1. Surgical treatment of esophageal cancer.

Society for Surgery of the Alimentary Tract (SSAT). Surgical treatment of esophageal cancer. Manchester (MA): Society for Surgery of the Alimentary Tract (SSAT); 2002. 3 p.

Treatment Treatment may be either curative or palliative, depending on the stage of the disease and the patient's condition. Curative treatment is most applicable to early lesions. If the lymph node spread is limited, even moderately advanced tumors may be cured by surgery. The earliest forms of cancer - high grade dysplasia and cancer contained within the mucosa may be treated by a limited esophagectomy with a high expectation of cure. Therapies directed at ablating the mucosa endoscopically for early cancer are still experimental. For more advanced but still potentially curable cancers, five year survival rates as high as 41% have been reported. Two recent studies have reported that even for patients with stage III disease, long-term survival can be achieved in 25-35% of patients following esophagectomy. Esophagectomy can be performed by either transthoracic or transhiatal approaches. Morbidity and mortality rates are now less than 10% as a result of improvements in surgical technique and perioperative care. The addition of chemotherapy or radiotherapy after operation (adjuvant therapy) has not been shown to be beneficial. The preoperative administration of chemotherapy and radiation (neo-adjuvant therapy) is gaining in popularity, and may possibly be superior to surgery alone but the evidence is not strong and the morbidity of the surgery may be increased by the preoperative therapy. In patients with advanced cancers, the disease is essentially incurable and the focus shifts towards palliation. If the tumor is resectable the best palliation is generally obtained by surgery. In unresectable tumors or where distant metastases are present, the survival is much shorter and excisional surgery is rarely justified. Dysphagia is fairly well palliated by a stent inserted endoscopically. 2. Neoadjuvant or adjuvant therapy for resectable esophageal cancer.

Gastrointestinal Cancer Disease Site Group. Malthaner RA, Wong RKS, Rumble RB, Zuraw L. Neoadjuvant or adjuvant therapy for resectable esophageal cancer. Toronto (ON): Cancer Care Ontario (CCO); 2005 Apr 13. 35 p. (Practice guideline report; no. 2-11). [65 references]

MAJOR RECOMMENDATIONS If surgery is considered appropriate, then surgery alone (i.e., without neoadjuvant or adjuvant therapy) is recommended as the standard practice for resectable thoracic esophageal cancer. 3. American Gastroenterological Association medical position statement: role of the gastroenterologist in the management of esophageal carcinoma.

Wang KK, Wongkeesong LM, Buttar NS. American Gastroenterological Association medical position statement: role of the gastroenterologist in the management of esophageal carcinoma. Gastroenterology 2005 May;128(5):146870. PubMed

Treatment of Esophageal Cancer Treatment of cancer is dependent on the stage of the cancer. Early cancers T1, N0, M0 by the American Joint Commission on Cancer are the most likely to be potentially curable. If the cancer is confined to the mucosa, these cancers are usually treated with esophagectomy, although endoscopic therapy has been shown to be effective in early squamous cell cancers of the esophagus treated in Japan using endoscopic mucosal resection. There is also some evidence that this approach may be successful in early adenocarcinoma. The risk of metastasis is very low if the cancer is confined to the mucosal layers. If there is penetration into the submucosa, the risk of metastasis becomes significant and esophagectomy would be recommended if there were no signs of distant metastasis or invasion of adjacent structures. If there is definite evidence of metastasis to regional lymph nodes, neoadjuvant chemotherapy in combination with radiation therapy administered before surgical resection may improve survival. Esophagectomy can be practiced by transhiatal or transthoracic routes. Minimally invasive esophagectomy has been advocated but is still associated with substantial morbidity and mortality. More advanced disease with metastasis to other organs or distant lymph node groups should be considered for palliative therapy with chemotherapy. Most commonly, combined therapy consists of chemotherapy with multiple courses of cis-platinum and 5-fluorouracil concomitantly given with ionizing radiation. 4. Management of oesophageal and gastric cancer. A national clinical guideline.

