Fig 1 - uploaded by Edward Chandy
Content may be subject to copyright.
Cyberknife plan of patient 4: A 5-year-old with ependymoma who recieved 20 Gy in a single fraction to a posterior fossa local recurrence. The patient required general aneasthetic and an endotracheal tube can be seen on the images.
Source publication
Aims:
Cancer remains a leading cause of death in children and adolescents in the developed world. Despite advances in oncological management, rates of primary treatment failure remain significant. Radiation of recurrent or metastatic disease improves survival in adults but there is little data to support clinical decision making in the paediatric/...
Context in source publication
Citations
... In recent years, other alternatives for treating neuroblastoma have been proposed [29,30]. Especially, proton beam therapy has been increasingly recommended for pediatric patients with neuroblastoma, even though this irradiation type can suffer dosimetric degradation from gastrointestinal air and tumor location and still requires large cohort studies to prove oncological benefit compared to state-of-the art photon therapy [31,32]. ...
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.
... For photon-specific data, one study of pediatric stereotactic radiosurgery/stereotactic ablative body radiotherapy (SRS/SABR), the risk of symptomatic brain radionecrosis was associated with an exceeding cumulative dose of 200 Gy biological equivalent dose (BED) Guan et al. Radiation Oncology (2023) 18:151 by Chandy et al. [20]. On the other hand, Bruni et al. reported that single-session SRS with frameless immobilization head-neck mask tomotherapy was a feasible and safe treatment option for patients with brain metastases, with a good overall response rate and acceptable toxicity. ...
Background
In patients with nasopharyngeal cancer (NPC), radiation-induced temporal lobe injury (TLI) is the most dreaded late-stage complication following radiation therapy (RT). We currently lack a definitive algorithmic administration for this entity. In the meantime, the pathogenesis of TLI and the mechanism-based interventions to prevent or treat this adverse effect remain unknown. To better answer the aforementioned questions, it is necessary to comprehend the intellectual foundations and prospective trends of this field through bibliometric analysis.
Methods
Articles were gathered from the Web of Science Core Collection (WoSCC) database between 2000 and 2022. CiteSpace was utilized to create a country/institutional co-authorship network, perform dual-map analysis, and find keywords with citation bursts. VOSviewer was used to build networks based on author co-authorship, journal citation, co-citation analysis of authors, references, and journals, and keyword co-occurrence.
Results
A total of 140 articles and reviews were included in the final analysis. The number of publications has steadily increased with some fluctuations over the years. The country and institution contributing most to this field are the China and Sun Yat-Sen University. Han Fei was the most prolific author, while Lee Awm was the most frequently cited. The analysis of co-occurrence revealed three clusters, including: “radiation-induced injury or necrosis in NPC,” “clinical studies on chemotherapy/radiotherapy complications and survival in recurrent NPC,” and “IMRT/chemotherapy outcomes and toxicities in head and neck cancer”). Most recent keyword bursts were “volume,” “temporal lobe injury,” “toxicities,” “model,” “survival,” “intensity modulated radiotherapy,” “induced brain injury,” “head and neck cancer,” and “temporal lobe.”
Conclusion
This study provides some insights of the major areas of interest in the field of radiation-induced TLI in patients with NPC by bibliometric analyses. This study assists scholars in locating collaborators and significant literature in this field, provides guidance for publishing journals, and identifies research hotspots. This analysis acknowledges significant contributions to the discipline and encourages the scientific community to conduct additional research.
... In patients with good performance status and no contraindications from other comorbidities, metastasectomy is usually considered to be the gold standard [7,8]. SRS and SABR have emerged relatively recently as treatment options for patients with cranial and extracranial oligometastatic disease, respectively [9,10]. Local control (LC) of the metastatic sites is proven to slow down further disease progression and, in selected patient groups, potentially improve the overall survival (OS) [11,12]. ...
... With this in mind, it becomes clearer to understand why most of the studies presented in this review include patients treated for "extra-axial" oligometastases/oligorecurrences, where the priority is either given to the preservation of the remaining organ (with parallel architecture, i.e., liver, lung) or to reducing late complications for in-field recurrences of previously irradiated tissues. The median dose per fraction in the studies presented was 4.15 Gy RBE (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), with standard or moderately hypofractionated regimens being the most common. ...
