WHO BENEFITS FROM ADJUVANT CHEMOTHERAPY RADIATION CHEMORADIATION? Dr. Paul Gardiner April 23, 2001 Discipline of Surgery Grand Rounds

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1 WHO BENEFITS FROM ADJUVANT CHEMOTHERAPY RADIATION CHEMORADIATION? Dr. Paul Gardiner April 23, 2001 Discipline of Surgery Grand Rounds

2 LUNG Dr. Greenland ESOPHAGUS Dr. Gardiner

3 ESOPHAGEAL CANCER 1200 new cases annually in US. Two (2) histologic subtypes squamous cell carcinoma and adenocarcinoma. Incidence of adenocarcinoma distal esophagus increasing dramatically in US & Europe. Primary risk factor is chronic heartburn leading to sequence of esophagitis Barrett's esophagus and ultimately adenocarcinoma. Overall 5 year survival rate remains a disappointing 5-10 %.

4 ESOPHAGEAL CANCER The decade of the 1990's saw the unprecedented introduction of new cancer chemotherpeutic agents. These drugs many with unique mechanisms of action and expanded spectra of activity have greatly improved the treatment options for many of the solid tumors such as lung, breast, colorectal, pancreatic and esophageal

5 ESOPHAGEAL CANCER Esophageal carcinoma is a lethal malignancy with an increasing incidence and a shift in histologic type from squamous carcinoma to adenocarcinoma. 30 % patients present with disseminated disease (STAGE IV) 50% STAGE II-III disease and are at high risk for systemic treatment failure and death despite adequate local therapy (surgery or chemoradiation) 20 % patients present with Stage 0 and Stage I disease.

6 ESOPHAGEAL CANCER Esophageal resection is the "gold standard " for esophageal cancer. Majority of patients are unable to undergo surgery however because of extent of disease or co-morbidities. Stage I - 5 year survival 80% Stage II - III (locally advanced) - 5 year survivals with complete resection 30-35%. (Poor long term success)

7 Is there a Role for Neoadjuvant Therapy in Esophageal Cancer?

8 Rationale for Neoadjuvant Therapy Improves local control Enhances resectability by downsizing Allows assessment of response of first degree tumor Treats potential micrometastases

9 STAGING OF ESOPHAGEAL CANCER Clinical Examination Lab Work Chest X-Ray Barium Swallow Endoscopy / Biopsy CT

10 STAGING OF ESOPHAGEAL CANCER EUS PET CT - PET MR Laparoscopy Thorascopy Molecular Biology

11 CT Staging of Esophageal Carcinoma Determination of T status Determination of N status and nonregional LN status Determination of non-nodal MIB status

12 EUS Staging of Esophageal Carcinoma Determination of T status Determination of N status and nonregional LN status Determination of non-nodal MIB status

13 PET STAGING OF ESOPHAGEAL CARCINOMA

14 INDUCTION RADIOTHERAPY INDUCTION CHEMOTHERAPY INDUCTION CHEMORADIOTHERAPY

15 INDUCTION CHEMORADIOTHERAPY

16 Table 1. Nonrandomized trials of induction chemoradiotherapy and surgery Author Year Patients Chemo Rad CR (P) Mort Years of Survival Lackey C/F (2 y) Forastiere C/F/V (5 y) Naunheim C/F (3 y) Bates C/F (3 y) Jones C/F (3 y) Suntharalingham C/F (3 y) Chidel C/F (3 y)

17 INDUCTION CHEMORADIOTHERAPY

18 Table 2. Randomized trials of induction chemoradiotherapy and surgery Author Year Patients Chemo Rad CR (P) Mort Years of Survival Nygaard C/B (3 y) Le Prise C/F (3 y) Walsh C/F (3 y) Bosset C (3 y)

19 INDUCTION CHEMORADIOTHERAPY Current Ongoing Trials RTOG (Planned 298 patients) High Dose v.s. conventional XRT Concomitant Cisplatinum/5FV CALGB 9781 (Planned 495 patients) Surgically resectable SCC/Adenocarcinoma Esophagus/ or/eg Junction Neoadjuvant Cisplatinum/ 5 FV and Concomitant Radiation and Surgery versus surgery alone.

20 FUTURE TRIALS May involve biochemical markers which may be predictive of chemotherapy response and resistance Thymidylate synthase P 53 and P 21 American College of Surgeons Oncology Group (ACOSOG) Trial Z0060 to determine utility of PET scanning in staging of patients with potentially operable carcinoma of esophagus.

21 FAQ'S Are further clinical trials essential to determine the role of chemotherapy, radiation and surgery...? Enthusiasm in the surgical community? Whether or not pathologic complete response patients still need surgery...? PET, Laparoscopy and Thoracoscopy and their roles in staging...? Other questions...?

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