Conversion to Complete Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma After Bidirectional Chemotherapy

Our plain-English summary of Conversion to Complete Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma After Bidirectional Chemotherapy, by F. Le Roy, M. Gelli, A. Hollebecque, et al (Annals of Surgical Oncology, 2017).

The study

• Authors: F. Le Roy, M. Gelli, A. Hollebecque, C. Honoré, V. Boige, P. Dartigues, L. Benhaim, D. Malka, M. Ducreux, D. Elias, D. Goéré
• Journal: Annals of Surgical Oncology
• Published: 2017;24(12):3640-3646
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: This report aims to describe preliminary results concerning secondary resectability after bidirectional chemotherapy for initially unresectable malignant peritoneal mesothelioma (MPM).

Methods: Between January 2013 and January 2016, 20 consecutive patients treated for diffuse MPM not suitable for upfront surgery received bidirectional chemotherapy associating intraperitoneal and systemic chemotherapy. Evaluation of the response to chemotherapy was assessed clinically and by laparoscopy.

Results: The median peritoneal cancer index (PCI) score at staging laparoscopy was 27 (range 15-39). Altogether, 118 intraperitoneal chemotherapy cycles were administered without any specific adverse catheter-related event. Concerning tolerance, 85% of the patients experienced no pain or mild pain during chemotherapy administration. The clinical response rate was 60% after a median of three chemotherapy cycles. At laparoscopic reevaluation, the median PCI was 18 (range 0-35), and a secondary resectability was considered for 55% of the patients. Complete cytoreduction surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) was finally achieved for 10 patients (50%), with a median intraoperative PCI score of 14 (range 6-30). After a median follow-up period of 18 months, the 2-year overall survival rate was 83.3% for the patients treated by CRS followed by HIPEC and 44% for the patients treated by bidirectional chemotherapy.

Conclusion: Bidirectional chemotherapy is a promising, well-tolerated treatment capable of increasing the resection rate for selected patients with diffuse MPM initially considered as unresectable or borderline resectable. For patients with definitively unresectable disease, bidirectional chemotherapy achieves a higher clinical response rate.

In plain English

This report from one French cancer center described 20 consecutive patients treated from January 2013 to January 2016 for malignant peritoneal mesothelioma, a cancer of the abdominal lining. All had been judged unsuitable for surgery at the outset. They received bidirectional chemotherapy: drugs given both into the abdomen through a catheter and into a vein. The article reported no asbestos exposure data. Across 118 cycles there was no catheter blockage or infection. One patient stopped abdominal treatment because the drug no longer spread properly, which the authors listed as catheter dysfunction. Seventeen patients (85%) had no or mild pain during treatment. Fluid buildup or pain improved in 12 (60%). Ten patients then had surgery the authors classed as complete tumor removal (nine scored CC0, one CC1), followed by heated abdominal chemotherapy (CRS plus HIPEC). Four operated patients had major complications; none died after surgery. At two years, 83% of the CRS plus HIPEC group and 44.4% of those given chemotherapy alone were alive (p = 0.02). The authors concluded the treatment was well tolerated and allowed surgery. They noted their survival results, from a small series, need cautious assessment.

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 case series of consecutive patients, prospectively recorded in a database (no randomized comparison group)
• Who was studied: 20 patients with histologically proven malignant peritoneal mesothelioma (epithelioid type) not suitable for upfront surgery, treated at Gustave Roussy, Villejuif, France, January 2013 to January 2016. Median age was 58 (range 28 to 77); 12 were male and 8 female. Disease was classed as borderline resectable in 12 patients and unresectable in 8. Fourteen (70%) had previously received intravenous chemotherapy.
• Exposure: The exposure studied was a treatment, not asbestos. The treatment was bidirectional chemotherapy. The main regimen was intraperitoneal pemetrexed 500 mg/m2 with intravenous cisplatin 75 mg/m2 or carboplatin, on a 21-day cycle. The alternative was intraperitoneal oxaliplatin 100 mg/m2 with intravenous gemcitabine 1000 mg/m2, on a 14-day cycle. Patients judged resectable then had cytoreductive surgery plus HIPEC. The article mentions 'a link with asbestos exposure' only in its introduction and reports no asbestos exposure data for these patients.
• Main results:
  • At the initial staging laparoscopy, the median peritoneal cancer index (PCI, a score of how much tumor is in the abdomen) for all 20 patients was 27 (range 15 to 39).
  • A total of 118 cycles were given, a median of 5 (range 1 to 15) per patient. No adverse event related to the catheter (occlusion or infection) was observed.
  • One patient had to stop intraperitoneal chemotherapy because of inadequate distribution of the drug in the abdomen, seen on a scan after eight cycles. The authors attributed this probably to chemotherapy-induced adhesions. Their table lists it as catheter dysfunction, 1 patient (5%).
  • During intraperitoneal chemotherapy, 17 patients (85%) had no pain or mild pain. The main toxicities came from the intravenous chemotherapy, with grade 3 neutropenia (low white blood cells) in nine patients (45%).
  • A clinical response was seen in 12 of 20 patients (60%) after a median of 3 cycles. The authors defined clinical response as disappearance or reduction of abdominal pain and ascites (fluid buildup).
  • Fifteen of the 20 patients had a laparoscopic re-evaluation, at which the median PCI was 18 (range 0 to 35). Surgery was considered possible for 11 of these patients (73.3%).
  • Ten patients had what the authors call complete resection (CC0-1) followed by HIPEC. Of the resected patients, nine were scored CC0 and one CC1. A further patient had a macroscopically incomplete resection (CC2).
  • Among patients who had CRS plus HIPEC, the median PCI fell from 27 (range 15 to 39) before bidirectional chemotherapy to 14 (range 6 to 30) at the time of surgery (p = 0.036).
  • Among operated patients, major complications (grades 3 to 4) occurred in four patients. The article does not say whether this count includes the patient with incomplete resection. No postoperative deaths occurred. The mean hospital stay was 30 days (standard deviation 20 days).
  • After a median follow-up of 18.5 months, survival for the whole cohort of 20 was 83.1% at 1 year and 65.8% at 2 years (median not reached).
  • Two-year overall survival was 83% for patients who had CRS plus HIPEC and 44.4% for patients treated with bidirectional chemotherapy alone (p = 0.02, log-rank test).
  • For the group treated with curative intent, two-year disease-free survival was 55.6% and median disease-free survival was 25.5 months.
  • Of the 9 patients treated only with bidirectional chemotherapy, 4 died of progressive disease, at 3, 10, 11 and 14 months.
• The authors' conclusion: The authors concluded that bidirectional chemotherapy is a well-tolerated and effective treatment allowing CRS plus HIPEC for patients with initially unresectable or borderline resectable malignant peritoneal mesothelioma. They also concluded that prospective inclusion in multicentric registries is needed to refine its indications.
• Limitations the authors state:
  • This was a small series. The authors stated that its good survival outcomes need to be assessed cautiously and studied in larger prospective cohorts with longer follow-up.
  • Disease extent was assessed by laparoscopy, which could have underestimated the PCI score.

Topics

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

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, HIPEC, Peritoneal Mesothelioma, Chemotherapy, Unresectable, Peritoneal Cancer Index (PCI), Staging, Overall Survival.

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)
• 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)
• 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 for malignant peritoneal mesothelioma: a systematic review and meta-analysis — J.H. Helm, J.T. Miura, et al. (2015)
• 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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