Institutional learning curve of cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion for peritoneal malignancies

Our plain-English summary of Institutional learning curve of cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion for peritoneal malignancies, by P.M. Polanco, Y. Ding, J.M. Knox, et al (Annals of Surgical Oncology, 2015).

The study

• Authors: P.M. Polanco, Y. Ding, J.M. Knox, L. Ramalingam, H. Jones, M.E. Hogg, A.H. Zureikat, M.P. Holtzman, J. Pingpank, S. Ahrendt, H.J. Zeh, D.L. Bartlett, H.A. Choudry
• Journal: Annals of Surgical Oncology
• Published: 2015;22(5):1673-9
• Cited by: 93 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemoperfusion (HIPEC) is routinely used to treat certain peritoneal carcinomatoses (PC), but it can be associated with relatively high complication rates, prolonged hospital length of stay, and potential mortality. Our objective was to determine the learning curve (LC) of CRS/HIPEC in our high-volume institution.

Methods: A total of 370 patients with PC from mucinous appendiceal neoplasms (MAN = 282), malignant peritoneal mesothelioma (MPM = 60), and gastric cancer (GC = 24) were studied. Outcomes analyzed included incomplete cytoreduction (IC), severe morbidity (SM), 60-day mortality, progression-free survival (PFS), and overall survival (OS). Risk-adjusted sequential probability ratio test (RA-SPRT) was employed to assess the LC of CRS/HIPEC for IC and SM using prespecified odds ratio (OR) boundaries derived from previously published data. Risk adjusted-cumulative average probability (RA-CAP) was used to analyze 1-year PFS and 2-year OS.

Results: Complete cytoreduction, severe morbidity, and 60-day mortality were 84.2, 30, and 1.9 % respectively. Higher simplified peritoneal cancer index was the major independent risk factor for IC, whereas high-grade histology, IC, and diagnosis of MPM and GC (compared with MAN) were predictors of SM after CRS/HIPEC (p < 0.05). RA-SPRT showed that approximately 180 cases are needed to achieve the lowest risk of IC and SM. Ninety cases were needed to achieve a steady 1-year PFS and 2-year OS in RA-CAP plots.

Conclusions: The completeness of cytoreduction, morbidity, and mortality rates for CRS/HIPEC at our institution are comparable to previously reported data. Approximately 180 and 90 procedures are required to improve operative and oncologic outcomes respectively.

In plain English

This University of Pittsburgh study examined how treatment results changed as the institution gained experience. The treatment, CRS/HIPEC, is tumor-removal surgery followed by heated chemotherapy, mostly mitomycin C, inside the abdomen. The authors reviewed 370 patients treated from May 2001 to July 2010: 282 with spread from mucinous appendiceal tumors, 65 with malignant peritoneal mesothelioma and 23 with gastric cancer. The study did not examine asbestos exposure. Overall, 84.2 % had complete cytoreduction, 30 % had severe complications and 1.9 % died within 60 days. Median overall survival was about 40 months for mesothelioma patients. On risk-adjusted charts plotting a cumulative score, the curve for incomplete tumor removal dropped below a preset lower boundary after case 180, and the curve for severe complications did so after case 188. Risk-adjusted 1-year progression-free survival leveled off after about 90 cases. Two-year overall survival rose more slowly after 90 cases and leveled off after about 200. The authors concluded that approximately 180 and 90 procedures are required to improve operative and cancer outcomes respectively. They named a relatively small sample, retrospective data and no analysis of individual surgeons as limitations.

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: Single-institution analysis of consecutive cases from a prospective database, which the authors describe as retrospective. They used risk-adjusted learning-curve methods (RA-SPRT and RA-CAP).
• Who was studied: 370 patients who underwent CRS/HIPEC at the University of Pittsburgh between May 2001 and July 2010. The results section and Table 1 give 282 with mucinous appendiceal neoplasms, 65 with malignant peritoneal mesothelioma and 23 with gastric cancer.
• Exposure: The exposure studied was the treatment itself, not asbestos: cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion at a tissue temperature of 42 C. Most patients received 40 mg of mitomycin C and some received cisplatin. Cases were analysed in date order to measure institutional experience.
• Main results:
  • Across all 370 patients, complete cytoreduction was 84.2 %, severe morbidity 30 % and 60-day mortality 1.9 %. Table 1 gives these as 309, 111 and 7 patients.
  • When outcomes were simply compared across seven sequential groups of cases, without risk adjustment, there was no significant difference.
  • After multivariate analysis, only higher SPCI (extent of disease) and lower operating time remained independent predictors of incomplete cytoreduction.
  • After multivariate analysis, high-grade histology, incomplete cytoreduction, and a diagnosis of malignant peritoneal mesothelioma or gastric cancer (compared with appendiceal neoplasms) predicted severe morbidity.
  • On the risk-adjusted chart for incomplete cytoreduction, the curve dropped below the lower control limit after case 180, after some fluctuation around that limit from case 96. The chart plots a cumulative risk-adjusted log-likelihood ratio score, not the rate itself.
  • On the risk-adjusted chart for severe morbidity, the curve crossed below the lower limit after case 188 and stayed below it for the most part.
  • The risk-adjusted probability of 1-year progression-free survival reached a plateau after the first 90 cases.
  • The risk-adjusted probability of 2-year overall survival rose more slowly after the first 90 cases and reached a plateau after 200 cases.
  • Median overall survival was 81 months for appendiceal neoplasms, 40 months for mesothelioma and 9 months for gastric cancer (80.8, 40.2 and 9.4 in Table 1). Median time to progression was 21, 14 and 7 months for the same groups.
  • A diagnosis of malignant peritoneal mesothelioma (compared with appendiceal neoplasms) was among the independent risk factors for disease progression.
  • Hospital length of stay fell to a plateau of approximately 15 days after the first 90 cases.
• The authors' conclusion: The authors concluded that, at an academic teaching hospital, approximately 180 procedures are required to improve operative outcomes and approximately 90 to improve oncologic outcomes.
• Limitations the authors state:
  • The sample size was relatively small, which could limit detection of significant differences in multivariate analysis.
  • The analysis did not account for individual surgeons' learning curves.
  • The retrospective analysis is prone to inaccurate data collection and missing data.
  • Patient selection, adjuvant therapies and tumor biology may have influenced oncologic outcomes and were not controlled for.
  • The specific survival probabilities were difficult to interpret because three different diagnoses were combined.

Topics

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

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, HIPEC, Neoplasm, Peritoneal Mesothelioma, Stomach Cancer, Progression-Free Survival, Overall Survival, Odds Ratio.

Related studies

• Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent or progressive diffuse malignant peritoneal mesothelioma: clinicopathologic characteristics and survival outcome — C. Ihemelandu, L. Bijelic, et al. (2015)
• Learning curve for cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis — Y. Huang, N.A. Alzahrani, et al. (2017)
• Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion in Adolescent and Young Adults with Peritoneal Metastases — M. Dhir, L. Ramalingam, et al. (2017)
• A Novel Tool for Predicting Major Complications After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy — J.M. Baumgartner, T.G. Kwong, et al. (2016)
• 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)
• Morbidity of the abdominal wall resection and reconstruction after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) — M.F. Nunez, A. Sardi, et al. (2015)

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