The introduction of advanced techniques and technology in radiotherapy has greatly improved our ability to deliver highly conformal tumor doses while minimizing the dose to adjacent organs at risk. ...Despite these tremendous improvements, there remains a general concern about doses to normal tissues that are not the target of the radiation treatment; any “nontarget” radiation should be minimized as it offers no therapeutic benefit. As patients live longer after treatment, there is increased opportunity for late effects including second cancers and cardiac toxicity to manifest. Complicating the management of these issues, there are unique challenges with measuring, calculating, reducing, and reporting nontarget doses that many medical physicists may have limited experience with. Treatment planning systems become dramatically inaccurate outside the treatment field, necessitating a measurement or some other means of assessing the dose. However, measurements are challenging because outside the treatment field, the radiation energy spectrum, dose rate, and general shape of the dose distribution (particularly the percent depth dose) are very different and often require special consideration. Neutron dosimetry is also particularly challenging, and common errors in methodology can easily manifest as errors of several orders of magnitude. Task Group 158 was, therefore, formed to provide guidance for physicists in terms of assessing and managing nontarget doses. In particular, the report: (a) highlights major concerns with nontarget radiation; (b) provides a rough estimate of doses associated with different treatment approaches in clinical practice; (c) discusses the uses of dosimeters for measuring photon, electron, and neutron doses; (d) discusses the use of calculation techniques for dosimetric evaluations; (e) highlights techniques that may be considered for reducing nontarget doses; (f) discusses dose reporting; and (g) makes recommendations for both clinical and research practice.
Thermoluminescent dosimeters (TLD) and optically stimulated luminescent dosimeters (OSLD) are practical, accurate, and precise tools for point dosimetry in medical physics applications. The charges ...of Task Group 191 were to detail the methodologies for practical and optimal luminescence dosimetry in a clinical setting. This includes: (a) to review the variety of TLD/OSLD materials available, including features and limitations of each; (b) to outline the optimal steps to achieve accurate and precise dosimetry with luminescent detectors and to evaluate the uncertainty induced when less rigorous procedures are used; (c) to develop consensus guidelines on the optimal use of luminescent dosimeters for clinical practice; and (d) to develop guidelines for special medically relevant uses of TLDs/OSLDs such as mixed photon/neutron field dosimetry, particle beam dosimetry, and skin dosimetry. While this report provides general guidelines for TLD and OSLD processes, the report provides specific details for TLD‐100 and nanoDotTM dosimeters because of their prevalence in clinical practice.
The impacts of radiotherapy dose and exposed cardiac volume, select chemotherapeutic agents, and age at exposure on risk for late-onset cardiac disease in survivors of childhood cancer remain ...unresolved.
We determined the rates of severe to fatal cardiac disease in 24,214 5-year survivors in the Childhood Cancer Survivor Study diagnosed between 1970 and 1999 at a median age of 7.0 years (range, 0 to 20.9 years), with a median attained age of 27.5 years (range, 5.6 to 58.9 years). Using piecewise exponential models, we evaluated the association between cardiac disease rates and demographic and treatment characteristics.
The cumulative incidence of cardiac disease 30 years from diagnosis was 4.8% (95% CI, 4.3 to 5.2). Low to moderate radiotherapy doses (5.0 to 19.9 Gy) to large cardiac volumes (≥ 50% of heart) were associated with an increased rate of cardiac disease (relative rate, 1.6; 95% CI, 1.1 to 2.3) compared with survivors without cardiac radiotherapy exposure. Similarly, high doses (≥ 20 Gy) to small cardiac volumes (0.1% to 29.9%) were associated with an elevated rate (relative rate, 2.4; 95% CI, 1.4 to 4.2). A dose-response relationship was observed between anthracycline chemotherapy and heart failure with younger children (age ≤ 13 years) at the greatest risk for heart failure after comparable dosing.
These observations support advances in radiation field design and delivery technology to reduce cardiac dose/volume and should guide future treatment protocols. They also inform clinical practice guidelines for post-therapy surveillance and risk-reducing strategies.
