01923f775fa54eb98c267ffe01366e7c HUHEsophageal Ca Study1

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					Esophageal Cancer Study Analysis of Hahnemann University Hospital Cancer Registry Data 1990-2002 Ari D. Brooks, MD Physician Advisor

In 2003, an estimated 13,900 new cases of esophageal cancer will be diagnosed in the United States and approximately 13,000 Americans will die of this disease. Etiology and risk factors: While risk factors for squamous cell carcinoma of the esophagus have been identified (such as tobacco, alcoholism, malnutrition, infection with human papillomavirus), the risk factors associated with esophageal adenocarcinoma are less well defined. The most important epidemiological difference between squamous cell cancer and adenocarcinoma, however, is the strong association between gastroesophageal reflux disease (GERD) and adenocarcinoma. Barrett’s Esophagus Long-term irritation can increase the risk of esophageal cancer. Tissues of the lower esophagus can become irritated if stomach acid frequently “backs up” into the esophagus (gastric reflux). Over time, abnormal intestinal epithelium replaces the stratified squamous epithelium that normally lines the distal esophagus. This condition is a premalignant condition that may develop into adenocarcinoma of the esophagus. The frequency, severity, and duration of reflux symptoms are positively associated with increased risk of esophageal adenocarcinoma. Signs and symptoms:  Difficult or painful swallowing  Severe weight loss  Pain in the throat or back, behind the breastbone or between the shoulder blades  Hoarseness or chronic cough  Vomiting  Coughing up blood  Regurgitation Diagnosis: The diagnosis of esophageal cancer is usually made by biopsy through a flexible, fiberoptic endoscope. Other diagnostic tests include the following: endoscopic ultrasound, CT scan, MRI, barium swallow, laparoscopy, and bronchoscopy. From 1990 through 2002, the Hahnemann University Hospital (HUH) Cancer Registry accessioned 107 patients with carcinoma of the esophagus.

HAHNEMANN UNIVERSITY HOSPITAL Esophageal Cancer Study – continued July 22, 2003

Esophageal Cancer at Hahnemann University Hospital 1990-2002 (n=107)
Number of Patients

21 15

20 15 10 5 0
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002

9 2 3

10 8 5 7 8

11 4 4

Year of Diagnosis

Esophageal cancers occur more commonly in men than women (3.3:1 in the HUH population; 82 males and 25 females) and Caucasians outnumbered African Americans by 2 to 1 (70 whites and 35 blacks). Two Asians were diagnosed with esophageal cancer during the time period.

Esophageal Cancer by Race at Hahnemann University Hospital 1990 - 2002 (n = 107)
Asian 2%

Black 33%

White 65%

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HAHNEMANN UNIVERSITY HOSPITAL Esophageal Cancer Study – continued July 22, 2003

Ages ranged from 39 to 90 years. The peak incidence is in the sixth and seventh decades of life as is illustrated below.
Esophageal Cancer 1990 - 2002 Hahnemann University Hospital Age at Diagnosis (n = 107)

45 40 35

Number of Patients

30 25 20 15 10 5 0 30-39 40-49 50-59 60-69 70-79 80-89

Female Male


Age in Years

Esophageal cancer by county of residence at diagnosis is shown below.
PA County Philadelphia Montgomery Bucks Luzerne PA unknown Carbon Lancaster Venango Delaware Lehigh Outside PA: New Jersey Delaware New York TOTAL Number 58 12 6 2 2 1 1 1 1 1 19 2 1 107 Percentage 54 11 6 2 2 <1 <1 <1 <1 <1 17 2 <1 100%

Topography: Cervical esophagus: The cervical esophagus begins at the lower border of the cricoid cartilage and ends at the thoracic inlet approximately 18 cm from the upper incisor teeth Intrathoracic esophagus:

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HAHNEMANN UNIVERSITY HOSPITAL Esophageal Cancer Study – continued July 22, 2003

Upper thoracic portion – the upper thoracic portion extends from the thoracic inlet to the level of the tracheal bifurcation, approximately 24 cm from the upper incisor teeth. Midthoracic portion – this is the portion of the esophagus between the tracheal bifurcation and the distal esophagus just above the esophago-gastric junction. The lower level of this portion is approximately 32 cm from the upper incisor teeth. Lower thoracic portion – approximately 8 cm in length, the lower thoracic esophagus includes the intra-abdominal portion of the esophagus and the esophago-gastric junction. The latter is approximately 40 cm from the upper incisor teeth.
Topography of Esophagus Upper 1/3, proximal 1/3, cervical, upper thoracic Thoracic esophagus Middle 1/3, mid-thoracic Lower 1/3, distal 1/3, lower thoracic, abdominal esophagus Overlapping lesion Esophagus, not otherwise specified (NOS) TOTAL ICDO Code C15.0 C15.3 C15.1 C15.4 C15.5 C15.2 C15.8 C15.9 Number Patients 18 7 13 57 6 6 107 Percentage 17 6 12 53 6 6 100%

