Radiotherapy toxicity De Ruysscher, Dirk; Niedermann, Gabriele; Burnet, Neil G ...
Nature reviews. Disease primers,
02/2019, Letnik:
5, Številka:
1
Journal Article
Recenzirano
Radiotherapy is used in >50% of patients with cancer, both for curative and palliative purposes. Radiotherapy uses ionizing radiation to target and kill tumour tissue, but normal tissue can also be ...damaged, leading to toxicity. Modern and precise radiotherapy techniques, such as intensity-modulated radiotherapy, may prevent toxicity, but some patients still experience adverse effects. The physiopathology of toxicity is dependent on many parameters, such as the location of irradiation or the functional status of organs at risk. Knowledge of the mechanisms leads to a more rational approach for controlling radiotherapy toxicity, which may result in improved symptom control and quality of life for patients. This improved quality of life is particularly important in paediatric patients, who may live for many years with the long-term effects of radiotherapy. Notably, signs and symptoms occurring after radiotherapy may not be due to the treatment but to an exacerbation of existing conditions or to the development of new diseases. Although differential diagnosis may be difficult, it has important consequences for patients.
For unbiased comparison of different radiation modalities and techniques, consensus on delineation of radiation sensitive organs at risk (OARs) and on their dose constraints is warranted. Following ...the publication of a digital, online atlas for OAR delineation in neuro-oncology by the same group, we assessed the brain OAR-dose constraints in a follow-up study.
We performed a comprehensive search to identify the current papers on OAR dose constraints for normofractionated photon and particle therapy in PubMed, Ovid Medline, Cochrane Library, Embase and Web of Science. Moreover, the included articles’ reference lists were cross-checked for potential studies that met the inclusion criteria. Consensus was reached among 20 radiation oncology experts in the field of neuro-oncology.
For the OARs published in the neuro-oncology literature, we summarized the available literature and recommended dose constraints associated with certain levels of normal tissue complication probability (NTCP) according to the recent ICRU recommendations. For those OARs with lacking or insufficient NTCP data, a proposal for effective and efficient data collection is given.
The use of the European Particle Therapy Network-consensus OAR dose constraints summarized in this article is recommended for the model-based approach comparing photon and proton beam irradiation as well as for prospective clinical trials including novel radiation techniques and/or modalities.
There are few randomized controlled trial data to confirm that improved homogeneity with simple intensity-modulated radiotherapy (IMRT) decreases late breast tissue toxicity. The Cambridge Breast ...IMRT trial investigated this hypothesis, and the 5-year results are reported.
Standard tangential plans of 1,145 trial patients were analyzed; 815 patients had inhomogeneous plans (≥ 2 cm(3) receiving 107% of prescribed dose: 40 Gy in 15 fractions over 3 weeks) and were randomly assigned to standard radiotherapy (RT) or replanned with simple IMRT; 330 patients with satisfactory dose homogeneity were treated with standard RT and underwent the same follow-up as the randomly assigned patients. Breast tissue toxicities were assessed at 5 years using validated methods: photographic assessment (overall cosmesis and breast shrinkage compared with baseline pre-RT photographs) and clinical assessment (telangiectasia, induration, edema, and pigmentation). Comparisons between different groups were analyzed using polychotomous logistic regression.
On univariate analysis, compared with standard RT, fewer patients in the simple IMRT group developed suboptimal overall cosmesis (odds ratio OR, 0.68; 95% CI, 0.48 to 0.96; P = .027) and skin telangiectasia (OR, 0.58; 95% CI, 0.36 to 0.92; P = .021). No evidence of difference was seen for breast shrinkage, breast edema, tumor bed induration, or pigmentation. The benefit of IMRT was maintained on multivariate analysis for both overall cosmesis (P = .038) and skin telangiectasia (P = .031).
Improved dose homogeneity with simple IMRT translates into superior overall cosmesis and reduces the risk of skin telangiectasia. These results are practice changing and should encourage centers still using two-dimensional RT to implement simple breast IMRT.
A key challenge in radiotherapy is to maximize radiation doses to cancer cells while minimizing damage to surrounding healthy tissue. As severe toxicity in a minority of patients limits the doses ...that can be safely given to the majority, there is interest in developing a test to measure an individual's radiosensitivity before treatment. Variation in sensitivity to radiation is an inherited genetic trait and recent progress in genotyping raises the possibility of genome-wide studies to characterize genetic profiles that predict patient response to radiotherapy.