Radiomics studies require many patients in order to power them, thus patients are often combined from different institutions and using different imaging protocols. Various studies have shown that ...imaging protocols affect radiomics feature values. We examined whether using data from cohorts with controlled imaging protocols improved patient outcome models. We retrospectively reviewed 726 CT and 686 PET images from head and neck cancer patients, who were divided into training or independent testing cohorts. For each patient, radiomics features with different preprocessing were calculated and two clinical variables-HPV status and tumor volume-were also included. A Cox proportional hazards model was built on the training data by using bootstrapped Lasso regression to predict overall survival. The effect of controlled imaging protocols on model performance was evaluated by subsetting the original training and independent testing cohorts to include only patients whose images were obtained using the same imaging protocol and vendor. Tumor volume, HPV status, and two radiomics covariates were selected for the CT model, resulting in an AUC of 0.72. However, volume alone produced a higher AUC, whereas adding radiomics features reduced the AUC. HPV status and one radiomics feature were selected as covariates for the PET model, resulting in an AUC of 0.59, but neither covariate was significantly associated with survival. Limiting the training and independent testing to patients with the same imaging protocol reduced the AUC for CT patients to 0.55, and no covariates were selected for PET patients. Radiomics features were not consistently associated with survival in CT or PET images of head and neck patients, even within patients with the same imaging protocol.
Exercise intolerance, associated with heart failure and death in general populations, is not well studied in survivors of childhood cancer. We examined prevalence of exercise intolerance in survivors ...exposed or not to cardiotoxic therapy, and associations among organ system function, exercise intolerance, and mortality.
Participants consisted of 1,041 people who had survived cancer ≥ 10 years (and had or did not have exposure to anthracyclines and/or chest-directed radiation) and 285 control subjects. Exercise intolerance was defined as peak oxygen uptake < 85% predicted from maximal cardiopulmonary exercise testing; organ functions were ascertained with imaging or clinical testing. Multivariable regression of the data was performed to compare exercise capacity between survivors exposed or unexposed to cardiotoxic therapy and control subjects, and to evaluate associations between treatment and organ function, and organ function and exercise intolerance. Propensity score methods in time-to-event analyses evaluated associations between exercise intolerance and mortality.
Survivors (mean age ± standard deviation SD, 35.6 ± 8.8 years) had lower mean (± SD) peak oxygen uptake (exposed: 25.74 ± 8.36 mL/kg/min; unexposed: 26.82 ± 8.36 mL/kg/min) than did control subjects (32.69 ± 7.75 mL/kg/min;
for all < .001). Exercise intolerance was present in 63.8% (95% CI, 62.0% to 65.8%) of exposed survivors, 55.7% (95% CI, 53.2% to 58.2%) of unexposed survivors, and 26.3% (95% CI, 24.0% to 28.3%) of control subjects, and was associated with mortality (hazard ratio, 3.9; 95% CI, 1.09 to 14.14). Global longitudinal strain (odds ratio OR, 1.71; 95% CI, 1.11 to 2.63), chronotropic incompetence (OR, 3.58; 95% CI, 1.75 to 7.31); forced expiratory volume in 1 second < 80% (OR, 2.59; 95% CI, 1.65 to 4.09), and 1 SD decrease in quadriceps strength (OR, 1.49; 95% CI, 1.23 to 1.82) were associated with exercise intolerance. Ejection fraction < 53% was not associated with exercise intolerance.
Exercise intolerance is prevalent among childhood cancer survivors and associated with all-cause mortality. Treatment-related cardiac (detected by global longitudinal strain), autonomic, pulmonary, and muscular impairments increased risk. Survivors with impairments may require referral to trained specialists to learn to accommodate specific deficits when engaging in exercise.
Risk-stratified therapy, which modifies treatment on the basis of clinical and biologic features, has improved 5-year overall survival of childhood acute lymphoblastic leukemia (ALL) to 90%, but its ...impact on long-term toxicity remains unknown.
We assessed all-cause and health-related late mortality (including late effects of cancer therapy), subsequent malignant neoplasms (SMNs), chronic health conditions, and neurocognitive outcomes among 6,148 survivors of childhood ALL (median age, 27.9 years; range, 5.9-61.9 years) diagnosed between 1970 and 1999. Therapy combinations and treatment intensity defined 6 groups: 1970s-like (70s), standard- or high-risk 1980s-like (80sSR, 80sHR) and 1990s-like (90sSR, 90sHR), and relapse/transplantation (R/BMT). Cumulative incidence, standardized mortality ratios, and standardized incidence ratios were compared between treatment groups and with the US population.
