ABSTRACT
PURPOSE: Splenectomy might be a risk factor for valvular heart disease (VHD) in adult Hodgkin lymphoma survivors. As this risk is still unclear for childhood cancer survivors (CCS), the aim of this study is to evaluate the association between treatments affecting splenic function (splenectomy and radiotherapy involving the spleen) and VHD in CCS. METHODS: CCS were enrolled from the DCCSS-LATER cohort, consisting of 6,165 five-year CCS diagnosed between 1963 and 2002. Symptomatic VHD, defined as symptoms combined with a diagnostic test indicating VHD, was assessed from questionnaires and validated using medical records. Differences in the cumulative incidence of VHD between CCS who received treatments affecting splenic function and CCS who did not were assessed using the Gray test. Risk factors were analyzed in a multivariable Cox proportional hazards model. RESULTS: The study population consisted of 5,286 CCS, with a median follow-up of 22 years (5-50 years), of whom 59 (1.1%) had a splenectomy and 489 (9.2%) radiotherapy involving the spleen. VHD was present in 21 CCS (0.4%). The cumulative incidence of VHD at the age of 40 years was significantly higher in CCS who received treatments affecting splenic function (2.7%, 95% confidence interval (CI) 0.4%-4.9%) compared with CCS without (0.4%, 95% CI 0.1%-0.7%) (Gray's test, p = 0.003). Splenectomy was significantly associated with VHD in a multivariable analysis (hazard ratio 8.6, 95% CI 3.1-24.1). CONCLUSIONS AND IMPLICATIONS: Splenectomy was associated with VHD. Future research is needed to determine if CCS who had a splenectomy as part of cancer treatment might benefit from screening for VHD.
ABSTRACT
INTRODUCTION: Surface guided radiotherapy (SGRT) is increasingly being implemented to track patient's surface movement and position during radiation therapy. However, limited information is available on the SGRT use in paediatrics. The aim of this double survey was to map SIOPE (European Society for Paediatric Oncology)-affiliated centres using SGRT and to gain information on potential indications, observed, or expected benefits. METHODS: A double online survey was distributed to 246 SIOPE-affiliated radiotherapy (RT) centres. Multiple choices, yes/no, and open answers were included. The first survey (41 questions) was active from February to March 2021. A shortened version (13 questions) was repeated in March 2023 to detect trends in SGRT use within the same community. RESULTS: Respectively, 76/142 (54%) and 28/142 (20%) responding centres used and planned to use SGRT clinically, including 4/34 (12%) new centres since 2021. Among the SGRT users, 33/76 (43%) already applied this technology to paediatric treatments. The main benefits of improved patient comfort, better monitoring of intrafraction motion, and more accurate initial patient set-up expected by future users did not differ from current SGRT-users (P = .893). Among non-SGRT users, the main hurdles to implement SGRT were costs and time for installation. In paediatrics, SGRT is applied to all anatomical sites. CONCLUSION: This work provides information on the practice of SGRT in paediatrics across SIOPE-affiliated RT centres which can serve as a basis for departments when considering the purchase of SGRT systems. ADVANCES IN KNOWLEDGE: Since little information is available in the literature on the use of SGRT in paediatrics, the results of this double survey can serve as a basis for departments treating children when considering the purchase of an SGRT system.
Subject(s)
Neoplasms , Radiation Oncology , Humans , Child , Neoplasms/radiotherapy , Radiotherapy, Image-Guided/methods , Surveys and Questionnaires , Pediatrics , Europe , Patient Positioning , Practice Patterns, Physicians'/statistics & numerical dataABSTRACT
BACKGROUND: Implementation of daily cone-beam CT (CBCT) into clinical practice in paediatric image-guided radiotherapy (IGRT) lags behind compared to adults. Surveys report wide variation in practice for paediatric IGRT and technical information remains unreported. In this study we report on technical settings from applied paediatric CBCT protocols and review the literature for paediatric CBCT protocols. METHODS: From September to October 2022, a survey was conducted among 246 SIOPE-affiliated centres across 35 countries. The survey consisted of 3 parts: 1) baseline information; technical CBCT exposure settings and patient set-up procedure for 2) brain/head, and 3) abdomen. Descriptive statistics was used to summarise current practice. The literature was reviewed systematically with two reviewers obtaining consensus RESULTS: The literature search revealed 22 papers concerning paediatric CBCT protocols. Seven papers focused on dose-optimisation. Responses from 50/246 centres in 25/35 countries were collected: 44/50 treated with photons and 10/50 with protons. In total, 48 brain/head and 53 abdominal protocols were reported. 42/50 centres used kV-CBCT for brain/head and 35/50 for abdomen; daily CBCT was used for brain/head = 28/48 (58%) and abdomen = 33/53 62%. Greater consistency was seen in brain/head protocols (dose range 0.32 - 67.7 mGy) compared to abdominal (dose range 0.27 - 119.7 mGy). CONCLUSION: Although daily CBCT is now widely used in paediatric IGRT, our survey demonstrates a wide range of technical settings, suggesting an unmet need to optimise paediatric IGRT protocols. This is in accordance with the literature. However, there are only few paediatric optimisation studies suggesting that dose reduction is possible while maintaining image quality.
