Hyperthermic Intraperitoneal Chemotherapy: Moving Toward Improved Outcomes

Theresa McDonnell, ACNP-BC

Theresa McDonnell, ACNP-BC

An increasing number of patients are presenting with peritoneal carcinomatosis, or widespread metastasis of the peritoneum, which can result from a variety of tumors, including digestive and gynecologic malignancies.¹ The diagnosis is devastating, with treatment often limited to palliation of symptoms, but a combination of cytoreductive surgical resection (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)—sometimes referred to as “hot chemotherapy bath”—has the potential to provide some patients with long-term survival.

This treatment approach is not new. According to Sanjay S. Reddy, MD, a surgical oncologist at Fox Chase Cancer Center, it began back in the 1970s with the use of intraperitoneal chemotherapy for the treatment of ovarian cancer.

“As advances in medicine have continued, more and more patients have undergone this type of therapy for treatment of a wide array of cancers,” he said in an interview with Oncology Nursing News. However, despite being around for decades, the procedure continues to be extensive, recovery remains difficult, and there is still no guarantee of improved survival. Reports have shown both success and failure, leading the oncology community to more closely examine which patients are appropriate candidates for this treatment, the techniques involved, and how to better care for patients undergoing this treatment.

Sanjay S. Reddy, MD

Sanjay S. Reddy, MD

Hot Chemotherapy Bath: Standardizing Treatment

HIPEC is administered after CRS, with CRS attempting to remove all visible disease from the abdomen and HIPEC targeting any microscopic disease. A variety of chemotherapeutic agents can be used, depending on tumor type.

According to Jesus Esquivel, MD, national director for HIPEC research, Department of Surgical Oncology, Cancer Treatment Centers of America, mitomycin C is the most frequently used drug for gastrointestinal malignancies, and a platinum-based agent is preferred for gynecologic malignancies. The selected agent is heated before it is infused into the abdominal cavity. The heat is thought to help the chemotherapeutic agent kill any residual cancer cells, and flooding the abdomen with the agent is thought to expose cancer cells to higher concentrations of the selected drug than can be achieved with systemic chemotherapy. After the drug has been deemed to sufficiently circulate through the abdomen (30-120 minutes), it is drained from the body, anastomoses are performed, and the abdomen is closed.² Patients may go on to receive systemic chemotherapy, particularly if they have more extensive or aggressive disease.

HIPEC has been criticized for its lack of standardization, with the literature showing variations in the seven parameters used to characterize the procedure: (1) method, (2) inflow temperature, (3) perfusate volume, (4) drug used, (5) dosage, (6) timing of drug delivery, and (7) total perfusion time.² Randomized controlled trials are still lacking to shed light on these issues; however, in 2009, an organization was started—the American Society of Peritoneal Surface Malignancies (ASPSM)—to improve the overall care of patients with peritoneal surface malignancies, and it set HIPEC standardization as its first goal.²

Jesus Esquivel, MD

Jesus Esquivel, MD

The organization strives to foster research collaboration between medical and surgical oncologists at cancer centers that provide HIPEC, and it published its first recommendations in 2014, focusing on the delivery of HIPEC to patients with peritoneal carcinomatosis from colorectal cancer.³ According to Esquivel, who is on the ASPSM’s board of directors, most institutions now follow the ASPSM’s recommendations, leading to more uniformity in how HIPEC is provided.

Selecting the Right Patients for HIPEC

Although controversy has surrounded various aspects of HIPEC, one matter on which the oncology community agrees is that proper patient selection is essential for success. According to Bassel El-Rayes, MD, director, Gastrointestinal Oncology Translational Research Program, Winship Cancer Institute, three key factors must be considered when making the determination: origin of the tumor, extent of disease, and tumor histology.

“Patients with tumors that are aggressive or have metastasized are not good candidates for this treatment, regardless of where their tumor originated,” said El-Rayes. In a recently published paper he coauthored, the CRS/HIPEC combination showed good results in patients with primary appendiceal mucinous adenocarcinomas.⁴ El-Rayes said that the results are likely to be favorable for other low-grade tumors and that the evidence for its use in treating higher grade tumors is lacking, though the role may evolve.

Julie Christensen, BSN, RN

Julie Christensen, BSN, RN

Esquivel, who has performed more than 500 CRS/HIPEC procedures, concurs. He said that his ideal patient is one with “a limited amount of peritoneal carcinomatosis and a diagnosis of a not very aggressive tumor, like mucinous tumors of the appendix, ovary, or colon,” noting that the results for more aggressive tumors like sarcomas and pancreatic and gastric tumors are not as good. He explained that the outcome of patients undergoing CRS and HIPEC is directly related to the burden of disease and the histology of the tumor.

“For many patients with low-grade tumors, like pseudomyxoma peritonei of the appendix, this procedure can be done with curative intent. For patients with colon cancer with peritoneal carcinomatosis, the outcomes continue to improve as systemic chemotherapy gets better,” Esquivel said. He also noted that patients now have a median survival of about 3 or more years, whereas it was only 12 months a decade ago when systemic chemotherapy was used alone.

Helping Patients Understand Hot Chemotherapy Bath

When this treatment approach is used, patients need to understand that recovery will take time because of how extensive the procedure is. One recent study that examined quality of life in patients receiving HIPEC for colorectal cancer showed that functional status declined the first 3 months postoperatively, but returned to or exceeded baseline levels over the next 3 to 6 months, with emotional wellbeing improving throughout the first 12 months following surgery.⁶

Because patients receiving HIPEC have complex care needs on their road to recovery, outstanding nursing care is essential, explained Reddy.