Scottish Intercollegiate Guidelines Network (SIGN). Management of oesophageal and gastric cancer. A national clinical guideline. Edinburgh (Scotland): Scottish Intercollegiate Guidelines Network (SIGN); 2006 Jun. 69 p. (SIGN publication; no. 87). [393 references]

Chemotherapy in patients with oesophageal cancer A - Postoperative adjuvant chemotherapy is not recommended for patients with oesophageal cancer 5. Information from the American Cancer Society Detailed Guide: Esophagus Cancer Surgery Depending on the stage of esophageal cancer, surgery may be used to remove the cancer and some of the surrounding tissue. Surgery can also be combined with other treatments such as chemotherapy and/or radiation therapy. An esophagectomy is a surgical procedure that involves removing the part of the

esophagus containing the cancer with a small amount of the proximal stomach and connecting the upper part of the esophagus, in most cases, to the remaining stomach. The stomach conduit becomes the new esophagus. Lymph nodes near the esophagus are also removed. The extent of the resection depends upon the stage of the tumor, its location, and the surgeons training. For cancers of the distal one third of the esophagus or GEJ, the part of the esophagus containing the cancer with a proximal margin of 8 to10 cm and the upper part of the stomach are removed. Depending on the approach, the stomach may be connected to the esophagus high in the chest or to the esophagus in the neck. If the tumor is in the upper or mid portion of the esophagus, the majority of the esophagus needs to be removed to get far enough above the cancer. The stomach will then be brought up and connected to the esophagus in the neck. If the stomach cannot be used, the surgeon may replace the removed part of the esophagus with a piece of the small or large intestine. This is a complex operation because the blood supply to that piece of intestine must be preserved. There are many different techniques and approaches used in operating on esophageal cancer. You will need to discuss this thoroughly with your surgeon, who may use pictures to describe how the operation will be done. Surgery can cure some patients whose cancer has not spread beyond the esophagus. Unfortunately, most esophageal cancers are not found early enough for doctors to offer curative surgery as a treatment option. Therefore, it is important to understand the goal of therapy, whether it is to cure or to ease symptoms. Surgery relieves dysphagia (difficulty swallowing) in more than 80% of patients. After they recover from the operation, patients find it easier to swallow food so they are better able to eat and maintain good nutrition. An esophagectomy is not a simple operation. Most patients remain in the hospital for 2 weeks after the surgery. Some surgeons are able to perform the operation using a laparoscopic technique. This means that small incisions are made to allow the placement of a laparoscope, which is like a tiny telescope that allows the surgeon to look into the area of interest. Then the surgery can be done with smaller incisions. This is called a minimally invasive procedure. Surgeons who perform these kinds of procedures must be highly skilled and experienced in this type of surgery. Like most operations, surgery of the esophagus has some risks that can lead to complications and lengthy hospitalization. A heart attack or a blood clot in the lungs or the brain can occur during the operation. There may be a leak at the place where the stomach connects to the esophagus. This complication is not as common as it used to be because of improvements in surgical techniques. After the operation, the stomach may empty too slowly because the nerves that control its contractions can be affected by surgery. This can, in a few cases, lead to frequent nausea and vomiting. Infection is a risk with any surgery. Strictures (narrowing) can form where the esophagus is surgically connected to the stomach and cause difficulty swallowing in about 10% to 15%

of patients. To relieve this symptom, these strictures can be expanded during an upper endoscopy procedure. After surgery, bile and stomach contents can enter the esophagus because the lower esophageal sphincter is often removed or changed by the surgery. This can cause symptoms such as heartburn. .Sometimes antacids or motility drugs can help relieve these symptoms. Some of these complications may be fatal. The risk of a fatal complication occurring is related to the hospital and doctor's experience with these operations. A study published in 1998 found that about 3% of patients die within 1 month of having this surgery at a hospital where the operations are done often. When the hospital has less experience, the rate may be as high as 17%. For this reason, patients should not hesitate to ask the surgeon about his or her experience with this procedure and what percent of their patients have died after this surgery. The hospital selected is also important and should make survival statistics available to its patients. In general, the best outcomes are achieved with surgeons and hospitals that have the most experience.