Subject(s)
Radiotherapy, Image-Guided , Spiral Cone-Beam Computed Tomography , Adult , Humans , Child , Radiotherapy, Image-Guided/methods , Radiotherapy Planning, Computer-Assisted/methods , Abdomen , Cone-Beam Computed Tomography/methods , Europe , Phantoms, Imaging , Radiotherapy Dosage , Review Literature as TopicABSTRACT
BACKGROUND/PURPOSE: To reduce inequalities among SIOPE-affiliated countries, standard and optional levels to deliver 'Good Clinical Practice' compliant treatment in pediatric radiation oncology have been published. The aim of this project was to map the availability of pediatric radiotherapy resources across SIOPE-affiliated radiotherapy departments. MATERIALS/METHODS: An online survey with 34 questions was distributed to 246 radiotherapy departments across 35 SIOPE-affiliated countries. In addition to demographic data, 15 general items related to the organization of the radiotherapy process, and 10 radiotherapy-specific items were defined. For each of the 25 items, sum scores were calculated per center and country. Mann-Whitney U tests were used to analyze associations. RESULTS: Between March-June 2019, 121 departments (49 %) out of 31 countries (89 %) completed the survey. At center level, involvement of core disciplines in tumor boards (28 %), and integration of dedicated pediatric radiation therapy technologists (24 %) are limited, while rare & complex brachytherapy procedures are performed in many centers (23 %). For general and radiotherapy-specific items respectively, a relevant variation of sum scores was observed across countries (Δgeneral: ≤10 points; ΔRT_specific: ≤5 points) and among centers within a country (Δgeneral: ≤9 points; ΔRT_specific: ≤6 points). Sum scores for general and radiotherapy-specific items were higher in countries with a high-income (p < 0.01) and higher health development index (p < 0.01). A larger annual number of irradiated pediatric patients was associated with higher sum scores for general items (p < 0.01). CONCLUSION: This survey demonstrates the disparities in organization of pediatric radiotherapy departments between SIOPE-affiliated countries and centers within the same country. Investment is needed to reduce inequalities in pediatric radiotherapy care.
Subject(s)
Brachytherapy , Neoplasms , Radiation Oncology , Child , Humans , Neoplasms/radiotherapy , Surveys and Questionnaires , EuropeABSTRACT
Background: Childhood cancer survivors (CCS) who received radiotherapy involving the spleen or total body irradiation (TBI) might be at risk for splenic dysfunction. A comprehensive screening test for examining splenic dysfunction is lacking. Objective: We investigated whether IgM memory B-cells could be used to assess splenic dysfunction in CCS who received a splenectomy, radiotherapy involving the spleen, or TBI. Methods: All CCS were enrolled from the DCCSS-LATER cohort. We analyzed differences in IgM memory B-cells and Howell-Jolly bodies (HJB) in CCS who had a splenectomy (n = 9), received radiotherapy involving the spleen (n = 36), or TBI (n = 15). IgM memory B-cells < 9 cells/µL was defined as abnormal. Results: We observed a higher median number of IgM memory B-cells in CCS who received radiotherapy involving the spleen (31 cells/µL, p=0.06) or TBI (55 cells/µL, p = 0.03) compared to CCS who received splenectomy (20 cells/µL). However, only two CCS had IgM memory B-cells below the lower limit of normal. No difference in IgM memory B-cells was observed between CCS with HJB present and absent (35 cells/µL vs. 44 cells/µL). Conclusion: Although the number of IgM memory B-cells differed between splenectomized CCS and CCS who received radiotherapy involving the spleen or TBI, only two CCS showed abnormal values. Therefore, this assessment cannot be used to screen for splenic dysfunction.