Background:
Stereotactic ablative radiotherapy (SABR) and stereotactic radiosurgery (SRS) with conventional photon radiotherapy (XRT) are well-established treatment options for selected patients with oligometastatic/oligorecurrent disease. The use of PBT for SABR-SRS is attractive given the property of a lack of exit dose. The aim of this review is to evaluate the role and current utilisation of PBT in the oligometastatic/oligorecurrent setting.
Methods:
Using Medline and Embase, a comprehensive literature review was conducted following the PICO (Patients, Intervention, Comparison, and Outcomes) criteria, which returned 83 records. After screening, 16 records were deemed to be relevant and included in the review.
Results:
Six of the sixteen records analysed originated in Japan, six in the USA, and four in Europe. The focus was oligometastatic disease in 12, oligorecurrence in 3, and both in 1. Most of the studies analysed (12/16) were retrospective cohorts or case reports, two were phase II clinical trials, one was a literature review, and one study discussed the pros and cons of PBT in these settings. The studies presented in this review included a total of 925 patients. The metastatic sites analysed in these articles were the liver (4/16), lungs (3/16), thoracic lymph nodes (2/16), bone (2/16), brain (1/16), pelvis (1/16), and various sites in 2/16.
Conclusions:
PBT could represent an option for the treatment of oligometastatic/oligorecurrent disease in patients with a low metastatic burden. Nevertheless, due to its limited availability, PBT has traditionally been funded for selected tumour indications that are defined as curable. The availability of new systemic therapies has widened this definition. This, together with the exponential growth of PBT capacity worldwide, will potentially redefine its commissioning to include selected patients with oligometastatic/oligorecurrent disease. To date, PBT has been used with encouraging results for the treatment of liver metastases. However, PBT could be an option in those cases in which the reduced radiation exposure to normal tissues leads to a clinically significant reduction in treatment-related toxicities.
... Characteristics of studies included for quantitative analysis Among 9 published studies meeting inclusion criteria, we identified 142 pediatric and AYA patients with cancer with 217 lesions treated with SBRT. [8][9][10]16,[26][27][28][29][30] Studies were published from 2014 to 2021 with patients from the United States, United Kingdom, and France. Table 1 shows respective data on both primary and secondary outcomes for each study as well as other relevant information regarding patient age, extent of follow-up, primary cancer histologies, primary lesion locations, and dose and fractionation schemes. ...
... Across 9 studies, 142 patients had available information on acute and late grade 3 to 5 toxicities. [8][9][10]16,[26][27][28][29][30] The estimated pooled acute and late grade 3 to 5 toxicity rate was 2.9% (95% CI, 0.4%-5.4%; Fig. 4). ...
Background
Limited data is currently available on clinical outcomes following stereotactic body radiation therapy (SBRT) for pediatric and AYA patients with cancer. We aimed to perform a systematic review and study-level meta-analysis to characterize associated local control (LC), progression-free survival (PFS), overall survival (OS), and toxicity following SBRT.
Methods
Relevant studies were queried utilizing a PICOS/PRISMA/MOOSE selection criteria. Primary outcomes were 1-year and 2-year LC as well as incidence of acute and late Grade 3-5 toxicities, with secondary outcomes of 1-year OS and 1-year PFS. Outcome effect sizes were estimated with weighted random effects meta-analyses. Mixed effects weighted regression models were performed to examine potential correlations between biologically effective dose (BED10), LC, and toxicity incidence.
Results
Across 9 published studies, we identified 142 pediatric and AYA patients with 217 lesions that were treated with SBRT. Estimated 1-year and 2-year LC rates were 83.5% (95% CI: 70.9-96.2%) and 74.0% (95% CI: 64.6-83.4%), respectively, with an estimated acute and late Grade 3-5 toxicity rate of 2.9% (95% CI: 0.4-5.4%) (all Grade 3). The estimated 1-year OS and PFS rates were 75.4% (95% CI: 54.5-96.3%) and 27.1% (95% CI: 17.3-37.0%), respectively. On meta-regression, higher BED10 was correlated with improved 2-year LC with every 10 Gy10 increase in BED10 associated with a 5% improvement in 2-year LC (p=0.02) in sarcoma-predominant cohorts.
