A single-center retrospective cohort study of perioperative systemic chemotherapy in diffuse malignant peritoneal mesothelioma

Our plain-English summary of A single-center retrospective cohort study of perioperative systemic chemotherapy in diffuse malignant peritoneal mesothelioma, by X. Wang, S. Katz, J. Miura, et al (PloS One, 2022).

The study

• Authors: X. Wang, S. Katz, J. Miura, G. Karakousis, L. Roshkovan, S. Walker, S. McNulty, C. Ciunci, K. Cengel, C.J. Langer, M.E. Marmarelis
• Journal: PloS One
• Published: 2022;17(9):e0275187
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare variant of malignant mesothelioma, representing 10-15% of malignant mesothelioma cases. The preferred therapeutic approach is cytoreductive surgery (CRS) accompanied by hyperthermic intraperitoneal chemotherapy (HIPEC); the role of systemic chemotherapy is not well established. While some limited retrospective studies report worse outcomes with neoadjuvant chemotherapy, our institution has favored the use of neoadjuvant chemotherapy for symptom relief and surgical optimization. The aim of our study was to assess the outcomes of patients receiving neoadjuvant chemotherapy, compared to those receiving adjuvant or no perioperative chemotherapy.

Patients And Methods: We conducted a single-center retrospective cohort study of treatment-naïve, non-papillary DMPM patients seen at our institution between 1/1/2009 and 9/1/2019. We explored the effect of type of systemic therapy on clinical outcomes and estimated median overall survival (mOS) using Kaplan-Meier curves. Hazard ratios (HR) calculated by Cox proportional hazard model were used to estimate effect of the exposures on overall survival.

Results: 47 patients were identified with DMPM (median age at diagnosis 61.2 years, 76.6% epithelioid histology, 74.5% white race, 55.3% known asbestos exposure). CRS was performed in 53.2% of patients (25/47); 76.0% of surgical patients received HIPEC (19/25). The majority received systemic chemotherapy (37/47, 78.7%); among patients receiving both CRS and chemotherapy, neoadjuvant chemotherapy was more common than adjuvant chemotherapy (12 neoadjuvant, 8 adjuvant). Overall mOS was 84.1 months. Among neoadjuvant patients, 10/12 underwent surgery, and 2 were lost to follow-up; the majority (9/10) had clinically stable or improved disease during the pre-operative period. There were numerical more issues with chemotherapy with the adjuvant patients (4/8: 2 switches in platinum agent, 2 patients stopped therapy) than with the neoadjuvant patients (2/10: 1 switch in platinum agent, 1 delay due to peri-procedural symptoms). Neoadjuvant chemotherapy was not associated with worse mOS compared to adjuvant chemotherapy (mOS NR vs 95.1 mo, HR 0.89, 95% CI 0.18-4.5, p = 0.89).

Conclusions: When used preferentially, the use of neoadjuvant chemotherapy in DMPM patients was not associated with worse outcomes compared to adjuvant chemotherapy. It was well-tolerated and did not prevent surgical intervention.

In plain English

This retrospective cohort study covered 47 patients with diffuse malignant peritoneal mesothelioma (abdominal lining cancer) treated at the University of Pennsylvania Health System, 2009 to 2019. Asbestos was not studied as a cause; 55.3% reported known or suspected exposure, with no fiber types given. Twelve patients had chemotherapy before planned surgery (all platinum plus pemetrexed), 8 after surgery (7 platinum plus pemetrexed, 1 pemetrexed alone), 7 surgery without such chemotherapy; 20 were not surgical candidates. Median overall survival was 84.1 months (95% CI 27.8 to 95.1). Among surgical patients, survival did not differ significantly between chemotherapy before and after surgery (median not reached vs 95.1 months; hazard ratio 0.89, 95% CI 0.18 to 4.5, p = 0.89). Of the 12 pre-surgery patients, 10 had surgery and 2 were lost to follow-up; in all, 22 of 47 had no surgery. Chemotherapy problems affected 4 of 8 post-surgery and 2 of 10 pre-surgery patients. The authors concluded that pre-surgery chemotherapy was not associated with worse survival and did not prevent surgery. They noted the study was small and retrospective.

