25 Oesophageal Cancer

Oesophageal Cancer Brachytherapy

20

THE GEC ESTROHANDBOOKOF BRACHYTHERAPY | Part II Clinical Practice Version 1 - 10/06/2019

Table 27.2 C: endoluminal brachytherapy (BT) with and without stenting – palliative indications.

Study

Patients (N)

Procedure (BT type; doses)

Endpoint (results)

Homs (phase III study) Amdal (phase III study)

209

BT* vs metal stent (single-dose BT 12 Gy) SEMS followed BT vs BT (BT 3 x 8 Gy at 7 mm mucosal depth with 10 - 15 mm applicators) BT vs UES (3 x 7 Gy plus 50 Gy) BT* vs UES (3 x 7 Gy plus 50 Gy)

AD (BT better long-term) AD (SEMS + BT better)

41

Bergquist (phase III study) Fuccio (meta-analysis)

66

AD (BT better)

DFS (67.2% 3 mo.) (BT highly effective)

AD = alleviation dysphagia, SEMS = Self expanding metal stent; UES = Ultraflex expandable stent; DFS=Dysphagia-free survival, *BT performed with single catheter diameter 4-10 mm and doses specified at 1 cm from the source axis

13. ADVERSE SIDE EFFECTS

14. KEYMESSAGES

In curative indications, when brachytherapy is given both as the sole treatment modality or as a boost procedure following or preceding external beam radiotherapy for curative treatments including concurrent chemotherapy, the acute toxicities that may occur are nausea, oesophagitis, bleeding, leukopenia and thrombocytopenia and late toxicities include fistulation, stenosis, chronic oesophagitis, pneumonitis, cardiac ischaemia and heart failure [Murakami et al., Tamaki et al.]. Those toxicities are acceptably low when the technique used is adequate [Nemoto et al.]. However, unacceptably high acute and chronic morbidity was linked with the use of concurrent chemotherapy with boost brachytherapy and inadequate technique (dose depth prescription >5mm from mucosa surface and too small applicator outer diameter), and possibly to high fraction doses [Gaspar et al.] with life-threatening toxicity in 24% of the treated patients, and treatment-related death in 6%. The main cause of mortality was fistula and perforation. Therefore, the main contraindication to brachytherapy which must be excluded by a gastrographin swallow and an endoscopic investigation is a fistula. Special attention to applied mucosal dose per fraction as a consequence of using small-diameter applicators may be crucial in this context. E.g. 5 Gy at 10 mm source axis distance applied by an applicator with a 2-3 mm radius may result in very high mucosal doses which are 3 to 4 times the prescription dose (15-20 Gy), (table 27.1). In palliative indications, meta-analysis identified after endoluminal brachytherapy treatment-related stenosis in 12.2% and fistula development in 8.3%. [Fuccio et al.]. Importantly however, procedural related mortality was very rare (0.3%), and usually in association with a perforation; acute toxicity was also low [Fuccio et al.]. In contrast, palliative oesophageal brachytherapy was associated with better dysphagia-free survival and quality of life.

• Endoluminal HDR or LDR brachytherapy boost in superficial OC after external beam radiotherapy (50-60 Gy) is a safe and effective treatment. • In operableOC, neoadjuvant preoperative chemo-radiation (CROSS protocol) followed by radical surgery is the standard established evidence-based procedure. In this indication endoluminal brachytherapy plays aminor or no role. Exceptionally, an upfront endoluminal brachytherapy boost may be used to alleviate dysphagia in obstructive tumours. • In inoperable OC (especially in tumours < 5cm length or in OSCC subtype), endoluminal brachytherapy plays amajor role to deliver a safe and effective boost dose following combined external radiotherapy and chemotherapy in a curative setting. • The risks of endoluminal brachytherapy dose boosting in definitive treatment with curative intent are related to fraction doses higher than 5-6 Gy, inappropriate applicator diameter and dose prescription. Concurrent chemotherapy during the brachytherapy boost may result in severe toxicity including oesophageal fistula and treatment-related death. • In palliative settings, endoluminal brachytherapy is the optimal local treatment in obstructive or bleeding OC with a long-lasting effect on dysphagia which is superior to stent placement. A combination of self-expandingmetal stents followed by endoluminal brachytherapy may be used. Endoluminal brachytherapy may also be used as a boost procedure after external beam radiotherapy (or chemoradiotherapy) in the palliative setting. However, there is no consensus on the optimal combination of treatment in this case.