Hyperthermic intrathoracic chemotherapy (HITHOC) treats pleural mesothelioma, a cancer of the lung’s linings. Doctors use heated chemotherapy drugs to bathe the pleural cavity after mesothelioma surgery, like pleurectomy/decortication. HITHOC may extend survival in some malignant mesothelioma cases.

01. What Is HITHOC?


Hyperthermic intrathoracic chemotherapy (HITHOC) is a heated, locally administered chemotherapy procedure. HITHOC generally occurs after thoracic surgery to remove tumors. Doctors may recommend HITHOC after surgery as a treatment for malignant pleural mesothelioma, a cancer caused by asbestos exposure.

Some chemotherapy is systemic, meaning it travels throughout the bloodstream to kill cancer cells. HITHOC takes a different approach, applying chemotherapy within the pleural cavity. This approach allows doctors to use a higher concentration of chemotherapy drugs right where the cancer is.

HITHOC and traditional chemotherapy are different in more ways than their delivery methods. With HITHOC, the healthcare team heats the chemotherapy drug. The high temperature improves the effectiveness of the chemotherapy and helps it reach more tumor cells. These properties may explain why some HITHOC-treated pleural mesothelioma patients have become long-term survivors.


HITHOC is similar to another therapy called hyperthermic intraperitoneal chemotherapy (HIPEC). Both use heated chemotherapy drugs administered locally following surgery to treat mesothelioma. But HIPEC differs in what it treats. HIPEC can treat peritoneal mesothelioma and some other cancers affecting the abdomen.

HITHOC consists of heated chemotherapy administered to the pleural cavity. HIPEC is heated chemotherapy administered to the abdominal cavity. Although administered in different areas, both heated chemotherapies happen right after surgery.

Comparing HITHOC and HIPEC

  • Treats pleural mesothelioma
  • Follows cytoreductive surgery, such as pleurectomy/decortication or extrapleural pneumonectomy
  • Generally uses cisplatin
  • At least one study used cisplatin with doxorubicin
  • Allows for highly concentrated, targeted chemotherapy application
  • May extend pleural mesothelioma patient survival when combined with surgery
  • Treats peritoneal mesothelioma
  • Generally follows cytoreductive surgery but may also be used as a palliative treatment
  • Commonly uses cisplatin, mitomycin or doxorubicin
  • May also use oxaliplatin, carboplatin or irinotecan
  • Allows for highly concentrated, targeted chemotherapy application
  • May extend peritoneal mesothelioma patient survival when combined with surgery
02. HITHOC for Pleural Mesothelioma

How Does HITHOC Treat Pleural Mesothelioma?

HITHOC treats pleural mesothelioma by putting heated chemotherapy in the pleural cavity. Patients may undergo HITHOC after pleural mesothelioma surgeries like:

P/D and EPP are cytoreductive surgeries, meaning they remove cancer tissue. But they may not remove every mesothelioma cell. HITHOC helps kill leftover cancer cells by washing the affected area with hot chemotherapy.

Why Does HITHOC Use Local Chemotherapy?

HITHOC’s local approach provides advantages traditional chemotherapy does not. These include a higher drug concentration and temperature, which help improve effectiveness.

Traditional systemic chemotherapy circulates drugs through the bloodstream. It hurts fast-growing cells, which include cancer cells and some healthy cells. But the drug concentration is limited because it can hurt normal cells throughout the body.

The HITHOC procedure delivers these drugs directly to the location of mesothelioma cancer. This limits its ability to harm cells outside the delivery area (the pleural cavity), allowing a higher concentration of chemotherapy.

HITHOC also enables heating of the chemotherapy drugs, which may boost effectiveness. Heat can make a difference because it affects cancer cells and healthy cells differently.

  • Cancer cells die at about 104°F.
  • Healthy cells die at about 111°F.

HITHOC chemotherapy drugs are heated to about 107°F. This temperature is high enough to kill cancer cells and low enough to let healthy cells live. The heat may also help the drugs reach deeper layers of cancer cells.

Researchers believe the higher temperature and chemotherapy concentration may improve overall drug effectiveness.

HITHOC Procedure

The HITHOC procedure can vary depending on where the procedure is performed. Different doctors may follow different steps. In general, HITHOC treatments may include the following:

  1. Hydration: Patients may go into the mesothelioma treatment center a couple of days before the procedure to get fluids through an IV. This perioperative hydration can help protect the kidneys during the procedure.
  2. Surgery: Cytoreductive surgery removes as much of the tumor tissue as possible. Doctors may perform an EPP or P/D, depending on the patient’s case.
  3. HITHOC preparation: Once the initial surgery is complete, the healthcare team may place one or more tubes into the pleural cavity. These tubes allow the chemotherapy drug solution to circulate. The team may also place a temperature monitor. Then, the doctor closes the chest wall. The team attaches a fluid circulator to the other end of the tubes in the chest cavity.
  4. Heated chemotherapy: With the tubes attached to a circulator, the heated chemotherapeutic agents flow through the pleural cavity and bathe the tissue. This process may take anywhere between 60 to 120 minutes.
  5. Saline rinse: The healthcare team may run a saline solution through the pleural cavity to wash away remaining chemotherapy drugs.
  6. Recovery: The healthcare team removes any tubes and monitoring devices, and the patient is moved to recovery. The patient may spend 12 to 24 hours in the intensive care unit once the treatment is complete.
03. HITHOC and Prognosis

Survival Benefits of HITHOC for Mesothelioma

Surgery followed by HITHOC may extend a pleural mesothelioma patient’s survival. The procedure may also help maintain or improve their quality of life. In studies, patients who received HITHOC after surgery had a survival range of 9 months to 42 months.

