Background and introduction
Radio-Induced Lung Injury (RILI) is one of the main studied radiotherapy (RT) side effects. It is described as acute (<6 months) or late (> 6 months) and can be defined by clinical or radiological symptoms (interstitial syndrome, lung fibrosis). In the context of breast cancer treatment, dose delivered to the homolateral lung [Citation1–5], concomitant tamoxifen use [Citation6, Citation7], respiratory disease medical records [Citation8] and other patient-related factors have been shown to be risk factors for its occurrence in 3D RT. In a previous work, we and others proposed the use of V30 Gy < 15% to further limit its occurrence after 3D RT. We also studied the V20 Gy parameter, and the best cutoff for the V20 Gy parameter in our study was V20 Gy< 15% [Citation8].
Modern intensity-modulated RT techniques such as tomotherapy can modify dose distribution in RT planning. It can reduce the maximum and mean doses delivered to the lungs [Citation9], even in the case of a simultaneously integrated boost [Citation10], but increases the proportion of the lung receiving low doses [Citation11]. The reported mean V20 Gy in various tomotherapy studies was 20% [Citation12], 19.6% [Citation9], and 17% [Citation11]. V30 Gy has rarely been reported. The cohort of tomotherapy-treated breast cancer patients of our institute, formerly published, reported interesting dosimetric parameters in this regard, with mean V20 Gy = 20.3 to 23% of homolateral lung, mean V30 Gy = 9.3 to 10.2% of homolateral lung depending on the irradiated volume and V5 Gy spanning from <67 to 100% of homolateral lung [Citation13].
As high-dose receiving volumes were significantly reduced in previous tomotherapy studies, we wanted to assess their impact on lung toxicity and thus to determine the incidence of RILI in a cohort of tomotherapy-treated breast cancer patients.
Material and methods
The cohort has already been described elsewhere [Citation13]. It included non-metastatic T1-T4, N0-N3 uni- or bilateral breast cancer-bearing women treated in a single institution between 2009 and 2015. The patients were presented with complex anatomy and volumes of irradiation or there were not able to keep and be treated in deep inspiration breath hold (DIBH). Fourteen (8%) patients had pulmonary disease medical records, and 15% were smokers as previously reported [Citation13]. The dose to OAR was reported previously [Citation13]. Medical yearly follow-up was recorded for all patients. Clinical files were assessed for the occurrence of respiratory symptoms of dyspnea or cough, and medical imaging was analyzed to assess RILI occurrence on chest radiography or on pulmonary CT scans. Radiological RILI was defined by the appearance of an interstitial syndrome or a fibrous scar in the radiation field after the beginning of radiotherapy. RILI was described as ‘clinical’ if symptoms and radiological images were present or ‘radiological’ if it was asymptomatic and only fortuitously detected on the CT scan. RILI events were retrospectively graded according to the RTOG criteria. Cough and dyspnea were retrospectively graded according to CTCAE criteria. Median follow-up was estimated from observation time distribution.
Results
In total, 179 patients and 194 breasts were treated. The median follow-up was 6.38 [0; 11.2] years. Sixty-seven (37.4%) patients were assessed by pulmonary CT scan during their follow-up, and 23 (12.8%) had a chest X-ray. Overall, 81 (45.3%) patients underwent pulmonary medical imaging during their follow-up ().
Table 1. RILI assessment results.
Dyspnea was reported for 8 (4.5%) patients, and cough was reported for 13 (7.3%) patients. Radiological RILI was found in 6 (3.35%) patients, and clinical RILI was diagnosed in only 1 (0.56%) patient. All events were grade I and appeared in patients who did not present pulmonary medical history. The majority of dyspnea and all the cough events noted during the follow-up did not translate into radiological images of RILI on CT scans and could not be related to RILI ().
Table 2. Distribution of RILI events according to clinical symptoms reported.
Discussion
This monocentric tomotherapy cohort description showed a low incidence of radiological (3.35%) and clinical (0.56%) RILI. It argues in favor of the safety of breast tomotherapy regarding lung treatment.
The safety and low incidence of RILI in this tomotherapy cohort is in accordance with previous observations of limited homolateral lung V20 Gy and V30 Gy using tomotherapy [Citation9–12].
One patient presented with dyspnea during RT and was treated with corticosteroids without medical imaging performed for this event. This event was unreliable and was not included as a RILI event.
Many patients report respiratory symptoms without proven RILI images on medical imaging. This was also the case in our previous work [Citation8]. Lung toxicity is complex and could be related to patient-related factors such as tobacco consumption, asthma, chronic lung disease, and treatment-related toxicity (chemotherapy, radiotherapy). In this work, we report a very low risk of radiation-induced lung toxicity, but all risk factors must be taken into account, and individualized treatment techniques must be proposed to every patient.
This work presents several limitations: symptoms were only assessed by clinical file analysis, an approach that has been shown to underestimate clinical symptoms half of the time [Citation8]. No pulmonary function test was performed for RILI definition, and no systematic imaging was performed to assess RILI in all patients. Eventually, no dosimetric parameter was analyzed, but the low frequency of pulmonary events would not enable dosimetric risk factor assessment.
On the other hand, this population frequently benefited from pulmonary medical imaging during the follow-up (45% of patients). Radiological RILI is always more frequent than clinical RILI, and its low incidence in this cohort favors the safety of breast tomotherapy for lung sparing. Additionally, the long median follow-up could retrieve early and late RILI events.
In conclusion, tomotherapy breast cancer treatment planning appears efficient at preventing RILI appearance.
Ethics declarations
No animal studies are presented in this manuscript.
No human studies are presented in this manuscript.
No potentially identifiable human images or data are presented in this study.
Disclosure statement
No potential conflict of interest was reported by the authors.
Data availability statement
The patient data recorded for the study are not available publicly.
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