On the feasibility of automatically selecting similar patients in highly individualized radiotherapy dose reconstruction for historic data of pediatric cancer survivors

Purpose: The aim of this study is to establish the first step toward a novel and highly individualized three-dimensional (3D) dose distribution reconstruction method, based on CT scans and organ delineations of recently treated patients. Specifically, the feasibility of automatically selecting the CT scan of a recently treated childhood cancer patient who is similar to a given historically treated child who suffered from Wilms' tumor is assessed.Methods: A cohort of 37 recently treated children between 2- and 6-yr old are considered. Five potential notions of ground-truth similarity are proposed, each focusing on different anatomical aspects. These notions are automatically computed from CT scans of the abdomen and 3D organ delineations (liver, spleen, spinal cord, external body contour). The first is based on deformable image registration, the second on the Dice similarity coefficient, the third on the Hausdorff distance, the fourth on pairwise organ distances, and the last is computed by means of the overlap volume histogram. The relationship between typically available features of historically treated patients and the proposed ground-truth notions of similarity is studied by adopting state-of-the-art machine learning techniques, including random forest. Also, the feasibility of automatically selecting the most similar patient is assessed by comparing ground-truth rankings of similarity with predicted rankings.Results: Similarities (mainly) based on the external abdomen shape and on the pairwise organ distances are highly correlated (Pearson rp ≥ 0.70) and are successfully modeled with random forests based on historically recorded features (pseudo-R2 ≥ 0.69). In contrast, similarities based on the shape of internal organs cannot be modeled. For the similarities that random forest can reliably model, an estimation of feature relevance indicates that abdominal diameters and weight are the most important. Experiments on automatically selecting similar patients lead to coarse, yet quite robust results: the most similar patient is retrieved only 22% of the times, however, the error in worst-case scenarios is limited, with the fourth most similar patient being retrieved.Conclusions: Results demonstrate that automatically selecting similar patients is feasible when focusing on the shape of the external abdomen and on the position of internal organs. Moreover, whereas the common practice in phantom-based dose reconstruction is to select a representative phantom using age, height, and weight as discriminant factors for any treatment scenario, our analysis on abdominal tumor treatment for children shows that the most relevant features are weight and the anterior-posterior and left-right abdominal diameters

Relating anatomical variations and patient features with dose-reconstruction accuracy of a 3D dose-reconstruction approach using CT scans of recently-treated children

Purpose Reconstructing 3D dose distributions for pre-1990 pediatric 2D radiotherapy plans is challenging, but key to research on late adverse effects. We studied the relation between dosimetric accuracy, anatomical variation, and other patient features of a 3D dose-reconstruction approach using CT scans of recently-treated patients, rather than phantoms. Materials and methods CT-scans of 22 Wilms’ tumor patients (age:2.5-5.3yrs; n boys/girls:11/11) treated between 2004 and 2015 were included. Two clinical plans as applied to a 4-year-old boy and girl with a left-sided Wilms’ tumor served as references. Each plan was applied to the CT scans of the other 21 patients, adjusted to correct for anatomical differences as visible in digitally-reconstructed-radiographs, and the resulting dose was calculated. Deviations in reconstructed dose, with respect to the reference dose, in organs-at-risk (spinal cord, right kidney, liver, and spleen) were characterized by the mean dose error normalized by the prescribed dose (DEmean). Deviations in organs’ location relative to a reference point (\Delta O_loc) and in organs’ shape captured by the Dice coefficient (DC) were calculated. We estimated the Pearson’s correlation between DEmean, on the one hand, and O­loc, DC, gender, age, height, and weight, on the other hand. Results Average(range) DEmean values were: spinal cord:3(0-8)%; right kidney:6(0-20)%; liver:9(0-20)%; and spleen:23(0-80)%. DC and DEmean in the right kidney were moderately negatively correlated (r2=0.41). DEmean in the liver was uncorrelated with any o