Conclusions
SBRT provided durable LC for pediatric and AYA patients with cancer with minimal severe toxicities. Dose escalation may result in improved LC for sarcoma-predominant cohorts without a subsequent increase in toxicity. However, further investigations with patient-level data and prospective inquiries are indicated to more better define the role of SBRT based on patient and tumor-specific characteristics.
... Current clinical experience is mainly limited to the use of radiosurgery or hypofractionated SBRT in the treatment of brain lesions (e.g. gliomas, medulloblastomas, ependymoma, or metastases [2][3][4][5][6] ). Regarding extra cranial tumors, available data are scarce, mainly consisting of case-reports or retrospective series of SBRT in lung, 7,8 bone/soft tissue, 2,9 or liver lesions. ...
... gliomas, medulloblastomas, ependymoma, or metastases [2][3][4][5][6] ). Regarding extra cranial tumors, available data are scarce, mainly consisting of case-reports or retrospective series of SBRT in lung, 7,8 bone/soft tissue, 2,9 or liver lesions. 10 Altogether, these data show promising local control results (in the order of >75%). ...
... 10 Altogether, these data show promising local control results (in the order of >75%). 2,5,9 Theoretically, the steep-dose gradient and tighter margins used in SBRT could also allow for better preservation of the healthy surrounding tissues. Nevertheless, significant toxicities have been reported, e.g. ...
Objectives
While hypofractionated stereotactic body radiotherapy (SBRT) has been largely adopted in the adult setting, its use remains limited in pediatric patients. This is due, among other factors, to fear of potential toxicities of hypofractionated regimens at a young age. In this context, we report the preliminary acute (<3 months from SBRT) and middle-term (3–24 months) toxicity results of a national prospective study investigating SBRT in pediatric patients.
Methods
Between 2013 and 2019, 61 patients were included. The first 40 patients (median age: 12 y, range: 3–20) who completed a 2-year-follow-up were included in the present analysis. SBRT was used for treating lung, brain or (para)spinal lesions, either as first irradiation (35%) or in the reirradiation setting (65%).
Results
Acute and middle-term grade ≥2 toxicities occurred in 12.5 and 7.5% of the patients, respectively. No grade ≥4 toxicities occurred. Almost all toxicities occurred in the reirradiation setting.
Conclusion
SBRT showed a favorable safety profile in young patients treated for lung, brain, and (para)spinal lesions.
Advances in knowledge
SBRT appeared to be safe in pediatric patients treated for multiple oncology indications. These results support further evaluation of SBRT, which may have a role to play in this patient population in the future.
... In adults, the current radiotherapy approach for oligometastatic disease is strongly focused on hypofractionation and outcomes are associated with favourable local tumour control and limited toxicity for lesions within the bone, lymph nodes and soft tissue [10][11][12][13]. In contrast, the available literature on hypofractionation in children is mainly limited to retrospective and case studies for both cranial and extra-cranial metastatic disease [14][15][16]. In these studies, dose and fractionation schedules varied widely (total dose range 20-60 Gy in 1-10 fractions, dose per fraction range 5-20 Gy). ...
Background and purpose:
The aim of this study was to determine the feasibility of hypofractionated schedules for metastatic bone/bone marrow lesions in children and to investigate dosimetric differences to the healthy surrounding tissues compared to conventional schedules.
Methods:
27 paediatric patients (mean age, 7 years) with 50 metastatic bone/bone marrow lesions (n=26 cranial, n=24 extra-cranial) from solid primary tumours (neuroblastoma and sarcoma) were included. The PTV was a 2 mm expansion of the GTV. A prescription dose of 36 and 54 Gy EQD2α/β=10 was used for neuroblastoma and sarcoma lesions, respectively. VMAT plans were optimized for each single lesion using different fractionation schedules: conventional (30/20fx, V95%≥99%, D0.1cm3≤107%) and hypofractionated (15/10/5/3fx, V100%≥95%, D0.1cm3≤120%). Relative EQD2 differences in OARs Dmean between the different schedules were compared.