A mesothelioma patient’s life expectancy may vary depending on many factors, such as the mesothelioma cell type, the patient’s age and the patient’s gender. A patient’s treatment plan may help improve life expectancy, and some patients have benefited from having HITHOC as part of their treatment plan.

In a 2013 study, researchers monitored 103 pleural mesothelioma patients. The patients received either P/D or EPP surgery. Some patients also received HITHOC with cisplatin and others did not. The study found that patients who did not receive HITHOC had a median survival of 22.8 months. Those who received HITHOC had a median survival of 35.3 months.

Another study published in 2019 showed promising results for patients who received HITHOC following P/D surgery. The study included patients who received one of two treatment options:

  1. P/D surgery, HITHOC and systemic chemotherapy
  2. Systemic chemotherapy, EPP surgery and radiation

Those who did not receive HITHOC had a median survival of 22.4 months. Those who received HITHOC had a median survival of 42.2 months.

Beyond improving survival, HITHOC may provide patients with other benefits, too.

04. Benefits of HITHOC

Other Benefits of HITHOC Treatment for Mesothelioma

HITHOC may offer benefits in addition to potentially extending survival for pleural mesothelioma patients. Research suggests the procedure is well tolerated. Patients recover from it quickly, which allows them to go on to additional treatments.

The HITHOC procedure takes place during a single surgical procedure, which may reduce office visits. But it still offers the benefits of a multimodal treatment. Research shows that multimodal treatment plans tend to be more effective than single treatments.

Additional benefits of HITHOC treatment for mesothelioma may include:

  • Fewer side effects: Targeted chemotherapy treatments, such as HITHOC, tend to have less toxicity than traditional chemotherapy. For patients, this means they may not experience some of the side effects commonly associated with systemic chemotherapy, like hair loss.
  • Higher chemotherapy concentration: Patients receive a higher concentration of chemotherapy drugs where it is needed.
  • Improved chemotherapy reach: High heat may increase the drugs’ effectiveness while enabling them to reach deeper tumor tissues.
  • Potential safety benefits: Studies suggest HITHOC has a low complication rate. Studies of HITHOC in pleural mesothelioma show zero treatment-associated deaths for 30 to 90 days after the procedure.

Those interested in HITHOC should talk to their doctor. Their care team can explain potential benefits and risks of the treatment.

05. Side Effects of HITHOC

HITHOC Side Effects

Any cancer treatment comes with the possibility of side effects, including HITHOC. It is not yet a standard treatment, so HITHOC side effects are not as well documented as those of more common therapies. One of the most commonly reported HITHOC side effects is an abnormal heart rhythm.

Potential Side Effects of HITHOC

  • Abnormal heart rhythms
  • Blood clots
  • Breathing difficulty
  • Kidney complications
  • Nerve problems
  • Pus collecting in the pleural cavity (empyema)

Source: Oncotarget

Through studies, researchers have found that HITHOC can damage kidneys or lead to kidney failure, and patients who have EPP surgery may have an elevated risk. But this may be avoidable.

Patients scheduled for HITHOC to treat pleural mesothelioma may benefit from pre- and intra-procedure hydration. These precautions may help decrease the risk of kidney injury during HITHOC.

Side effects are possible with HITHOC, but doctors have tools for managing them. Patients may want to discuss concerns about side effects with their doctors.

06. HITHOC Research

HITHOC Treatment Clinical Trials

HITHOC is the subject of multiple clinical trials for pleural mesothelioma. Completed studies of HITHOC and surgery produced a range of results for mesothelioma patient survival.

One study looked at P/D surgery followed by HITHOC with cisplatin. The median survival was 25 months. If the surgeon was able to remove all visible cancer tissue, median survival was 32 months.

Neoadjuvant therapy is treatment given prior to the primary therapy to enhance efficacy.

Adjuvant therapy is treatment given after the primary therapy to reduce risk of recurrence.

Another study investigated P/D surgery and HITHOC with cisplatin and doxorubicin. Some of those patients also received neoadjuvant or adjuvant chemotherapy and radiation therapy. Researchers found the following survival results in the study:

  • Median survival for patients with epithelioid mesothelioma was 17.9 months.
  • Median survival for sarcomatoid mesothelioma patients was 9.2 months.
  • Median survival was 28.2 months when surgical resection was able to remove all visible tumors. Surgical resection means removing tissue surgically.

A phase 1 trial compared different surgery approaches followed by HITHOC. The surgeries included EPP, P/D and debulking surgery. HITHOC consisted of gemcitabine with or without cisplatin. The results showed:

  • The median survival for patients in the P/D group was 38.8 months.
  • The median survival for patients in the EPP group and the same regimen was 17.7 months.

In this study, P/D with HITHOC improved survival by nearly two years versus EPP with HITHOC.

Research into HITHOC for pleural mesothelioma is ongoing. One upcoming mesothelioma clinical trial will investigate using Opdivo® (nivolumab) after HITHOC treatment. This means the researchers will study the effects of immunotherapy after HITHOC. Patients interested in HITHOC treatment should talk to their doctor to see if it is right for them.

07. HITHOC Eligibility

Who Is Eligible for HITHOC Treatment?

HITHOC may be an option for pleural mesothelioma patients. It is not considered standard therapy, so doctors have not established clear eligibility criteria for it yet. Patients who are interested in learning more about HITHOC and if it can help them are encouraged to speak with their doctors.

A mesothelioma doctor can help the patient understand the potential benefits and risks of HITHOC.