1. Seasoning with... CPPD, 5FU? Uhm... Chopped Chopped first or at the end? BBQed, Steamed or microwaved Then... cooked or..... Marinating? With Taxanes, oxaliplatin Yummmy Sterilising? With heat and chemicals Oesophagus Think this is hard... Wait till you see the rest The Surgical/ Medical/ Rad Onc dilemma

2. OESOPHAGEAL CARCINOMA Uncommon cancer, accounting for approximately 1% of all malignancies and 6% of all gastrointestinal malignancies. Significant advances have been made in the staging and clinical treatment of patients with oesophageal cancer, the outcome for these patients remains bleak.

3. CARCINOMA OF THE OESOPHAGUS New cases per year Deaths per year 5 y OS Worldwide412,000338,000NR United States13,90013,00013.7% Europe44,00040,00012% Australia1208114715-20%

8. SURGERY ALONE

9. The more we chop,..... the better it gets! Dr Lee Surgeon

12. Surgical 5-year survival Stage I 50-80% Stage IIA 30-40% Stage IIB 10-30% Stage III 10-15%

14. RADIATION THERAPY ALONE COMPARED WITH CHEMORADIATION

15. A bit well done Dr Cook

16. NEJM, Volume 326:1593-1598 June 11, 1992Number 24 Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus A Herskovic, K Martz, M al-Sarraf, L Leichman, J Brindle, V Vaitkevicius, J Cooper, R Byhardt, L Davis, and B EmamiJune 11, 1992 CRTXRT median survival months 12.58.9 1 y Survival5033 2 y Survival3810 survivors257 G3-4 SE44-2025 -3 Local recurrence 16%24% 121 pts with SCC or adenocarcinoma of the thoracic oesophagus N- 61 CIV 5FU 1000 d 1-4 and cisplatin 75 d1 plus 50 Gy of XRT N=60 64 Gy of XRT alone The trial was stopped after the accumulated results in 121 patients demonstrated a significant advantage for survival in the patients who received CRT RTOG 8501

17. TI-3N0-IMO lesions adeno or SCC RT arm: 64 Gy (10 Gy per week in five fractions) CT-RT arm, RT 50 Gy plus Cisplatin 75 day 1, and 5FU 1.000 days 1-4 W 1 and 4 Cisplatin 75 day 1, and 5FU 1.000 days 1- 4 q 3/52 x 2

18. Time to first failureOverall Survival RTOG 8501 at 5 years, survival rates were 30% and 0%,

19. Oesophageal carcinoma: Single agent response rate Older drugsNewer drugs DrugResponse rate %DrugResponse rate % Antimetabolites 5 FU MTX Gemcitabine 21 11 6 Xeloda Pemetrexed S1 30 24 26 Antibiotics Mitomycin30 Anthracyclin Doxorubicin Epirubicin 17 18 Heavy Metal Cisplatin Carboplatin 23 9 OxaliplatinNA Topoisomerase Inh. Etoposide8Irinotecan21 Taxanes Paclitaxel Docetaxel 13 21

20. NEOADJUVANT CHEMORADIATION COMPARED WITH SURGERY ALONE Dinner is ready,.. I hope so anyway

21. 113 patients with adenocarcinoma of oesophagus Surgery N= 55 Cisplatin 75 d7 and 5FU 15 mg/kg/d CIV d1-5 W# 1 and 6 concurrent with Radiotherapy 40 Gy in 3 weeks N=58 surgery IRISH TRIAL

22. Median survival was 16 vs 11 months p= 0.01

23. 100 patients, squamous and adenocarcinoma Transhiatal oesophagectomy Cisplatin 20mg/m2/d d1-5 and d 17-21 5FU CIV 300mg/m2/d d1- 21 Vinblastin 1mg/m2/d d 1- 4 and 17-20 Plus Radiation 45 Gy 1.5 Gy bd Transhiatal oesophagectomy

24. 3 year survival 30% vs 16% p=0.15 mS= 17 months Median survival 50 mo vs 12 mo

25. 282 patients with SCC of oesophagus Surgery N= 55 Cisplatin 80 d1 and 21 concurrent with Radiotherapy 37 Gy 3.7 Gy fr split –course with 2 week interval surgery EORTC

26. m survival = 18.6 mo

27. Cisplatin 80 day 1, fluorouracil 800 days 1–4, with concurrent radiotherapy of 35 Gy given in 15 fr TROG IG 9401

28. M survival 19 vs 22 mo HR 0.89 p=0.57 Neoadjuvant therapy had a 13% pathologic complete resection. Also were more likely to undergo curative resection and have negative lymph nodes on histologic examination.

30. 56 patients with SCC and adeno of oesophagus Surgery Cisplatin 100 d1, 29 and 5FU 1000 CIV d1-4, 29-32 concurrent with Radiotherapy 50.4 Gy Surgery 5 yS 39 vs 16%, p=0.008

38. THANKS AND HAVE A GOOD NIGHT THANKS AND ENJOY YOUR LUNCH