Results:
PTV coverage was met for all plans independently of the fractionation schedule and for all lesions (V95% range 95.5-100%, V100% range 95.1-100%), with exception of the vertebrae (V100% range 63.5-91.0%). For most OARs, relative mean reduction in the Dmean was seen for the hypofractionated plans compared to the conventional plans, with largest sparing in the 5fx (<43%) followed by the 3fx schedule (<40%). In case of PTV overlap with an OAR, a significant increase in dose for the OAR was observed with hypofractionation.
Conclusions:
For the majority of the cases, iso-effective plans with hypofractionation were feasible with similar or less dose in the OARs. The most suitable fractionation schedule should be personalised depending on the spatial relationship between the PTV and OARs and the prescription dose.
... Deciding between conventional and stereotactic approaches depended on reasons including the number of lesions, volume size and dose constraints for organs at risk. Six out of 20 departments, four in France, used a stereotactic technique according to an institutional or a national protocol [38,39], yielding varying dose prescriptions (16e50 Gy) and fractionation schemes (1e7 fractions), depending on the primary tumour type, metastatic site, as well as radiotherapy department. ...
... Also in the literature, evidence for hypofractionated stereotactic radiotherapy in children is limited. Some studies showed the feasibility of a stereotactic technique, with varying dose and fractionation schemes [26,39,45]. Local control rates ranged from 50 to 85% at a median follow-up of 2 years, with no acute or severe late toxicities observed [26,39,44]. ...
... Some studies showed the feasibility of a stereotactic technique, with varying dose and fractionation schemes [26,39,45]. Local control rates ranged from 50 to 85% at a median follow-up of 2 years, with no acute or severe late toxicities observed [26,39,44]. Casey et al. retrospectively evaluated the indications for a radiotherapy dose and fractionation schedule with curative intent of 49 bone metastases in RMS and ES patients [12]. ...
Purpose/objective
About 20% of children with solid tumours (ST) present with distant metastases (DM). Evidence regarding the use of radical radiotherapy of these DM is sparse and open for personal interpretation.
The aim of this survey was to review European protocols and to map current practice regarding the irradiation of DM across SIOPE-affiliated countries.
Materials/methods
Radiotherapy guidelines for metastatic sites (bone, brain, distant lymph nodes, lung and liver) in eight European protocols for rhabdomyosarcoma, non-rhabdomyosarcoma soft-tissue sarcoma, Ewing sarcoma, neuroblastoma and renal tumours were reviewed. SIOPE centres irradiating ≥50 children annually were invited to participate in an online survey.
Results
Radiotherapy to at least one metastatic site was recommended in all protocols, except for high-risk neuroblastoma. Per protocol, dose prescription varied per site, and information on delineation and treatment planning/delivery was generally missing.
Between July and September 2019, 20/27 centres completed the survey. Around 14% of patients were deemed to have DM from ST at diagnosis, of which half were treated with curative intent. A clear cut-off for a maximum number of DM was not used in half of the centres. Regardless of the tumour type and site, conventional radiotherapy regimens were most commonly used to treat DM. When stereotactic radiotherapy was used, a wide range of fractionation regimens were applied.
Conclusion
Current radiotherapy guidelines for DM do not allow a consistent approach in a multicentre setting. Prospective (randomised) trials are needed to define the role of radical irradiation of DM from paediatric ST.
... We enrolled young patients because that patients receiving SBRT reported overall good quality of life in general, associated with better global health status and lower indirect costs of productivity loss [15,16], which are much more important in young rather than old patients. In children and young adults, SBRT prolonged overall survival without signi cant toxicities [17]. The maturation of SBRT contributed to decades of technical and clinical advancement, including managing cardiac and respiratory motions, de ning safe radiation dosing levels for critical organs, and setting quality assurance standards globally. ...
