TREATMENTS FOR PERITONEAL CARCINOSIS
Sommaire
Systemic Chemotherapy (Intravenous or Oral)
What is chemotherapy?
Chemotherapy is a combination of medications designed to destroy cancer cells. It can be administered intravenously or orally to reach the disease wherever it is located in the body.
Chemotherapy can either destroy cells directly or prevent them from multiplying.
For more information, visit the website of the National Cancer Institute
Before surgery
Chemotherapy before surgery is called neoadjuvant chemotherapy. Its purpose is to reduce the size of the tumor in order to facilitate the surgical procedure. It also serves to limit the risk of recurrence. Above all, in our specific case, it provides doctors with information about the effectiveness of chemotherapy on the tumor. The same chemotherapy molecules can be used before, during, and after the operation.
Neoadjuvant chemotherapy often consists of 4 to 6 courses. In most cases, it is administered via an implantable port fitted by a specialist doctor.
After surgery
Even if the surgery was complete and there is no remaining disease, chemotherapy may be offered to patients. This chemotherapy is called adjuvant chemotherapy. Its purpose is to reduce the risk of recurrence (whether local recurrence directly in the peritoneum or distant recurrence in organs such as the lungs or liver).
If patients have not had neoadjuvant chemotherapy, it can involve up to 12 courses, and if patients have already had between 4 and 6 courses, it can involve between 8 and 6 courses.
Long term
Chemotherapy may sometimes be offered as the only treatment if surgery is not possible.
The aim will then be either to significantly reduce the tumor mass and then keep it at a minimum, or to limit the growth of the tumor mass.
This chemotherapy is often considered as a long-term treatment, lasting several months or even years, in order to maintain an acceptable quality of life.
Which chemotherapy drugs are used?
In most cases, the drugs used to treat rare diseases of the peritoneum such as pseudomyxoma and mesothelioma are 5FU, oxaliplatin, irinotecan, cisplatin, and doxorubicin. They can be combined to form protocols such as FOLFOX and FOLFIRI, for example. FOLFOX and FOLFIRI can also be combined with targeted therapies such as monoclonal antibodies such as Bevacizumab and Panitumumab.
In the case of primary serous peritoneal cancer, chemotherapy tends to focus on drugs such as carboplatin, taxol, caelyx, etc.
Clinical trial
In 2020, the TALAMESO clinical trial was launched in France. It is coordinated by Prof. Benoît You and Dr. Vahan Kepenekian of the Hospices Civils de Lyon. This is a phase II trial evaluating the efficacy of maintenance therapy with talazoparib after first-line platinum-based chemotherapy for malignant peritoneal and pleural mesothelioma.
For more information: summary, in English..
Intraperitoneal Chemotherapy
What is intraperitoneal chemotherapy?
Chemotherapy is a combination of drugs designed to destroy cancer cells. In intraperitoneal chemotherapy, treatments are administered directly into the peritoneal cavity, in contact with the abdominal organs.
How does intraperitoneal chemotherapy work?
During surgery, a doctor inserts a catheter directly into the abdomen. This catheter allows chemotherapy to be administered over several cycles.
Chemotherapy treatments then take place in the oncology department, just like conventional intravenous chemotherapy, with only the route of administration changing.
For more information, the National Cancer Institute has made information available..
Cytoreduction
Definition of cytoreduction?
Cytoreduction is a surgical procedure aimed at resecting or destroying all peritoneal implants of the disease visible to the naked eye.
History of cytoreduction
During the 1990s, Professor Paul H. Sugarbaker worked on standardizing the surgical procedure for peritoneal carcinomatosis. He is considered one of the pioneers in this field, notably with the creation of the PCI (Peritoneal Cancer Index), which maps the extent of peritoneal disease and the involvement of different abdominal organs.
Today, this score is considered a global benchmark, and various tools have been created to facilitate its use, such ase Promise, developed by the RENAPE team.
What is cytoreduction?
