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