Cancer Health Center

continued...

Also, cranial radiation therapy damages the hypothalamic-pituitary axis (HPA) in an age- and dose-response fashion, often leading to growth hormone deficiency (GHD).[14,15] If untreated during the growing years, and sometimes, even with appropriate treatment, this leads to a substantially lower final height. Patients with a central nervous system (CNS) tumor [14,16] or acute lymphoblastic leukemia (ALL)[17,18,19] treated with 18 Gy or more of cranial radiation therapy are at highest risk. Also, patients treated with total-body irradiation (TBI), particularly single fraction TBI, are at risk of GHD.[20,21,22,23] In addition, if the spine is also irradiated (e.g., craniospinal radiation therapy for medulloblastoma or early ALL therapies in the 1960s), growth can be affected by two separate mechanisms-GHD and direct damage to the spine.

Amputation and limb-sparing surgery

Amputation and limb-sparing surgery prevent local recurrence of bone tumors by removal of all gross and microscopic disease. If optimally executed, both procedures accomplish an en bloc excision of tumor with a margin of normal uninvolved tissue. The type of surgical procedure, the primary tumor site, and the age of the patient affect the risk of postsurgical complications.[24] Complications in survivors treated with amputation include stump-prosthetic problems, chronic stump pain, phantom limb pain, and bone overgrowth.[25,26] While limb-sparing surgeries may offer a more aesthetically pleasing outcome, complications have been reported more frequently in survivors undergoing these procedures compared with those treated with amputation. Complications after limb-sparing surgery include non-union, pathologic fracture, aseptic loosening, limb-length discrepancy, endoprosthetic fracture, poor joint movement, and stump-prosthesis problems.[25,27] Occasionally, refractory complications develop after limb-sparing surgery and require amputation.[28,29] A number of studies have compared functional outcomes after amputation and limb-sparing surgery, but results have been limited by inconsistent methods of functional assessment and small cohort sizes. Overall, data suggest that limb-sparing surgery results in better function than amputation, but differences are relatively modest.[25,29] Similarly, long-term quality of life outcomes among survivors undergoing amputation and limb sparing procedures have not differed substantially.[28]

Joint contractures

Hematopoietic cell transplantation with any history of chronic graft-versus-host disease is associated with joint contractures.[30,31,32]

Osteoporosis/fractures

Maximal peak bone mass is an important factor influencing the risk of osteoporosis and fracture associated with aging. Methotrexate has a cytotoxic effect on osteoblasts, resulting in a reduction of bone volume and formation of new bone.[33,34] This effect may be exacerbated by the chronic use of corticosteroids, another class of agents routinely used in the treatment of hematological malignancies and in supportive care for a variety of pediatric cancers. Radiation-related endocrinopathies, such as GHD or hypogonadism, may contribute to ongoing bone mineral loss.[35,36] In addition, suboptimal nutrition and physical inactivity may further predispose to deficits in bone mineral accretion.