Overall, 20-year all-cause late mortality was 6.6% (95% CI, 6.0 to 7.1). Compared with 70s, 90sSR and 90sHR experienced lower health-related late mortality (rate ratio 95% CI: 90sSR, 0.2 0.1 to 0.4; 90sHR, 0.3 0.1 to 0.7), comparable to the US population (standardized mortality ratio 95% CI: 90sSR, 1.3 0.8 to 2.0; 90sHR, 1.7 0.7 to 3.5). Compared with 70s, 90sSR had a lower rate of SMN (rate ratio 95% CI, 0.3 0.1 to 0.6) that was not different from that of the US population (standardized incidence ratio 95% CI, 1.0 0.6 to 1.6). The 90sSR group had fewer severe chronic health conditions than the 70s (20-year cumulative incidence 95% CI, 11.0% 9.7% to 12.3%
22.5% 19.4% to 25.5%) and a lower prevalence of impaired memory (prevalence ratio 95% CI, 0.7 0.6 to 0.9) and task efficiency (0.5 0.4 to 0.7).
Risk-stratified therapy has reduced late morbidity and mortality among contemporary survivors of standard-risk ALL, represented by 90sSR. Health-related late mortality and SMN risks among 5-year survivors of contemporary, standard-risk childhood ALL are comparable to the general population.
Purpose
Using 3D printing to fabricate patient‐specific devices such as tissue compensators, boluses, and phantoms is inexpensive and relatively simple. However, most 3D printing materials have not ...been well characterized, including their radiologic tissue equivalence. The purposes of this study were to (a) determine the variance in Hounsfield Units (HU) for printed objects, (b) determine if HU varies over time, and (c) calculate the clinical dose uncertainty caused by these material variations.
Methods
For a sample of 10 printed blocks each of PLA, NinjaFlex, ABS, and Cheetah, the average HU and physical density were tracked at initial printing and over the course of 5 weeks, a typical timeframe for a standard course of radiotherapy. After initial printing, half the blocks were stored in open boxes, the other half in sealed bags with desiccant. Variances in HU and density over time were evaluated for the four materials. Various clinical photon and electron beams were used to evaluate potential errors in clinical depth dose as a function of assumptions made during treatment planning. The clinical depth error was defined as the distance between the correctly calculated 90% isodose line and the 90% isodose line calculated using clinically reasonable, but simplified, assumptions.
Results
The average HU measurements of individual blocks of PLA, ABS, NinjaFlex, and Cheetah varied by as much as 121, 30, 178, and 30 HU, respectively. The HU variation over 5 weeks was much smaller for all materials. The magnitude of clinical depth errors depended strongly on the material, energy, and assumptions, but some were as large as 9.0 mm.
Conclusions
If proper quality assurance steps are taken, 3D printed objects can be used accurately and effectively in radiation therapy. It is critically important, however, that the properties of any material being used in patient care be well understood and accounted for.
Three commercial metal artifact reduction methods were evaluated for use in computed tomography (CT) imaging in the presence of clinically realistic metal implants: Philips O-MAR, GE's monochromatic ...gemstone spectral imaging (GSI) using dual-energy CT, and GSI monochromatic imaging with metal artifact reduction software applied (MARs). Each method was evaluated according to CT number accuracy, metal size accuracy, and streak artifact severity reduction by using several phantoms, including three anthropomorphic phantoms containing metal implants (hip prosthesis, dental fillings and spinal fixation rods). All three methods showed varying degrees of success for the hip prosthesis and spinal fixation rod cases, while none were particularly beneficial for dental artifacts. Limitations of the methods were also observed. MARs underestimated the size of metal implants and introduced new artifacts in imaging planes beyond the metal implant when applied to dental artifacts, and both the O-MAR and MARs algorithms induced artifacts for spinal fixation rods in a thoracic phantom. Our findings suggest that all three artifact mitigation methods may benefit patients with metal implants, though they should be used with caution in certain scenarios.
Treatments for childhood cancer have evolved over the past 50 years, with the goal of maximising the proportion of patients who achieve long-term survival, while minimising the adverse effects of ...therapy. We aimed to assess incidence patterns of serious chronic health conditions in long-term survivors of childhood cancer across three decades of diagnosis and treatment.
