25 Oesophageal Cancer

Oesophageal Cancer Brachytherapy

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

20%partial remission, total remission rate 100%) and alleviation of dysphagia which was initiated within few days after brachytherapy and was maintained in 80% of the treated patients until the end of therapy [55, Safaei et al.]. Significant literature for curative treatment with endoluminal brachytherapy in inoperable oesophageal cancer is detailed in table 27.2B 12.C. Curative indications (boost procedure) in operable OC (cT2-3 cN+ cM0) An oesophageal brachytherapy boost may be used in curative treatment to substantially reduce the lung and heart doses with the consequence of decreasing the radiation pneumonitis risk and chronic cardiac morbidity. Abou Yehia et al. demonstrated that the lung volume covered by 5 Gy (V5) > 55% correlates with increased risk of radiation pneumonitis by 1.14-fold andmean lung doses >13.5 Gy were associated with increased risk of radiation pneumonitis by 4.24-fold [41, Abou Yehia et al.]. Darby and co- workers showed the association of mean heart dose and subsequent probability of ischemic chronic heart disease [42, Darby et al.]. In their study with 2168 patients who underwent radiotherapy, rates of major coronary events increased linearly with the mean heart dose by 7.4% per Gray with no minimal threshold indicating a “safe dose limit” (p<0.0001). A series of randomised controlled trials [17, Homs et al., 18, Amdal et al. 19, Bergquist et al.] confirmed the use of oesophageal brachytherapy to alleviate dysphagia since this is significant in improving or maintaining nutritional status and consequently operability. Bergquist et al. compared high-dose-rate endoluminal brachytherapy with 7 Gy x 3 given in 2-4 weeks versus insertion of self-expandable stents in 65 patients and found a significantly better and more stable health-related quality of life (scores for dysphagia, p < 0.005) after brachytherapy. An endoluminal brachytherapy boost within neoadjuvant treatment in operable oesophageal cancer may be also used in cases of inadequate response (<70% SUVmax drop in FDG PET pre- operative restaging) following neoadjuvant radio-chemotherapy. The meta-analysis by Fiorica et al. underlined the positive effect of downsizing on outcomes in patients treated with multimodal concepts [58, Fiorica et al.]. In addition, Higuchi et al. found that lack of fludeoxyglucose F18 uptake in FDG-PET was the only preoperative predictor in Cox regression analyses (p=0.0071) for both histologic response and postoperative survival following neoadjuvant chemoradiotherapy and radical surgery for advanced oesophageal cancer. Cause-specific survival and distant recurrence was 67.7% and 4.8% respectively in patients with no uptake versus 36.5% and 37% in patients with uptake. [59, Higuchi et al.]. The authors of this study stated that this tool could be used to optimize and individualize further treatment according to individual early PET responses. One or two fractions of HDR brachytherapy (4-5 Gy) would be the optimal effective and safe radiotherapy method to tailor further treatment in cases of insufficient downsizing immediately after neoadjuvant chemoradiotherapy and prior to radical surgery.

versus surgery in the management of patients with advanced oesophageal cancer (cT3-4 and cN+) and revealed equivalent survival rates. Stahl et al. analysed 86 patients with squamous cell carcinoma treatedwith cisplatin, 5-FU, leucovorin, etoposide, 40 Gy external radiation plus esophagectomy versus 86 patients treated with cisplatin, 5-FU, leucovorin, etoposide and 65 Gy external radiation. The corresponding 2-year survival rates were 40% and 35% with no statistically significant difference [60, Stahl et al.]. Bedenne and co-workers compared 129 patients with squamous cell carcinoma treated with cisplatin, 5-FU, 46 Gy EBRT plus oesophagostomy with 130 patients treated with cisplatin, 5-FU and 66 Gy EBRT. The corresponding 2-year survival rates were 34% and 40% with no significant difference [61, Bedenne et al.]. Thus, in advanced locoregional and especially squamous cell OC, the utilization of the Herskovic protocol (combination chemoradiotherapy) may be considered standard of care in patients with ECOG status 0-2. Cooper et al. demonstrated in a phase III trial the superiority of chemoradiotherapy versus radiotherapy alone with clear benefit on overall survival (26% versus 0%) with acceptable toxicity [12, Cooper et al.]. The addition of endoluminal brachytherapy to chemoradiation may be recommended in order to achieve further downstaging or locoregional tumour control. However, the prerequisites are fistula exclusion by radiological work up and a residual oesophageal lumen passable to the endoscope. According to the adaptive treatment concept the high risk (HR) CTV (residual tumour following combination chemotherapy and external beam irradiation) is the basis for the target volume for the endoluminal brachytherapy boost procedure and is best defined by endoscopic assessment along with EUS performed by an experienced specialized gastro-enterologist in cooperation with the radiation oncologist. In very advanced stages with poor prognosis the use of chemotherapy in addition to external beam radiotherapy is reserved for patients with good performance status (e.g. Herskovic protocol, see above). In patients with poor performance scores not likely to tolerate an aggressive chemoradiation regimen, endoluminal brachytherapy should be used especially for obstructive or bleeding lesions or significant tumour-related pain. The meta-analysis published by Fuccio et al. in 2017 [Fuccio et al.] comprised six prospective trials with 623 patients and showed significant benefit from endoluminal brachytherapy in obstructive OC with dysphagia-free survival (DFS) of 86.9% at one month, and 67.2% at 3 months. A total radiation dose of 18 Gy or 21 Gy delivered in 2 or 3 fractions was foundmore effective than a single dose of 12 Gy. A series of phase III trials confirmed better relief of dysphagia for endoluminal brachytherapy than stent placement [Amdal et al., Bergquist et al.], especially long-term [Homs et al.]. Since brachytherapy was associated with less toxicity it should be regarded as the primary treatment for tumour-related dysphagia. 12.E. Palliative indications (brachytherapy alone) to treat tumour local relapse and/or alleviate cancer- related dysphagia

Significant literature for palliative treatment of endoluminal brachytherapy in oesophageal cancer is detailed in table 27.2C.

12.D. Palliative indications (boost procedure) in inoperable OC (cT3-4 cN0-3 cM0-1) Several trials have examined the role of definitive chemoradiation