30. Paediatric malignancies - The GEC-ESTRO Handbook of Brachytherapy

Paediatric malignancies

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THE GEC ESTRO HANDBOOK OF BRACHYTHERAPY | Part II Clinical Practice Version 1 - 01/09/2023

5. WORK UP

Favourable tumour sites in EpSSG FAR RMS are defined as the orbit, the head and neck area (except for parameningeal sites), bladder-prostate, genital and bile ducts. Unfavourable sites include limbs, parameningeal sites, and other parts of the body. Recent data showed an excellent prognosis for patients with BP RMS treated with BT [12, 13]. Risk classification for paediatric RMS is different between European and North American groups. In general, it is based on primary site (favourable/unfavourable), tumour size (< or > 5 cm) and patient age (< or > 10 years), regional lymph node extension, distant metastasis, extent of initial surgical procedures performed prior to systemic treatment (IRS1: Localized tumour, completely removed with pathologically clear margins and no regional lymph node involvement ; IRS2 : localized tumour, grossly removed with (a) microscopically involved margins, (b) involved, grossly resected regional lymph nodes, or (c) both ; IRS3 : Localized tumour, with gross residual disease after incomplete removal, or biopsy only ; IRS4 : Distant metastases present at diagnosis), and biopathology findings (i.e. histology or FOXO1 fusion). According to data from the IRS (International Rhabdomyosarcoma Study)-IV study, the three-year failure free survival rate is 83-86% in IRS group I and II, 73% in group III, and less than 30% in IRS group IV [7]. Radiotherapy has a major role in the treatment of paediatric RMS, in combination with multi-agent chemotherapy regimens [3, 6, 59, 60). Various chemotherapy regimens do exist, according to risk group. BT is indicated for treatment of the tumour residuum, following chemotherapy. Usually, the treatment decision for BT is taken after 4 cycles. However, the local treatment can be delivered after additional cycles, to achieve optimal tumour regression, with regular imaging (every 2 cycles) to monitor tumour response. Main sites that are suitable for BT in paediatric tumours are: gynaecological tumours (vulva, vagina, cervix), urological tumours (bladder, prostate, urethra), perineal tumours, anus-rectum, tumours of the trunk and of the extremities, head and neck tumours (orbit, non-parameningeal tumours, parameningeal tumours). In most cases, local treatment is mandatory in patients with RMS. However, for gynaecological sites, up to 40% of patients can be cured without local treatment, if there is clinical and radiological complete response confirmed by biopsies after four cycles [36, 52]. On the contrary, all BP/RMS patients and parameningeal patients should receive local treatment, as only 10% of BP RMS can be cured without local treatment in historical cohorts [60, 61] BT is indicated as an alternative to external radiotherapy and mutilating surgery, in the context of organ sparing strategies. It is proposed schematically in the following situations: 1/ as exclusive treatment for in situ tumours (that have not been removed by surgery), to treat the post-chemotherapy residuum, to avoid the long-term morbidity associated with external beam radiotherapy in very young patients or with mutilating surgery (e.g., prostate RMS, gynaecological RMS) 6. INDICATIONS AND CONTRA-INDICATIONS

RMS are very chemo-sensitive tumours. It is therefore crucial to have tumour extent assessed prior to any chemotherapy, after surgery (if any), then after every 2-3 chemotherapy cycles, and prior to BT. In addition to clinical examination, which is an important component of workup, radiological assessment for soft tissue rhabdomyosarcoma mainly relies on MRI. Though radiological procedures are specific to each tumour site, MRI provides the most accurate morphological staging to accurately assess tumour extents. Computed Tomography (CT) scans can be also useful to preclude bone invasion, that would contra-indicate solely BT procedures (e.g., for floor of the mouth RMS). In case of bone invasion macroscopic radical surgery in combination with BT is advised; the AMORE procedure (see paragraph Technique). For gynaecological tumours, an examination under general anaesthesia should be performed prior to any chemotherapy if feasible. If tumour volume does not allow the gynaecological examination, for example in a vaginal botryoid RMS, it may be postponed. Colposcopy should be performed as far as tumour regression allows. At the time of colposcopy, a vaginal impression may be performed to properly see tumour extents at the level of the vaginal mucosa, and serve as a basis for customizing a personalized vaginal mould applicator (Figure 1). For bladder and prostate RMS (BP RMS), MRI should be performed with full bladder to better show tumour extent, and select patients that are good candidates for a conservative approach based on BT. Adequate nodal staging is also important at diagnosis (using conventional imaging and FDG PET/CT and if appropriate, sentinel lymph node biopsy), especially for alveolar RMS (and some specific sites such as limb RMS). When patients are referred for adjuvant BT, for example after surgical treatment of a limb RMS, it is crucial to have a complete report and description of the operative findings and to discuss thoroughly with the surgeon, to better define the area that should be treated.

Figure 1. Example of a vaginal mould applicator with four catheters for intracavitary treatment of a vaginal rhabdomyosarcoma