Laser ablation-inductively coupled plasma-mass spectrometry analysis reveals differences in chemotherapeutic drug distribution in surgically resected pleural mesothelioma

Our plain-English summary of Laser ablation-inductively coupled plasma-mass spectrometry analysis reveals differences in chemotherapeutic drug distribution in surgically resected pleural mesothelioma, by A. Tisza, T. Klikovits, M. Benej, et al (British Journal of Clinical Pharmacology, 2023).

The study

• Authors: A. Tisza, T. Klikovits, M. Benej, S. Torok, B. Szeitz, Z. Valko, M.A. Hoda, B. Hegedus, M. Bonta, W. Nischkauer, K. Hoetzenecker, A. Limbeck, K. Schelch, V. Laszlo, Z. Megyesfalvi, B. Dome
• Journal: British Journal of Clinical Pharmacology
• Published: 2023;89(11):3364-3374
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Aims: Pleural mesothelioma (PM) is a highly aggressive thoracic tumour with poor prognosis. Although reduced tissue drug accumulation is one of the key features of platinum (Pt) resistance, little is known about Pt distribution in human PM.

Methods: We assessed Pt levels of blood samples and surgically resected specimens from 25 PM patients who had received neoadjuvant Pt-based chemotherapy (CHT). Pt levels and tissue distributions were measured by laser ablation-inductively coupled plasma-mass spectrometry and correlated with clinicopathological features.

Results: In surgically resected PM specimens, mean Pt levels of nontumourous (fibrotic) areas were significantly higher (vs tumourous regions, P = 0.0031). No major heterogeneity of Pt distribution was seen within the tumourous areas. Pt levels correlated neither with the microvessel area nor with apoptosis rate in the tumourous or nontumourous regions. A significant positive correlation was found between serum and both full tissue section and tumourous area mean Pt levels (r = 0.532, P = 0.006, 95% confidence interval [95% CI] 0.161-0.771 and r = 0.415, P = 0.039, 95% CI 0.011-0.702, respectively). Furthermore, a significant negative correlation was detected between serum Pt concentrations and elapsed time from the last cycle of CHT (r = -0.474, P = 0.017, 95% CI -0.738--0.084). Serum Pt levels correlated negatively with overall survival (OS) (P = 0.029).

Conclusions: There are major differences in drug distribution between tumourous and nontumourous areas of PM specimens. Serum Pt levels significantly correlate with full section and tumourous area average Pt levels, elapsed time from the last CHT cycle, and OS. Further studies investigating clinicopathological factors that modulate tissue Pt concentration and distribution are warranted.

© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

In plain English

This study measured where platinum from platinum-based chemotherapy drugs ended up in pleural mesothelioma patients. It did not examine asbestos exposure. The authors analysed blood and surgical tissue from 25 patients operated on at the Medical University of Vienna between 2011 and 2017. All had received cisplatin or carboplatin, given across Austria, before surgery. Tissue platinum was mapped with laser-based mass spectrometry. Mean platinum was higher in non-tumour, scar-like (fibrotic) areas than in tumour areas (1.23 versus 0.83 micrograms per gram, P = 0.0031). Blood platinum correlated with platinum in the whole tissue section (r = 0.532, 95% CI 0.161 to 0.771) and in tumour areas (r = 0.415, 95% CI 0.011 to 0.702). It was lower the more time had passed since the last chemotherapy cycle. Patients with blood platinum below the median (177.78 micrograms per litre) lived longer than those at or above it (median overall survival 873 versus 476 days, P = 0.029). Tissue platinum showed no statistically significant association with survival, blood-vessel area or apoptosis (cell-death) rate. The authors called their findings, from a small, varied group, hypothesis-generating.

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: Clinical laboratory study of blood and surgical tissue samples, with clinical data collected retrospectively from medical records
• Who was studied: 25 patients with histologically confirmed pleural mesothelioma. Their chemotherapy before surgery was given across Austria, and their surgery (extrapleural pneumonectomy) took place at the Department of Thoracic Surgery, Medical University of Vienna, Austria, between 2011 and 2017. Of the 25, 21 had epithelioid and 4 had nonepithelioid tumours. Median age was 64.5 years and 76% were male.
• Exposure: Platinum-based chemotherapy given before surgery: cisplatin (n = 16) or carboplatin (n = 7); two patients received both. Platinum was measured as an element in blood and tissue. Asbestos exposure was not studied.
• Main results:
  • Serum platinum in the 25 patients ranged from 50.7 to 408.4 micrograms per litre, with a mean of 205.1.
  • In the tissue specimens, mean platinum was significantly higher in nontumourous (fibrotic) areas than in tumourous areas: 1.23 versus 0.83 micrograms per gram (P = 0.0031).
  • Serum platinum correlated positively with mean platinum in the full tissue section (r = 0.532, P = 0.006, 95% CI 0.161 to 0.771) and with platinum in tumourous areas (r = 0.415, P = 0.039, 95% CI 0.011 to 0.702).
  • The correlation between serum platinum and platinum in nontumourous areas was not statistically significant (Spearman r = 0.406, P = .095).
  • Serum platinum correlated negatively with the time elapsed since the last chemotherapy cycle (Spearman r = -0.474, P = .017). The minus sign is lost in the article text, but the article calls this a negative correlation.
  • Patients with serum platinum below the median (less than 177.78 micrograms per litre) had longer median overall survival than those at or above it: 873 versus 476 days (P = 0.029).
  • Platinum levels in the full section, tumourous areas and nontumourous areas showed no statistically significant association with overall survival.
  • No statistically significant correlation was found between tissue platinum levels and either microvessel area or apoptotic rate.
  • Tissue and serum platinum levels did not differ significantly by age, gender, histological subtype or tumour pathological stage.
• The authors' conclusion: The authors concluded that platinum distribution differed markedly between tumourous and nontumourous fibrotic areas of resected pleural mesothelioma, with higher mean levels in the fibrotic areas. They also concluded that serum platinum correlated with full-section and tumourous-area platinum, with time since the last chemotherapy cycle, and with overall survival.
• Limitations the authors state:
  • The number of patients was relatively small.
  • The patients' clinical and pathological features varied widely, which made subgroup analyses difficult.
  • The time from the last chemotherapy cycle to surgery varied widely, which might have influenced platinum levels. Multivariate analyses were not feasible.
  • Only two patients received bevacizumab, so its effect on tissue platinum could not be estimated.
  • Vascular tortuosity and permeability were not assessed.
  • The authors described their findings as hypothesis-generating and said validation studies are needed.

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, Prognosis, Chemotherapy, Apoptosis, confidence interval, Overall Survival.

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