Akshra Verma, MD, MS Dr. Sohail A. Chaudhry MD Esophageal Cancer Akshra Verma, MD, MS Dr. Sohail A. Chaudhry MD

Epidemiology ~ 13,900 new cases each year (2003) ~ 13,000 deaths each year Seventh leading cause of death Risk increases with age Mean age at diagnosis 67yrs Lifetime risk 0.8% for men 0.3% for women

Changing trends Until the 1970s Past 20-30yrs Squamous Cell Ca 75% AdenoCa 25% Past 20-30yrs Incidence of SCC has decreased both in AA and Caucasian Incidence of AdenoCa increased by 450% in Caucasian men and 50% in black AA men In 1994 60% of all esophageal cancers were adenocarcinoma.

Annual rate of neoplastic transformation of ~0.5% NEJM 2003; 349:2241-52

Progression of Barrett’s Esophagus 4% per year 1% per year 0.5 % per year

Clinical Symptoms Dysphagia Odynophagia Weight loss Less often: Dyspnea, cough, hoarseness and pain in retro-sternal, back or right upper abdominal Metastatic Disease: Lymphadenopathy (Virchow’s node), hepatomegaly, pleural effusion

Esophageal Carcinoma Adenocarinoma : 75% in distal esophagus Squamous Cell Ca: evenly distributed in middle and lower third AT DIAGNOSIS: More than 50% have unresectable tumors or radiographically visible metastasis

Esophagogram Showing a Malignant Esophageal Stricture NEJM 2003; 349:2241-52

Transmural Adenocarcinoma of the Esophagus Associated with Barrett's Esophagus NEJM 2003; 349:2241-52

Cancer of the Distal Esophagus with Metastasis to a Paraesophageal Lymph Node NEJM 2003; 349:2241-52

Current AJCC 2002 staging Cervical- 18cm from upper incisors Upper thoracic: 24 cm Mid thoracic- 32 cm Lower thoracic 40 cm Tumors of mid thoracic eso No A category as prognosis of a and b is the same

Predictors of prognosis. Staging of disease at diagnosis Weight loss of more than 10 percent of body mass Dysphagia Large tumors Advanced age lymphatic micrometastases (identified by immunohistochemical analysis) are

Treatment Surgical resection is the standard treatment for early esophageal cancer : Stages I, II and some cases of III During the past decade, outcomes with surgery have improved resulting in a better 5 year survival due to: Better staging techniques Improved surgical technique Recent Data Rate of curative resection : 54 to 69% Rate of operative mortality :4 to 10% perioperative complications : 26 to 41%

Types of esophagectomies Transhiatal ** Exposure is provided by an upper midline laparotomy and a left neck incision. The thoracic esophagus is bluntly dissected, and a cervical anastomosis created; thoracotomy is not required. Drawbacks: inability to perform a full thoracic lymphadenectomy, and lack of visualization of the midthoracic dissection. Transthoracic The Ivor Lewis esophagectomy combines a laparotomy with right thoracotomy, and produces an intrathoracic anastomosis. This technique permits direct visualization of the thoracic esophagus, and allows the surgeon to perform a limited lymphadenectomy. However formal dissection of lymph nodes is not performed **Lower rate of peri-operative complications (mainly fewer pulmonary complication, lower incidence of chylous leakage)

Five-Year Survival Rates for Esophageal Carcinoma

Role of Radiotherapy Radiotherapy : In pt with SCC of esophagaus and poor surgical candidates Advantage: avoidance of perioperative morbidity and mortality Not as effective palliative maneuver as surgery for dysphagia and odynophagia higher probability of local complications like esophagotracheal fistula Preoperative Radiotherapy: No survival advantage

Role of Chemotherapy Preoperative Chemotherapy (Cisplatin and Fluorouracil) : possible small benefit Preoperative Chemotherapy and Radiation therapy

Comparing Preoperative Chemotherapy and Radiotherapy with Surgery Alone NEJM 2003; 349:2241-52

Surgery alone Vs Combined modality therapy. Phase III study Median Survival: 11m 1 yr survival: 44% 2 yr survival: 26% 3 yr survival 6% Surgery N=55 Randomize N=113 Adeno Cis/5FU XRT Surgery N=58 Median Survival :16m 1 yr survival 52% 2 yr survival37% 3 yr survival 32% Two courses of chemotherapy in weeks 1 and 6 5 FU 15 mg per kg daily for five days Cisplatin, 75 mg per square m2 on day 7 Radiotherapy, 40 Gy, administered in 15 fractions over a 3-week period, beginning concurrently with the first course of chemotherapy. Walsh et al NEJM

Walsh et al Kaplan–Meier Plot of Survival of Patients with Esophageal Adenocarcinoma, According to the Intention-to-Treat Analysis. NEJM Vol 335:462-467

Walsh et al At the time of surgery: 42 % (23 of 55) of patients treated with preoperative multimodal therapy who could be evaluated had positive nodes or metastases versus 82 % (45 of 55) of patients who underwent surgery alone (P<0.001). 25 % of patients who underwent surgery after multimodal therapy had complete responses, as determined pathologically. NEJM Vol 335:462-467

Post op Chemo and Radiation Role is currently undefined No proven benefit in node negative patients Node positive patients may be benefited and should be enrolled in clinical trials as there is currently no evidence of benefit. Patients with incompletely resected tumors or positive margins should receive adjuvant chemoradiation if they can tolerate it, otherwise only XRT

Role of Chemotherapy Contd.. Preoperative Chemotherapy (Cisplatin and Fluorouracil) : possible small benefit Preoperative Chemotherapy and Radiation therapy Post op Chemotherapy and radiation therapy offered to pt with incomplete resection Non surgical Chemotherapy and radiation therapy: Long term survival in 25% of pts

Management of Advanced Stage IV Disease Chemoradiotherapy for palliation of symptoms Infusional 5-FU 1000 mg/m2 per day, days 1 to 4, and 29 to 33 Cisplatin 75 mg/m2, on days 1 and 29 Concurrent external beam RT (50.4 Gy in daily 2 Gy fractions) Shrinkage of the tumor by at least 50 percent may occur in 15 to 30% of patients who are treated with fluorouracil, a taxane (paclitaxel or docetaxel), or irinotecan Addition of cisplatin : 35 to 55 percent Response to chemotherapy typically lasts a few months, and survival rarely exceeds one year

Future Directions Cetuximab : Ab that blocks EGFR Synergy with both chemo and rad therapy in head & neck Ca and colorectal Ca Trastuzumab, targeted at HER-2/neu pathway in addition to cisplatin, paclitaxel and combined radiotherapy Bevacizumab, targeted at VEGF ligand Oral agents: inhibits tyrosine kinase associated with EGFR, OSI-774 and ZD 1839

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