Subject(s)
Cancer Survivors , Neoplasms , Humans , Child , Spleen , Splenectomy/adverse effects , Immunoglobulin MABSTRACT
Background and purpose: Children receiving radiotherapy for head-and-neck tumours often experience severe dentofacial side effects. Despite this, recommendations for contouring and dose constraints to dentofacial structures are lacking in clinical practice. We report on a survey aiming to understand current practice in contouring and dose assessment to dentofacial structures. Methods: A digital survey was distributed to European Society for Paediatric Oncology members of the Radiation Oncology Working Group, and member-affiliated centres in Europe, Australia, and New Zealand. The questions focused on clinical practice and aimed to establish areas for future development. Results: Results from 52 paediatric radiotherapy centres across 27 countries are reported. Only 29/52 centres routinely delineated some dentofacial structures, with the most common being the mandible (25 centres), temporo-mandibular joint (22), dentition (13), orbit (10) and maxillary bone (eight). For most bones contoured, an 'As Low As Reasonably Achievable' dose objective was implemented. Only four centres reported age-adapted dose constraints.The largest barrier to clinical implementation of dose constraints was firstly, the lack of contouring guidance (49/52, 94%) and secondly, that delineation is time-consuming (33/52, 63%). Most respondents who routinely contour dentofacial structures (25/27, 90%) agreed a contouring atlas would aid delineation. Conclusion: Routine delineation of dentofacial structures is infrequent in paediatric radiotherapy. Based on survey findings, we aim to 1) define a consensus-contouring atlas for dentofacial structures, 2) develop auto-contouring solutions for dentofacial structures to aid clinical implementation, and 3) carry out treatment planning studies to investigate the importance of delineation of these structures for planning optimisation.
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Karyomegalic interstitial nephropathy (KIN) has been reported as an incidental finding in patients with childhood cancer treated with ifosfamide. It is defined by the presence of tubular epithelial cells (TECs) with enlarged, irregular, and hyperchromatic nuclei. Cellular senescence has been proposed to be involved in kidney fibrosis in hereditary KIN patients. We report that KIN could be diagnosed 7-32 months after childhood cancer diagnosis in 6/6 consecutive patients biopsied for progressive chronic kidney disease (CKD) of unknown cause between 2018 and 2021. The morphometry of nuclear size distribution and markers for DNA damage (γH2AX), cell-cycle arrest (p21+, Ki67-), and nuclear lamina decay (loss of lamin B1), identified karyomegaly and senescence features in TECs. Polyploidy was assessed by chromosome fluorescence in situ hybridization (FISH). In all six patients the number of p21-positive TECs far exceeded the typically small numbers of truly karyomegalic cells, and p21-positive TECs contained less lysozyme, testifying to defective resorption, which explains the consistently observed low-molecular-weight (LMW) proteinuria. In addition, polyploidy of TEC was observed to correlate with loss of lysozyme staining. Importantly, in the five patients with the largest nuclei, the percentage of p21-positive TECs tightly correlated with estimated glomerular filtration rate loss between biopsy and last follow-up (R2 = 0.93, p < 0.01). We conclude that cellular senescence is associated with tubular dysfunction and predicts CKD progression in childhood cancer patients with KIN and appears to be a prevalent cause of otherwise unexplained CKD and LMW proteinuria in children treated with DNA-damaging and cell stress-inducing therapy including ifosfamide. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Subject(s)
Neoplasms , Nephritis, Interstitial , Renal Insufficiency, Chronic , Humans , Child , Nephritis, Interstitial/genetics , Muramidase/genetics , Ifosfamide , In Situ Hybridization, Fluorescence , Neoplasms/pathology , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/genetics , Renal Insufficiency, Chronic/complications , Proteinuria/pathology , Kidney/pathology , Biopsy , Cellular Senescence , PolyploidyABSTRACT
BACKGROUND: Overweight and obesity are common challenges among childhood cancer survivors. Overweight may be disguised, as survivors can have normal weight but high fat percentage (fat%) on dual-energy X-ray absorptiometry (DXA). We aimed to assess prevalence, identify determinants and biomarkers, and assess which method captures overweight best, in a nationwide cohort. METHODS: The prevalence of overweight and obesity, primarily defined by body mass index (BMI), was assessed in the DCCSS-LATER cohort of adult survivors treated from 1963-2002, with the LifeLines cohort as reference. The associations between risk factors and overweight metrics were investigated using logistic regression. Additional overweight metrics included DXA fat%, waist circumference (WC), waist/hip ratio (WHR), waist/height ratio (WHtR), and high-molecular-weight (HMW) adiponectin. RESULTS: A total of 2338 (mean age 35.5 years, follow-up 28.3 years) survivors participated. The overweight prevalence was 46.3% in men and 44.3% in women (obesity 11.2% and 15.9%, morbid obesity 2.4% and 5.4%), with highest rates among brain tumor survivors. Compared to controls, there was no overall increased overweight rate, but this was higher in women > 50 years, morbid obesity in men > 50 years. Overweight at cancer diagnosis (adjusted odds ratio [aOR] = 3.83, 95% CI 2.19-6.69), cranial radiotherapy (aOR = 3.21, 95% CI 1.99-5.18), and growth hormone deficiency (separate model, aOR = 1.61, 95% CI 1.00-2.59) were associated with overweight. Using BMI, WC, WHR, and WHtR, overweight prevalence was similar. Low HMW adiponectin, present in only 4.5% of survivors, was an insensitive overweight marker. Dual-energy X-ray absorptiometry-based classification identified overweight in an additional 30%, particularly after abdominal radiotherapy, total body irradiation, anthracyclines, and platinum. CONCLUSIONS: Overweight occurs in almost half of long-term survivors. There was no overall increased incidence of overweight compared to controls. We identified factors associated with overweight, as well as subgroups of survivors in whom DXA can more reliably assess overweight.