•In total, more than 4000 adult patients are currently treated with PT across Europe annually.•CNS and HNC tumours are the most frequently treated tumour sites.•Most centres use national or ...institutional guidelines for selecting patients for PT.•Treatments are usually reimbursed by national health care systems.•Most patients are included in prospective data registries and clinical trials.
Major differences exist among proton therapy (PT) centres regarding PT delivery in adult cancer patient. To obtain insight into current practice in Europe, we performed a survey among European PT centres.
We designed electronic questionnaires for eight tumour sites, focusing on four main topics: 1) indications and patient selection methods; 2) reimbursement; 3) on-going or planned studies, 4) annual number of patients treated with PT.
Of 22 centres, 19 (86%) responded. In total, 4233 adult patients are currently treated across Europe annually, of which 46% consists of patients with central nervous system tumours (CNS), 15% head and neck cancer (HNC), 15% prostate, 9% breast, 5% lung, 5% gastrointestinal, 4% lymphoma, 0.3% gynaecological cancers. CNS are treated in all participating centres (n = 19) using PT, HNC in 16 centres, lymphoma in 10 centres, gastrointestinal in 10 centres, breast in 7 centres, prostate in 6 centres, lung in 6 centres, and gynaecological cancers in 3 centres. Reimbursement is provided by national health care systems for the majority of commonly treated tumour sites. Approximately 74% of centres enrol patients for prospective data registration programs. Phase II-III trials are less frequent, due to reimbursement and funding problems. Reasons for not treating certain tumour types with PT are lack of evidence (30%), reimbursement issues (29%) and/or technical limitations (20%).
Across European PT centres, CNS tumours and HNC are the most frequently treated tumour types. Most centres use indication protocols. Lack of evidence for PT and reimbursement issues are the most reported reasons for not treating specific tumour types with PT.
To create a digital, online atlas for organs at risk (OAR) delineation in neuro-oncology based on high-quality computed tomography (CT) and magnetic resonance (MR) imaging.
CT and 3 Tesla (3T) MR ...images (slice thickness 1 mm with intravenous contrast agent) were obtained from the same patient and subsequently fused. In addition, a 7T MR without intravenous contrast agent was obtained from a healthy volunteer. Based on discussion between experienced radiation oncologists, the clinically relevant organs at risk (OARs) to be included in the atlas for neuro-oncology were determined, excluding typical head and neck OARs previously published. The draft atlas was delineated by a senior radiation oncologist, 2 residents in radiation oncology, and a senior neuro-radiologist incorporating relevant available literature. The proposed atlas was then critically reviewed and discussed by European radiation oncologists until consensus was reached.
The online atlas includes one CT-scan at two different window settings and one MR scan (3T) showing the OARs in axial, coronal and sagittal view. This manuscript presents the three-dimensional descriptions of the fifteen consensus OARs for neuro-oncology. Among these is a new OAR relevant for neuro-cognition, the posterior cerebellum (illustrated on 7T MR images).
In order to decrease inter- and intra-observer variability in delineating OARs relevant for neuro-oncology and thus derive consistent dosimetric data, we propose this atlas to be used in photon and particle therapy. The atlas is available online at www.cancerdata.org and will be updated whenever required.
We report our experience of functional imaging with (11)C-methionine positron emission tomography-computed tomography (PET-CT) co-registered with 3D gradient echo (spoiled gradient recalled (SPGR)) ...magnetic resonance imaging (MRI) in the investigation of ACTH-dependent Cushing's syndrome.
Twenty patients with i) de novo Cushing's disease (CD, n=10), ii) residual or recurrent hypercortisolism following first pituitary surgery (±radiotherapy; n=8) or iii) ectopic Cushing's syndrome (n=2) were referred to our centre for functional imaging studies between 2010 and 2015. Six of the patients with de novo CD and five of those with persistent/relapsed disease had a suspected abnormality on conventional MRI.
All patients underwent (11)C-methionine PET-CT. For pituitary imaging, co-registration of PET-CT images with contemporaneous SPGR MRI (1 mm slice thickness) was performed, followed by detailed mapping of (11)C-methionine uptake across the sella in three planes (coronal, sagittal and axial). This allowed us to determine whether suspected adenomas seen on structural imaging exhibited focal tracer uptake on functional imaging.
In seven of ten patients with de novo CD, asymmetric (11)C-methionine uptake was observed within the sella, which co-localized with the suspected site of a corticotroph microadenoma visualised on SPGR MRI (and which was subsequently confirmed histologically following successful transsphenoidal surgery (TSS)). Focal (11)C-methionine uptake that correlated with a suspected abnormality on pituitary MRI was seen in five of eight patients with residual or recurrent Cushing's syndrome following first TSS (and pituitary radiotherapy in two cases). Two patients elected to undergo repeat TSS with histology confirming a corticotroph tumour in each case. In two patients with the ectopic ACTH syndrome, (11)C-methionine was concentrated in sites of distant metastases, with minimal uptake in the sellar region.