Histologic Types:

Esophageal Cancer by Histology 1990-2002 (n=107)
2% 3% 8%

Squamous Cell Ca Adenocarcinoma Neoplasm/Carcinoma Ca in situ



Adenosquamous Ca All others

Historically, most esophageal cancers were squamous cell tumors. Recently, however, there has been a marked increase in adenocarcinoma of the esophagus, primarily among white men. In fact, among white men, rates of adenocarcinoma of the esophagus nearly equal those of squamous cell tumors. At HUH, there were 31 white males with squamous cell carcinoma and 29 white males with adenocarcinoma.

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HAHNEMANN UNIVERSITY HOSPITAL Esophageal Cancer Study – continued July 22, 2003

Esophageal Cancer by Race and Histology 1990 - 2002 (n=107)


Other Adenoca SCC

Number of Patients





29 2


Black Race

Asian 0

Staging system: Although esophageal cancers may extend over wide areas of the mucosal surface, only the depth of penetration is considered in staging. Regional lymph nodes, distant lymph nodes and distant sites are assessed to complete the staging of these tumors. Stage of disease at the time of diagnosis for 107 patients diagnosed at HUH from 1990 to 2002, is illustrated below.
Esophageal Cancer 1990 - 2002 Hahnemann University Hospital Stage of Disease at Diagnosis (n=107)
Unstaged 14% Stage 0 3%

Stage I 4%

Stage IV 20%

Stage II 29% Stage III 30%

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HAHNEMANN UNIVERSITY HOSPITAL Esophageal Cancer Study – continued July 22, 2003

Staging of Esophageal Cancer: Stage 0 I IIA T Tis T1 T2 T3 IIB T1 T2 III T3 T4 IV IVA N N0 N0 N0 N0 N1 N1 N1 Any N M M0 M0 M0 M0 M0 M0 M0 M0 M1 Description
Carcinoma in situ Tumor invades lamina propria or submucosa Tumor invades muscularis propria Tumor invades adventitia Tumor invades lamina propria or submucosa and regional lymph node metastasis Tumor invades muscularis propria and regional lymph node metastasis Tumor invades adventitia and regional lymph node metastasis Tumor invades adjacent structures Distant metastasis (liver, lung, pleura, and kidneys are most common sites)

# pts %

3 4

3 4





Any T Any N Any T Any N

M1a Lower thoracic esophagus - mets to celiac LNs
Upper thoracic esophagus – mets in cervical LNs




Any T Any N

M1b Lower thoracic esophagus - other distant mets
Midthoracic esophagus - nonregional LNs and/or other distant metastasis Upper thoracic esophagus – other distant mets




Treatment: Treatment of esophageal cancer depends on a number of factors, including the size, location, and extent of the tumor, and the general health of the patient. Patients often need a team of specialists including a gastroenterologist, surgeon, medical oncologist, and radiation oncologist. Because cancer treatment may make the mouth sensitive and at risk for infection, patients are often advised to see a dentist for a dental exam and treatment before cancer treatment begins.
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HAHNEMANN UNIVERSITY HOSPITAL Esophageal Cancer Study – continued July 22, 2003

Many different treatments and combinations of treatments may be used to control the cancer and/or improve the patient’s quality of life by reducing symptoms. Surgery Surgery is the most common treatment for esophageal cancer. Usually the tumor along with all or a portion of the esophagus, nearby lymph nodes, and other tissue in the area are removed. Radiation therapy Radiation therapy may be used alone or combined with chemotherapy as primary treatment instead of surgery, especially if the size or location of the tumor would make an operation difficult. Radiation therapy with chemotherapy may be used to shrink the tumor before surgery. Even if the tumor cannot be removed by surgery or destroyed entirely by radiation therapy, radiation therapy can often help relieve pain and make swallowing easier. Chemotherapy Chemotherapeutic drugs used to treat esophageal cancer include 5-fluorouracil (5FU), cisplatin, bleomycin, mitomycin, doxorubicin, methotrexate, paclitaxel (Taxol), vinorelbine, topotecan, and irinotecan. Laser therapy High-intensity light may be used to destroy cancerous tissue and relieve a blockage in the esophagus when the cancer cannot be removed by surgery. Photodynamic therapy (PDT) In PDT, the photosensitizing agent is injected into the bloodstream and absorbed by cells all over the body. The agent remains in cancer cells for a longer time than it does in normal cells. When the treated cancer cells are exposed to laser light, the photosensitizing agent absorbs the light and produces an active form of oxygen that destroys the treated cancer cells. Combined Modality treatment Postoperative combined modality treatment (chemotherapy plus radiation therapy) is recommended for patients with Stage II and III esophageal carcinoma. Nutrition for Cancer Patients Eating well during cancer treatment means getting enough calories and protein to control weight loss and maintain strength. Eating well often helps people with cancer feel better and have more energy. However, many people with esophageal cancer find it hard to eat well because they have difficulty swallowing. Patients may not feel like eating if they are uncomfortable or tired. Also, the common side effects of treatment, such as poor appetite, nausea, vomiting, dry mouth, or mouth sores, can make eating difficult. Foods may taste different. Many patients receive a temporary gastrostomy tube for nutritional support.
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HAHNEMANN UNIVERSITY HOSPITAL Esophageal Cancer Study – continued July 22, 2003