Subject(s)
Brain Neoplasms , Cancer Survivors , Obesity, Morbid , Male , Adult , Humans , Child , Female , Obesity, Morbid/complications , Obesity, Morbid/epidemiology , Prevalence , Adiponectin , Overweight/epidemiology , Risk Factors , Waist Circumference , Body Mass Index , SurvivorsABSTRACT
BACKGROUND: In pediatric radiotherapy treatment planning of abdominal tumors, dose constraints to the pancreatic tail/spleen are applied to reduce late toxicity. In this study, an analysis of inter- and intrafraction motion of the pancreatic tail/spleen is performed to estimate the potential benefits of online MRI-guided radiotherapy (MRgRT). MATERIALS AND METHODS: Ten randomly selected neuroblastoma patients (median age: 3.4 years), irradiated with intensity-modulated arc therapy at our department (prescription dose: 21.6/1.8 Gy), were retrospectively evaluated for inter- and intrafraction motion of the pancreatic tail/spleen. Three follow-up MRIs (T2- and T1-weighted ± gadolinium) were rigidly registered to a planning CT (pCT), on the vertebrae around the target volume. The pancreatic tail/spleen were delineated on all MRIs and pCT. Interfraction motion was defined as a center of gravity change between pCT and T2-weighted images in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) direction. For intrafraction motion analysis, organ position on T1-weighted ± gadolinium was compared to T2-weighted. The clinical radiation plan was used to estimate the dose received by the pancreatic tail/spleen for each position. RESULTS: The median (IQR) interfraction motion was minimal in LR/AP, and largest in CC direction; pancreatic tail 2.5 mm (8.9), and spleen 0.9 mm (3.9). Intrafraction motion was smaller, but showed a similar motion pattern (pancreatic tail, CC: 0.4 mm (1.6); spleen, CC: 0.9 mm (2.8)). The differences of Dmean associated with inter- and intrafraction motions ranged from - 3.5 to 5.8 Gy for the pancreatic tail and - 1.2 to 3.0 Gy for the spleen. In 6 out of 10 patients, movements of the pancreatic tail and spleen were highlighted as potentially clinically significant because of ≥ 1 Gy dose constraint violation. CONCLUSION: Inter- and intrafraction organ motion results into unexpected constrain violations in 60% of a randomly selected neuroblastoma cohort, supporting further prospective exploration of MRgRT.
Subject(s)
Neuroblastoma , Radiotherapy, Intensity-Modulated , Humans , Child , Child, Preschool , Spleen/diagnostic imaging , Retrospective Studies , Gadolinium , Movement , Radiotherapy, Intensity-Modulated/methods , Magnetic Resonance Imaging , Neuroblastoma/diagnostic imaging , Neuroblastoma/radiotherapy , Radiotherapy Planning, Computer-Assisted/methodsABSTRACT
OBJECTIVE: Nephrotoxicity can occur as a side effect after treatment for kidney tumor in childhood. The use of radiotherapy (RT) has a potential additional effect. METHODS: A systematic electronic literature search that combined childhood kidney cancer with different treatments and nephrotoxicity terms was performed in EMBASE. Studies were included based on the reporting of nephrotoxicity occurrence after treatment for kidney tumor during pediatric age, with 75% of participants being under the age of 25 years at the time of diagnosis, and having been treated with any type of kidney surgery, chemotherapy, and/or RT. RESULTS: A pooled analysis did not show significant difference in estimated glomerular filtration rate between the group of patients who received RT compared with the group treated without RT (SMD -0.11 [95% CI -1.07-0.84] p = .733). CONCLUSION: The current literature suggests that the use of RT does not have a significant impact on the decline of kidney function as independent factor.