(11)C-methionine PET-CT can aid the detection of ACTH-secreting tumours in Cushing's syndrome and facilitate targeted therapy.
There is increasing evidence supporting the role of genetic variants in the development of radiation-induced toxicity. However, previous candidate gene association studies failed to elucidate the ...common genetic variation underlying this phenotype, which could emerge years after the completion of treatment. We performed a genome-wide association study on a Spanish cohort of 741 individuals with prostate cancer treated with external beam radiotherapy (EBRT). The replication cohorts consisted of 633 cases from the UK and 368 cases from North America. One locus comprising TANC1 (lowest unadjusted P value for overall late toxicity=6.85×10(-9), odds ratio (OR)=6.61, 95% confidence interval (CI)=2.23-19.63) was replicated in the second stage (lowest unadjusted P value for overall late toxicity=2.08×10(-4), OR=6.17, 95% CI=2.25-16.95; Pcombined=4.16×10(-10)). The inclusion of the third cohort gave unadjusted Pcombined=4.64×10(-11). These results, together with the role of TANC1 in regenerating damaged muscle, suggest that the TANC1 locus influences the development of late radiation-induced damage.
•Introduction to issue with variable RBE in proton therapy.•Overview of the pre-clinical data of variable RBE.•Evaluation of published clinical studies and data sets.•Examples on how clinical centers ...are currently dealing with the uncertainty of a variable RBE.•Discussion on whether variable RBE has a possible clinical impact.•Suggestions for future strategies in both pre-clinical and clinical RBE research.
Clinical treatment with protons uses the concept of relative biological effectiveness (RBE) to convert the absorbed dose into an RBE-weighted dose that equals the dose for radiotherapy with photons causing the same biological effect. Currently, in proton therapy a constant RBE of 1.1 is generically used. However, empirical data indicate that the RBE is not constant, but increases at the distal edge of the proton beam. This increase in RBE is of concern, as the clinical impact is still unresolved, and clinical studies demonstrating a clinical effect of an increased RBE are emerging.
Within the European Particle Therapy Network (EPTN) work package 6 on radiobiology and RBE, a workshop was held in February 2020 in Manchester with one day of discussion dedicated to the impact of proton RBE in a clinical context. Current data on RBE effects, patient outcome and modelling from experimental as well as clinical studies were presented and discussed. Furthermore, representatives from European clinical proton therapy centres, who were involved in patient treatment, laid out their current clinical practice on how to consider the risk of a variable RBE in their centres. In line with the workshop, this work considers the actual impact of RBE issues on patient care in proton therapy by reviewing preclinical data on the relation between linear energy transfer (LET) and RBE, current clinical data sets on RBE effects in patients, and applied clinical strategies to manage RBE uncertainties. A better understanding of the variability in RBE would allow development of proton treatments which are safer and more effective.
Radiotherapy, surgery and chemotherapy play key roles in the curative treatment of cancer, alone and in combination. Quantifying their roles is essential for equipment provision and workforce ...planning. The estimate that 40% of cancer patients are cured by RT has been used extensively to inform and influence policy but is relatively old and warrants review.
Patient, tumour and treatment event data was obtained for the 5 year period from 2009 to 2013, allowing a further 5 years for survival outcomes to be known. We analysed patient-level data on utilisation of surgery, radiotherapy, and chemotherapy in cancer patients in England. Data were sourced from Public Health England, using National Cancer Registrations, the National Radiotherapy Dataset (RTDS) and the Systemic Anti-Cancer Therapy Dataset (SACT). All tumour sites (excluding C44) and ages were included. We analysed three cohorts: all patients
= 1,029,569, patients who survived 5 years or more
= 537,970 and patients who survived <5 years
= 491,599.
Overall cancer-specific 5-year survival was 52%, and in those patients, surgery was the most common curative treatment, with 80% receiving surgery, alone or in combination; radiotherapy was delivered to 39% and chemotherapy to 29%; 45% received two and 13% all three modalities.
The high proportion receiving multi-modality treatment emphasises the importance of integrated, resourced, multidisciplinary cancer care. Radiotherapy was delivered to almost 40% of patients who survived 5 years which underlines its importance in cancer management.
The results are essential in planning cancer services. They also inform the public health narrative.
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