Detailed Guide: Esophagus Cancer

Radiation Therapy
Radiation therapy uses high-energy radiation to kill cancer cells. External-beam radiation therapy focuses radiation from outside the body on the cancer. This type of radiation therapy is most often used to treat esophageal cancer. Internal radiation therapy, also known as brachytherapy, places radioactive material directly into the cancer. Radiation therapy is used as the primary (main) treatment of esophageal cancer in some patients, especially people whose general health is too poor to undergo surgery. In fact, combined with chemotherapy, some doctors think radiation therapy is as effective as surgery. One recent clinical trial that compared surgery alone with radiation alone in early stage esophageal cancer found no difference in outcomes. The study was presented at the 2006 meetings of the American Society of Clinical Oncology. After surgery, radiation therapy can be used to kill tiny deposits of cancer that cannot be seen and removed during surgery. Radiation therapy can also be used to ease the symptoms of esophageal cancer such as pain, bleeding, difficulty swallowing, and symptoms caused by esophageal cancer that has spread to the brain. In advanced esophageal cancer, radiation therapy by itself does not cure esophageal cancer, but it can be a very effective therapy for relieving dysphagia. More than 70% of all patients treated with radiation will have at least temporary relief from dysphagia (difficulty swallowing). The advantage of this therapy for relief of symptoms is that it causes relatively few side effects. Most often, radiation therapy is combined with surgery and/or chemotherapy. Use of radiation therapy combined with chemotherapy might be curative for some people and provide good relief of symptoms and extend survival for others. Brachytherapy is useful in shrinking tumors so a patient can swallow more easily. In this procedure, radioactive seeds are placed into the tumor through an endoscope. It is used mainly to relieve symptoms because it cannot be used to treat a very large area. Side effects of radiation therapy may include skin problems, upset stomach, diarrhea, and fatigue.

The major problem people have is pain with swallowing as the radiation kills the normal lining cells of the esophagus. This will go away as these cells regrow. Most of the side effects are temporary. Chemotherapy may also make the side effects of radiation worse. Chest radiation therapy may cause lung damage and lead to difficulty breathing and shortness of breath. It is important to talk with your doctor before and during treatment about ways to reduce the side effects of treatment.

Detailed Guide: Esophagus Cancer

Chemotherapy
Chemotherapy involves the use of drugs that are given through a vein or by mouth. These drugs enter the bloodstream and reach all areas of the body, making this treatment useful for cancer that has spread to organs beyond the esophagus. Depending on the type and stage of esophageal cancer, chemotherapy may be given as a main (primary) treatment or before (neoadjuvant) or after (adjuvant) surgery. Primary chemotherapy will usually not cure esophageal cancer unless radiation therapy and, in some cases, surgery is also used. There are 3 situations in which chemotherapy is used: Palliative therapy: The goal of palliative therapy is to control symptoms, such as dysphagia (difficulty swallowing) and pain. Palliative therapy can be used in combination with other treatments that are intended to cure disease, or it can be used alone when a cure is not possible. Preoperative chemotherapy: Chemotherapy may be given before surgery to reduce the tumor size and possibly allow a more complete surgical removal of the tumor. Use of chemotherapy alone in this situation is still being studied and is not a standard treatment. Chemoradiotherapy: Chemotherapy together with radiation therapy can shrink the cancer and is sometimes used before surgery to make surgery easier. Many doctors think the chances for cure are better if chemoradiotherapy is given before surgery. A recent report from a national group of researchers called CALGB found that the triple therapy is better than surgery alone. Patients who received chemoradiotherapy followed by surgery had a 5 year survival of 39% versus 16% for people who only had surgery. The study was presented at the 2006 meetings of the American Society of Clinical Oncology. Other studies have not yet shown this benefit. Chemotherapy and radiation therapy may also be used together in some patients who are not able to undergo surgery. Many people think this may be as effective as surgery, although there are no clinical trials to prove this. The chemotherapy drugs used to treat esophageal cancer include 5-fluorouracil (5-FU), cisplatin, carboplatin, bleomycin, mitomycin, doxorubicin, methotrexate, paclitaxel, vinorelbine, topotecan, and irinotecan. In chemoradiotherapy, the most frequently used drugs are 5-FU and cisplatin given together. About 10% to 40% of patients respond to these drugs and their tumors shrink significantly. About 17% to 50% of patients with advanced disease respond to combinations of these drugs. Chemotherapy drugs kill cancer cells but also damage some normal cells, causing side effects. Therefore, careful attention must be given to avoid or minimize these side effects, which depend on the specific drugs used, their dose, and the length of treatment. Temporary side effects might include nausea and vomiting, loss of appetite, loss of hair, and mouth sores. It is important for people receiving chemotherapy to tell the cancer care team right away if they have any of these side effects, so they can be managed effectively. Because chemotherapy can damage the blood-producing cells of the bone marrow, patients may have low blood cell counts. This can result in an increased chance of infection (because of a

