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Prophylactic radiotherapy to prevent procedure-tract metastases
Correspondence
Prophylactic radiotherapy to prevent procedure-tract metastases We congratulate Amelia Clive and colleagues1 on doing an excellent study, published in The Lancet Oncology in an area with little previous high-quality evidence. The authors concluded no difference in the incidence of procedure-tract metastases between the immediate and deferred radiotherapy groups, despite a despite an odds ratio (OR) of 0·51 (95% CI 0·19–1·32) in the intention-to-treat analysis in favour of radiotherapy. In the field of thoracic oncology, a 20% benefit is often considered worthwhile. For example, pemetrexed in mesothelioma, which is the standard of care in the UK, has a hazard ratio (HR) of 0·77 (p=0·028).2 There are few interventions in thoracic oncology associated with benefits in overall survival greater than 20%. However, the authors’ conclusion of no significant difference between immediate and deferred radiotherapy is because of the parameters stipulated in sample size calculations. The expected intervention effect was a reduction in the incidence of procedure tract metastases from 15% in the deferred radiotherapy group to 2% in the immediate radiotherapy group—we calculated an odds ratio of 0·12—which many would consider to be overly optimistic. Therefore, we disagree with the Comment by Giovanni Luca Ceresoli and colleagues, who stated that the SMART trial was adequately powered.3 We would have preferred to see the analysis undertaken as a time-to-event analysis and the results expressed as an HR for disease-free survival (the conventional outcome). The authors handled the time-to-event data in a series of bar plots over a 12-month period and used the OR as the primary outcome of analysis, which does not take into account time, death, or other forms of censoring. www.thelancet.com/oncology Vol 17 October 2016
To rephrase the results obtained by the authors (absolute differences in incidence of procedure-tract metastases of nine [9%] in the immediate vs 16 [16%] in the deferred radiotherapy group), one could report a calculated relative risk of 0·56 for the incidence of procedure tract metastasis in patients randomly assigned to early prophylactic radiotherapy. This corresponds to a number needed to treat of 14, implying that for every 14 patients treated, one case of pleural tract metastasis could be avoided with no downside for early radiotherapy in terms of toxicity and quality of life (ie, improved progression-free survival). Whether or not this represents a meaningful reduction would be up to the individual patient to decide. We are looking forward to the results of the PIT study (NCT01604005) to determine if a similar intervention effect to the SMART trial is observed and to pool the results of these two studies to strengthen the analysis before a potentially useful clinical intervention is inappropriately abandoned. DL declares no competing interests. EL reports personal fees from Abbott Molecular, Glaxo Smith Kline, Pfizer, Norvatis, Covidien, Roche, Lily Oncology, Boehringer Ingelheim, Ethicon, and Medela; and grants and personal fees from ScreenCell outside the submitted work. EL is the founder of Informative Genomics, a blood based molecular diagnostic company in London.
*David Landau, Eric Lim [email protected] Guy’s and St Thomas’ NHS Trust, London SE1 9RT, UK (DL); and Academic Division of Thoracic Surgery, The Royal Brompton Hospital, London, UK (EL) 1
2
3
Clive AO, Taylor H, Dobson L, et al. Prophylactic radiotherapy for the prevention of procedure-tract metastases after surgical and large-bore pleural procedures in malignant pleural mesothelioma (SMART): a multicentre, open-label, phase 3, randomised controlled trial. Lancet Oncol 2016; 17: 1094–104. Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003; 21: 2636–44. Ceresoli GL, Vavassori V. Radiotherapy to intervention sites in mesothelioma: no more? Lancet Oncol 2016; 17: 1025–27.
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Prophylactic radiotherapy to prevent procedure-tract metastases We congratulate Amelia Clive and colleagues1 on doing an excellent study, published in The Lancet Oncology in an area with little previous high-quality evidence. The authors concluded no difference in the incidence of procedure-tract metastases between the immediate and deferred radiotherapy groups, despite a despite an odds ratio (OR) of 0·51 (95% CI 0·19–1·32) in the intention-to-treat analysis in favour of radiotherapy. In the field of thoracic oncology, a 20% benefit is often considered worthwhile. For example, pemetrexed in mesothelioma, which is the standard of care in the UK, has a hazard ratio (HR) of 0·77 (p=0·028).2 There are few interventions in thoracic oncology associated with benefits in overall survival greater than 20%. However, the authors’ conclusion of no significant difference between immediate and deferred radiotherapy is because of the parameters stipulated in sample size calculations. The expected intervention effect was a reduction in the incidence of procedure tract metastases from 15% in the deferred radiotherapy group to 2% in the immediate radiotherapy group—we calculated an odds ratio of 0·12—which many would consider to be overly optimistic. Therefore, we disagree with the Comment by Giovanni Luca Ceresoli and colleagues, who stated that the SMART trial was adequately powered.3 We would have preferred to see the analysis undertaken as a time-to-event analysis and the results expressed as an HR for disease-free survival (the conventional outcome). The authors handled the time-to-event data in a series of bar plots over a 12-month period and used the OR as the primary outcome of analysis, which does not take into account time, death, or other forms of censoring. www.thelancet.com/oncology Vol 17 October 2016
To rephrase the results obtained by the authors (absolute differences in incidence of procedure-tract metastases of nine [9%] in the immediate vs 16 [16%] in the deferred radiotherapy group), one could report a calculated relative risk of 0·56 for the incidence of procedure tract metastasis in patients randomly assigned to early prophylactic radiotherapy. This corresponds to a number needed to treat of 14, implying that for every 14 patients treated, one case of pleural tract metastasis could be avoided with no downside for early radiotherapy in terms of toxicity and quality of life (ie, improved progression-free survival). Whether or not this represents a meaningful reduction would be up to the individual patient to decide. We are looking forward to the results of the PIT study (NCT01604005) to determine if a similar intervention effect to the SMART trial is observed and to pool the results of these two studies to strengthen the analysis before a potentially useful clinical intervention is inappropriately abandoned. DL declares no competing interests. EL reports personal fees from Abbott Molecular, Glaxo Smith Kline, Pfizer, Norvatis, Covidien, Roche, Lily Oncology, Boehringer Ingelheim, Ethicon, and Medela; and grants and personal fees from ScreenCell outside the submitted work. EL is the founder of Informative Genomics, a blood based molecular diagnostic company in London.
*David Landau, Eric Lim [email protected] Guy’s and St Thomas’ NHS Trust, London SE1 9RT, UK (DL); and Academic Division of Thoracic Surgery, The Royal Brompton Hospital, London, UK (EL) 1
2
3
Clive AO, Taylor H, Dobson L, et al. Prophylactic radiotherapy for the prevention of procedure-tract metastases after surgical and large-bore pleural procedures in malignant pleural mesothelioma (SMART): a multicentre, open-label, phase 3, randomised controlled trial. Lancet Oncol 2016; 17: 1094–104. Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003; 21: 2636–44. Ceresoli GL, Vavassori V. Radiotherapy to intervention sites in mesothelioma: no more? Lancet Oncol 2016; 17: 1025–27.
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