Visual, auditory, sensory, and motor impairments in long-term survivors of hematopoietic stem cell transplantation performed in childhood

BACKGROUND Because of treatment-related toxicity, research is increasingly being focused on long-term sequelae secondary to hematopoietic stem cell transplantation (HSCT) in survivor populations. METHODS This study describes the incidence of auditory, sensory, motor, and visual impairments, including cataracts, among 235 individuals who were treated with HSCT during childhood or adolescence. Outcomes were compared with 705 siblings of childhood cancer survivors. Participants completed a survey with questions on posttransplant organ system impairments. Approximately half of survivors were transplanted when younger than 10 years of age. The median length of followup was 11 years. RESULTS The cumulative incidence of cataracts was 36% at 15 years post-HSCT, although cataracts occurred only in those who received total body irradiation as an HSCT conditioning agent or head irradiation before transplant. Persistent pain was reported by 21% of survivors. Loss of hearing in one or both ears, and legal blindness in one or both eyes, each occurred after transplant in 2% of survivors. Occurrences were uncommon, but survivors were 4.3 times (95% confidence interval [CI]: 2.0–9.4) more likely to report coordination problems, 7.7 times (95% CI: 3.2–18.5) more likely to report chewing or swallowing problems, and 3.5 times (3.5; 95% CI: 1.6–7.9) more likely to report muscle weakness than those in the comparison group. Muscle weakness was strongly associated with positive history of chronic graft-versus-host disease. CONCLUSIONS Increased risks were found for motor impairments, hearing loss, vision loss, and persistent pain among study participants. Cataracts were a frequent adverse effect, suggesting that close monitoring with appropriate intervention for preservation of vision, particularly among those who received total body irradiation, should be a primary goal in survivors of HSCT performed in childhood. Cancer 2006. © 2006 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49517/1/21752_ftp.pd

Whole breast proton irradiation for maximal reduction of heart dose in breast cancer patients

PURPOSE: In left-sided breast cancer radiotherapy, tangential intensity modulated radiotherapy combined with breath-hold enables a dose reduction to the heart and left anterior descending (LAD) coronary artery. Aim of this study was to investigate the added value of intensity modulated proton therapy (IMPT) with regard to decreasing the radiation dose to these structures. METHODS: In this comparative planning study, four treatment plans were generated in 20 patients: an IMPT plan and a tangential IMRT plan, both with breath-hold and free-breathing. At least 97 % of the target volume had to be covered by at least 95 % of the prescribed dose in all cases. Specifically with respect to the heart, the LAD, and the target volumes, we analyzed the maximum doses, the mean doses, and the volumes receiving 5-30 Gy. RESULTS: As compared to IMRT, IMPT resulted in significant dose reductions to the heart and LAD-region even without breath-hold. In the majority of the IMPT cases, a reduction to almost zero to the heart and LAD-region was obtained. IMPT treatment plans yielded the lowest dose to the lungs. CONCLUSIONS: With IMPT the dose to the heart and LAD-region could be significantly decreased compared to tangential IMRT with breath-hold. The clinical relevance should be assessed individually based on the baseline risk of cardiac complications in combination with the dose to organs at risk. However, as IMPT for breast cancer is currently not widely available, IMPT should be reserved for patients remaining at high risk for major coronary events

Radiotherapy for Graves' orbitopathy: randomised placebo-controlled study

Background The best treatment (steroids, irradiation, or both) for moderately severe Graves' orbitopathy, a self-limiting disease is not known. We tested the efficacy of external beam irradiation compared with sham-irradiation. Methods In a double-blind randomised clinical trial, 30 patients with moderately severe Graves' orbitopathy had radiotherapy (20 Gy in ten fractions), and 30 were assigned sham-irradiation (ten fractions of 0 Gy). Treatment outcome was measured qualitatively by changes in major and minor criteria and quantitatively in several ophthalmic and other variables, such as eyelid aperture, proptosis, eye movements, subjective eye score, and clinical-activity score at 24 weeks. Findings The qualitative treatment outcome was successful in 18 of 30 (60%) irradiated patients versus nine of 29 (31%) sham-irradiated patients at week 24 (relative risk [RR]=1.9 [95% CI 1.0-3.6], p=0.04). This difference was caused by improvements in diplopia grade, but not by reduction of proptosis, nor of eyelid swelling. Quantitatively, elevation improved significantly in the radiotherapy group, whereas all other variables remained unchanged. The field of binocular single vision was enlarged in 11 of 17 patients after irradiation compared with two of 15 after sham-irradiation. Nevertheless, only 25% of the irradiated patients were spared from additional strabismus surgery. Interpretation In these patients with moderately severe Graves' orbitopathy, radiotherapy should be used only to treat motility impairment

Left-sided breast cancer radiotherapy with and without breath-hold: Does IMRT reduce the cardiac dose even further?

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Less increase of CT-based calcium scores of the coronary arteries

Development and application of statistical models for medical scientific researc

Cataract-free interval and severity of cataract after total body irradiation and bone marrow transplantation: influence of treatment parameters

PURPOSE: To determine prospectively the cataract-free interval (latency time) after total body irradiation (TBI) and bone marrow transplantation (BMT) and to assess accurately the final severity of the cataract. METHODS AND MATERIALS: Ninety-three of the patients who received TBI as a part of their conditioning regimen for BMT between 1982 and 1995 were followed with respect to cataract formation. Included were only patients who had a follow-up period of at least 23 months. TBI was applied in one fraction of 8 Gy or two fractions of 5 or 6 Gy. Cataract-free period was assessed and in 56 patients, who could be followed until stabilization of the cataract had occurred, final severity of the cataract was determined using a classification system. With respect to final severity, two groups were analyzed: subclinical low-grade cataract and high-grade cataract. Cataract-free period and final severity were determined with respect to type of transplantation, TBI dose, and posttransplant variables such as graft versus host disease (GVHD) and steroid treatment. RESULTS: Cataract incidence of the analyzed patients was 89%. Median time to develop a cataract was 58 months for autologous transplanted patients. For allogeneic transplanted patients treated or not treated with steroids, median times were 33 and 46 months, respectively. Final severity was not significantly different for autologous or allogeneic patients. In allogeneic patients, however, final severity was significantly different for patients who had or had not been treated with steroids for GVHD: 93% versus 35% high-grade cataract, respectively. Final severity was also different for patients receiving 1 x 8 or 2 x 5 Gy TBI, from patients receiving 2 x 6 Gy as conditioning therapy: 33% versus 79% high-grade cataract, respectively. The group of patients receiving 2 x 6 Gy comprised, however, more patients with steroid treatment for GVHD. So the high percentage of high-grade cataract in the 2 x 6 Gy group might also have been caused to a significant extent by steroid treatment. The percentage of patients with high-grade cataract was lower in allogeneic transplanted patients without steroid treatment for GVHD than in autologous transplanted patients: 35% versus 48%. An explanation for this could be pretransplant therapy containing high-dose steroids. CONCLUSIONS: After high-dose-rate TBI in one or two fractions, steroids for GVHD influence latency time of a cataract and are of great importance for the severity the cataract finally attains. Although a cataract will develop in all patients, a clinically important high-grade cataract is relatively infrequent in patients not treated with steroids. Pretransplant therapy might also influence final severity of catarac