We used data from the Childhood Cancer Survivor Study, a retrospective cohort with longitudinal follow-up of 5-year survivors of common childhood cancers (leukaemia, tumours of the CNS, Hodgkin lymphoma, non-Hodgkin lymphoma, Wilms tumour, neuroblastoma, soft tissue sarcoma, or bone tumours) who were diagnosed before the age of 21 years and from 1970 to 1999 in North America. We examined the cumulative incidence of severe to fatal chronic health conditions occurring up to 20 years post-diagnosis among survivors, compared by diagnosis decade. We used multivariable regression models to estimate hazard ratios per diagnosis decade, and we added treatment variables to assess whether treatment changes attenuated associations between diagnosis decade and chronic disease risk.
Among 23 601 survivors with a median follow-up of 21 years (IQR 15–25), the 20-year cumulative incidence of at least one grade 3–5 chronic condition decreased significantly from 33·2% (95% CI 32·0–34·3) in those diagnosed 1970–79 to 29·3% (28·4–30·2; p<0·0001) in 1980–89, and 27·5% (26·4–28·6; p=0·012 vs 1980–89) in 1990–99. By comparison, the 20-year cumulative incidence of at least one grade 3–5 condition in 5051 siblings was 4·6% (95% CI 3·9–5·2). The 15-year cumulative incidence of at least one grade 3–5 condition was lower for survivors diagnosed 1990–99 compared with those diagnosed 1970–79 for Hodgkin lymphoma (17·7% 95% CI 15·0–20·5 vs 26·4% 23·8–29·1; p<0·0001), non-Hodgkin lymphoma (16·9% 14·0–19·7 vs 23·8% 19·9–27·7; p=0.0053), astrocytoma (30·5% 27·8–33·2 vs 47·3% 42·9–51·7; p<0·0001), Wilms tumour (11·9% 9·5–14·3 vs 17·6% 14·3–20·8; p=0·034), soft tissue sarcoma (28·3% 23·5–33·1 vs 36·5% 31·5–41·4; p=0·021), and osteosarcoma (65·6% 60·6–70·6 vs 87·5% 84·1–91·0; p<0·0001). By contrast, the 15-year cumulative incidence of at least one grade 3–5 condition was higher (1990–99 vs 1970–79) for medulloblastoma or primitive neuroectodermal tumour (58·9% 54·4–63·3 vs 42·9% 34·9–50·9; p=0·00060), and neuroblastoma (25·0% 21·8–28·2 vs 18·0% 14·5–21·6; p=0·0045). Results were consistent with changes in treatment as a significant mediator of the association between diagnosis decade and risk of grade 3–5 chronic conditions for astrocytoma (HR per decade without treatment in the model = 0·77, 95% CI 0·64–0·92; HR with treatment in the model=0·89, 95% CI 0·72–1·11; pmediation=0·0085) and Hodgkin lymphoma (HR without treatment=0·75, 95% CI 0·65–0·85; HR with treatment=0·91, 95% CI 0·73–1·12; pmediation=0·024). Temporal decreases in 15-year cumulative incidence comparing survivors diagnosed 1970–79 to survivors diagnosed 1990–99 were noted for endocrinopathies (5·9% 5·3–6·4 vs 2·8% 2·5–3·2; p<0·0001), subsequent malignant neoplasms (2·7% 2·3–3·1 vs 1·9% 1·6–2·2; p=0·0033), musculoskeletal conditions (5·8% 5·2–6·4 vs 3·3% 2·9–3·6; p<0·0001), and gastrointestinal conditions (2·3% 2·0–2·7 vs 1·5% 1·3–1·8; p=0·00037), while hearing loss increased (3·0% 2·6–3·5 vs 5·7% 5·2–6·1; p<0·0001).
Our results suggest that more recently treated survivors of childhood cancer had improvements in health outcomes, consistent with efforts over the same time period to modify childhood cancer treatment regimens to maximise overall survival, while reducing risk of long-term adverse events. Continuing advances in cancer therapy offer promise of further reducing the risk of long-term adverse events in childhood cancer survivors. However, achieving long-term survival for childhood cancer continues to come at a cost for many survivors, emphasising the importance of long-term follow-up care for this population.
National Cancer Institute and the American Lebanese-Syrian Associated Charities.
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