Hematological toxicities associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Our plain-English summary of Hematological toxicities associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, by E.Y.T. Wong, G.H.C. Tan, M. Kumar, et al (Asia-Pacific Journal of Clinical Oncology, 2020).

The study

• Authors: E.Y.T. Wong, G.H.C. Tan, M. Kumar, M.C.C. Teo
• Journal: Asia-Pacific Journal of Clinical Oncology
• Published: 2020;16(2):e38-e46
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been found to prolong survival in selected patients with peritoneal disease, but the extent of cytoreduction and chemoperfusion can result in systemic toxicities. We evaluate the incidence of perioperative hematological complications and its associated risk factors.

Methods: Retrospective analysis of a prospectively collected database of CRS-HIPEC cases between April 2001 and October 2016 was performed. Patients were stratified based on the clinicopathological characteristics, perioperative incidence, grade, and duration of leukopenia (white blood cells < 4000/mm3 ), neutropenia (absolute neutrophils < 2000/mm3 ), and thrombocytopenia (platelets < 140 000/mm3 ).

Results: Two hundred and thirty-five CRS-HIPEC were performed in 220 patients with peritoneal metastasis of colorectal, ovarian, primary peritoneal, appendiceal, or mesothelioma origins. The incidences of leukopenia, neutropenia, and thrombocytopenia were 15.3%, 3.8%, and 37.9%, respectively. Median time to onset was 1 day (0-16 days), 0 day (0-2 days), and 1 day (1-2 days), respectively, after operation. Median duration of leukopenia, neutropenia, and thrombocytopenia was 1 day (1-3 days), 1 day (1-2days), and 3 days (range 0-16 days), respectively. Age > 60 (odds ratio [OR] 0.229 [95% CI: 0.105-0.502], P < .001) and the use of prior chemotherapy (OR 2.46 [95% CI: 1.24, 4.83], P = .010) were independent risk factors for thrombocytopenia on multivariable logistic regression.

Conclusion: Hematological toxicities are common after hyperthermic intraperitoneal chemotherapy with thrombocytopenia being most common. Patients with age > 60, and who have undergone chemotherapy, are at risk of these toxicities and should be closely monitored post CRS-HIPEC.

© 2019 John Wiley & Sons Australia, Ltd.

In plain English

This retrospective study from the National Cancer Centre Singapore looked at blood-count problems after cytoreductive surgery combined with heated chemotherapy delivered inside the abdomen (CRS-HIPEC). It covered 235 procedures in 220 patients treated between April 2001 and October 2016 for cancer spread to the abdominal lining. Of the 219 patients whose cancer origin was recorded, 10 had mesothelioma. Results were not reported separately for them. Within 30 days, low white cell counts (leukopenia) followed 15.3% of procedures (36 of 235), low neutrophils (neutropenia) 3.8% (9), and low platelets (thrombocytopenia) 37.9% (89). Most cases were grade 1, the mildest grade. The authors reported no deaths related to these problems. In the adjusted analysis, prior chemotherapy was linked to higher odds of low platelets (odds ratio 2.46, 95% CI 1.24 to 4.83). Age over 60 was linked to lower odds (0.229, 95% CI 0.105 to 0.502), which the discussion called a possible protective effect. Even so, the authors concluded that patients over 60 and those given prior chemotherapy are at risk and should be closely monitored. They noted that the retrospective design made bias and confounding hard to control.

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 collected database (single-institution case series)
• Who was studied: 220 patients (235 CRS-HIPEC procedures, including 15 repeat procedures) with peritoneal metastases of colorectal, ovarian, primary peritoneal, appendiceal, mesothelioma or other origin, treated with curative intent at the National Cancer Centre, Singapore, April 2001 to October 2016. 10 of 219 patients with a recorded origin (4.6%) had mesothelioma. Median age was 53 (range 10 to 76), and 164 (74.5%) were female.
• Exposure: Not an asbestos exposure study. The exposure studied was cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy, given at 41 to 43 degrees C. The drug was mitomycin C (12.5 mg/m2 for males, 10 mg/m2 for females) or cisplatin (50 mg/m2). Cisplatin was used for gastric, ovarian, primary peritoneal and mesothelioma origins.
• Main results:
  • Across 235 procedures, thrombocytopenia occurred after 89 (37.9%) and leukopenia after 36 (15.3%).
  • Neutropenia occurred after 9 procedures (3.8%).
  • Thrombocytopenia began a median of 1 day after surgery (range 0 to 5 days) and lasted a median of 3 days (range 0 to 16 days).
  • Grade 4 (most severe) toxicity occurred in one patient (0.4%) for leukopenia, one (0.4%) for neutropenia and three (1.3%) for thrombocytopenia. There were no deaths related to hematological toxicity.
  • In the multivariate analysis for thrombocytopenia, age over 60 was associated with lower odds (OR 0.229, 95% CI 0.105 to 0.502, P less than .001). Previous chemotherapy was associated with higher odds (OR 2.46, 95% CI 1.24 to 4.83, P = .010).
  • In the multivariate analysis for neutropenia, only duration of surgical ICU stay was identified as an independent risk factor (OR 1.00, 95% CI 0.900 to 1.19, P = .001).
  • In univariate analysis, leukopenia was associated with intraoperative transfusion (OR 3.20, 95% CI 1.00 to 9.40, P = .027).
  • In the discussion, the authors described older age as possibly protective against thrombocytopenia.
• The authors' conclusion: The authors concluded that hematological toxicities are common after HIPEC, with thrombocytopenia the most common. They stated that patients over 60 and those who have had chemotherapy are at risk and should be closely monitored after CRS-HIPEC.
• Limitations the authors state:
  • The retrospective design makes it difficult to control for bias and confounders.
  • Data collection was limited by the number of blood tests each patient's physician ordered.
  • Many other patient and surgical factors could contribute, so the authors cautioned against definitive conclusions.
  • Hematological data were collected only until discharge from the surgical admission.

Topics

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, HIPEC, Neutropenia, Metastasis, Mesothelioma, Odds Ratio, Chemotherapy.

Related studies

• Early recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) — G.H.C. Tan, C.S. Chia, et al. (2018)
• A Novel Tool for Predicting Major Complications After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy — J.M. Baumgartner, T.G. Kwong, et al. (2016)
• Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: long-term results at St George Hospital, Australia — N. Alzahrani, J.S. Ferguson, 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)
• 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)
• 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)

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