Treatment by Stage of Disease in Esophageal Cancer: Treatment of 92 patients with esophageal cancer diagnosed between 1990 and 2002 are shown below. Fifteen patients diagnosed during this time period are excluded because a stage of disease was not assigned at diagnosis. Treatment by Stage of 92 esophageal cancer patients:
1st Course Rx Summary Stage 0 Stage I Stage II Stage III Stage IV Total

Surgery only Radiation only Chemotherapy only Surgery + Radiation Radiation + Chemo Surgery + ChemoRx Surgery + RT + Chemo Chemo + Other None TOTAL Survival Analysis:



1 1 1 3

10 4 1 1 7 3 5

6 7 1 2 6 2 3 6 33

4 4 1 4 1 1 6 21



24 15 3 3 18 5 10 1 13 92

United States mortality rates for esophageal cancer are nearly as high as incidence rates in the SEER regions, reflecting the generally poor survival for patients with this cancer. Five-year survival analysis for 64 patients diagnosed with esophageal cancer between January 1, 1990 and December 31, 1998 was done using the observed (actuarial) method. SEER 5-year survival rates for patients diagnosed in 1992-1999 are also illustrated.

AJCC TNM Stage at Diagnosis 0 I II III IV Overall

HUH (1990 – 1998) # of cases 1 1 23 23 16 64 cases % 5-year Survival 0% 0% 26.1% 14.5% 0% 13.3%

SEER (1992 – 1999) % 5-year Survival -29.1% 13.1% 2.2% 14.0% Summary Stage -Localized Regional Distant 7,012 cases

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HAHNEMANN UNIVERSITY HOSPITAL Esophageal Cancer Study – continued July 22, 2003

Survival rates were computed by the actuarial method, compounding survival in onemonth intervals from the date of diagnosis, with death from any cause as the endpoint.
Esophageal Cancer 5-Year Survival at Hahnemann University Hospital by AJCC Stage at Diagnosis 1990-1998 (n = 64)
100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60

Percent Surviving

Stage 0 (1 pt) Stage I (1 pt) Stage II (23 pts) Stage III (23 pts) Stage IV (16 pts)

Number of Months

There was some survival difference if analyzed by gender (12.7% of males survived 5 years versus 18.2% of females). But analysis by race showed little difference (13.3% of whites survived 5 years versus 11.2% of blacks). The histologic type of tumor also influenced survival. Patients with squamous cell carcinoma did better than those diagnosed with adenocarcinoma (20.4% versus 5%). Age at diagnosis also played a role in overall survival. Patients over the age of 60, did worse than younger patients. Five-year survival by age group was: under 60 years: 30.7%, 60-69 years: 5.6%, and 70+ years: 4.3%. The two graphs below illustrate survival differences based on histology and age.

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HAHNEMANN UNIVERSITY HOSPITAL Esophageal Cancer Study – continued July 22, 2003

Esophageal Cancer 5-Year Survival at Hahnemann University Hospital by Histologic Type 1990-1998 (n = 62)

Percent Surviving

80% 60% 40% 20% 0%
0 3 6

Squamous Cell Ca (42 pts) Adenocarcinoma (20 pts)

9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60

Number of Months

Esophageal Cancer 5-Year Survival at Hahnemann University Hospital by Age at Diagnosis 1990-1998 (n = 72)
Age under 60 (25 pts)

100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60

Age 60-69 (24 pts) Age 70+ (23 pts)

Percent Surviving

Number of Months

Heavy alcohol consumption, cigarette smoking, and possibly, other types of tobacco use each substantially increase the risk of esophageal cancer among persons in developed countries. The use of tobacco and alcohol, in combination, results in even larger elevations in risk. In developing countries, nutritional deficiencies related to lack of fresh fruit and vegetables, drinking hot beverages, and a range of chewing and smoking habits are also important risk factors.
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