HIPEC Heated Chemotherapy

HIPEC Heated Chemotherapy

In this procedure, the heated chemotherapeutic agent is administered in the abdominal cavity in patients, who have cancer, that spread to the peritoneum. The heated chemotherapy solution is administered into the abdominal cavity after cytoreductive surgery. Successful results can be obtained in certain types of cancer with this method. Heated chemotherapy (HIPEC) is implemented in combination with cytoreductive surgery. Successful results can be achieved with the combination of cytoreductive surgery and heated chemotherapy in the following cancer types:

1. Appendix Cancers (mucinous adenocarcinoma of the appendix)
2. Peritoneal Mesothelioma
3. Colorectal Cancers (cancers of colon and ileum)
4. Ovarian Cancer
5. Neuroendocrine Tumors
6. Stomach Cancer
7. Other Cancers Related to the Gastrointestinal System

These cancers may sometimes spread to the peritoneum and other organs. In such cases, neither surgery nor chemotherapy can be effective as a monotherapy. Heated chemotherapy combined with cytoreductive surgery is a new and effective approach in these hard-to-treat cancers. The first step in this treatment method is the removal of the visible tumor. (the goal of the cytoreductive treatment is to decrease the number of tumor cells in the body.)

Cytoreductive Surgery

The surgical approach to the advanced-stage ovarian, primary peritoneal, colon and stomach cancers evolved from the tumor-resection procedures towards more comprehensive surgical methods. The goal of this surgical intervention is the removal of all visible tumors affecting the peritoneum. Cytoreductive surgery is a rather complicated intervention, may last long hours, and can be carried out only by an experienced surgeon. During cytoreductive surgery, the surgeon removes the tumors using an electrosurgical handpiece. This device produces high temperatures with high-voltage electric current and cauterizes the cancerous tissue. These complicated procedures, which require obtainment of samples from several organs, take usually a long time, and require an experienced surgeon, who is highly educated about the abdominal anatomy.

Heated Chemotherapy

In heated chemotherapy, all enclosed organs are washed for once with a heated high-concentration chemotherapy drug after the removal of all visible tumor tissues. Research has shown that this special type of chemotherapy is effective against microscopic cancer, which cannot be removed with cytoreductive surgery. This approach may alleviate the necessity of a long and exhausting conventional chemotherapy in some patients.

Are You a Suitable Candidate for Heated Chemotherapy?

Patients with the following diagnoses are the most suitable candidates for heated chemotherapy:

1. Appendix cancer
2. Colon cancer
3. Desmoplastic small round cell tumors (usually common among adolescents and young adults)
4. Malignant ascites
5. Mesothelioma
6. Ovarian cancer
7. Peritoneal cancer
8. Stomach Cancer
9. Advanced cancers in the abdominal area

Heated chemotherapy is a long-term treatment for abdominal cancer in some patients. In other cases, heated chemotherapy enables an approach to untreatable cancers as if they were chronic rather than fatal diseases. Heated chemotherapy should not be used in the following conditions:

Heated chemotherapy is definitively not suitable for the following conditions:

1. ECOG performance>2
2. Cancers, which are considered inoperable with the imaging techniques
3. Cancers spread to extra-abdominal areas
4. Concomitant diseases, which prevent a comprehensive surgery (renal failure, heart disease, COPD, etc.)
5. High PCI (high score of intraabdominal pressure)

What Should You Expect?

Heated chemotherapy has several benefits in the advanced-stage intraabdominal cancers:

1. Fewer side effects
2. Improved quality of life
3. Minimum exposure to chemotherapy in other body parts
4. Increased cytotoxic effect of chemotherapy

INCREASE IN THE EXPECTED SURVIVAL TIME!

Heated Chemotherapy Procedure

The overall concept of the operation is always the same, although it varies slightly depending on the doctor and treatment center. The procedure has two phases: Surgical implementation and heated chemotherapy bath.

• Stage: Surgery

First of all, the tumor is removed with cytoreductive surgery as much as possible. This procedure may contain various surgical techniques, which aim the clearance of all visible cancerous structures in the abdominal cavity. Heated chemotherapy is not effective without surgery because the chemotherapeutic agent cannot penetrate the deep tissues. Cytoreductive surgery is a challenging intervention, as cancer may consist of thousands of small tumors spread to the whole peritoneum. In some cases, complete removal of the tumor cannot ve achieved and consequently other treatment options should be considered.

