Hot Chemotherapy

Hot Chemotherapy

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Terminology: In English, we can translate the definition of “Hyperthermic Intraperitoneal Chemotherapy” as “Hot chemotherapy into the abdomen”. We will briefly refer to it as “Hot Chemotherapy”.

Why is chemotherapy applied to the abdomen?

Many types of cancer originating from intra-abdominal organs can hold onto the intraperitoneal membrane called the “peritoneum”. The peritoneum is a thin tissue that covers both the inner face of the abdominal wall and the surface of the organs and secretes fluid in small quantities to ensure that the organs are slippery. In a cancer originating from intra-abdominal organs, cancer cells may spread to the peritoneum by spilling into the neighborhood or into the abdomen. This usually indicates that the cancer has reached the last stage. Systemic chemotherapies, meaning intravenous chemotherapies, are insufficient in peritoneal cancers because drugs cannot reach peritoneum completely in these treatments. The main principle of this treatment is to remove residual cancer cells by giving chemotherapeutic agent that has been heated in the abdomen (cytoreductive surgery) after removing the intra-abdominal cancer organs and tissues.

The aim of “Hot Chemotherapy”

Why is chemotherapy given by heating? What are the effects of heat?

*  Heat facilitates penetration of the drug into the tissue

*  Heat enhances the killing effect of the selected chemotherapeutic agent on cancer cells.

*  The heat itself has anti-tumor effect

*  Intraoperative chemotherapy can be manually manipulated to spread within the abdomen, contributing to the uniform distribution of the drug to all surfaces within the abdomen

*  During the operation, the adverse effects of the drug on the kidney and urine output can be monitored very well (can be tracked and measures can be taken).

*  During the course of hot chemotherapy, many physiological parameters of the patient (body temperature, coagulation, hemodynamics, etc.) can be normalized over time.

*  During hot chemotherapy (60 min), tumor cells are mechanically cleared from the small intestine surfaces and through the clot-fibrin layers

Hot Chemotherapy is applied in which patients-diseases?

It is most commonly used in the treatment of women with ovarian cancer. However, it is also used in the colon (rectum), stomach, appendix cancers, and peritoneum cancers (pseudomyxoma peritonei). It has been used in pancreatic cancers in recent years.

Peritoneal involvement often involves accumulation of fluid (acid) in the abdomen. This fluid causes both the swelling of the patient’s abdomen and the spread of cancer cells into the diaphragm and the entire abdomen. Occasionally, there is too much acid accumulated to allow the patients to lie down. Sometimes even the discharge of the liquid is not a solution to the problem. The acid will continue for as long as the underlying reason is present. Many of these patients are sent home being told that they are in the final stage of the disease and there is nothing left to do. Here, cytoreductive surgery and hot chemotherapy are used in the cases and in clinical situations mentioned above.

Is Hot chemotherapy alone enough?

No. Hot Chemotherapy alone is not enough; it is a part of the treatment. This treatment is a three-stage treatment.
First of all, a surgery is required that provides a total or nearly total cytoreduction in which peritoneum and organs with abdominal involvement (colon, ovary, gall bladder, involved part of the abdomen …) are removed and all tumor tissues are cleaned. In this surgery, the abdomen is opened from end to end and the whole abdomen is evaluated. The involved peritoneum and organs are removed. In the meantime, it may be necessary to remove a part of the colon or small intestine and to make enteroanastomosis into the abdominal wall of the intestine (colostomy or ileostomy). This practice is usually a temporary practice and the intestines are taken in again after the treatment is over. HIPEC application is meaningless without this surgery. Or there is no place to practice this surgery without the application of Hot Chemotherapy. Systemic chemotherapy should follow the cytoreductive surgery and hot chemotherapy.
In other words, the trio of “Cytoreductive Surgery + Hot Chemotherapy + Systemic Chemotherapy”.

In which situations cannot the hot chemotherapy be applied?

