A systematic review of selected musculoskeletal late effects in survivors of childhood cancer.

Survivors of childhood cancer are at risk for treatment-related musculoskeletal late effects. Early detection and orthopedic intervention can help ameliorate musculoskeletal late effects and prevent subsequent complications. This systematic review summarizes the literature describing associations between cancer, its treatment, and musculoskeletal late effects. We searched PubMed and Web of Science for English language articles published between January 1970 and December 2012. The search was limited to investigations with at least 15 participants and conducted at least 2 years after completion of therapy for childhood, adolescent, or young adult cancer. Some late skeletal effects, including low bone mineral density, osteonecrosis, slipped capital femoral epiphyses, oncogenic rickets, and hormonerelated growth disturbances have been previously reviewed and were excluded, as were outcomes following amputation and limb-salvage procedures. Of 2347 references identified, 30 met inclusion criteria and were retained. An additional 54 studies that met inclusion criteria were found in reference lists of retained studies. Of 84 studies, 60 focused on associations between radiotherapy, six between chemotherapy, and 18 between surgery and musculoskeletal late effects. We found that younger age, higher radiation dosage, and asymmetric or partial bone radiation volume influences the effects of radiation on the musculoskeletal system. Methotrexate and vincristine are associated with long-term muscular strength and flexibility deficits. Laminectomy and chest wall resection are associated with spinal malalignment, and enucleation is associated with orbital deformities among survivors. Radiotherapy, chemotherapy, and surgery are associated with musculoskeletal late effects independently and additively. Associations are additionally influenced by host and treatment characteristics.

Enrichment and terminal differentiation of striated muscle progenitors in vitro.

Enrichment and terminal differentiation of mammalian striated muscle cells is severely hampered by fibroblast overgrowth, de-differentiation and/or lack of functional differentiation. Herein we report a new, reproducible and simple method to enrich and terminally differentiate muscle stem cells and progenitors from mice and humans. We show that a single gamma irradiation of muscle cells induces their massive differentiation into structurally and functionally intact myotubes and cardiomyocytes and that these cells can be kept in culture for many weeks. Similar results are also obtained when treating skeletal muscle-derived stem cells and progenitors with Mitomycin C.

On the clinical spatial resolution achievable with protons and heavier charged particle radiotherapy beams.

The 'sub-millimetre precision' often claimed to be achievable in protons and light ion beam therapy is analysed using the Monte Carlo code SHIELD-HIT for a broad range of energies. Based on the range of possible values and uncertainties of the mean excitation energy of water and human tissues, as well as of the composition of organs and tissues, it is concluded that precision statements deserve careful reconsideration for treatment planning purposes. It is found that the range of I-values of water stated in ICRU reports 37, 49 and 73 (1984, 1993 and 2005) for the collision stopping power formulae, namely 67 eV, 75 eV and 80 eV, yields a spread of the depth of the Bragg peak of protons and heavier charged particles (carbon ions) of up to 5 or 6 mm, which is also found to be energy dependent due to other energy loss competing interaction mechanisms. The spread is similar in protons and in carbon ions having analogous practical range. Although accurate depth-dose distribution measurements in water can be used at the time of developing empirical dose calculation models, the energy dependence of the spread causes a substantial constraint. In the case of in vivo human tissues, where distribution measurements are not feasible, the problem poses a major limitation. In addition to the spread due to the currently accepted uncertainties of their I-values, a spread of the depth of the Bragg peak due to the varying compositions of soft tissues is also demonstrated, even for cases which could be considered practically identical in clinical practice. For these, the spreads found were similar to those of water or even larger, providing support to international recommendations advising that body-tissue compositions should not be given the standing of physical constants. The results show that it would be necessary to increase the margins of a clinical target volume, even in the case of a water phantom, due to an 'intrinsic basic physics uncertainty', adding to those margins usually considered in normal clinical practice due to anatomical or therapeutic strategy reasons. Individualized patient determination of tissue composition along the complete beam path, rather than CT Hounsfield numbers alone, would also probably be required even to reach 'sub-centimetre precision'.