Subject(s)
Kidney Neoplasms , Kidney , Humans , Child , Adult , Kidney Neoplasms/therapy , Survivors , Glomerular Filtration RateABSTRACT
BACKGROUND: For accurate thoracic and abdominal radiotherapy, inter- and intrafractional geometrical uncertainties need to be considered to enable accurate margin sizes. We aim to quantify interfractional diaphragm and abdominal organ position variations, and intrafractional diaphragm motion in a large multicenter cohort of pediatric cancer patients (< 18 years). We investigated the correlation of interfractional position variations and intrafractional motion with age, and with general anesthesia (GA). METHODS: In 189 children (mean age 8.1; range 0.4-17.9 years) from six institutes, interfractional position variation of both hemidiaphragms, spleen, liver, left and right kidneys was quantified using a two-step registration. CBCTs were registered to the reference CT relative to the bony anatomy, followed by organ registration. We calculated the group mean, systematic and random errors (standard deviations Σ and σ, respectively) in cranial-caudal (CC), left-right and anterior-posterior directions. Intrafractional right hemidiaphragm motion was quantified using CBCTs on which the breathing amplitude, defined as the difference between end-inspiration and end-expiration peaks, was assessed (N = 79). We investigated correlations with age (Spearman's ρ), and differences in motion between patients treated with and without GA (N = 75; all < 5.5 years). RESULTS: Interfractional group means were largest in CC direction and varied widely between patients, with largest variations in the right hemidiaphragm (range -13.0-17.5 mm). Interfractional group mean of the left kidney showed a borderline significant correlation with age (p = 0.047; ρ = 0.17). Intrafractional right hemidiaphragm motion in patients ≥ 5.5 years (mean 10.3 mm) was significantly larger compared to patients < 5.5 years treated without GA (mean 8.3 mm) (p = 0.02), with smaller Σ and σ values. We found a significant correlation between breathing amplitude and age (p < 0.001; ρ = 0.43). Interfractional right hemidiaphragm position variations were significantly smaller in patients < 5.5 years treated with GA than without GA (p = 0.004), but intrafractional motion showed no significant difference. CONCLUSION: In this large multicenter cohort of children undergoing thoracic and abdominal radiotherapy, we found that interfractional position variation does not depend on age, but the use of GA in patients < 5.5 years showed smaller systematic and random errors. Furthermore, our results showed that breathing amplitude increases with age. Moreover, variations between patients advocate the need for a patient-specific margin approach.
Subject(s)
Diaphragm , Neoplasms , Humans , Child , Child, Preschool , Organ Motion , Radiotherapy Planning, Computer-Assisted/methods , Abdomen , Neoplasms/radiotherapy , MotionABSTRACT
BACKGROUND: Childhood craniopharyngioma (cCP) has excellent survival, but quality of life may be severely hampered by hypothalamic dysfunction. We aimed to evaluate treatment and hypothalamic outcomes of a Dutch cCP cohort, and evaluate the effect of centralization of care. METHODS: A retrospective cohort study was performed, including cCP patients diagnosed between 2004 and 2021. Treatment characteristics and hypothalamic outcomes were evaluated and compared before and since centralization of care in May 2018. RESULTS: We included 87 cCP patients. Cyst drainage/fenestration was performed in 29.9%, limited resection in 27.6%, near-total resection in 16.1%, and gross total resection (GTR) in 25.4%. Radiotherapy was given in 46.0%. After a median follow-up of 6.5 years, hypothalamic obesity (HO) was present in 24.7% and panhypopituitarism with diabetes insipidus in 71.3%. Higher body mass index (BMI) SDS at diagnosis and Muller grade II at last magnetic resonance imaging of follow-up were associated with overweight/obesity. No association was found between extensiveness of resection and overweight/obesity at last follow-up. When comparing before and after centralization of care, rates of GTR remained similar, but BMI outcomes changed; mean ΔBMI SDS 1 year after diagnosis from 1.12 (SD 1.15) to 0.81 (SD 1.24), and HO after 1 year decreased from 33.3% to 12.0% (P = .067), and after 2 years from 28.6% to 6.7% (P = NS). CONCLUSIONS: In our nationwide cohort, GTR was performed in a relatively low percentage of patients and extensiveness of resection was no longer associated with HO at follow-up. A trend toward improvement of BMI is observed since centralization of care, which needs further exploration.
