Delivering clinical research to make patients, and the NHS, better

OG neoadjuvant therapyBrachytherapyStephen Falk

dd/mm/yyyy

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

3

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

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.

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

.

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

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).

17

Trials

• DEBIOC• CROSS v MAGIC• ST03 sub-study

• Currently bulky T3/4 tumours type 1 and 2 predicted by EUS and CT