Paediatric Molecular Radiotherapy: Challenges and Opportunities.

The common contemporary indications for paediatric molecular radiotherapy (pMRT) are differentiated thyroid cancer and neuroblastoma. It may also have value in neuroendocrine cancers, and it is being investigated in clinical trials for other diseases. pMRT is the prototypical biomarker-driven, precision therapy, with a unique mode of delivery and mechanism of action. It is safe and well tolerated, compared with other treatments. However, its full potential has not yet been achieved, and its wider use faces a number of challenges and obstacles. Paradoxically, the success of radioactive iodine as a curative treatment for metastatic thyroid cancer has led to a 'one size fits all' approach and limited academic enquiry into optimisation of the conventional treatment regimen, until very recently. Second, the specialised requirements for the delivery of pMRT are available in only a very limited number of centres. This limited capacity and geographical coverage results in reduced accessibility. With few enthusiastic advocates for this treatment modality, investment in research to improve treatments and broaden indications from both industry and national and charitable research funders has historically been suboptimal. Nonetheless, there is now an increasing interest in the opportunities offered by pMRT. Increased research funding has been allocated, and technical developments that will permit innovative approaches in pMRT are available for exploration. A new portfolio of clinical trials is being assembled. These studies should help to move at least some paediatric treatments from simply palliative use into potentially curative protocols. Therapeutic strategies require modification and optimisation to achieve this. The delivery should be personalised and tailored appropriately, with a comprehensive evaluation of tumour and organ-at-risk dosimetry, in alignment with the external beam model of radiotherapy. This article gives an overview of the current status of pMRT, indicating the barriers to progress and identifying ways in which these may be overcome.

Hearing loss in survivors of childhood head and neck rhabdomyosarcoma: a long-term follow-up study.

OBJECTIVES: To determine the hearing status of survivors treated for head and neck rhabdomyosarcoma (HNRMS) at long-term follow-up. DESIGN: Cross-sectional long-term follow-up study. SETTING: Tertiary comprehensive cancer centre. PARTICIPANTS: Survivors treated for HNRMS during childhood in two concurrent cohorts; survivors in London had been treated with external beam radiotherapy (EBRT-based local therapy); survivors in Amsterdam were treated with AMORE (Ablative surgery, MOuld technique afterloading brachytherapy and surgical REconstruction) if feasible, otherwise EBRT (AMORE-based local therapy). MAIN OUTCOME MEASURES: We assessed hearing status of HNRMS survivors at long-term follow-up. Hearing thresholds were obtained by pure-tone audiometry. METHODS: We assessed the hearing thresholds, the number of patients with clinically relevant hearing loss and hearing impairment graded according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAEv4) and Boston criteria. Furthermore, we compared hearing loss between survivors treated with EBRT-based local therapy (London) and AMORE-based local therapy (Amsterdam). RESULTS: Seventy-three survivors were included (median follow-up 11 years). We found clinically relevant hearing loss at speech frequencies in 19% of survivors. Multivariable analysis showed that survivors treated with EBRT-based treatment and those with parameningeal tumours had significantly more hearing impairment, compared to survivors treated with AMORE-based treatment and non-parameningeal tumours. CONCLUSIONS: One in five survivors of HNRMS developed clinically relevant hearing loss. AMORE-based treatment resulted in less hearing loss compared to EBRT-based treatment. As hearing loss was highly prevalent and also occurred in survivors with orbital primaries, we recommend systematic audiological follow-up in all HNRMS survivors.