Preoperative Risk Score for Predicting Incomplete Cytoreduction: A 12-Institution Study from the US HIPEC Collaborative

Our plain-English summary of Preoperative Risk Score for Predicting Incomplete Cytoreduction: A 12-Institution Study from the US HIPEC Collaborative, by M.Y. Zaidi, R.M. Lee, A.C. Gamboa, et al (Annals of Surgical Oncology, 2020).

The study

• Authors: M.Y. Zaidi, R.M. Lee, A.C. Gamboa, S. Speegle, J.M. Cloyd, C. Kimbrough, T. Grotz, J. Leiting, K. Fournier, A.J. Lee, S. Dineen, S. Dessureault, K.J. Kelly, N.V. Kotha, C. Clarke, T.C. Gamblin, S.H. Patel, T.C. Lee, R.J. Hendrix, L. Lambert, S. Ronnekleiv-Kelly, C. Pokrzywa, A.M. Blakely, B. Lee, F.M. Johnston, N. Fackche, M.C. Russell, S.K. Maithel, C.A. Staley
• Journal: Annals of Surgical Oncology
• Published: 2020;27(1):156-164
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: For patients with peritoneal carcinomatosis undergoing cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC), incomplete cytoreduction (CCR2/3) confers morbidity without survival benefit. The aim of this study is to identify preoperative factors which predict CCR2/3.

Methods: All patients who underwent curative-intent CRS/HIPEC of low/high-grade appendiceal, colorectal, or peritoneal mesothelioma cancers in the 12-institution US HIPEC Collaborative from 2000 to 2017 were included (n = 2027). The primary aim is to create an incomplete-cytoreduction risk score (ICRS) to predict CCR2/3 CRS utilizing preoperative data. ICRS was created from a randomly selected cohort of 50% of patients (derivation cohort) and verified on the remaining patients (validation cohort).

Results: Within our derivation cohort (n = 998), histology was low-grade appendiceal neoplasms in 30%, high-grade appendiceal tumor in 41%, colorectal tumor in 22%, and peritoneal mesothelioma in 8%. CCR0/1 was achieved in 816 patients and CCR 2/3 in 116 patients. On multivariable analysis, preoperative factors associated with incomplete cytoreduction were male gender [odds ratio (OR) 3.4, p = 0.007], presence of ascites (OR 2.8, p = 0.028), cancer antigen (CA)-125 ≥ 40 U/mL (OR 3.4, p = 0.012), and carcinoembryonic antigen (CEA) ≥ 4.2 ng/mL (OR 3.2, p = 0.029). Each preoperative factor was assigned a score of 0 or 1 to form an ICRS from 0 to 4. Scores were grouped as zero (0), low (1-2), or high (3-4). Incidence of CCR2/3 progressively increased by risk group from 1.6% in zero to 13% in low and 39% in high. When ICRS was applied to the validation cohort (n = 1029), this relationship was maintained.

Conclusion: The incomplete cytoreduction risk score incorporates preoperative factors to accurately stratify the risk of CCR2/3 resection in CRS/HIPEC. This score should not be used in isolation, however, to exclude patients from surgery.

In plain English

This retrospective study used records from 12 US academic centers to build a score predicting, before surgery, which patients would be left with tumor nodules of 2.5 mm or more (incomplete cytoreduction, called CCR2/3) after cytoreductive surgery with or without heated abdominal chemotherapy (HIPEC). It included 2027 patients treated from 2000 to 2017 for appendiceal or colorectal cancer or peritoneal mesothelioma (154 patients). The study did not examine asbestos exposure. Patients were randomly split into one half used to build the score and one half used to test it. In the first half, four factors were linked to incomplete cytoreduction: male sex, fluid in the abdomen (ascites), CA-125 of 40 U/mL or more, and CEA of 4.2 ng/mL or more. Each factor counted one point. Incomplete cytoreduction occurred in 1 of 64 patients scoring zero, 23 of 177 scoring 1 to 2, and 12 of 31 scoring 3 to 4. The test half showed a similar pattern. Only 536 patients had all four measurements. The authors concluded the score should not be used alone to exclude patients from surgery.