• Stage: Chemotherapy Bath

Even though the surgeon removes all visible tumors, microscopic tumor cells will be most probably left behind. These cells are a serious risk for the recurrence of cancer. Therefore, these cells are targeted with heated chemotherapy just after surgery. The goal is to kill as many tumor cells as possible and thus to prolong the expected survival rate and prevent a recurrence. As soon as the surgical intervention is completed, plastic tubes called catheters are inserted into the abdominal cavity. Then, these tubes are connected to the perfusion system (a device that heats and pumps the chemotherapeutic solution in the body and sucks it back). In addition, special catheters are placed into the abdominal cavity to monitor the temperature of the chemotherapeutic solution. After the insertion of all tubes and catheters, the incision is closed with stitches or clips. Then the perfusion system is switched on. The perfusion system pumps the saline solution into the abdominal cavity and then sucks it back. The solution is heated up to the targeted temperature (40.5-43 degrees) while passing through the device. Cancer cells start to die at 40 degrees, while normal cells can stay alive until 44 degrees. After the solution is heated to the desired temperature, one or more chemotherapeutic agents are added. The surgeon gives a massage to the abdominal wall during the pumping process of the solution and distributes the drug mixture into the abdomen. This massage provides a homogeneous mixing of the solution and facilitates the penetration of the cytotoxic agents to penetrate to all tissue levels. The chemotherapeutic agents are circulated between the device and the abdominal cavity for a given period. Although the process continued for 2 hours, most surgeons prefer approx. a 1-hour implementation. After the completion of the chemotherapy bath, the solution is drawn back. Then, the abdominal cavity is washed with a saline solution that does not contain any drug. Finally, the surgeon re-opens the incision and removes the tubes and catheters and then re-closes the incision for the last time. Cytoreductive surgery and heated chemotherapy may last together between 6 and 18 hours (it depends on the duration of the surgical procedure, which may change according to the clinical condition). The more cancer has spread into the abdominal cavity, the longer the surgery will last.

After the Procedure

Following the heated chemotherapy process, the patient is hospitalized for 10-12 days on average. Weakness is common after surgery and the mobilization of the patient is critical to prevent complications such as thrombosis. The postoperative recovery may last a few months. Your surgeon will inform you about all issues related to the recovery period including wound care. The feeling of weakness is usually the most challenging complication during the recovery period. You will probably feel normal after 2-3 months. Until then, it is important that you return to an active daily life (within your standards) and follow a suitable diet. During the recovery period, you should try to stand up and walk. You should increase your activity slowly from day to day.

Treatment after Heated Chemotherapy

Even though heated chemotherapy is administered for therapeutic purposes, peritoneal cancer is an aggressive disease and it can still relapse after a successful heated chemotherapy. The course of the disease after heated chemotherapy depends on several factors like the origin of the disease and disease stage at diagnosis, the extent of the possible resection during surgery, and the patient’s clinical condition. Not all patients get over the disease after heated chemotherapy but after this procedure, the survival period of the patient is not expressed in months but in years. Some patients may even be cured completely after this procedure. The physician may recommend continuing with systemic chemotherapy after heated chemotherapy to increase the success rate of this procedure. Systemic chemotherapy, which is initiated in 4-6 weeks after heated chemotherapy, is administered via oral and/or intravenous routes. This additional chemotherapy aims to delay the recurrence and metastasis to other organs like the liver and lungs. This procedure is called adjuvant chemotherapy. Adjuvant chemotherapy after heated chemotherapy is not useful in every patient. Several factors related to the special condition of the patient should be considered before the decision on adjuvant chemotherapy is made. In patients, who have undergone heated chemotherapy, certain problems may emerge after many years. There may be several issues patients want to ask. Therefore, a physician, who is experienced in peritoneal cancer and heated chemotherapy, should monitor the patient closely during this period. The outcome of heated chemotherapy may vary significantly from patient to patient. The outcome may change e.g. according to the origin of peritoneal cancer and the stage of the disease at diagnosis. In patients with Pseudomyxoma peritonei, in whom the tumor can be completely removed, satisfying results can be achieved following heated chemotherapy. In these patients, the disease can sometimes be totally cured. In patients with colon cancer or malignant mesothelioma, the full recovery is more uncommon. Nevertheless, the survival period is expressed in years rather than months after heated chemotherapy.

