Utility of Chemoresponse Assay in Patients Undergoing Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy

Our plain-English summary of Utility of Chemoresponse Assay in Patients Undergoing Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy, by S. Bhagwandin, S. Naffouje, G. Salti (Annals of Surgical Oncology, 2015).

The study

• Authors: S. Bhagwandin, S. Naffouje, G. Salti
• Journal: Annals of Surgical Oncology
• Published: 2015;22(8):2573-7
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: Our aim was to evaluate the utility of in vitro drug sensitivity testing in patients with peritoneal surface malignancies undergoing cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods: We found data for 27 patients who underwent CRS plus HIPEC from September 2009 to May 2012 and whose tumors were submitted for in vitro drug sensitivity (ChemoFx(®)). Intraperitoneal chemotherapy agents included mitomycin C, cisplatin + doxorubicin, or cisplatin alone.

Results: There were 12 (44.4 %) appendiceal adenocarcinomas, 5 (18.5 %) colon cancers, 4 (14.8 %) sarcomas, 3 (11.1 %) ovarian cancers, 2 (7.4 %) mesotheliomas, and one (3.7 %) gastric cancer. In all, 15 patients (55.5 %) underwent complete cytoreduction (CC ≤ 1). Seventeen tumors (63 %) displayed in vitro sensitivity to the agents used. Mean overall (OS) and progression-free (PFS) survivals for the entire group were 34.4 ± 4.5 months (median 41 months) and 12.5 ± 2.1 months (median 8 months), respectively. There were no significant differences in OS and PFS for patients whose tumors displayed in vitro drug sensitivity versus those whose tumors did not (p = 0.101 and p = 0.403, respectively). These results also did not differ when evaluating only the patients who underwent complete cytoreduction. In vitro, the drug sensitivity did not correlate with primary tumor pathology or preoperative systemic chemotherapy administration. In vitro drug sensitivity correlated with the drug used at the time of HIPEC (p = 0.003). None of the tumors tested showed in vitro sensitivity to cisplatin and/or doxorubicin. Eight nonresponsive tumors, however, showed in vitro activity to other agents.

Conclusions: Data indicate a high rate of in vitro resistance to the intraperitoneal chemotherapeutic agents used. In vitro drug sensitivity is not useful in patients undergoing CRS plus HIPEC.

In plain English

This retrospective study looked at 27 patients treated from September 2009 to May 2012 with surgery to remove tumor from the abdominal lining plus heated chemotherapy delivered into the abdomen (CRS plus HIPEC). Two of the 27 had mesothelioma; most had appendiceal or colon cancer. The article does not discuss asbestos. Tumor samples were tested in the laboratory (the ChemoFx assay) to see whether they responded to the drugs used. Tumors from 17 patients (63%) were classed as sensitive. Survival did not differ significantly between patients with sensitive and resistant tumors. Mean overall survival was 33.0 versus 32.4 months (p = 0.101), and mean progression-free survival was 11.9 versus 13.5 months (p = 0.403). Results were similar among the 15 patients with complete cytoreduction. The article's abstract states that no tumor tested was sensitive to cisplatin and/or doxorubicin. The authors noted the small, mixed patient group, and that lab tests may not reflect heated treatment in the body. They concluded that they did not recommend using these assays in such patients because of the lack of clinical validation.

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: Retrospective study of a small cohort (single series of patients, nonconsecutive), comparing laboratory drug-sensitivity results with survival
• Who was studied: 27 nonconsecutive patients (11 men, 16 women; mean age 52.9 years, range 30–79) with cancer spread on the peritoneal surface who underwent CRS plus HIPEC from September 2009 to May 2012. Tumors were 12 appendiceal cancers, 5 colon cancers, 4 sarcomas, 3 ovarian cancers, 2 mesotheliomas and 1 gastric cancer. The authors are affiliated with the University of Illinois at Chicago Medical Center and Edward Cancer Center, Illinois. The article does not otherwise state where patients were treated.
• Exposure: No asbestos exposure was studied. The study examined a laboratory chemoresponse test (ChemoFx) on tumor tissue, in relation to the heated intraperitoneal chemotherapy given at 42–43 C. Patients with gastrointestinal cancers received mitomycin C (40 mg), except one patient who received cisplatin (45 mg/L). Patients with non-gastrointestinal cancers received cisplatin (45 mg/L) with doxorubicin (15 mg/L). In total, 17 patients received mitomycin C, 9 received cisplatin plus doxorubicin, and 1 received cisplatin.
• Main results:
  • Tumors from 17 of 27 patients (63%) showed laboratory sensitivity. Responsive and intermediate-responsive results were both counted as sensitive.
  • For the whole group of 27, mean overall survival was 34.4 months (median 41 months) and mean progression-free survival was 12.5 months (median 8 months).
  • Mean overall survival was 33.0 months (median 41) in patients with chemosensitive tumors and 32.4 months (median not reached) in those with chemoresistant tumors. The difference was not statistically significant (p = 0.101).
  • Mean progression-free survival was 11.9 months (median 9) in chemosensitive patients and 13.5 months (median 9) in chemoresistant patients (p = 0.403).
  • Among the 15 patients with complete cytoreduction, mean overall survival was 44.0 months (median not reached) in chemosensitive patients and 36.8 months (median 41) in chemoresistant patients (p = 0.639). Mean progression-free survival was 15.7 months (median 9) versus 12.1 months (median 16) (p = 0.648).
  • Laboratory drug sensitivity did not correlate with the type of primary tumor (p = 0.309) or with chemotherapy given before surgery (p = 0.786).
  • Per the article's abstract, laboratory sensitivity correlated with the drug used during HIPEC (p = 0.003).
  • Per the article's abstract, none of the tumors tested showed laboratory sensitivity to cisplatin and/or doxorubicin.
  • Per the article's abstract, eight tumors that did not respond to the HIPEC drugs showed laboratory activity to other agents.
• The authors' conclusion: The authors concluded that they found no correlation between laboratory sensitivity to drugs typically used for HIPEC and clinical outcomes. They did not recommend using these assays in decision-making for such patients because of the lack of clinical validation.
• Limitations the authors state:
  • The patient group was relatively small.
  • The patients had a mix of cancer types, although most were of gastrointestinal origin.
  • Laboratory tests may not reflect what happens in the body when drugs are given under heated conditions during surgery.
  • The study did not evaluate how postoperative chemotherapy related to the assay results and outcomes.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Ovarian cancer, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, HIPEC, Chemotherapy, Mitomycin C, Cisplatin, Doxorubicin, Adenocarcinoma, Colorectal Cancer.

Related studies

• Quality of life after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: a prospective study of 216 patients — G. Passot, N. Bakrin, et al. (2014)
• The results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in 1200 patients with peritoneal malignancy — B. Moran, T. Cecil, et al. (2015)
• Iterative procedures combining cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for isolated peritoneal recurrence — M. Vaira, M. Robella, et al. (2014)
• Repeat cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent diffuse malignant peritoneal mesothelioma — Y. Huang, N.A. Alzahrani, et al. (2015)
• Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for limited peritoneal metastasis. The PSOGI international collaborative registry — A. Arjona-Sanchez, O. Aziz, et al. (2021)
• Anesthetic management and renal function in pediatric patients undergoing cytoreductive surgery with continuous hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin — P. Owusu-Agyemang, R. Arunkumar, et al. (2012)

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