Osteosarcoma
Mifamurtide is a macrophage modulator thought to be active in reducing the incidence of lung metastases in OS.75 Its potential benefit has been investigated in a trial randomizing over 600 patients with localized OS to receive MAP alone or with the addition of mifamurtide and/or ifosfamide. Although increased overall survival (from 70 to 78% at 6y, P =0.03) was reported for the mifamurtide arms, the lack of significantly improved EFS and concerns about a possible interaction between mifamurtide and ifosfamide ensured the results were insufficient to support global approval by regulatory authorities, restricting the use of mifamurtide to selected countries.75-77
Surgical resectability is a cornerstone of curative treatment for OS. For some patients, especially with tumors of the pelvis, axial skeleton and skull, complete surgical resection is not possible. There is a lack of evidence for adjuvant or definitive RT in this situation. RT may be used where resection is not possible or anticipated to lead to unacceptable morbidity.44,78-80 Doses of 60Gy or higher, and ideally 70Gy are indicated.78,81-83Strategies to improve outcomes, including comprehensive evaluation of particle beam therapy in this setting, are a priority. The role ofadjuvant chemotherapy in patients undergoing complete surgical resection of relapsed disease , either local or distant, remains unclear.34-37,42
Identification of metastatic disease at diagnosis is essential for prognosis and management. Although only 20% of patients have clinically evident metastases at onset, sensitivity of cross sectional imaging demonstrates 30-45% have pulmonary nodules of uncertain clinical significance that do not meet defined COG criteria for metastases and about one third of these progress to metastatic disease.84-86 Surgical sampling is undertaken in some centers but its value in determining overall survival and guiding treatment is unproven.85,87 Data to support the use of FDG-PET/CT scanning both for accurate staging, especially of the skeleton, and to determine response to chemotherapy, supports its use in selected patients.88-90
Approaches to follow-up after treatment vary in visit intervals, pulmonary imaging modalities and monitoring for late effects of treatment. Access to rehabilitation, assistance in resuming progress on achieving life skills and identifying psychological impacts are all vital parts of effective follow up for AYAs but there is considerable variation in recommendations and practice, indicating a need for collaborative prospective evaluation and evidence-seeking.91-94