Complications after proton radiotherapy in children, focusing on severe late complications. A complete Swedish cohort 2008-2019.

BACKGROUND: Proton radiotherapy (RT) is an attractive tool to deliver local therapy with minimal dose to uninvolved tissue, however, not suitable for all patients. The aim was to explore complications, especially severe late complications (grades 3-4), following proton RT delivered to a complete Swedish cohort of paediatric patients aged <18 years treated 2008-2019. MATERIAL AND METHODS: Data was downloaded from a national registry. Complications with a possible causation with RT are reported. Proton treatments until July 2015 was performed with a fixed horizontal 172 MeV beam (The Svedberg Laboratory (TSL), Uppsala) in a sitting position and thereafter with gantry-based pencil-beam scanning technique (Skandion Clinic, Uppsala) in a supine position. RESULTS: 219 courses of proton RT (77 at TSL and 142 at Skandion) were delivered to 212 patients (mean age 9.2 years) with various tumour types (CNS tumours 58%, sarcomas 26%, germ cell tumours 7%). Twenty-five patients had severe acute complications (skin, mucous membrane, pharynx/oesophagus, larynx, upper gastrointestinal canal, lower gastrointestinal canal, eyes, ears). Fifteen patients had severe late complications; with increased proportion over time: 4% at 1-year follow-up (FU), 5% at 3-year, 11% at 5-year. Organs affected were skin (1 patient), subcutaneous tissue (4), salivary glands (1), upper GI (1), bone (7), joints (2), CNS (2), PNS (1), eyes (1) and ears (5). Twenty-one of the 28 patients with 10-year FU had at least one late complication grades 1-4 and fourteen of them had more than one (2-5 each). CONCLUSION: The most important result of our study is the relatively low proportion of severe late complications, comparable with other proton studies on various tumours. Furthermore, the numbers of late complications are lower than our own data set on a mixed population of photon and proton treated paediatric patients, assuring the safety of using proton therapy also in the clinical practice.

Dose escalation to 84 Gy with concurrent chemotherapy in stage III NSCLC appears excessively toxic: Results from a prematurely terminated randomized phase II trial.

OBJECTIVES: Concurrent chemoradiotherapy is the mainstay treatment for NSCLC stage III disease. To investigate whether radiation dose escalation based on individual normal tissue constraints can improve outcome, the Swedish lung cancer study group launched this randomized phase II trial. MATERIALS AND METHODS: NSCLC patients with stage III disease, good performance status (0-1) and adequate lung function (FEV1 > 1.0 L and CO diffusion capacity > 40%) received three cycles of cisplatin (75 mg/m2 day 1) and vinorelbine (25 mg/m2 day 1 and 8) every third week. Radiotherapy started concurrently with the second cycle, with either 2 Gy daily, 5 days a week, to 68 Gy (A) or escalated therapy (B) based on constraints to the spinal cord, esophagus and lungs up to 84 Gy by adding an extra fraction of 2 Gy per week. RESULTS: A pre-planned safety analysis revealed excessive toxicity and decreased survival in the escalated arm, and the study was stopped. Thirty-six patients were included during 2011-2013 (56% male, 78% with adenocarcinoma, 64% with PS 0 and 53% with stage IIIB). The median progression-free survival (PFS) and overall survival (OS) were 11 and 17 months in arm B compared to the encouraging results of 28 and 45 months in the standard arm. The 1- and 3-year survival rates were 56% and 33% (B) and 72% and 56% (A), respectively. There were seven toxicity-related deaths due to esophageal perforations and pneumonitis: five in the escalated group and two with standard treatment. CONCLUSION: Dose-escalated concurrent chemoradiotherapy to 84 Gy to primary tumor and nodal disease is hazardous, with a high risk of excessive toxicity, whereas modern standard dose chemoradiotherapy with proper staging given in the control arm shows a promising outcome with a median survival of 45 months and a 3-year survival of 56% (NCT01664663).

Parents' Experiences and Responses to an Intervention for Psychological Preparation of Children and Families During the Child's Radiotherapy.

The aim of this study was to evaluate parents' experiences and responses to a systematic intervention for psychological preparation of children and families during the child's radiotherapy (RT) treatment. In this case-control study at 3 pediatric RT centers, an intervention with a preparatory kit, including age-adjusted information on tablets, gift of a stuffed toy or a pair of headphones, a parent booklet, and toy models of the computed tomography and RT machines was implemented. For evaluation, a mixed methods data collection was conducted. A total of 113 parents of children undergoing RT were included-n = 59 in the baseline group and n = 54 in the intervention group. Health-related quality of life was rated low, but parents in the intervention group expressed less anxiety after the RT compared with the baseline group. They found information suitable for their young children, siblings, and friends were involved and the toy models were used for play. Parents expressed positive feelings due to close interaction with staff and each other within the family. The solutions developed within a human-centered design approach and shaped as a systematic family-centered strategy contributed to parents understanding and coping with the child's RT.