shortage of white blood cells), bleeding or bruising after minor cuts or injuries (due to a shortage of blood platelets), and fatigue or shortness of breath (due to low red blood cell counts). Most side effects disappear once treatment is stopped. There are medications or strategies to treat many of the temporary side effects of chemotherapy. For example, drugs to prevent or reduce nausea and vomiting can be given.

Overview: Esophagus Cancer

Moving on After Treatment

Follow-up tests: Tests such as the upper GI, barium swallow and CT scans may be done to see if the cancer has come back or if you have a new tumor. It is important that you report any new symptoms to the doctor right away, especially if they include trouble swallowing or chest pain. Early treatment can relieve many symptoms and may improve your quality of life. Cancer of the esophagus often causes trouble with swallowing. For this reason, weight loss and weakness due to poor nutrition are common problems. Your doctor can help you find the information you need to cope with nutrition problems. If you have pain from your cancer, be sure to tell your doctor. There are many ways to control cancer pain. If you smoke, its very important to quit. Your appetite will improve and so will your overall health. And quitting helps reduce the chance of getting a new cancer. Remember that your body is unique, and so are your emotional needs and your personal circumstances. In some ways, your cancer is like no one else's. No one can predict how your cancer will respond to treatment. Statistics can paint an overall picture, but you may have special strengths such as a healthy immune system, a strong family support system, or a deep spiritual faith. All of these have an impact on how you cope with cancer. Your doctor or nurse can suggest other resources that might help you during your recovery from treatment. There are many support groups that provide emotional support, friendship, and understanding. If at any time you are having trouble coping, talk with your doctor, nurse, or social worker about your concerns. They may also suggest a therapist or mental health professional to help you.

Overview: Esophagus Cancer

Whats New in Esophageal Cancer Research?

Research on the treatment and prevention of this cancer is now being done at many places across the nation. For example, changes in certain genes seem to cause normal cells to change into cancer cells. Once more is known, we might be able to design tests to find cancer of the esophagus at an earlier stage. In the future it might even be possible to find a way to repair these cancer cells. Studies are also being done on new ways to combine chemotherapy drugs to get the best results. Other studies are testing ways to combine chemotherapy and radiation treatment. Likewise, drugs that block new blood vessels from forming and feeding the tumor will be tested for cancer of the esophagus. There are also studies going on of treatments that boost the patients immune system to better fight the cancer. One approach uses special antibodies (monoclonal antibodies) made in the lab to seek out cancer cells. Right now, this method is being tested in clinical trials.

Efforts are also being made to reduce obesity, a major risk factor for this cancer. Researchers are also looking at ways to find and treat Barrett esophagus.

