The effect of chemotherapy on health-related quality of life in mesothelioma: results from the SWAMP trial

Our plain-English summary of The effect of chemotherapy on health-related quality of life in mesothelioma: results from the SWAMP trial, by D.T. Arnold, C.E. Hooper, A. Morley, et al (British Journal of Cancer, 2015).

The study

• Authors: D.T. Arnold, C.E. Hooper, A. Morley, P. White, I.D. Lyburn, J. Searle, M. Darby, T. Hall, D. Hall, N.M. Rahman, E. De Winton, A. Clive, V. Masani, A. Dangoor, S. Guglani, P. Jankowska, S.A. Lowndes, J.E. Harvey, J.P. Braybrooke, N.A. Maskell
• Journal: British Journal of Cancer
• Published: 2015;112(7):1183-9
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The effect of chemotherapy on health-related quality of life (HRQoL) in malignant pleural mesothelioma (MPM) is poorly understood. Patient-individualised prognostication and prediction of treatment response from chemotherapy is useful but little evidence exists to guide practice.

Method: Consecutive patients with MPM who were fit for first-line chemotherapy with pemetrexed and cisplatin\carboplatin were recruited and followed up for a minimum of 12 months. This study focussed on the HRQoL outcomes of these patients using the EQ-5D, EORTC QLQ-C30 and LC13.

Results: Seventy-three patients were recruited of which 58 received chemotherapy and 15 opted for best supportive care (BSC). Compliance with HRQoL questionnaires was 98% at baseline. The chemotherapy group maintained HRQoL compared with the BSC group whose overall HRQoL fell (P=0.006) with worsening dyspnoea and pain. The impact of chemotherapy was irrespective of histological subtype although those with non-epithelioid disease had worse HRQoL at later time points (P=0.012). Additionally, those with a falling mesothelin or improvement on modified-RECIST CT at early follow-up had a better HRQoL at 16 weeks.

Conclusions: HRQoL was maintained following chemotherapy compared with a self-selected BSC group. Once chemotherapy is initiated, a falling mesothelin or improved RECIST CT findings infer a quality-of-life advantage.

In plain English

This was a sub-study of the SWAMP trial, a multi-centre prospective observational study in the South West of England. Between September 2008 and December 2011 it recruited 73 patients with malignant pleural mesothelioma who had not had previous chemotherapy and were judged fit for first-line chemotherapy (pemetrexed with cisplatin or carboplatin). Of these, 58 had chemotherapy and 15 declined it, forming a self-selected comparator group. Patients filled in three quality-of-life questionnaires. Because of deaths and falling questionnaire returns, analysis stopped at 16 weeks. Both groups started with similar quality of life. On the EQ-5D measure, the chemotherapy group stayed stable while the comparator group worsened, a statistically significant difference by 16 weeks. The comparator group also reported worse breathlessness and arm pain. The chemotherapy group had temporary nausea, vomiting and sore mouth, and later hair loss. Among chemotherapy patients, quality of life fell in those with non-epithelioid tumours. It was better in those whose blood mesothelin fell or whose CT scans improved. The authors cautioned that the comparator group was self-selected and could not be classed as a control group.

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: Sub-study of a multi-centre prospective observational study (the SWAMP trial), focusing on health-related quality of life. It compared chemotherapy patients with a self-selected comparator group that declined chemotherapy. It was not a randomised trial.
• Who was studied: 73 patients with treatment-naive malignant pleural mesothelioma, WHO performance status 0, 1 or 2, recruited from seven centres in the South West of England between September 2008 and December 2011. 58 received chemotherapy and 15 declined it after discussion with their oncologist (comparator group). 63 were male and 10 female.
• Exposure: The exposure studied was first-line chemotherapy with pemetrexed and cisplatin or carboplatin, compared with no chemotherapy (best supportive care). Asbestos exposure was not studied.
• Main results:
  • On the EQ-5D, the chemotherapy group maintained overall health while the comparator group worsened considerably. By time point 3 (16 weeks) the difference between the groups was significant (P = 0.006, ANCOVA).
  • At 16 weeks the EQ-5D difference between the chemotherapy and comparator groups was 0.20. The authors said this was greater than the published minimally important difference for lung cancer.
  • Chemotherapy group: at visit 2 (6 weeks) social function, nausea and vomiting, and sore mouth worsened. By visit 3 (16 weeks) these had resolved but alopecia (hair loss) had worsened significantly.
  • Comparator group: at visit 3, dyspnoea (breathlessness) and arm pain were significantly worse than at baseline.
  • Within the chemotherapy group, EQ-5D from baseline to 16 weeks declined by 0.110 in patients with non-epithelioid histology (n = 11) and rose by 0.032 in those with epithelioid histology (n = 31), P = 0.012. The same pattern was seen in the comparator group.
  • Within the chemotherapy group, patients whose serum mesothelin fell at 6 weeks (n = 18) had an EQ-5D change of +0.085 to 16 weeks. This was an improvement compared with patients whose mesothelin rose (n = 22), P = 0.049.
  • Within the chemotherapy group, disease improvement on CT (RECIST criteria) at 8 weeks was positively correlated with quality of life. The improvement group (n = 6) had an EQ-5D change of +0.119, compared with the stable or progressing group (n = 35), P = 0.045.
  • At baseline, in the whole cohort, a higher EQ-5D score (P = 0.026) and less breathlessness on the LC13 (P = 0.010) predicted longer survival in Cox proportional hazards modelling.
  • Questionnaire compliance was 98% at baseline (72 of 73 forms), 82% at 6 weeks and 58% at 12 months. The authors therefore limited analysis to visit 3 (16 weeks).
• The authors' conclusion: The authors concluded that patients who received chemotherapy had better quality-of-life outcomes at 16 weeks than the self-selected comparator group, with better breathlessness and pain scores. They concluded that non-epithelioid histology was linked to worse quality of life later on, which they attributed likely to more aggressive disease. They also concluded that a falling mesothelin after two cycles, or disease response on CT, predicted improved quality of life.
• Limitations the authors state:
  • The study was not a randomised controlled trial, so the authors said comparisons between the chemotherapy and self-selected comparator groups must be interpreted with caution.
  • The comparator group was small and self-selected and could not be classed as a control group. It was older and had a higher proportion of females.
  • Analysing several questionnaires with many dimensions increased the risk of type I (false-positive) errors.
  • There was significant attrition in questionnaire completion due to patient death and falling compliance, so analysis was limited to 16 weeks.

Topics

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

Medical terms in this study, explained in our Lexicon: Chemotherapy, Quality of Life, Mesothelioma, Pleural Mesothelioma, Pemetrexed (Alimta), Cisplatin, Carboplatin, Histological Subtype.

Related studies

• The South West Area Mesothelioma and Pemetrexed trial: a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication — C.E. Hooper, I.D. Lyburn, et al. (2015)
• Quality of life after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: a prospective study of 216 patients — G. Passot, N. Bakrin, et al. (2014)
• Evaluating quality of life and cost implications of prophylactic radiotherapy in mesothelioma: Health economic analysis of the SMART trial — S.A. Stewart, A.O. Clive, et al. (2018)
• Influence of Pleurectomy and Decortication in Health-Related Quality of Life Among Patients with Malignant Pleural Mesothelioma — W.T. Vigneswaran, D.Y. Kircheva, et al. (2018)
• Chemotherapy management of malignant pleural mesothelioma: a phase II study comparing two popular chemotherapy regimens — E.E. Habib, E.S. Fahmy (2013)
• Health-related quality of life and inflammatory markers in malignant pleural mesothelioma — S.C. Kao, J. Vardy, et al. (2013)

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