Cytoreduction is the reduction of tumor volume. Its goal is to remove the various implants of the disease scattered throughout the peritoneum. To achieve complete disappearance of the visible disease, the surgeon must perform peritonectomies. This involves removing the affected peritoneal membranes. Unfortunately, if several organs inside the abdomen are deeply affected, it is often necessary to remove them. These are visceral resections. They can range from a short segment of the intestine to complete removal of the stomach, depending on the extent of the disease.
The duration of the surgery can vary. It can range from one to two hours for a very localized disease to more than nine or ten hours if the disease is more advanced.
Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Definition of HIPEC?
HIPEC is the acronym for Hyperthermic Intraperitoneal Chemotherapy.
History of HIPEC in France
The first closed-abdomen HIPEC procedure was performed in Europe in 1989, on the initiative of Professor François-Noël Gilly of the Lyon-Sud Hospital. The second open-abdomen procedure was performed in 1990 at the Gustave Roussy Institute by Professor Dominique Elias.
What is HIPEC?
For more than 30 years, HIPEC has been used to treat peritoneal carcinomatosis, whether primary or secondary. This technique was born out of a completely different approach to peritoneal disease. Peritoneal carcinomatosis is a regional extension of the disease, limited to the peritoneum and therefore to the abdominal cavity. This vision has made it possible to consider curative treatment for patients without distant metastases.
HIPEC, or intraperitoneal hyperthermic chemotherapy, consists of “bathing” all organ surfaces and the various walls in the abdomen with a chemotherapy product diluted in saline solution. Various molecules that have proven effective when administered intravenously are used, such as oxaliplatin, cisplatin, irinotecan, mitomycin C, etc.
There are two main techniques for performing this treatment, depending on the center. One is closed and the other is open. Both have been used since the beginning.
Hyperthermia involves raising the temperature in the abdominal cavity to between 42°C and 43°C. It destroys tumor cells through direct action, increases the penetration of chemotherapy into the tissues, and potentiates its effect.
The duration of HIPEC varies between 30 minutes, 60 minutes, and 90 minutes.
How is HIPEC performed?
Before the procedure
It is quite common for patients to have undergone several courses of neoadjuvant chemotherapy before considering surgery. As HIPEC is considered a relatively “major” procedure, the decision to offer it to patients is made during a multidisciplinary team meeting (MDT) involving radiologists, surgeons, pathologists, oncologists, geriatricians, etc.
Preoperative imaging tests are often performed on patients to better assess the extent of the disease. In the case of neoadjuvant chemotherapy, these tests, such as CT scans, MRIs, or PET scans, are used to evaluate the “response” to chemotherapy.
A consultation with the specialist surgeon takes place before any decision is made. During this consultation, the doctor explains the risks of the surgery and the expected benefits. Digestive preparation to “clean” the digestive tract may be recommended, and immuno-nutrition to aid recovery and reduce the risk of post-operative complications may be prescribed.
As such, more and more hospitals now offer prehabilitation to improve the speed of post-surgical recovery. The aim is to “prepare” patients for these “major” surgeries in advance.
A consultation appointment with an anesthesiologist then takes place. This specialist reviews each patient’s medical treatments, the risks of anesthesia, and the pain management options available for the postoperative period. Anticipating and providing information about pain management allows for better control of pain once the procedure is complete. Various techniques are available today, such as epidural anesthesia, morphine pumps, etc.
During the procedure
The surgical procedure is performed in a sterile operating room under general anesthesia. Patients are placed in the supine position (on their back) to allow the surgeon to perform a laparotomy. A laparotomy is the opening of the abdominal wall, from the pubis to the lower edge of the sternum.
First, the surgeon conducts a thorough examination of the entire abdominal cavity. He or she assesses the extent of the disease using Sugarbaker’s PCI score. Next, the surgeon can either perform cytoreductive surgery or proceed directly to HIPC.
There are currently two HIPC techniques used in France. The “open abdomen” technique, known as the coliseum technique, and the “closed abdomen” technique .” While the former is performed before any skin closure, the latter requires the placement of drains and closure of the skin with sutures or staples.
