PurposeEURAMOS-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 MethodsAt 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).ResultsGood 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.ConclusionAt 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.

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.

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BACKGROUND. With increasing numbers of childhood cancer survivors, direct sequelae of cancer therapy and psychosocial outcomes are becoming more important. The authors described psychosocial outcomes (education, employment, health insurance, and marriage) for survivors of pediatric lower extremity bone tumors. METHODS. The long-term follow-up study of the Childhood Cancer Survivor Study is a multiinstitutional cohort study comprising 14,054 individuals who have survived for 5 or more years after treatment for cancer diagnosed during childhood or adolescence. Baseline demographic and medical information were obtained. Six hundred ninety-four survivors had osteosarcoma or Ewing sarcoma of the lower extremity or pelvis and were classified by amputation status and by age at diagnosis. The median age at diagnosis was 14 years old with a median of 16 years of follow up since diagnosis. Demographic characteristics were used to analyze the rates of psychosocial outcomes. RESULTS. Amputation status and age at diagnosis did not significantly influence any of the measured psychosocial outcomes. Education was a significant positive predictor of employment, having health insurance, and being currently in their first marriage. Male gender predicted ever being employed and female gender predicted having health insurance and marriage. When compared with siblings, amputees had significant deficits in education, employment, and health insurance. CONCLUSIONS. Overall, no differences between amputees and nonamputees were found. However, gender and education play a prominent role. When compared with siblings, amputees in this cohort may benefit from additional supports.

Limb-sparing surgeries have been performed more frequently than amputation based on the belief that limb-sparing surgeries provide improved function and quality-of-life (QOL). However, this has not been extensively studied in the paediatric population, which has unique characteristics that have implications for function and QOL. Using the Childhood Cancer Survivor Study, 528 adult long-term survivors of pediatric lower extremity bone tumours, diagnosed between 1970 and 1986, were contacted and completed questionnaries assessing function and QOL. Survivors were an average of 21 years from diagnosis with an average age of 35 years. Overall they reported excellent function and QOL. Compared to those who had a limb-sparing procedure, amputees were not more likely to have lower function and QOL scores and self-perception of disability included general health status, lower educational attainment, older age and female gender. Findings from this study suggest that, over time, amputees do as well as those who underwent limb-sparing surgeries between 1970 and 1986. However, female gender, lower educational attainment and older current age appear to influence function, QOL and disability.

The past four decades have seen tremendous progress in the treatment of pediatric and adolescent cancers. As a consequence, there are increasing numbers of adult childhood cancer survivors. This has prompted investigation into the long-term consequences of cancer treatments. One group that merits special study is the survivors of lower-extremity bone tumors. Their function and quality of life may depend in part on both the surgery and the age at which it was performed. Comparisons between studies are difficult because small numbers of patients and the use of varying research designs and methods have limited research in this area. The purpose of this article is to review the major surgical approaches to lower-limb bone tumors and their impact on pediatric patients. The results show that survival is equivalent between amputation and limb salvage. Complications occur more frequently in limb salvage. The long-term outcomes of those undergoing amputation and limb salvage have not been found to be substantially different in regard to quality of life. In conclusion, prospective long-term follow-up of pediatric patients with lower-limb tumors is needed to (1) determine in a uniform manner the long-term complications, quality of life, and functionality of this population and describe differences within this patient population based on age at diagnosis and surgical procedure, (2) identify areas of concern that are amenable to intervention, and (3) provide clinicians and future patients a better understanding of the surgical options.

A B S T R A C TPhysical performance limitations are one of the potential long-term consequences following diagnosis and treatment for childhood cancer. The purpose of this review is to describe the risk factors for and the participation restrictions that result from physical performance limitations among childhood cancer survivors who participated in the Childhood Cancer Survivor Study (CCSS). Articles previously published from the CCSS cohort related to physical performance limitations were reviewed and the results summarized. Our review showed that physical performance limitations are prevalent among childhood cancer survivors and may increase as they age. Host-based risk factors for physical disability include an original diagnosis of bone tumor, brain tumor, or Hodgkin's disease; female sex; and an income less than $20,000 per year. Treatmentbased risk factors include radiation and treatment with a combination of alkylating agents and anthracyclines. Musculoskeletal, neurologic, cardiac, pulmonary, sensory, and endocrine organ system dysfunction also increase the risk of developing a physical performance limitation. In summary, monitoring of physical performance limitations in an aging cohort of childhood cancer survivors is important and will help determine the impact of physical performance limitations on morbidity, mortality, and caregiver burden. In addition, in developing restorative and preventive interventions for childhood cancer survivors, we must take into account the special needs of survivors with physical disability to optimize their health and enhance participation in daily living activities.

Poor health status, low levels of income, education, and employment appear to be predictors of distress for survivors of solid tumors. Thus, interventions that promote health and facilitate educational advancement, income attainment and social interaction to minimize isolation and maximize social support may reduce psychological distress and promote quality of life for childhood cancer survivors.