Subject(s)
Craniopharyngioma , Pituitary Neoplasms , Humans , Child , Craniopharyngioma/therapy , Craniopharyngioma/pathology , Cohort Studies , Retrospective Studies , Overweight/complications , Quality of Life , Pituitary Neoplasms/pathology , Obesity/complications , Treatment OutcomeABSTRACT
PURPOSE: Numerous studies investigated generic psychosocial outcomes in survivors of childhood cancer (CCS). The present study aimed to describe survivor-specific psychosocial consequences in CCS, and to identify socio-demographic and medical associated factors. METHODS: CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed 1963-2001) part 2 (age ≥ 18 years, diagnosed < 18 years, ≥ 5 years since diagnosis) completed the Benefit & Burden Scale (BBSC) and the Impact of Cancer-Childhood Cancer (IOC-CS). Items were scored on a 5-point Likert scale (range 1-5). We examined outcomes with descriptive statistics, and socio-demographic and medical associated factors with regression analyses, corrected for multiple testing (p < 0.004). RESULTS: CCS, N = 1713, age mean (M) 36 years, 49% female, ≥ 15 years since diagnosis, participated. On average, CCS reported 'somewhat' Benefit (M = 2.9), and 'not at all' to 'a little' Burden (M = 1.5) of childhood cancer. Average scores on IOC-CS' positive impact scales ranged from 2.5 (Personal Growth) to 4.1 (Socializing), and on the negative impact scales from 1.4 (Financial Problems) to 2.4 (Thinking/Memory). Apart from cognitive problems, CCS reported challenges as worries about relationship status, fertility, and how cancer had affected siblings. Female sex was associated with more Personal Growth, and more negative impact. CCS more highly educated, partnered, and employed had higher positive and lower negative impact. CCS older at diagnosis reported more positive impact. CNS tumor survivors and those who had head/cranium radiotherapy had higher negative impact. CNS tumor survivors reported less positive impact. CONCLUSION AND IMPLICATIONS: The majority of CCS reported positive impact of cancer while most CCS reported little negative impact. While this may indicate resiliency in most CCS, health care providers should be aware that they can also experience survivor-specific challenges that warrant monitoring/screening, information provision and psychosocial support.
ABSTRACT
Growth hormone deficiency (GHD) is a common complication in survivors of cancer and patients with tumors of the pituitary region. Growth hormone replacement therapy (GHT) has proven beneficial effects, including increased growth velocity, positive effects on body composition and skeletal integrity, and increased quality of life. However, due to known pro-proliferative, angiogenic, and anti-apoptotic properties of growth hormone, there are still some concerns about the safety of GHT in survivors. This narrative review aims to provide an overview of the long-term sequelae, and subsequently long-term safety, of GHT in survivors of (childhood) cancer and patients with tumors of the pituitary region. We identified predominantly reassuring results regarding the safety of survivors with GHT, although we must take into account the shortcomings of some studies and limited information on adult cancer survivors. Besides the already increased risk for second neoplasms, recurrences, or mortality in survivors due to host-, disease-, and treatment-related factors, we could not identify an increased risk due to GHT in particular. Therefore, we support the consensus that GHT can be considered in survivors after careful individual risk/benefit analysis and in open discussion with the patients and their families, taking into account the known morbidity of untreated GHD in cancer survivors and the positive effects of GHT.
