Interval between cytoreductions as a marker of tumor biology in selecting patients for repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy

Our plain-English summary of Interval between cytoreductions as a marker of tumor biology in selecting patients for repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, by I.T. Konstantinidis, E.A. Levine, K. Chouliaras, et al (Journal of Surgical Oncology, 2017).

The study

• Authors: I.T. Konstantinidis, E.A. Levine, K. Chouliaras, G. Russell, P. Shen, K.I. Votanopoulos
• Journal: Journal of Surgical Oncology
• Published: 2017;116(6):741-745
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background And Objectives: Repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for recurrence of peritoneal surface malignancies is safe and effective. Patient selection and factors associated with a favorable outcome are still evolving.

Methods: A prospectively maintained institutional database consisting of 1314 CRS/HIPEC procedures performed between February 1993 and December 2015 was reviewed. Clinicopathologic data from 103 patients and 112 (8.5%) repeat CRS/HIPEC procedures were retrospectively analyzed.

Results: Primary tumors were appendiceal for 60 patients (58.3%), mesothelioma for 14 (13.6%), colorectal for 9 (8.7%), ovarian for 8 (7.8%). R0/R1 resection was achieved in 46 (46.5%) patients. The time interval between the initial and the repeat CRS/HIPEC was <1 year for 21 (20.4%), 1-2 years for 40 (38.8%), and >2 years for 42 patients (40.8%). Overall median survival was 4.3 years and correlated with the time interval (1.3 years for <1 years, 3.7 years for 1-2 years, and 7 years for >2 years; P < 0.001). In multivariate analysis, the R status (P = 0.005) and a time interval of more than 2 years (P = 0.0002) were strongly associated with survival with each additional month between the surgeries conferring a 2.6% reduction in the risk of death.

Conclusions: The current series validates time interval between cytoreductions as a major surrogate of tumor biology in selection of patients with recurrent peritoneal surface malignancies for repeat CRS/HIPEC. Complete repeat cytoreduction more than 2 years from the initial surgery is associated with a favorable outcome.

© 2017 Wiley Periodicals, Inc.

In plain English

This study looked back at patients who had a second round of cytoreductive surgery (removal of visible tumor in the abdomen) combined with heated chemotherapy delivered into the abdomen (HIPEC). The operations took place at Wake Forest University School of Medicine Baptist Hospital between February 1993 and December 2015. From 1314 procedures, the authors analyzed 112 repeat procedures in 103 patients. Most tumors started in the appendix (60 patients), and 14 patients had mesothelioma. The article does not discuss asbestos. Median survival after the repeat operation was 4.3 years overall and 2.4 years for the mesothelioma patients. Survival was longer when more time had passed between the two operations: a median of 1.3 years for under 1 year, 3.7 years for 1 to 2 years, and 7 years for more than 2 years. In the statistical model, the completeness of tumor removal and the interval between surgeries were associated with survival. Each extra month between surgeries was linked to a 2.6% lower risk of death. The authors concluded that the interval reflects tumor biology. They noted that the single-institution, retrospective design may introduce selection bias.

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 analysis of a prospectively maintained single-institution database of surgical procedures
• Who was studied: 103 patients who had 112 repeat CRS/HIPEC procedures, selected from 1314 CRS/HIPEC procedures performed at Wake Forest University School of Medicine Baptist Hospital between February 1993 and December 2015. Primary tumors were appendiceal (60, 58.3%), mesothelioma (14, 13.6%), colorectal (9, 8.7%), ovarian (8, 7.8%) and others (12). Mean age was 47.4 years and 56.3% were female.
• Exposure: No asbestos exposure was studied. The factor studied was the time interval between the initial and the repeat CRS/HIPEC, grouped as within 1 year (21 patients), 1 to 2 years (40) and more than 2 years (42).
• Main results:
  • Median overall survival for all 103 patients was 4.3 years, measured from the repeat operation.
  • By time interval between operations, median overall survival was 1.3 years for under 1 year, 3.7 years for 1 to 2 years, and 7 years for more than 2 years (P < 0.001).
  • For the 14 mesothelioma patients, median overall survival after the repeat operation was 2.4 years (range 0.3 to 7.2 years).
  • In Table 2, mesothelioma patients (3, 6 and 5 patients in the three interval groups) had median survival of 1.3 years for under 1 year, 3.7 years for 1 to 2 years, and 1.8 years for more than 2 years.
  • On multivariate analysis, R0 resection (P = 0.005) and the time interval between operations (P = 0.0002) were associated with survival. Each additional month between surgeries was associated with a 2.6% decrease in the risk of death.
  • Complete macroscopic cytoreduction (R0/R1) was achieved in 51.5% of patients after the first operation and 46.5% after the second. Postoperative morbidity and mortality were 39.8% and 0% after the initial operation and 38% and 1% after the repeat operation.
• The authors' conclusion: The authors concluded that the time interval between cytoreductions serves as a major surrogate of tumor biology in selecting patients for repeat CRS/HIPEC. They found that complete repeat cytoreduction more than 2 years after the first surgery is associated with a favorable outcome. In their view, patients with peritoneal carcinomatosis who recur in less than a year and had a prior incomplete CRS should in general not be offered repeat cytoreduction.
• Limitations the authors state:
  • Selection bias from a single-institution retrospective analysis
  • Selection criteria evolved over 25 years, and the results may not be easily extrapolated to other institutions
  • The outcomes do not include patients who were considered for repeat surgery but whose operative findings did not allow complete cytoreduction
  • Survival in the under-1-year group was driven mostly by tumor types with favorable biology and should be regarded with caution

Topics

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, HIPEC, Mesothelioma, Median Overall Survival, Multivariate Analysis.

Related studies

• The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — S. Kusamura, P.A. Torres Mesa, et al. (2016)
• Cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for children, adolescents, and young adults: the first 50 cases — A. Hayes-Jordan, H. Green, et al. (2015)
• A Novel Tool for Predicting Major Complications After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy — J.M. Baumgartner, T.G. Kwong, et al. (2016)
• Outcomes of repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal surface malignancy — K.I. Votanopoulos, C. Ihemelandu, et al. (2012)
• Is Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy Justified for Biphasic Variants of Peritoneal Mesothelioma? Outcomes from the Peritoneal Surface Oncology Group International Registry — K.I. Votanopoulos, P. Sugarbaker, et al. (2018)
• Early recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) — G.H.C. Tan, C.S. Chia, et al. (2018)

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