteomyelitis and CRMO. MR imaging provides accurate information on both the soft tissues and bones and is our imaging study of choice for evaluating the local extent of musculoskeletal infections.

EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment.

This manuscript describes the experience from registration until randomisation for a cohort of 2260 patients with osteosarcoma who joined the EURAMOS-1 trial. This includes pre-operative chemotherapy and surgery. It sets out the practical issues in collaboration and in achieving randomisation.

Imaging guidelines for children with Ewing sarcoma and osteosarcoma: A report from the Children's Oncology Group Bone Tumor Committee

The Childrens Oncology Group (COG) is a multi‐institutional cooperative group dedicated to childhood cancer research that has helped to increase the survival of children with cancer through clinical trials. These clinical trials include a standardized regimen of imaging examinations performed prior to, during, and following therapy. This article presents imaging guidelines developed by a multidisciplinary group from the COG Bone Tumor Committee. These guidelines provide both required and recommended studies. Recommended examinations may become required in the future. These guidelines should be considered a work in progress that will evolve with advances in imaging and childhood cancer research. Pediatr Blood Cancer 2008;51:163–170.

Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial

Purpose EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy. Patients and Methods At diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ≥ two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN-α-2b (0.5 to 1.0 μg/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary). Results Good response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN-α-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-α-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-α-2b and for stopping prematurely, respectively. Median IFN-α-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-α-2b and provided toxicity information reported grade ≥ 3 toxicity during IFN-α-2b treatment. With median follow-up of 44 months, 3-year EFS for all 716 randomly assigned patients was 76% (95% CI, 72% to 79%); 174 EFS events were reported (MAP, n = 93; MAP plus IFN-α-2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P = .214) from an adjusted Cox model. Conclusion At the preplanned analysis time, MAP plus IFN-α-2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN-α-2b or stopped prematurely. Long-term follow-up for events and survival continues.

Pyomyositis in children and adolescents : Report of 12 cases and review of the literature

Pyomyositis initially was observed more commonly in the developing world but now is reported with increasing frequency in the United States. The presentation is nonspecific and the differential diagnoses are many. We found the clinical history, laboratory findings, and response to treatment similar to those observed in different areas of the world. Magnetic resonance imaging (MRI) with gadolinium injection, in addition to helping to make the diagnosis, may help differentiate between early and late stages that help guide treatment. Coexisting bone changes (58%) may represent either the sensitivity of MRI to reactive inflammatory changes or the presence of a coexisting osteomyelitis. All patients responded to antibiotics and drainage if abscesses were present. Although the optimal duration of antibiotic therapy remains unclear, a shorter course should be considered in patients with a good clinical response, even when MRI shows nonspecific bony abnormalities. Percutaneous drainage was successful in five cases and may represent an alternative to the traditional surgical approach.

Role of magnetic resonance imaging and clinical criteria in predicting successful nonoperative treatment of osteochondritis dissecans in children.

Magnetic resonance imaging (MRI) offers promise as a noninvasive method to determine the potential of an osteochondritis dissecans (OCD) lesion to heal without surgical intervention. The purpose of this study was to compare the value of MRI, plain radiographs, and clinical findings in predicting the success of nonoperative treatment of juvenile OCD lesions. Twenty-seven lesions in 24 patients (mean age 12.2 y) with OCD of the distal femur diagnosed based on MRI were identified. A radiologist or orthopaedist, blinded to the clinical status of the patients, correlated the MRIs with patient outcome. MRIs were assessed for lesion size, location, and four criteria evaluating signal intensity changes and articular surface defects to determine lesion stability. Older, more skeletally mature patients with at least one sign of instability on MRI were most likely to have nonoperative treatment fail. Nonoperative treatment failed most often in patients with large lesions in weightbearing areas, as seen on lateral radiographs. However, location based on anteroposterior radiographs was not statistically significant for predicting treatment outcome. Although no single factor was uniformly predictive of successful nonoperative treatment, younger, skeletally immature patients with no MRI criteria of instability were most amenable to nonoperative treatment.

Ovarian torsion: Clinical and imaging presentation in children

Ovarian torsion is uncommon and has a nonspecific clinical presentation. To determine the impact of imaging on clinical management, the authors reviewed their recent experience with 12 children who had a total of 13 episodes of ovarian torsion. Three children presented as neonates, six were premenarchal, and three were postmenarchal. Ultrasound was the imaging study of choice. In all three neonates, ultrasonography showed complex abdominopelvic cysts indicating the need for surgery. In five of 10 episodes in older patients, ultrasonography showed a solid mass with an appearance strongly suggestive of torsion. Same-day surgery was performed in three patients, and the involved ovary was salvaged in one. Another patient had a small piece of normal-appearing ovary left in situ. This low rate of ovarian salvage is attributable to the combination of delay in patient presentation and surgical delay owing to the often nonspecific clinical and imaging presentation of ovarian torsion. A high level of clinical suspicion, expeditious imaging, and familiarity with the varied clinical and imaging presentations of ovarian torsion should decrease the surgical delay and improve the likelihood of ovarian salvage.

Diagnosing aneurysmal and unicameral bone cysts with magnetic resonance imaging.

The differential between aneurysmal bone cysts and unicameral bone cysts usually is clear clinically and radiographically. Occasionally there are cases in which the diagnosis is not clear. Because natural history and treatment are different, the ability to distinguish between these two entities before surgery is important. The authors reviewed, in a blinded fashion, the preoperative magnetic resonance images to investigate criteria that could be used to differentiate between the two lesions. All patients had operative or pathologic confirmation of an aneurysmal bone cyst or unicameral bone cyst. The authors analyzed the preoperative magnetic resonance images of 14 patients with diagnostically difficult bone cysts (eight children with unicameral bone cysts and six children with aneurysmal bone cysts) and correlated these findings with diagnosis after biopsy or cyst aspiration and contrast injection. The presence of a double density fluid level within the lesion strongly indicated that the lesion was an aneurysmal bone cyst, rather than a unicameral bone cyst. Other criteria that suggested the lesion was an aneurysmal bone cyst were the presence of septations within the lesion and signal characteristics of low intensity on T1 images and high intensity on T2 images. The authors identified a way of helping to differentiate between aneurysmal bone cysts and unicameral bone cysts on magnetic resonance images. Double density fluid level, septation, and low signal on T1 images and high signal on T2 images strongly suggest the bone cyst in question is an aneurysmal bone cyst, rather than a unicameral bone cyst. This may be helpful before surgery for the child who has a cystic lesion for which radiographic features do not allow a clear differentiation of unicameral bone cyst from aneurysmal bone cyst.