Subject(s)
Dwarfism, Pituitary , Human Growth Hormone , Hypopituitarism , Pituitary Neoplasms , Adult , Humans , Child , Quality of Life , Pituitary Neoplasms/drug therapy , Pituitary Neoplasms/complications , Human Growth Hormone/adverse effects , Hypopituitarism/drug therapy , Hypopituitarism/etiology , Dwarfism, Pituitary/complications , Dwarfism, Pituitary/drug therapy , Growth Hormone , Survivors , Hormone Replacement Therapy/adverse effectsABSTRACT
BACKGROUND: Adverse late health outcomes after multimodal treatment for pediatric cancer are diverse and of prime interest. Currently available evidence and survivorship care guidelines are largely based on studies addressing side-effects of two dimensional planned radiotherapy. AIMS: The Dutch pediatric 3D-planned radiotherapy (3D-RT) study aims to gain insight in the long-term health outcomes among children who had radiotherapy in the 3D era. Here, we describe the study design, data-collection methods, and baseline cohort characteristics. METHODS AND RESULTS: The 3D-RT study represents an expansion of the Dutch Childhood Cancer Survivor study (DCCSS) LATER cohort, including pediatric cancer patients diagnosed during 2000-2012, who survived at least 5 years after initial diagnosis and 2 years post external beam radiotherapy. Individual cancer treatment parameters were obtained from medical files. A national infrastructure for uniform collection and archival of digital radiotherapy files (Computed Tomography [CT]-scans, delineations, plan, and dose files) was established. Health outcome information, including subsequent tumors, originated from medical records at the LATER outpatient clinics, and national registry-linkage. With a median follow-up of 10.9 (interquartile range [IQR]: 7.9-14.3) years after childhood cancer diagnosis, 711 eligible survivors were identified. The most common cancer types were Hodgkin lymphoma, medulloblastoma, and nephroblastoma. Most survivors received radiotherapy directed to the head/cranium only, the craniospinal axis, or the abdominopelvic region. CONCLUSION: The 3D-RT study will provide knowledge on the risk of adverse late health outcomes and radiation-associated dose-effect relationships. This information is valuable to guide follow-up care of childhood cancer survivors and to refine future treatment protocols.
Subject(s)
Cancer Survivors , Cerebellar Neoplasms , Hodgkin Disease , Medulloblastoma , Child , Humans , Medulloblastoma/radiotherapy , Cerebellar Neoplasms/radiotherapy , Outcome Assessment, Health CareABSTRACT
BACKGROUND AND PURPOSE: To establish an international quality standard for contouring and planning for high-risk neuroblastoma within the prospective High-Risk Neuroblastoma Study 2 of SIOP-Europe-Neuroblastoma (SIOPEN HR-NBL2), which includes a randomized question on dose escalation for residual disease. MATERIALS AND METHODS: Data on four patients with high-risk neuroblastoma were selected and distributed to the radiotherapy committee of the HR-NBL2 study for independent contouring and planning. Differences in contouring were analyzed using apparent and kappa-corrected agreement. Plans were analyzed regarding the dose-volume histogram metrics. Results were discussed among experts and agreement was obtained. RESULTS: Substantial agreement was found for contouring of the heart (0.64), liver (0.70), left lung (0.74), and right lung (0.74). For contouring of the gastrointestinal tract (0.54), left kidney (0.60), and right kidney (0.59) moderate agreement was obtained. For target volume delineation, agreement for preoperative tumour extent was moderate (0.42), for CTV fair (0.35) and only low (0.06) for residual tumour, respectively. The dose planning strategies appeared to be relatively homogeneous among all experts. CONCLUSION: Considerable variability was found for the delineation of target volumes, particularly the boost volume, whereas the contouring of the organs at risk and the planning strategy were reasonably consistent. In order to obtain reliable results from the randomized HR-NBL2 trial, standardization of target volume delineation based on adequate imaging is crucial.
Subject(s)
Neuroblastoma , Radiation Oncology , Humans , Radiotherapy Planning, Computer-Assisted/methods , Prospective Studies , Lung , Neuroblastoma/diagnostic imaging , Neuroblastoma/radiotherapy , Observer VariationABSTRACT
BACKGROUND: Childhood cancer survivors are at risk for developing long-term adverse health outcomes. To identify the risk of and risk factors for specific health outcomes, well-established cohorts are needed with detailed information on childhood cancer diagnosis, treatment, and health outcomes. We describe the design, methodology, characteristics, and data availability of the Dutch Childhood Cancer Survivor Study LATER cohort (1963-2001) part 1; questionnaire and linkage studies. METHODS: The LATER cohort includes 5-year childhood cancer survivors, diagnosed in the period 1963-2001, and before the age of 18 in any of the seven former pediatric oncology centers in the Netherlands. Information on health outcomes from survivors and invited siblings of survivors was collected by questionnaires and linkages to medical registries. RESULTS: In total, 6165 survivors were included in the LATER cohort. Extensive data on diagnosis and treatment have been collected. Information on a variety of health outcomes has been ascertained by the LATER questionnaire study and linkages with several registries for subsequent tumors, health care use, and hospitalizations. CONCLUSION: Research with data of the LATER cohort will provide new insights into risks of and risk factors for long-term health outcomes. This can enhance risk stratification for childhood cancer survivors and inform surveillance guidelines and development of interventions to prevent (the impact of) long-term adverse health outcomes. The data collected will be a solid baseline foundation for future follow-up studies.
