1. Delivering clinical research to make patients, and the NHS, better OG neoadjuvant therapy Brachytherapy Stephen Falk dd/mm/yyyy

2. OG therapy 1. Neoadjuvant chemoradiation prior to curative surgery. 2. Brachytherapy for palliation. Trials to be published at ASCO 2015 OE 05 Adjuvant therapies ST 03 Adjuvant therapies All well designed trials that can change international practice

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4. Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia from oesophageal cancer: multicentre randomised trial. Homs MY et al. Lancet 2004 Oct 23-29;364(9444):1497-504. Treatment / Results (n=209): Stent placement (n=108) single-dose (12 Gy) brachytherapy (n=101) Dysphagia improved more rapidly after stent placement than after brachytherapy, but long-term relief of dysphagia was better after brachytherapy. Stent placement had more complications (36 [33%] of 108 vs. 21 [21%] of 101; p=0.02). Groups did not differ for persistent or recurrent dysphagia (p=0.81), or for median survival (p=0.23).

5. Stent insertion or endoluminal brachytherapy as palliation of patients with advanced cancer of the esophagus and gastroesophageal junction. Results of a randomized, controlled clinical trial. Bergquist H et al. Dis Esophagus 2005;18(3):131-9. Ultraflex expandable stent or HDR endoluminal brachytherapy with 7 Gy x 3 given in 2-4 weeks Endpoints: Clinical assessment and health-related quality of life (HRQL) were measured at inclusion and 1, 3, 6, 9 and 12 months later Results (n=65): For stent group significantly better HRQL scores for dysphagia (P < 0.05) at the 1-month follow-up, but most other HRQL scores, including functioning and symptom scales deteriorated. Among brachytherapy-treated patients, improvement was found for the dysphagia-related scores at 3-months follow-up. No difference in median survival

6. Endoluminal stent group: rapid relief of dysphagia is seen within 2 weeks of treatment initiation, with 85% of patients being able to achieve a dysphagia score of 0 or 1. In the radiation therapy group [brachytherapy or external-beam (EBRT)], an initial lag period of 6–8 weeks is observed before effective relief of dysphagia is noted. The percentage of patients who achieve a dysphagia score of 1 or 0 at the 10-week follow-up is higher with brachytherapy (85%) and with EBRT (90%), than with stenting (72% Palliation

7. Brachytherapy for palliation ABS guidelines –Palliative treatment: Patients with adeno- or squamous cancers of the thoracic esophagus with distant metastases or unresectable local disease progression/recurrence after definitive radiation treatment should be considered for brachytherapy with palliative intent. 7

8. Individual Patient Data-based Meta-analysis Assessing Pre-operative Chemotherapy in Resectable Oesophageal Cancer Thirion P et al. Abstr. 4512, ASCO 2007

9. Current Status 0E05 Between January 2005 and October 2011, 897 patients were randomised from 70 UK centres. The primary outcome measure is overall survival, and will be reported at ASCO 2015.

10. OE05 summary 411 CF (91%) and 386 ECX (86%) patients had surgery. Four patients (2 in each arm) did not receive any protocol treatment. Overall, 379 CF (84%) and 308 ECX (69%) received all planned chemotherapy cycles and underwent a resection. 47 (5% in each arm) had an open and close operation. # Resection rates, surgical complications and 90 day post-operative mortality rates were similar.

11. MRC OEO2 vs INT113 OEO2INT113 surgical resection C+S92%80% S97%96% complete surgical resection C+S78%62% (path) S70%59% Inoperable C+S13%24% S17%11%

12. OEO5 conclusions Eagerly await survival and full surgical data This data says 4 cycles of chemotherapy safe and tolerable Will become the standard of care of pre-operative chemo therapy The outstanding questions are –Appropriate patient selection –Tri or bi-modality therapy.

13. Peri-operative Chemotherapy of Gastric Cancer: MAGIC trial Post-operative complications rates: similar –(CSC 47% S 45%), –as were deaths within 30 days of surgery 5-year survival rates: –Chemo+surgery:36% (30-43%) –surgery alone: 23% (17-29%)

14. ST03 projected accrual

15. ST03 Updated anastomotic leak numbers Oesophago-gastrectomy patients only

16. CROSS trial 368 patients, –275 (75%) had adenocarcinoma, –84 (23%) had squamous-cell carcinoma, and –7 (2%) had large-cell undifferentiated carcinoma R0 resection was achieved in –92% of patients in the chemoradiotherapy–surgery group versus –69% in the surgery group (P<0.001). Pathological complete response was achieved in –(29%) who underwent resection after chemoradiotherapy. –Postoperative complications were similar –in-hospital mortality was 4% in both. Median overall survival was –49.4 months in the trimodality group versus –24.0 months in the surgery group. (hazard ratio, 0.657; 95% confidence interval, 0.495 to 0.871; P=0.003). 16

17. Trials DEBIOC CROSS v MAGIC ST03 sub-study Currently bulky T3/4 tumours type 1 and 2 predicted by EUS and CT 17