WHO BENEFITS FROM ADJUVANT CHEMOTHERAPY RADIATION CHEMORADIATION? Dr. Paul Gardiner April 23, 2001 Discipline of Surgery Grand Rounds
LUNG Dr. Greenland ESOPHAGUS Dr. Gardiner
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 %.
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
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.
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)
Is there a Role for Neoadjuvant Therapy in Esophageal Cancer?
Rationale for Neoadjuvant Therapy Improves local control Enhances resectability by downsizing Allows assessment of response of first degree tumor Treats potential micrometastases
STAGING OF ESOPHAGEAL CANCER Clinical Examination Lab Work Chest X-Ray Barium Swallow Endoscopy / Biopsy CT
STAGING OF ESOPHAGEAL CANCER EUS PET CT - PET MR Laparoscopy Thorascopy Molecular Biology
CT Staging of Esophageal Carcinoma Determination of T status Determination of N status and nonregional LN status Determination of non-nodal MIB status
EUS Staging of Esophageal Carcinoma Determination of T status Determination of N status and nonregional LN status Determination of non-nodal MIB status
PET STAGING OF ESOPHAGEAL CARCINOMA
INDUCTION RADIOTHERAPY INDUCTION CHEMOTHERAPY INDUCTION CHEMORADIOTHERAPY
INDUCTION CHEMORADIOTHERAPY
Table 1. Nonrandomized trials of induction chemoradiotherapy and surgery Author Year Patients Chemo Rad CR (P) Mort Years of Survival Lackey 1989 15 C/F 30 29 6 35 (2 y) Forastiere 1993 43 C/F/V 45 24-35 (5 y) Naunheim 1995 28 C/F 36 17 0 38 (3 y) Bates 1996 35 C/F 45 51 8.5 41 (3 y) Jones 1997 54 C/F 45 41 11 32 (3 y) Suntharalingham 1997 32 C/F 50.4 13-41 (3 y) Chidel 1999 70 C/F 45 20 15.7 41 (3 y)
INDUCTION CHEMORADIOTHERAPY
Table 2. Randomized trials of induction chemoradiotherapy and surgery Author Year Patients Chemo Rad CR (P) Mort Years of Survival Nygaard 1992 47 C/B 35-24 17 (3 y) Le Prise 1994 41 C/F 20-8.5 19 (3 y) Walsh 1996 41 C/F 50 25 9.4 32 (3 y) Bosset 1997 143 C 37 26 12.3 18 (3 y)
INDUCTION CHEMORADIOTHERAPY Current Ongoing Trials RTOG 94-05 (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.
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.
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...?