6. Anticancer Res. 2007 Jul-Aug;27(4C):2845-8. A phase II trial of weekly irinotecan in cisplatin-refractory esophageal cancer. Burkart C, Bokemeyer C, Klump B, Pereira P, Teichmann R, Hartmann JT. BACKGROUND: This study [in Germany] investigated the efficacy and toxicity of weekly single-agent irinotecan in patients with metastatic disease relapsing after cisplatin-based chemotherapy. PATIENTS AND METHODS: Fourteen patients were enrolled. A total number of 29 cycles (one cycle consisted of CPT-11 100 mg/m2 on days 1, 8, 15, qd 28) were applied. Irinotecan was continued until disease progression or unacceptable toxicity occurred. Where toxicity was less than WHO grade 3, the dose of irinotecan was escalated in 20 mg steps in subsequent cycles up to a maximum dose of 140 mg/m2. Patients were assessed for response according to WHO criteria every second cycle. RESULTS: Of the 13 evaluable patients, 2 achieved a partial response (PR) and 3 disease stabilisation (NC); progressive disease (PD) was noted in 8 patients. Median time to progression was 2 months (range: 1-8 months) and median survival from start of study treatment was 5 months (range: 2-16 months). Grade 3 toxicity consisted of diarrhea (n=3), fever (n=1) and pain (n=1). CONCLUSION: Single-agent irinotecan has moderate activity in cisplatinrefractory esophageal cancer.

7. Prospective nonrandomized comparison of two modes of argon beamer (APC) tumor desobstruction: effectiveness of the new pulsed APC versus forced APC.
Eickhoff A, Jakobs R, Schilling D, Hartmann D, Weickert U, Enderle MD, Eickhoff JC, Riemann JF. Medical Department C, Klinikum Ludwigshafen GmbH, Ludwigshafen, Germany. eickhofa@klilu.de BACKGROUND AND STUDY AIM: Argon plasma coagulation (APC) has become an established noncontact method of tumor palliation in a variety of locations. The present prospective study evaluated a new APC system (APC-2) using amplified power settings and different application modes, such as intermittent energy delivery (pulsed APC) in comparison with the conventional technique (forced APC). PATIENTS AND METHODS: A total of 100 patients with esophageal, gastric, or rectal tumors were alternately (but not randomized) enrolled and treated with either pulsed APC (n = 46) or forced APC (n = 54). Parameters to assess the palliative effect were: amount of lumen restoration ((1/3), (2/3), complete), objective planimetry, stenosis length, treatment time, and number of

APC sessions. RESULTS: Overall response rate was similar in both groups (pulsed 83 %, forced 87 %), the same was found in the subgroups with different amounts of lumen restoration and for the other objective parameters. However, the tumor debulking effect was achieved in a significantly shorter median treatment time with forced compared with pulsed APC (13.6 vs. 18.2 minutes, P = 0.03), with a similar number of treatment sessions in both groups. Complications also occurred with similar frequency in both groups. CONCLUSIONS: There was no significant difference in overall local tumor response between the two modes of APC application. However, data from this nonrandomized study suggest a faster achievement of response with forced APC. A combination of both modes may be superior. PMID: 17611919 [PubMed - indexed for MEDLINE] 8. Semin Surg Oncol. 1992 Jul-Aug;8(4):191-203.

Links

Laser and photodynamic therapy of esophageal cancer.

Overholt BF. Laser/Hyperthermia Department, Thompson Cancer Survival Center, Knoxville, Tennessee 37916. With proper selection of patients with non-operative esophageal cancer, palliative therapy with Nd:YAG laser enhances the quality of life by improving the patient's ability to swallow soft or solid food. Also, the use of non-thermal laser light to initiate the process of photodynamic therapy (PDT) is an additional laser technique that appears effective, not just in palliative treatment, but also in the cure of early esophageal cancer. For PDT, considerable work will be necessary to provide standard techniques in tumor staging, light and drug delivery and in light dosimetry. Ultimately, palliative and curative therapy of esophageal cancer will most likely incorporate multiple modalities, including surgery, radiation, chemotherapy, stents, laser and other thermal modalities, photodynamic therapy, and combinations of these methods. PMID: 1379371 [PubMed - indexed for MEDLINE] 9. Esophageal Cancer (PDQ): Treatment (from the National Cancer Institute) http://www.cancer.gov/cancertopics/pdq/treatment/esophageal/healthprofessional/