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-center retrospective cohort study
• Who was studied: 47 patients with diffuse malignant peritoneal mesothelioma (DMPM) treated at the University of Pennsylvania Health System, Philadelphia, USA, between January 1, 2009 and September 1, 2019. Well-differentiated papillary DMPM was excluded. Median age was 61.2 years; 46.8% were female, 76.6% were white and 76.6% had epithelioid histology. 55.3% reported known or suspected asbestos exposure.
• Exposure: The exposure studied was the timing of systemic chemotherapy around cytoreductive surgery. Groups were: chemotherapy before planned surgery (neoadjuvant, n = 12, of whom 2 were lost to follow-up before surgery), chemotherapy after surgery (adjuvant, n = 8), surgery alone (n = 7) and a 'No Surgery' group of patients who were not surgical candidates (n = 20). All neoadjuvant patients received a platinum agent (cisplatin or carboplatin) plus pemetrexed, median 4 cycles. In the adjuvant group, 7 of 8 received a platinum agent plus pemetrexed and 1 of 8 received pemetrexed alone, median 5 cycles. Asbestos exposure was recorded only as a patient characteristic, and no fiber types were reported.
• Main results:
  • Median overall survival for all 47 patients was 84.1 months (95% CI 27.8 to 95.1).
  • Among patients who had surgery, no statistically significant difference in median overall survival was found between the neoadjuvant group (not reached) and the adjuvant group (95.1 months): HR 0.89, 95% CI 0.18 to 4.5, p = 0.89.
  • In a multivariable model including smoking status, neoadjuvant chemotherapy still showed no statistical advantage over adjuvant chemotherapy (HR 0.69, 95% CI 0.09 to 5.4, p = 0.729).
  • Patients who had surgical debulking (n = 25) had a median overall survival of 93.2 months (95% CI 46.4 to 95.2). Patients without surgery (n = 22: the 20-patient 'No Surgery' group plus 2 neoadjuvant patients lost to follow-up) had 20.2 months. Log-rank p = 0.03.
  • Among surgical patients, HIPEC was not associated with a statistically significant difference in outcomes (HR 0.48, 95% CI 0.13 to 1.69, p = 0.25).
  • In the neoadjuvant group, 10 of 12 (83.3%) proceeded to planned debulking surgery and 2 (16.7%) were lost to follow-up. Only 1 of those 10 had disease progression during the pre-surgery chemotherapy period.
  • Issues with the chemotherapy course occurred in 4 of 8 adjuvant patients (50%) and 2 of 10 neoadjuvant patients (20%). In the adjuvant group: 2 switched from cisplatin to carboplatin, and 2 stopped treatment. In the neoadjuvant group: 1 switched from cisplatin to carboplatin, and 1 had a surgical delay.
  • HIPEC was given to 9 of 10 (90.0%) neoadjuvant surgical patients, 5 of 8 (62.5%) adjuvant patients and 5 of 7 (71.4%) surgery-only patients. The authors describe this difference as not statistically significant.
• The authors' conclusion: The authors concluded that neoadjuvant chemotherapy was not associated with inferior overall survival compared with adjuvant chemotherapy in DMPM patients with similar baseline characteristics. They also concluded that it did not compromise surgical candidacy and may have increased the proportion of patients eligible for HIPEC. They called for prospective studies.
• Limitations the authors state:
  • The study was retrospective and had a small sample size.
  • All patients came from one tertiary referral center, so the results may not apply to a wider population or to community settings.
  • Unmeasured factors may have influenced which patients received neoadjuvant therapy; only randomization could account for them.
  • No staging system such as the Peritoneal Cancer Index was routinely used, so disease stage was not extracted or analyzed.
  • Baseline and follow-up images were available for only 4 neoadjuvant patients. The rest were assessed from imaging reports only.

Topics

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

Medical terms in this study, explained in our Lexicon: Cohort Study, Chemotherapy, Peritoneal Mesothelioma, Malignant Mesothelioma, Cytoreductive Surgery, HIPEC, Neoadjuvant Chemotherapy, Systemic Therapy.

Related studies

• Evolution of locoregional treatment for peritoneal carcinomatosis: single-center experience of 308 procedures of cytoreductive surgery and perioperative intraperitoneal chemotherapy — T.C. Chua, W. Liauw, et al. (2011)
• Systemic chemotherapy with pemetrexed and cisplatin for malignant peritoneal mesothelioma: a single institution experience — G. Lainakis, F. Zagouri, et al. (2011)
• Long-term survival outcomes of cytoreductive surgery and perioperative intraperitoneal chemotherapy: Single-institutional experience with 1225 cases — L.S. Kyang, N.A. Alzahrani, et al. (2019)
• The role of "closed abdomen" hyperthermic intraperitoneal chemotherapy (HIPEC) in the palliative treatment of neoplastic ascites from peritoneal carcinomatosis: report of a single-center experience — L. Orgiano, F. Pani, et al. (2016)
• Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial — N.L. de Boer, J.P. van Kooten, et al. (2019)
• Learning curve for cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis — Y. Huang, N.A. Alzahrani, et al. (2017)

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