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 multi-institution study using a shared database. Patients were randomly split 1:1 into a cohort used to derive a risk score and a cohort used to validate it.
• Who was studied: 2027 of 2372 patients in the US HIPEC Collaborative database who underwent curative-intent cytoreductive surgery, with or without HIPEC, at 12 US centers from 2000 to 2017. Tumor types were noninvasive appendiceal, invasive appendiceal, colorectal, or peritoneal mesothelioma (154 patients, 7.6%). The derivation cohort had 998 patients and the validation cohort 1029.
• Exposure: No asbestos or fiber exposure was studied. The study examined preoperative clinical factors and their association with incomplete cytoreduction (CCR2/3). These factors included sex, age, tumor histology, ascites, prior surgery, and serum CA-125, CA 19-9, CEA and albumin.
• Main results:
  • Surgeons scored the result at the end of surgery. CCR0 meant no visible peritoneal disease, and CCR1 meant remaining tumor nodules smaller than 2.5 mm; these two counted as complete cytoreduction. CCR2 and CCR3, with larger remaining nodules, counted as incomplete cytoreduction.
  • In the derivation cohort's multivariable analysis, three factors were associated with increased odds of incomplete cytoreduction: male gender (OR 3.4, 95% CI 1.4 to 8.6, p = 0.007), ascites (OR 2.8, CI 1.1 to 7.2, p = 0.028), and CA-125 of 40 U/mL or more (OR 3.3, 95% CI 1.3 to 8.8, p = 0.012).
  • In the derivation cohort, CA-125 of 40 U/mL or more had an odds ratio for incomplete cytoreduction of 3.3 (95% CI 1.3 to 8.8, p = 0.012) in the full text.
  • In the derivation cohort, CEA of 4.2 ng/mL or more was also associated with incomplete cytoreduction in multivariable analysis (OR 3.2, 95% CI 1.1 to 9.1, p = 0.029).
  • Histologic tumor type, including peritoneal mesothelioma, was not independently associated with incomplete cytoreduction in the multivariable model.
  • In the derivation cohort (272 patients with all four factors available), incomplete cytoreduction rose with score group: 2% for zero (1/64), 13% for low (23/177), and 39% for high (12/31).
  • In the validation cohort (264 patients with data available), incomplete cytoreduction was 2% in the zero group (1/65), 12% in the low group (21/169) and 27% in the high group (8/30), p = 0.001.
  • Among patients with peritoneal mesothelioma in the whole study, 29% (n = 44) had ascites.
  • Among patients with peritoneal mesothelioma in the whole study, 18% (n = 25) had incomplete cytoreduction.
  • In the derivation cohort, 5-year overall survival was 63% after complete cytoreduction (CCR0/1) and 36% after incomplete cytoreduction (CCR2/3).
  • In the derivation cohort, 5-year overall survival by score group was 87.4% for zero, 59.1% for low and 58.4% for high (p = 0.042).
  • In the validation cohort, survival was not statistically significantly associated with score group.
• The authors' conclusion: The authors concluded that the score is associated with incomplete cytoreduction. They also concluded that it should not be used on its own to exclude patients from surgery.
• Limitations the authors state:
  • Of more than 2000 patients, only 536 could be included in the final score analysis because data on all four factors were missing for the rest.
  • The study was retrospective.
  • Tumor marker measurements may have varied between the 12 institutions.
  • Surgery and pathology examination were not standardized across institutions.
  • The score was designed only to predict incomplete cytoreduction, not survival.
  • No formal analysis of the score within each tumor type was done.
  • The database did not distinguish mucinous from malignant ascites before surgery.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Colon cancer.

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, HIPEC, Chemotherapy, Peritoneal Mesothelioma, Histology, Neoplasm, Odds Ratio, Ascites.

Related studies

• Long-term Survival and Propensity Score Matched Outcomes of Bilateral vs. Unilateral Diaphragm Interventions in Cytoreductive Surgery plus Intra-peritoneal Chemotherapy — B. Singh, G. Singh, et al. (2018)
• Repeat Cytoreductive Surgery and HIPEC for Peritoneal Surface Malignancy and Peritoneal Carcinomatosis — J.F. Wong, G.H. Tan, et al. (2015)
• CRS/HIPEC with Major Organ Resection in Peritoneal Mesothelioma Does not Impact Major Complications or Overall Survival: A Retrospective Cohort Study of the US HIPEC Collaborative — D. Roife, B.D. Powers, et al. (2020)
• Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in Asian patients: 100 consecutive patients in a single institution — M.C. Teo, G.H. Tan, et al. (2013)
• The results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in 1200 patients with peritoneal malignancy — B. Moran, T. Cecil, et al. (2015)
• Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion in Adolescent and Young Adults with Peritoneal Metastases — M. Dhir, L. Ramalingam, et al. (2017)

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