delivering clinical research to make patients, and the nhs, better og neoadjuvant therapy...
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Delivering clinical research to make patients, and the NHS, better
OG neoadjuvant therapyBrachytherapyStephen Falk
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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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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).
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 weeksEndpoints: Clinical assessment and health-related quality of life (HRQL) weremeasured 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 thedysphagia-related scores at 3-months follow-up.
No difference in median survival
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
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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.
Individual Patient Data-based Meta-analysis Assessing Pre-operative Chemotherapy in Resectable Oesophageal Cancer
Thirion P et al. Abstr. 4512, ASCO 2007
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
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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.
MRC OEO2 vs INT113
OEO2INT113surgical resection
C+S 92%80%
S 97%96%
complete surgical resectionC+S 78%
62% (path)S 70%
59%Inoperable
C+S 13%24%
S 17%
11%
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.
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%)
ST03 projected accrual
ST03 Updated anastomotic leak numbersOesophago-gastrectomy patients only
Total (14%) ECX (8%) ECX + B (21%)
418
214 204
60
1842
Total Oesophagogastrectomies Leak
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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).
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Trials
• DEBIOC• CROSS v MAGIC• ST03 sub-study
• Currently bulky T3/4 tumours type 1 and 2 predicted by EUS and CT