25 Oesophageal Cancer

Oesophageal Cancer Brachytherapy

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

Main indications for oesophageal brachytherapy include:

1. Single (boost) procedures in superficial tumours following non-radical surgery - curative indications in the definitive treatment of superficial tumours (T1). 2. Boost procedure following combination treatment of external beam radiotherapy and chemotherapy or as an upfront procedure in selected cases – curative indications in the definitive treatment of inoperable tumours (T2 and T3). 3. Boost procedure following combination treatments of external beam radiotherapy and chemotherapy or as an upfront procedure in appropriate cases – selected curative indications in the neo-adjuvant treatment of operable tumours in order to reduce radiation pneumonitis risk and chronic cardiac morbidity and alleviate dysphagia with the goal of improving detrimental nutritional status and operability (T2 and T3). 4. Combination treatment with external radiotherapy with or without chemotherapy - palliative indications in advanced tumour stages after excluding a fistula by radiological work up. 5. Single procedure or combination treatment with stents to ameliorate severe dysphagia symptoms – palliative indications in advanced tumour stages after excluding a fistula by radiological work up.

2. INTRODUCTION

in operable OC since its publication [Sjoquist et al.]. A head-to- head comparison of the two multimodal therapeutic principles (perioperative chemotherapy versus neoadjuvant chemoradiation) has not been performed yet. The initiated prospective randomized controlled trial ESOPEC (Trial registration NCT02509286), however, aims to compare FLOT against CROSS protocols and to definitely answer this open question [Hoeppner et al.]. Sanford and co-workers demonstrated in 215 patients treated with neoadjuvant chemoradiation impressive pathologic complete responses (pCR) in one third and a downstaging in two-thirds of the analysed patients [Sanford et al.]. The complete response rate was significantly higher (60.7% versus 18.4%) in patients with OSCC than in OAC [Sanford et al.]. Definitive external beam radiation therapy combined with chemotherapy is the better alternative in inoperable patients for whom surgery is not possible, e.g. because of surgically inaccessible locoregional tumour burden or clinical conditions with an unacceptable anaesthetic risk. Cooper et al. demonstrated in a randomized controlled trial the superiority (26% versus 0%) of chemoradiotherapy (Herskovic protocol: 50 Gy plus 5-fluorouracil and cisplatin in weeks 1, 5, 8 and 11) versus radiotherapy alone in terms of overall survival with acceptable toxicity [Cooper et al.]. A local brachytherapy boost may be added with caution to the combination of external beam locoregional radiotherapy and chemotherapy [Okawa et al., Ishikawa et al., Gaspar et al.]. Very advanced stages have a poor prognosis and are usually treated with palliative (chemo-)radiation in patients with good performance status (e.g. Herskovic protocol, see above). Radiation therapy alone is given externally, or in combination with brachytherapy in patients with poor performance status not likely to tolerate an aggressive chemoradiation regimen. In addition, oesophageal brachytherapy alone may be used for advanced or recurrent disease and in patients with bleeding, ulcerating or obstructive tumours [Rosenblatt et al.]. Alternatively, different types of local palliative treatments are available such as: non-radical surgery, thermal ablative treatment, metal stents, self-expandable metal stents (SEMS), plastic stents, and self-expandable plastic stents (SEPS). Several randomized controlled trials have been conducted

Oesophageal cancer (OC) is the sixth leading cause of cancer-related mortality worldwide. OC generally occurs in elderly patients and is associated with a prolonged history of tobacco smoking and alcohol dependence, especially in oesophageal squamous cell carcinoma subtype (OSCC) [Yang et al.]. In developed countries, the oesophageal adenocarcinoma (OAC) subtype is increasing and is aetiologically linked with Barrett’s oesophagus, gastro- oesophageal-reflux-disease (GERD) and abdominal obesity as GERD’s most common cause [Yang et al.]. Dietary factors, including carcinogens and low level of fruits and vegetables, are a common aetiology for both subtypes [1, Yang et al.]. Radical surgery remains the standard in early disease (cT1-2, cN0, cM0). In early superficial OC (cT1) non-radical surgery and brachytherapy may be considered as an alternative. Meta-analyses have revealed inferior outcomes in patients with squamous cell carcinomas compared to adenocarcinomas following surgery alone [Pennathur et al., Graham et al.]. For more advanced operable locoregional disease (cT2-3, cN0-2, cM0) the treatment strategy has evolved from classical monotherapy with radical surgery to multimodality therapy. Usually, oesophageal cancer is diagnosed in advanced inoperable stages (cT3-4, any cN+) [Krug et al.]. In operable patients, perioperative chemotherapy [Al-Batran et al.] or multimodality protocols including neoadjuvant preoperative chemoradiation followed by radical surgery compare favourably with previous reported results [Agranovich et al.]. In randomized phase 3 trials, the FLOT protocol (docetaxel, oxaliplatin, and fluorouracil/ leucovorin) was proven superior to previous used perioperative chemotherapy schemes [Al-Batran et al.], and perioperative chemotherapy compared superiorly in terms of overall survival versus surgery alone in resectable OC [Ychou et al.]. Van Hagen et al. have proven in a randomized controlled trial the superiority of neoadjuvant chemoradiation to surgery alone as well [Van Hagen et al.].This neoadjuvant chemoradiation protocol with 41.4 Gy plus carboplatin/paclitaxel (CROSS protocol) has provided the clearest evidence for survival benefit and has become the clinical standard