Subject(s)
Cancer Survivors , Neoplasms , Child , Humans , Neoplasms/epidemiology , Neoplasms/therapy , Neoplasms/pathology , Follow-Up Studies , Survivors , Surveys and QuestionnairesABSTRACT
Radiotherapy (RT) is essential for multimodality treatment of pediatric renal tumors, particularly in higher-risk and metastatic disease. Despite decades of use, particularly for Wilms tumor, there remain controversies regarding RT indications, timing, dose, and targets. To align global management, we address these issues in this international HARMONIsation and CollAboration (HARMONICA) project. There are multiple knowledge gaps and opportunities for future research including: (1) utilization of advanced RT technologies, including intensity-modulated RT, proton beam therapy, combined with image-guided RT to reduce target volumes; (2) impact of molecular biomarkers including loss of heterozygosity at 1p, 16q, and 1q gain on RT indications; (3) mitigation of reproductive toxicity following RT; (4) promotion of RT late effects research; and (5) support to overcome challenges in RT utilization in low- and middle-income countries where 90% of the world's children reside. Here, we outline current status and future directions for RT in pediatric renal tumors.
Subject(s)
Kidney Neoplasms , Wilms Tumor , Child , Humans , Consensus , Wilms Tumor/pathology , Kidney Neoplasms/pathology , Disease Progression , Combined Modality TherapyABSTRACT
The European Society for Paediatric Oncology (SIOPE) Radiation Oncology Working Group presents the QUARTET Project: a centralised quality assurance programme designed to standardise care and improve the quality of radiotherapy and imaging for international clinical trials recruiting children and adolescents with cancer throughout Europe. QUARTET combines the paediatric radiation oncology expertise of SIOPE with the infrastructure and experience of the European Organisation for Research and Treatment of Cancer to deliver radiotherapy quality assurance programmes for large, prospective, international clinical trials. QUARTET-affiliated trials include children and adolescents with brain tumours, neuroblastoma, sarcomas including rhabdomyosarcoma, and renal tumours including Wilms' tumour. With nine prospective clinical trials and two retrospective studies within the active portfolio in March 2022, QUARTET will collect one of the largest repositories of paediatric radiotherapy and imaging data, support the clinical assessment of radiotherapy, and evaluate the role and benefit of radiotherapy quality assurance for this cohort of patients within the context of clinical trials.
Subject(s)
Kidney Neoplasms , Radiation Oncology , Wilms Tumor , Adolescent , Child , Europe , Humans , Kidney Neoplasms/drug therapy , Prospective Studies , Retrospective Studies , Wilms Tumor/drug therapyABSTRACT
Purpose: The aim of this study is to investigate the spectrum of neurological triad improvement in patients with diffuse intrinsic pontine glioma (DIPG) treated by re-irradiation (re-RT) at first progression. Methods: We carried out a re-analysis of the SIOP-E retrospective DIPG cohort by investigating the clinical benefits after re-RT with a focus on the neurological triad (cranial nerve deficits, ataxia, and long tract signs). Patients were categorized as "responding" or "non-responding" to re-RT. To assess the interdependence between patients' characteristics and clinical benefits, we used a chi-square or Fisher's exact test. Survival according to clinical response to re-RT was calculated by the Kaplan-Meier method. Results: As earlier reported, 77% (n = 24/31) of patients had any clinical benefit after re-RT. Among 25/31 well-documented patients, 44% (n = 11/25) had improvement in cranial nerve palsies, 40% (n = 10/25) had improvement in long-tract signs, and 44% (11/25) had improvement in cerebellar signs. Clinical benefits were observed in at least 1, 2, or 3 out of 3 symptoms of the DIPG triad, in 64%, 40%, and 24%, respectively. Patients irradiated with a dose ≥20 Gy versus <20 Gy may improve slightly better with regard to ataxia (67% versus 23%; p-value = 0.028). The survival from the start of re-RT to death was not different between responding and non-responding DIPG patients (p-value = 0.871). Conclusion: A median re-irradiation dose of 20 Gy provides a neurological benefit in two-thirds of patients with an improvement of at least one symptom of the triad. DIPG patients receiving ≥20 Gy appear to improve slightly better with regard to ataxia; however, we need more data to determine whether dose escalation up to 30 Gy provides additional benefits.