Esophageal cancer is a treatable disease, but it is rarely curable. The overall 5-year survival rate in patients amenable to definitive treatment ranges from 5% to 30%. The occasional patient with very early disease has a better chance of survival. Patients with severe dysplasia in distal esophageal Barrett mucosa often have in situ or even invasive cancer within the dysplastic area. Following resection, these patients usually have excellent prognoses. Primary treatment modalities include surgery alone or chemotherapy with radiation therapy. Combined modality therapy (i.e., chemotherapy plus surgery, or chemotherapy and radiation therapy plus surgery) is under clinical evaluation. Effective palliation may be obtained in individual cases with various combinations of surgery, chemotherapy, radiation therapy, stents,[5] photodynamic therapy,[6-8] and endoscopic therapy with Nd:YAG laser. [9] 10. Additional information from the National Cancer Institute on ongoing clinical trials: http://www.cancer.gov/search/ResultsClinicalTrials.aspx?protocolsearchid=3711037

11. Medical

News Summary: New treatment for esophageal cancer involves laser light

About: New treatment for esophageal cancer involves laser light Date: 3 January 2005 Source: Kansas City Nursing News Author: Lisa Waterman Gray Medical News Summary (summary of medical news story as reported by Kansas City Nursing News): A novel treatment is now available in some places for treatment of esophageal carcinoma. The treatment, called Photodynamic Therapy (PDT), involves treating the cancer cells with photosensitive drugs and then applying red laser light to destroy the target cells. The therapy is highly effective for treating Barretts esophagus which usually develops in GERD patients. Traditionally, surgical esophagectomy was the only treatment available and it required a 3-4 week hospital stay. The new therapy is much quicker and cheaper and less invasive. Surgery has a complication rate of 29% and costs more than $88,000 compared to PDT which is about $35,000. Side effects of PDT include nausea, mild constipation, chest discomfort and a constricted feeling in throat. A major side effect of the treatment is extreme light sensitivity which means that treated patients must virtually totally avoid direct and indirect sunlight for a minimum of six weeks. The treatment is not suitable for people who have had previous high-dose radiotherapy treatment, have poor pulmonary function, have multifocal or multilobar disease as well as certain other conditions. 10-15% of GERD sufferers eventually develop Barretts esophagus

of which only 1-2% develop into esophageal cancer. 13,000 new cases of esophageal cancer are diagnosed annually and it causes 12,500 deaths annually. URL: http://www.zwire.com/site/news.cfm? newsid=13671092&BRD=1441&PAG=461&dept_id=155395&rfi=6 12. Yale Cancer Center http://ycctrials.med.yale.edu/detail.asp?nm=cdr62960
Stage IV Esophageal Cancer

Treatment of stage IV esophageal cancer may include the following:

External or internal radiation therapy as palliative therapy to relieve symptoms and improve quality of life. Laser surgery or electrocoagulation as palliative therapy to relieve symptoms and improve quality of life. Chemotherapy. Clinical trials of chemotherapy.

This summary section refers to specific treatments under study in clinical trials, but it may not mention every new treatment being studied. Information about ongoing clinical trials is available from the NCI Web site.

Treatment Options for Recurrent Esophageal Cancer

Treatment of recurrentesophagealcancer may include the following:

Use of any standard treatments as palliative therapy to relieve symptoms and improve quality of life. Clinical trials of new therapies used before or after surgery.

This summary section refers to specific treatments under study in clinical trials, but it may not mention every new treatment being studied. Information about ongoing clinical trials is available from the NCI Web site.