Hyperthermic intraoperative thoracoabdominal chemotherapy

Our plain-English summary of Hyperthermic intraoperative thoracoabdominal chemotherapy, by P.H. Sugarbaker, D. Chang, O.A. Stuart (Gastroenterology Research and Practice, 2012).

The study

• Authors: P.H. Sugarbaker, D. Chang, O.A. Stuart
• Journal: Gastroenterology Research and Practice
• Published: 2012;2012:623417
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for selected patients with pseudomyxoma peritonei (PMP) and diffuse malignant peritoneal mesothelioma (DMPM). Tumor infiltration of the hemidiaphragm requiring partial resection occurs as a result of large volume and/or invasive disease at this anatomic site. Transmission of disease from abdomen to chest is a great danger in this group of patients. From a prospective database, patients who had diaphragm resection and then hyperthermic thoracoabdominal chemotherapy (HITAC) as a component of a cytoreductive surgical procedure were identified. Data from control patients receiving HIPEC or hyperthermic intrathoracic chemotherapy (HITOC) were analyzed for comparison. The morbidity, mortality, survival, and recurrence rate within the thoracic space were presented. Thirty patients had partial resection of a hemidiaphragm as part of a cytoreductive surgical procedure that utilized HITAC. The pharmacologic benefit of intracavitary chemotherapy administration was documented with an area under the curve ratio of intracavitary concentration times time to plasma concentration times time of 27 ± 10 for mitomycin C and 75 ± 26 for doxorubicin. Comparing percent chemotherapy absorbed for a ninety-minute treatment showed the largest for HIPEC, then for HITAC, and lowest for HITOC. The incidence of grade 3 and 4 adverse events was 43%. There was no mortality. Adjustments in the chemotherapy dose are not necessary with HITAC. The morbidity was high, the survival was acceptable, and intrathoracic recurrence was low.

In plain English

This article reported on 30 patients with peritoneal metastases (cancer spread over the abdominal lining) whose surgery, from January 2000 to September 2011, required removing part of the diaphragm. Sixteen had appendiceal mucinous neoplasm, 5 colon cancer, 8 peritoneal mesothelioma and 1 gastric cancer. Heated mitomycin C and doxorubicin were washed through both abdomen and chest during surgery (HITAC). In 12 patients, drug exposure in cavity fluid was 27 (plus or minus 10) times that in plasma for mitomycin C and 75 (plus or minus 26) times for doxorubicin. After 90 minutes, 67% of mitomycin C had been absorbed with HITAC, versus 75% in comparison patients treated in the abdomen only and 41% in the chest only. The postoperative complication records showed no deaths, and 43% had a serious (grade III or IV) complication. Median survival was 129 months for appendiceal malignancy, 44.6 months for peritoneal mesothelioma and 13.4 months for colon cancer. Three patients had recurrence in the pleural space, two with mesothelioma. The authors concluded that complications were frequent, survival acceptable, intrathoracic recurrence low, and dose adjustments unnecessary.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Analysis of patients identified from a prospective database at the authors' institution, with comparison groups treated with heated chemotherapy in the abdomen only (HIPEC) or chest only (HITOC); includes drug-level (pharmacokinetic) measurements
• Who was studied: 30 patients with peritoneal metastases whose cytoreductive surgery required diaphragm excision, January 2000 to September 2011; compared with 25 patients receiving abdominal-only chemotherapy (HIPEC) and a small group receiving chest-only chemotherapy (HITOC)
• Exposure: Not an asbestos exposure study. The treatment studied was cytoreductive surgery with partial diaphragm resection, followed by heated chemotherapy with mitomycin C (15 mg/m2) and doxorubicin (15 mg/m2) circulated through the abdomen and chest (HITAC)
• Main results:
  • Diagnoses among the 30 HITAC patients: 16 appendiceal mucinous neoplasm, 5 colon cancer, 8 peritoneal mesothelioma, 1 gastric cancer
  • In 12 HITAC patients, the area under the curve ratio (cavity fluid to plasma) for mitomycin C was 27 plus or minus 10
  • In the same 12 HITAC patients, the area under the curve ratio for doxorubicin was 75 plus or minus 26
  • Mitomycin C absorbed at 90 minutes: 75% in HIPEC patients and 67% in HITAC patients
  • Mitomycin C absorbed at 90 minutes in HITOC (chest-only) patients was 41%, significantly different from HITAC (P = .0015)
  • Doxorubicin absorption over 90 minutes was very similar for HIPEC and HITAC (about 90% each); 72% was absorbed with HITOC, which differed significantly from HITAC (P < .001)
  • The prospective postoperative morbidity/mortality database for the 30 HITAC patients recorded no deaths; deaths did occur later during follow-up (for example, the gastric cancer patient died at 5 months)
  • 11 of 30 HITAC patients (37%) had at least one grade III adverse event, and 8 (27%) at least one grade IV event; the combined incidence of grade III and IV events was 43%
  • Median survival in HITAC patients: 129 months for appendiceal malignancy, 44.6 months for peritoneal mesothelioma, 13.4 months for colon cancer; the single gastric cancer patient died at 5 months
  • Recurrence within the pleural space occurred in one appendiceal malignancy patient (both sides of the chest entered) and two mesothelioma patients
  • The authors interpreted their data as showing that HITAC does not require chemotherapy dose adjustments compared with HIPEC
• The authors' conclusion: The authors concluded that the 43% rate of grade III or IV adverse events was higher than reported for most cytoreductive surgery and HIPEC groups, but survival was acceptable and intrathoracic recurrence was low

Topics

Medical terms in this study, explained in our Lexicon: Chemotherapy, Cytoreductive Surgery, HIPEC, Peritoneal Mesothelioma, Diaphragm, Intrathoracic, Mitomycin C, Doxorubicin.

Related studies

• Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection — D.J. Sugarbaker, R.R. Gill, et al. (2013)
• Role of hyperthermic intraoperative peritoneal chemotherapy in the management of peritoneal metastases — D. Elias, D. Goéré, et al. (2014)
• Cytoreductive surgery and intraoperative hyperthermic intrathoracic chemotherapy in patients with malignant pleural mesothelioma or pleural metastases of thymoma — E. de Bree, S. van Ruth, et al. (2002)
• Pharmacokinetics of doxorubicin and cisplatin used in intraoperative hyperthermic intrathoracic chemotherapy after cytoreductive surgery for malignant pleural mesothelioma and pleural thymoma — S. van Ruth, O. van Tellingen, et al. (2003)
• Intraoperative hyperthermic chemotherapy perfusion for malignant pleural mesothelioma: an in vitro evaluation — R.B. Cameron, D. Hou (2013)
• Acute kidney injury after cytoreductive surgery and hyperthermic intraoperative cisplatin chemotherapy for malignant pleural mesothelioma — T. Hod, K.J. Freedberg, et al. (2021)

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