A dose based approach for evaluation of inter-observer variations in target delineation.

BACKGROUND AND PURPOSE: Substantial inter-observer variations in target delineation have been presented previously. Target delineation for paediatric cases is difficult due to the small number of children, the variation in paediatric targets, the number of study protocols, and the individual patient's specific needs and demands. Uncertainties in target delineation might lead to under-dosage or over-dosage. The aim of this work is to apply the concept of a consensus volume and good quality treatment plans to visualise and quantify inter-observer target delineation variations in dosimetric terms in addition to conventional geometrically based volume concordance indices. MATERIAL AND METHODS: Two paediatric cases were used to demonstrate the potential of adding dose metrics when evaluating target delineation diversity; Hodgkin's disease (case 1) and rhabdomyosarcoma of the parotid gland (case 2). The variability in target delineation (PTV delineations) between six centres was quantified using the generalised conformity index, CIgen, generated for volume overlap. The STAPLE algorithm, as implemented in CERR, was used for both cases to derive a consensus volumes. STAPLE is a probabilistic estimate of the true volume generated from all observers. Dose distributions created by each centre for the original target volumes were then applied to this consensus volume. RESULTS: A considerable variation in target segmentation was seen in both cases. For case 1 the variation was 374-960 cm3 (average 669 cm3) and for case 2; 65-126 cm3 (average 109 cm3). CIgen were 0.53 and 0.70, respectively. The DVHs in absolute volume displayed for the delineated target volume as well as for the consensus volume adds information on both "compliant" target volumes as well as outliers which are hidden with just the use of concordance indices. CONCLUSIONS: The DVHs in absolute volume add valuable and easily understood information to various indices for evaluating uniformity in target delineation.

It Is Tough and Tiring but It Works--Children's Experiences of Undergoing Radiotherapy.

Approximately 300 children ages 0 to 18 are diagnosed with cancer in Sweden every year, and 80 to 90 of them undergo radiotherapy treatment. The aim was to describe children's experiences of preparing for and undergoing radiotherapy, and furthermore to describe children's suggestions for improvement. Thirteen children between the ages of 5 and 15 with various cancer diagnoses were interviewed. Data was analyzed using qualitative content analysis. The findings revealed five categories: positive and negative experiences with hospital stays and practical arrangements; age-appropriate information, communication, and guidance to various degrees; struggle with emotions; use of distraction and other suitable coping strategies; and children's suggestions for improvement during radiotherapy. An overarching theme emerged: "It is tough and tiring but it works". Some key areas were: explanatory visits, the need for information and communication, being afraid, discomfort and suffering, the need for media distraction, dealing with emotions, and the need for support. A systematic, family-centered preparation program could possible help families prepare and individualized distraction during radiotherapy could contribute to reducing distress. Further studies with interventions could clarify successful programs.

Children Undergoing Radiotherapy: Swedish Parents' Experiences and Suggestions for Improvement.

Approximately 300 children, from 0 to 18 years old, are diagnosed with cancer in Sweden every year. Of these children, 80-90 of them undergo radiotherapy treatment for their cancer. Although radiotherapy is an encounter with advanced technology, few studies have investigated the child's and the parent's view of the procedure. As part of an ongoing multicenter study aimed to improve patient preparation and the care environment in pediatric radiotherapy, this article reports the findings from interviews with parents at baseline. The aim of the present study was twofold: to describe parents' experience when their child undergoes radiotherapy treatment, and to report parents' suggestions for improvements during radiotherapy for their children. Sixteen mothers and sixteen fathers of children between 2-16 years old with various cancer diagnoses were interviewed. Data were analyzed using content analysis. The findings showed that cancer and treatment turns people's lives upside down, affecting the entire family. Further, the parents experience the child's suffering and must cope with intense feelings. Radiotherapy treatment includes preparation by skilled and empathetic staff. The parents gradually find that they can deal with the process; and lastly, parents have suggestions for improvements during the radiotherapy treatment. An overarching theme emerged: that despair gradually turns to a sense of security, with a sustained focus on and close interaction with the child. In conclusion, an extreme burden was experienced around the start of radiotherapy, though parents gradually coped with the process.