Multimodality treatment of malignant pleural mesothelioma with or without immunotherapy: does it change anything?

Our plain-English summary of Multimodality treatment of malignant pleural mesothelioma with or without immunotherapy: does it change anything?, by M. Lucchi, A. Picchi, G. Alí, et al (Interactive Cardiovascular and Thoracic Surgery, 2010).

The study

• Authors: M. Lucchi, A. Picchi, G. Alí, A. Chella, G. Guglielmi, A. Cristaudo, G. Fontanini, A. Mussi
• Journal: Interactive Cardiovascular and Thoracic Surgery
• Published: 2010;10(4):572-6
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The purpose of this study was to investigate immunological effector cells and angiogenesis in malignant pleural mesothelioma (MPM) patients, who underwent multimodality treatments. Clinical and pathological characteristics of 57 patients, with International Mesothelioma Interest Group stage II-III MPM, who underwent two different multimodality treatments (with and without immunotherapy) between 1999 and 2008 were analyzed. CD8+, CD4+ and Foxp3+ tumor-infiltrating lymphocytes, tryptase and chymase mast cells (MCs), CD34, number of microvessels and vascular endothelial growth factor were determined by immunohistochemistry. The histology was 51 epitheliomorf and 6 biphasic. The stage was III in 41 cases and II in 16 cases. With an average follow-up of 69 months (range 9-115) 14 patients are still alive and the overall median actuarial survival is 21.4 months. Tryptase MCs, CD8+ and Foxp3+ lymphocytes had significantly increased in the interleukin 2 (IL-2) treated group. Moreover, the number of microvessels was significantly lower in IL-2 treated patients. This study indicates that immunotherapy leads to an increase in cytotoxic CD8+ lymphocytes and tryptase MCs and to a decrease of the tumoral neoangiogenesis. Changes in MPM microenvironment induced by immunotherapy may play a major role in the local control of this disease and need further investigations.

In plain English

This institutional report from Pisa, Italy, compared tumor tissue and survival in two sequential groups of patients with stage II to III malignant pleural mesothelioma who had multimodality treatment. Thirty-four patients treated between 1999 and 2004 received preoperative intrapleural interleukin 2 (IL-2). Twenty-three treated between 2005 and 2008 did not. Two pathologists who did not know each patient's treatment counted immune cells and small blood vessels in tumor samples. The IL-2 group had significantly more tryptase mast cells, CD8 lymphocytes and Foxp3 lymphocytes, and significantly fewer microvessels. Chymase mast cells and VEGF expression did not differ significantly. Two-year actuarial survival was 44.8% in the IL-2 group and 43.2% in the other group, a difference that was not statistically significant. Patients with low Foxp3 expression survived longer. The authors concluded that intrapleural IL-2 increased these immune cells and inhibited tumor blood-vessel growth, and they called for further studies. They noted that because the groups were treated one after the other, the second group's survival was estimated over a shorter follow-up. The article does not report patients' asbestos exposure.

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 comparison of two sequential series of patients treated at one center with different multimodality treatments (with and without preoperative IL-2), using immunohistochemistry on tumor specimens and survival analysis
• Who was studied: 57 patients (49 male, 8 female) with IMIG stage II to III malignant pleural mesothelioma treated in Pisa, Italy, between 1999 and 2008. The first group had 34 patients treated 1999 to 2004 and the second group had 23 patients treated 2005 to 2008. Histology was 51 epithelioid and 6 biphasic.
• Exposure: The exposure compared was treatment, not asbestos. The first group received multimodality treatment that included preoperative intrapleural interleukin 2 (IL-2). The second group had primary pleurectomy/decortication, hyperthermic intrapleural chemotherapy with epidoxorubicin and cisplatin, adjuvant radiotherapy, and systemic chemotherapy with cisplatin and pemetrexed. Asbestos exposure and fiber types are not reported.
• Main results:
  • Tryptase-positive mast cells were significantly higher in the IL-2 treated group (mean 29.61 vs 4.26 in the group without IL-2, P = 0.01).
  • Chymase mast cells did not differ between the two groups (mean 25.95 with IL-2 vs 20.07 without, P = 0.17).
  • CD8 lymphocytes (mean 88.04 with IL-2 vs 58.05 without, P = 0.001) and Foxp3 lymphocytes (mean 10.43 vs 3.58, P = 0.006) were significantly higher in the IL-2 treated group.
  • The mean microvessel count was significantly lower in IL-2 treated patients (56.47 vs 130.43 in untreated patients; P printed as 0.000000).
  • VEGF expression did not differ significantly between the groups (mean 38.43 with IL-2 vs 44.34 without, P = 0.52).
  • Average follow-up was 86.7 months (range 51 to 115) in the first (IL-2) group and 26 months (range 9 to 46) in the second group. At the time of analysis 2 and 12 patients, respectively, were still alive.
  • Two-year actuarial survival was 44.8% in the first (IL-2) group and 43.2% in the second group, and the difference was not statistically significant.
  • Performance status at diagnosis significantly affected survival (P = 0.005). Survival was better in stage II than stage III, but that difference was not statistically significant.
  • Among the pathological variables, only Foxp3 expression (median value as cut-off) affected outcome: patients with low Foxp3 expression survived longer (P = 0.001).
• The authors' conclusion: The authors concluded that treatment of malignant pleural mesothelioma with intrapleural IL-2 leads to an increase in tryptase-positive mast cells and in CD8 and Foxp3 lymphocytes, and to an inhibition of tumor angiogenesis. They stated that further studies are required.
• Limitations the authors state:
  • The two groups were treated in sequence, so follow-up and survival were observed for the first series but actuarial and short for the second. The authors called this a major bias.
  • Cytological or histological proof of disease progression was rarely obtained.
  • In the conference discussion, the corresponding author explained that more IL-2 patients had been treated than were analyzed, because specimens from the others were no longer available.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Immunotherapy, Angiogenesis, Mesothelioma, Tumor-Infiltrating Lymphocytes, CD34, Immunohistochemistry, Histology.

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