To the Editor,
We read with interest the article by Iacovelli et al. in a recent issue of Acta Oncologica, entitled ‘Incidence and risk of pulmonary toxicity in patients treated with mTOR inhibitors for malignancy. A meta- analysis of published trials’ [Citation1]. This article calls attention to pulmonary toxicity (PT) as an adverse event of treatment with mTOR (mammalian target of rapamycin) inhibitors. PT poses a significant clinical problem because it has important consequences for patients’ quality of life and it may require interruption of this anticancer treatment. The clinical presentation is non-specific and therefore this diagnosis can be missed. As a consequence the reported incidence of PT varies widely. A meta-analysis of the incidence of PT in patients treated with mTOR inhibitors such as performed by Iacovelli et al. is therefore of great importance.
Unfortunately, an error was made in the analysis of the data from the article by Motzer et al. [Citation2]. The number of patients with PT was incorrectly interpreted as absolute numbers instead of percentages. As a result all grade PT was stated as occurring in 14 instead of 37 patients (14% of 274 patients). High grade PT was stated as occurring in four instead of 10 patients, (4% of 274 patients). Therefore, in their meta-analysis the mean incidence should be 12.1% instead of 10.4% for all grade PT and 2.8% instead of 2.4% for high grade PT.
Since Iacovelli et al. only included phase II or III randomized controlled trials in their meta-analysis the data of several retrospective or non-randomized trials were not included. When considering the data of these studies an even higher incidence of all grade PT of 19–54% is found [Citation3–9]. The large variation in incidence of PT can be explained by differences in clinical awareness as well as varying methods of diagnosing PT. Diagnosis of PT can easily be missed since PT can occur radiographically while patients are still asymptomatic. This is illustrated in the RECORD-1 trial where PT was reported in 14% of 274 patients as abovementioned, but with dedicated radiological review findings consistent with PT were found in 39% of patients [Citation2,Citation8]. Also, in the global ARCC trial the incidence of all grade PT was first reported as 14% based on clinical findings, but a re-analysis of all computed tomography (CT) scans showed a much higher incidence of 29% [Citation7,Citation10]. The significance of subtle radiologic changes in the absence of clinical symptoms however, is not clear.
With this letter, we want to emphasize the high incidence of PT as an adverse event of treatment with mTOR inhibitors. We agree with and highlight the remarks by Iacovelli et al. that accurate monitoring for PT should be recommended in all patients treated with mTOR inhibitors. Awareness of this toxicity and appropriate diagnostic and medical management is important to optimize patients’ quality of life and compliance to treatment.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References
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