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Clinical Trial
. 2023 May;30(5):2678-2688.
doi: 10.1245/s10434-023-13116-z. Epub 2023 Feb 8.

Perioperative Systemic Therapy Versus Cytoreductive Surgery and HIPEC Alone for Resectable Colorectal Peritoneal Metastases: Patient-Reported Outcomes of a Randomized Phase II Trial

C Bakkers #  1 , K P Rovers #  1 , A Rijken  1 , G A A M Simkens  1 , C S Bonhof  2   3 , S W Nienhuijs  1 , J W A Burger  1 , G J M Creemers  4 , A R M Brandt-Kerkhof  5 , J B Tuynman  6 , A G J Aalbers  7 , M J Wiezer  8 , P R de Reuver  9 , W M U van Grevenstein  10 , P H J Hemmer  11 , C J A Punt  12 , P J Tanis  13 , F Mols  2   3 , I H J T de Hingh  14   15 ; Dutch Peritoneal Oncology Group and the Dutch Colorectal Cancer Group
Collaborators, Affiliations
Clinical Trial

Perioperative Systemic Therapy Versus Cytoreductive Surgery and HIPEC Alone for Resectable Colorectal Peritoneal Metastases: Patient-Reported Outcomes of a Randomized Phase II Trial

C Bakkers et al. Ann Surg Oncol. 2023 May.

Abstract

Background: As part of a randomized phase II trial in patients with isolated resectable colorectal peritoneal metastases (CPMs), the present study compared patient-reported outcomes (PROs) of patients treated with perioperative systemic therapy versus cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) alone. Also, PROs of patients receiving perioperative systemic therapy were explored.

Patients and methods: Eligible patients were randomized to perioperative systemic therapy (experimental) or CRS-HIPEC alone (control). PROs were assessed using EORTC QLQ-C30, QLQ-CR29, and EQ-5D-5L questionnaires at baseline, after neoadjuvant treatment (experimental), and at 3 and 6 months postoperatively. Linear mixed modeling was used to compare five predefined PROs (visual analog scale, global health status, physical functioning, fatigue, C30 summary score) between arms and to longitudinally analyze PROs in the experimental arm.

Results: Of 79 analyzed patients, 37 (47%) received perioperative systemic therapy. All predefined PROs were comparable between arms at all timepoints and returned to baseline at 3 or 6 months postoperatively. The experimental arm had worsening of fatigue [mean difference (MD) + 14, p = 0.001], loss of appetite (MD + 15, p = 0.003), hair loss (MD + 18, p < 0.001), and loss of taste (MD + 27, p < 0.001) after neoadjuvant treatment. Except for loss of appetite, these PROs returned to baseline at 3 or 6 months postoperatively.

Conclusions: In patients with resectable CPM randomized to perioperative systemic therapy or CRS-HIPEC alone, PROs were comparable between arms and returned to baseline postoperatively. Together with the trial's previously reported feasibility and safety data, these findings show acceptable tolerability of perioperative systemic therapy in this setting.

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Conflict of interest statement

Prof. I.H.J.T. de Hingh received grants (paid to institute) from QP&S/RanD Biotech for research unrelated to the submitted work. Prof. Dr. P.J. Tanis received an unrestricted research grant from Allergan (LifeCell) unrelated to the submitted work. Prof. C.J.A. Punt has an advisory role for Nordic Pharma. All remaining authors have declared no conflicts of interest.

Figures

Fig. 1
Fig. 1
Patient pathway and response rates (including reasons for non-response) at all timepoints. CRS–HIPEC cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, PRO patient-reported outcome. aReasons for discontinuation to CRS–HIPEC (experimental): four unresectable peritoneal metastases. bReasons for discontinuation to CRS–HIPEC (control): five unresectable peritoneal metastases, one unexpected liver metastases. cAll due to progressive disease (experimental + control). dBaseline and 3 and 6 months postoperatively
Fig. 2
Fig. 2
Primary comparison of five predefined PROs between both arms. Lines represent mean scores; dashed lines represent standard deviations
Fig. 3
Fig. 3
PROs with a statistically significant difference in scores between baseline and after neoadjuvant treatment in secondary explorative analyses in the experimental arm. Lines represent mean scores; dashed lines represent standard deviations; hollow dots indicate a statistically significant difference compared with baseline
See this image and copyright information in PMC

Comment in

References

    1. Klaver CE, Groenen H, Morton DG, Laurberg S, Bemelman WA, Tanis PJ. Recommendations and consensus on the treatment of peritoneal metastases of colorectal origin: a systematic review of national and international guidelines. Colorectal Dis. 2017;19:224–236. doi: 10.1111/codi.13593. - DOI - PubMed
    1. Rovers KP, Simkens GA, Punt CJ, van Dieren S, Tanis PJ, de Hingh IH. Perioperative systemic therapy for resectable colorectal peritoneal metastases: sufficient evidence for its widespread use? A critical systematic review. Crit Rev Oncol Hematol. 2017;114:53–62. doi: 10.1016/j.critrevonc.2017.03.028. - DOI - PubMed
    1. Bushati M, Rovers KP, Sommariva A, et al. The current practice of cytoreductive surgery and HIPEC for colorectal peritoneal metastases: results of a worldwide web-based survey of the Peritoneal Surface Oncology Group International (PSOGI) Eur J Surg Oncol. 2018;44:1942–1948. doi: 10.1016/j.ejso.2018.07.003. - DOI - PubMed
    1. Rovers KP, Bakkers C, Simkens GAAM, et al. Perioperative systemic therapy and cytoreductive surgery with HIPEC versus upfront cytoreductive surgery with HIPEC alone for isolated resectable colorectal metastases: protocol of a multicentre, open-label, parallel-group, phase II-III, randomised, superiority study (CAIRO6) BMC Cancer. 2019;19:390. doi: 10.1186/s12885-019-5545-0. - DOI - PMC - PubMed
    1. Braun MS, Seymour MT. Balancing the efficacy and toxicity of chemotherapy in colorectal cancer. Ther Adv Med Oncol. 2011;3:43–52. doi: 10.1177/1758834010388342. - DOI - PMC - PubMed

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