“Most patients come out of the operating room with a central line, arterial line, nasogastric decompressive tubes, Foley catheters, and various other drains,” he said, noting that the nasogastric tubes are typically left in for some time because of a high incidence of profound ileus following surgery.

Bassel El-Rayes, MD

Bassel El-Rayes, MD

In addition to properly managing all of this equipment, nurses can help improve and potentially speed patients’ recovery.

“Just like with any operation, the more proactive patients are about walking and deep breathing, the quicker the recovery they will make,” said Reddy. But this is not an easy task because inflammation, the metabolic stress response, and postoperative pain are known to impair a patient’s ability or motivation to get up and move.⁵

In addition, for HIPEC patients, the systemic effects of intra-abdominal chemotherapy begin to manifest around postoperative days 6 and 7, Reddy noted. During this period, patients may develop pancytopenia and other complications. Nurses can help promptly identify and manage these and other obstacles on the patient’s road to recovery and communicate any complications, challenges, and progress to the care team.

“Communication between the physician, nursing team, and other ancillary staff is most important,” Reddy said. “Attention to details is essential for a smooth hospital course.”

The Oncology Nurse’s Role in HIPEC

Oncology Nursing News asked two nurses what their experience has been treating patients who have received HIPEC. As their perspectives show, outcomes can be quite different, but care can be improved by focusing on the needs of the whole patient.

Julie Christensen, BSN, RN, is a Physician Practice/HIPEC coordinator at the Cancer Treatment Centers of America. Theresa McDonnell, ACNP-BC, is nursing director for the cancer center's outpatient clinic at Massachusetts General Hospital.

What outcomes have you observed for patients who have undergone hot chemotherapy bath, and do you think they are improving? If so, what do you attribute this to?

Christensen: As a registered nurse who has cared for patients who have undergone HIPEC through the past 4 years, I have seen this procedure enhance the quality of life and lengthen life. This surgical offering provides hope for patients with advanced-stage cancers who have few other treatment options available to them. I think outcomes continue to improve because technology is improving. We are in an amazing period for cancer treatment as advancements in surgery and critical care are happening every day.

McDonnell: Since the original article was published in 2011, I have seen one success story and unfortunately more failures. The success was in a young woman who had limited peritoneal disease. I think that careful selection of patients is important for improving outcomes because currently those with less extensive disease appear to do better.

Do nurses face any unique challenges when caring for these patients?

Christensen: Nurses face many challenges when caring for surgical oncology patients. This includes caring for the physical, spiritual, and emotional needs of the patient and family. It is important for the nurse to be aware of all of these challenges and gear care toward each specific patient. We must treat the patient as a whole, not just the cancer. And pain control, as with any surgery, can be a unique challenge as well, due to the fact that every person experiences pain differently.

McDonnell: The psychosocial aspects around recovery and managing the disappointment and sadness when there is recurrence are unique challenges to this population.

How long are HIPEC patients generally hospitalized, and what is the recovery like?

Christensen: Patients who undergo HIPEC may be in the hospital between 6 to 14 days. However, the exact number of days varies by patient because there are several factors to consider, including comorbidities, extent of disease, and the recovery period. The typical recovery time is not too extensive and patients are encouraged to get up and walk (with assistance) within 12 hours of surgery.

McDonnell: It varies by patient, but we are seeing improvement in length of stay and acuity.

What do you think nurses should know when it comes to caring for patients who have undergone this therapy, both in the immediate postoperative period and more long-term?

Christensen: Nurses should know that HIPEC is an invasive procedure and every patient will recover differently. It is important to consider the whole patient when providing care. We as nurses are truly blessed to be able to comfort and care for these families on their difficult journey with cancer.

McDonnell: From an oncology nursing perspective it’s important to understand the potential postoperative complications as well as the potential for recurrence.

References

• Chia CS, Tan WJ, Wong JF, et al. Quality of life in patients with peritoneal surface malignancies after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Eur J Surg Oncol. 2014;40(8):909-916.
• Esquivel J. Current status and future directions of hyperthermic intraperitoneal chemotherapy (HIPEC). http://www.interventionaloncology360.com/content/current-status-and-future-directions-hyperthermic-intraperitoneal-chemotherapy-hipec. Published June 23, 2104. Accessed July 14, 2015.
• Turaga K, Levine E, Barone R, et al. Consensus guidelines from The American Society of Peritoneal Surface Malignancies on standardizing the delivery of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer patients in the United States. Ann Surg Oncol. 2014;21(5):1501-1505.
• Shaib WL, Martin LK, Choi M, et al. Hyperthermic intraperitoneal chemotherapy following cytoreductive surgery improves outcome in patients with primary appendiceal mucinous adenocarcinoma: a pooled analysis from three tertiary care centers. Oncologist. http://www.ncbi.nlm.nih.gov/pubmed/26070916. Published online ahead of print June 12, 2015. Accessed July 14, 2015.
• Maillard J, Elia N, Haller CS, Delhumeau C, Walder B. Preoperative and early postoperative quality of life after major surgery - a prospective observational study. Health Qual Life Outcomes. 2015;13:12.
• Levine EA, Stewart JH, Russell G, Loggie BW, Geisinger KR, Shen P. Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal surface malignancy: experience with 501 procedures. J Am Coll Surg. 2007;204(5):943-955.