A HIPEC machine is then used to circulate the chemotherapy fluid diluted in several liters of saline solution heated to 42°C. The aim is to bathe all the abdominal organs for a period ranging from 30 to 90 minutes.
Once the HIPEC is complete, only the surgical drains remain in place to remove fluids such as blood and to monitor any surgical sutures that may have been performed. Patients are then transferred to the intensive care unit for one night in most cases.
After the procedure
The patient is quickly woken up and extubated. Their pain is managed immediately, either with continuous administration techniques such as epidural or “on demand” techniques such as intravenous painkillers.
Paramedical staff encourage patients to get up quickly in order to reduce muscle loss through early mobilization. This also prevents certain complications associated with prolonged bed rest, such as phlebitis or respiratory infections.
Some health and dietary advice to help you after the operation.
PIPAC
Definition of PIPAC
PIPAC is pressurized intraperitoneal aerosol chemotherapy. It involves spraying chemotherapy directly into the peritoneal cavity in the form of an aerosol via a surgical approach performed under laparoscopy.
History of PIPAC in France
The PIPAC technique was developed by Prof. Marc-André Reymond in Germany in 2013. The first PIPAC was performed in France in 2016, thanks to the work of Dr. Naoual Bakrin at the Lyon-Sud Hospital Center. Currently, many surgeons at RENAPE specialized centers have been trained and many offer access to this new technique.
What is PIPAC?
Based on the principle that peritoneal disease is localized in the peritoneal cavity, PIPAC involves administering chemotherapy directly to the tumor nodules in the peritoneal cavity. The stated objective of this technique is to limit the side effects of intravenous chemotherapy and to have a greater effect by immediately destroying the target.
PIPAC can be offered to all patients with rare diseases of the peritoneum or peritoneal carcinomatosis that have not metastasized to other parts of the body. Currently, it does not replace HIPEC. Rather, it is offered to patients who cannot benefit from HIPEC for various reasons (age, extent of the disease, medical history, etc.). Today, in France, this treatment is combined with systemic chemotherapy in most cases.
How is PIPAC performed?
Before the procedure
Patients have a surgical consultation with a specialist doctor. The doctor explains the procedure and the expected benefits and risks.
This is followed by an anesthesia consultation. As with any surgical procedure, this consultation provides an opportunity to review the patient’s medical treatments, take their medical history into account, and discuss post-operative pain management.
Patients are admitted to the hospital the day before or on the day of PIPAC. They may have a blood test either at the hospital or in town.
During the procedure
The surgical procedure is performed under general anesthesia in a sterile operating room. The surgeon creates a pneumoperitoneum at 12 mmHG using standard laparoscopic equipment. Once air has entered the peritoneal cavity, a camera and surgical instruments can be safely inserted.
An analysis of the extent of the disease is performed using Sugarbaker’s PCI and tools such as Promise developed by the RENAPE team. Biopsies can then be performed to monitor the disease’s “response” to chemotherapy.
The nebulizer is inserted into a trocar and sprays the chemotherapy directly into the abdominal cavity in the form of fine droplets. Doctors use a camera to ensure that the procedure is proceeding smoothly in real time. In practical terms, nebulization lasts a few minutes, after which the abdomen remains inflated for 30 minutes to allow the product to spread as widely as possible. After that, exsufflation consists of removing the air that caused the pneumothorax. The equipment and trocars are removed and the incisions are closed.
After the procedure
Once PIPAC is complete, patients are transferred to the recovery room for a few hours. They then return to the surgery or outpatient department. They are discharged either the same evening or the following day. A prescription is systematically given with pain relief medication for post-operative care at home.
A clinical trial
In 2019, a clinical trial was launched on PIPAC for patients with peritoneal mesothelioma. Today, several centers in France are offering to participate in this research project called MESOTIP: a randomized phase 2 study evaluating the use of PIPAC chemotherapy alternating with systemic chemotherapy, compared to systemic chemotherapy alone, as first-line treatment in patients with malignant peritoneal mesothelioma.
For more information: MESOTIP study