There is no application of the therapy for extra-abdominal involvement (such as brain, lung, and bone metastases). The disease should be limited within the abdomen. Also, hot chemotherapy treatment has no place in those having a number of liver metastases (spread), or liver metastases that cannot be excised. It’s not an obstacle for hot chemotherapy if there is three or fewer liver metastasis that can be removed.

The patients with very spread and dense small bowel involvement are not suitable for hot Chemotherapy treatment, since removal of the majority of small intestine is not compatible with the life. It may not be possible to detect most of the patients before the surgery, but it can be detected when the patient is operated.

Are there cases where hot chemotherapy is used alone?

In some patients, only hot chemotherapy can be done to treat the acid and help the patient’s comfort. In this case, surgery is not performed, and Hot Chemotherapy can be performed with laparoscopic catheters placed in the abdomen. However, it is usually palliative treatment. It does not contribute much to the survival time of the patient.

How is hot chemotherapy applied?

Hot chemotherapy is a part of the operation process. It is applied at the end of a long and arduous operation, while the patient is still under anesthesia following intra-abdominal tumor clearance. Before the abdomen is closed, two drains are placed on the lower and upper quadrants of the abdomen. The connection between these drains and the special device heating the chemotherapy fluid is established and two temperature probes are placed to monitor the temperature level on the lower and upper abdomen. These probes ensure that as long as chemotherapy is administered, the temperature remains constant at the desired level. The temperature should be between 41-43 degrees. The duration of chemotherapy varies from 60 to 90 minutes on average. 3.5 liters of chemotherapy fluid is administered to the abdomen. During this time, the abdomen is shaken from the outside by hand to allow the chemotherapy to reach everywhere in the abdomen. At the end of this period, the liquid in the abdomen is withdrawn and the process is terminated.

Who should be involved in the team to apply cytoreductive surgery and hot chemotherapy?
The operation lasts for 8-10 hours. Both pelvic and hepatobiliary surgeries require experience. In addition, experienced radiologists for preoperative imaging, medical oncologists for the regulation of chemotherapy programs and treatments for patients, experienced pathologists for the accuracy of diagnoses, nuclear medicine specialist who will evaluate PET tomography, specialist dieticians for the regulation of nutrition, experienced anesthesiologists who follow the patients in intensive care unit, experienced and equipped intensive care and service personnel and nurses are essential parts of this large team. This treatment is a multidisciplinary method.

What is the effect of hot chemotherapy on the survival time (life)?

The majority of the candidates for this treatment are patients at advanced stage of the disease and those having life expectancy limited to months. This important detail should be kept in mind when talking about the survival time.

Hot chemotherapy has different long-term results in different cancers. The most common is ovary cancer and 5-year survival is around 50%. In colon cancers, this rate is around 30%. In stomach cancer, 43% one year survival and 11% 5-year survival have been reported. Success of the given rates can be recognized especially considering that the advanced stage peritoneal metastatic stomach cancers indicate a survival period of 6 months or less.
The 5-year survival rate of pseudomyxoma peritonei is 66-97%.

What are the risks in the treatment of hot chemotherapy?

This is a complex treatment. Therefore, the risk rate is higher than standard surgery. However, although complicated, good results are obtained in well managed patients that are well prepared before surgery and well observed during surgery. The most frequent risk is a temporary cessation (loss of function) of gastrointestinal system. Complications such as hemorrhage during operation, kidney failure due to treatment, lung or brain thrombosis, bone marrow failure due to chemotherapy, wound infection, wound dissociation, anastomotic leakage can be seen. However, the vast majority of the risks are overcome with measures taken at experienced centers and good patient management. While different rates are given in different studies, the risk of losing patients after this treatment is 0-7%. The risk of complications and death is at an acceptable level when the stage and severity of the disease are considered and the risk-benefit assessment is performed.

CONCLUSION

In conclusion, the application of cytoreductive surgery and hot chemotherapy is a long, and laborious procedure requiring attention and adaptation of experienced surgeons and teams, but it is a hopeful, promising and contemporary treatment method. The “Cytotherapy Surgery + Hot Chemotherapy + Systemic Chemotherapy” triple therapy is now the only treatment method that gives a long-life chance (20-50%).

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