The ‘Survivorship Passport’ for childhood cancer survivors

Abstract Background: Currently, there are between 300,000 and 500,000 childhood cancer survivors (CCSs) in Europe. A significant proportion is at high risk, and at least 60% of them develop adverse health-related outcomes that can appear several years after treatment completion. Many survivors are unaware of their personal risk, and there seems to be a general lack of information among healthcare providers about pathophysiology and natural history of treatment-related complications. This can generate incorrect or delayed diagnosis and treatments

The 'Survivorship Passport' for childhood cancer survivors

Background: Currently, there are between 300,000 and 500,000 childhood cancer survivors (CCSs) in Europe. A significant proportion is at high risk, and at least 60% of them develop adverse health-related outcomes that can appear several years after treatment completion. Many survivors are unaware of their personal risk, and there seems to be a general lack of information among healthcare providers about pathophysiology and natural history of treatment-related complications. This can generate incorrect or delayed diagnosis and treatments. Method: The Survivorship Passport (SurPass) consists of electronic documents, which summarise the clinical history of the childhood or adolescent cancer survivor. It was developed by paediatric oncologists of the PanCare and SIOPE networks and IT experts of Cineca, together with parents, patients, and survivors' organisations within the European Union–funded European Network for Cancer research in Children and Adolescents. It consists of a template of a web-based, simply written document, translatable in all European languages, to be given to each CCS. The SurPass provides a summary of each survivor's clinical history, with detailed information about the original cancer and of treatments received, together with personalised follow-up and screening recommendations based on guidelines published by the International Guidelines Harmonization Group and PanCareSurFup. Results: The SurPass data schema contains a maximum of 168 variables and uses internationally approved nomenclature, except for radiotherapy fields, where a new classification was defined by radiotherapy experts. The survivor-specific screening recommendations are mainly based on treatment received and are automatically suggested, thanks to built-in algorithms. These may be adapted and further individualised by the treating physician in case of special disease and survivor circumstances. The SurPass was tested at the Istituto Giannina Gaslini, Italy, and received positive feedback. It is now being integrated at the institutional, regional and national level. Conclusions: The SurPass is potentially an essential tool for improved and more harmonised follow-up of CCS. It also has the potential to be a useful tool for empowering CCSs to be responsible for their own well-being and preventing adverse events whenever possible. With sufficient commitment on the European level, this solution should increase the capacity to respond more effectively to the needs of European CCS

Increased risk of cardiac ischaemia in a pan-European cohort of 36 205 childhood cancer survivors: a PanCareSurFup study.

OBJECTIVE In this report, we determine the cumulative incidence of symptomatic cardiac ischaemia and its risk factors among European 5-year childhood cancer survivors (CCS) participating in the PanCareSurFup study. METHODS Eight data providers (France, Hungary, Italy (two cohorts), the Netherlands, Slovenia, Switzerland and the UK) participating in PanCareSurFup ascertained and validated symptomatic cardiac events among their 36 205 eligible CCS. Data on symptomatic cardiac ischaemia were graded according to the Criteria for Adverse Events V.3.0 (grade 3-5). We calculated cumulative incidences, both overall and for different subgroups based on treatment and malignancy, and used multivariable Cox regression to analyse risk factors. RESULTS Overall, 302 out of the 36 205 CCS developed symptomatic cardiac ischaemia during follow-up (median follow-up time after primary cancer diagnosis: 23.0 years). The cumulative incidence by age 60 was 5.4% (95% CI 4.6% to 6.2%). Men (7.1% (95% CI 5.8 to 8.4)) had higher rates than women (3.4% (95% CI 2.4 to 4.4)) (p<0.0001). Of importance is that a significant number of patients (41/302) were affected as teens or young adults (14-30 years). Treatment with radiotherapy/chemotherapy conferred twofold risk (95% CI 1.5 to 3.0) and cases in these patients appeared earlier than in CCS without treatment/surgery only (15% vs 3% prior to age 30 years, respectively (p=0.04)). CONCLUSIONS In this very large European childhood cancer cohort, we found that by age 60 years, 1 in 18 CCS will develop a severe, life-threatening or fatal cardiac ischaemia, especially in lymphoma survivors and CCS treated with radiotherapy and chemotherapy increases the risk significantly