Stereotactic body radiation therapy (SBRT) has been proved to be effective in refractory ventricular arrhythmia (VA). We report the first Asian series of SBRT for refractory VA in a group of Taiwanese. This study included patients with treatment-failure VA. 3D electroanatomic maps, delayed enhancement magnetic resonance imaging (DE-MRI) and dual energy computed tomography (CT) were used to identify scar substrates. The target volume was treated with a single radiation dose of 20 Gy delivered by Varian TrueBeam System. Efficacy was assessed by VA events recorded by implantable cardioverter defibrillator (ICD) or 24-hour Holter. Pre- and post-radiation therapy image studies were also performed. Adverse events were monitored during follow-up. From February 2019 to December 2019, 7 patients were enrolled. Six male and one female patients, mean age 55 years, received the treatment. Among the 7 patients with variety of cardiomyopathy, one patient died of hepatic failure. For the other 6 patients, at a median follow-up of 14.5 months, the burden of VA decreased significantly. Increased intensity of DE-MRI might be associated with lower risk of VA recurrence while the dual energy CT had lower sensitivity in the detection. No acute and minimal late adverse events were reported. We conclude that, in patients with refractory VA, SBRT was associated with a marked reduction in the burden of VA and DE-MRI might be useful to monitor treatment effect.
... While mostly limited to single-institution retrospective series, there are some compelling data reporting outcomes with the use of SBRT in pediatric patients which can apply to oligometastatic patients (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). ...
... No acute or late toxicity was reported in the patients with extracranial disease. Similarly, in a series from the Royal Marsden Hospital evaluating toxicity in the setting of radiosurgery for oligometastatic patients (median age 15), higher rates of toxicity were seen for those with CNS treatment (38). This series found that a cumulative BED (α/β of 2) of greater than 200 Gy resulted in a higher probability of experiencing late toxicity (P=0.04). ...
There is a growing body of prospective evidence describing an oligometastatic phenotype in adults for whom local metastasis-directed therapy can improve outcomes in select patients. However, a relative paucity of data for pediatric patients with oligometastatic disease creates challenges in choosing optimal treatment. The purpose of this review is to evaluate the literature surrounding pediatric oligometastatic disease and treatment, specifically focusing on the role of radiotherapy. A review of studies ranging from 2008 to 2020 was performed. The radiotherapy techniques evaluated included conventionally fractionated radiotherapy, stereotactic body radiotherapy (SBRT), and stereotactic radiosurgery (SRS). Our search yielded 6 studies evaluating conventionally fractionated radiotherapy, 9 studies of SBRT, and 3 studies of spine SRS. Metastasis-directed therapy for treatment of pediatric oligometastasis is generally well-tolerated, is associated with favorable local control, and is shown to improve event-free survival and progression-free survival (PFS) outcomes in select pediatric patients. Pediatric patients with oligometastatic disease may benefit from aggressive local therapy to metastatic sites in conjunction with a comprehensive treatment paradigm. Retrospective data have led to promising prospective trials that will further clarify patient selection and management. Additional data are needed to elucidate long term oncologic and toxicity outcomes.
Stereotactic radiosurgery and stereotactic body radiation therapy are commonly used modalities for the treatment of benign and malignant conditions in adults, with extensive literature available in regard to oncologic control and toxicity outcomes. Stereotactic radiosurgery has been used in pediatric patients as well, and the indications for offering this treatment to the pediatric patient population have increased in recent years. While these techniques have been utilized and studied for many years in pediatric patients for some conditions like arteriovenous malformation, there is a relative paucity of data for newer indications such as oligometastatic disease. In general, radiosurgery and stereotactic body radiation therapy may play an important role in the management of residual disease after resection and/or focal recurrences, and, more recently, for treatment of oligometastatic disease and consolidation of metastatic disease. Given the potential constellation of toxicities in the pediatric population, appropriate patient selection is crucial. Special considerations may be needed for patient setup and treatment planning. This chapter will review the evolving indications and the corresponding outcomes and toxicity for this treatment in the pediatric population.