What are the benefits of heated chemotherapy?

Heated chemotherapy has several advantages over standard chemotherapy:
• Heated chemotherapy is usually implemented once. On the other hand, standard chemotherapy requires several sessions, which are implemented for weeks or months. If standard chemotherapy is implemented for a long period, it may become very expensive and distract the patient from the daily activities because of the repeated hospital visits.
• In heated chemotherapy, the chemotherapeutic drugs are directly administered into the abdominal cavity. This minimizes the toxic reactions because the drugs do not enter into the vascular circulation. Furthermore, the side effects are transient compared to standard chemotherapy, as the abdominal cavity is washed with a saline solution for the removal of the drugs. In standard oral and intravenous chemotherapy, chemotherapeutic drugs penetrate to all body parts and cause adverse effects.
• Heated chemotherapy is a more “focused” treatment and applied directly for certain cancer types. As the treatment is much more focused, higher doses of the chemotherapeutic agents can be used. Thus, the possibility to kill more cancer cells is higher compared to standard chemotherapy.
• Heating the chemotherapeutic agents enables a more effective destruction of the tumor cells compared to standard chemotherapy.
• Although heated chemotherapy is a relatively new treatment method, recent studies have shown that 25% of patients, who are diagnosed in the early stages of mesothelioma, can fully recover from the disease. This is a statistically significant improvement in the treatment outcome compared to standard chemotherapy, in which full recovery is rare.
• Several studies have demonstrated that heated chemotherapy increases the survival of carefully selected cancer patient groups. It was also reported that heated chemotherapy combined with cytoreductive surgery is more effective and useful compared to chemotherapy or surgery alone.
• Quality of life also increases significantly after heated chemotherapy following cytoreductive surgery. The rate of long-term side effects is minimized. After the recovery period, patients can return to their daily activities and the recovery is usually faster than in conventional surgery.
• This method can clear all visible cancer cells without causing complications like fluid accumulation and/or intestinal obstruction.

Side Effects

The majority of the side effects are caused by surgery rather than chemotherapy. According to the international literature, the rate of the serious side effects in surgery is 30%. An experienced surgeon with a highly qualified team will decrease the complication risk, that is why finding the appropriate surgeon is crucial. Possible side effects related to surgery:
• Pancreatitis (6-7%)
• Postoperative bleeding or intestinal leakage due to tissue damage (4-5%)
• Infection and bleeding risk due to a decrease in the number of leukocytes (10%)

Some of the possible side effects related to the chemotherapeutic agents:

• Nausea and vomiting: The severity of these side effects changes from patient to patient. An anti-emetic agent is administered if needed. After the surgery, you will notice a tube inserted into your stomach through your nose. This tube helps to prevent nausea (although it can cause also some discomfort).
• Predisposition to the infections: As chemotherapy is applied directly into your abdomen, the risk of a regional infection will increase. The infection risk is increased even no chemotherapy is administered. However, chemotherapy increases this risk in any case.
• Delay in recovery: Chemotherapy may slightly delay the recovery rate in your abdomen.
• Fatigue: Chemotherapy may make you feel tired and weak. You will need a long time to rest and recover up to your normal energy level especially chemotherapy is combined with a major surgical intervention.
• Diarrhea: This may also be an important problem. However, it will depend mostly on surgery rather than chemotherapy.
• Oral wounds: Wounds may appear in your mouth after the intervention. However, they are fairly uncommon. Consult your physician if you encounter this problem. You may have to use mouthwash.
All of these listed side effects are possible. You may experience none of them. The chemotherapeutic agents remain in the abdomen and do not enter the bloodstream. Therefore, most of the side effects (e.g. increased risk of infection and decrease in the recovery rate) will be related to the abdominal region.