br Clinical material br Discussion TLI is regarded as a
Discussion TLI is regarded as a well-tolerated, simple procedure with few acute or late clinical sequelae reported. However, pulmonary irradiation as a therapeutic modality for metastatic bone sarcomas is, although introduced 30 years ago, insufficiently evaluated to clearly determine its benefits [1,3,4]. Pneumonitis has been reported after TLI in Ewing\'s sarcoma , but no serious toxicity like we reported in these two patients has previously been presented [1,6,7]. The radiation treatments in our patients were audited internally at our institution, but no abnormalities found. When retrospectively comparing the clinical courses of these two young girls, they were both under 20 years of age and had considerable toxicity during chemotherapy. They were both treated with 19.5Gy (13 fractions) to their total lung volume. This is according the generally accepted total lung tolerance to radiation [1,6,7]. In Case 1, we cannot rule out a contribution from the radiation of electrons emitted from Quadramet 153Sm-EDTMP. However, the track-length of these electrons is very short and lung toxicity has not been reported among groups of osteosarcoma patients given up to as much as 30 times the injected amount given to our patient [13–18]. Among the 39 patients that subsequently succumbed to their disease (Fig. 6). We have no information in their medical records indicating lung or 4-ethylphenyl sulfate toxicity due to the chemotherapy or radiotherapy given. One patient committed suicide. In the 42% (8/19) with Ewing\'s sarcoma and 9% (3/34) of the osteosarcoma who were long-term survivors, no clinically significant lung or heart toxicity were documented, although lung function tests were not performed (Table 1). Interestingly, all three osteosarcoma patients still alive received TLI following complete metastatic surgical removal of visible metastases. In fact they all have fewer metastases and two of them without overt metastases at diagnosis. Hence, the contribution of TLI is questionable. The cytostatic drugs given to our two patients (Figs. 1 and 3) are not known to give pulmonary side effects except for MTX. The latter may cause pneumonitis, pulmonary fibrosis, interstitial pneumonia and pleural effusion [22,23]. Additive effects might be expected combined with lung irradiation [24,25]. In our two patients, TLI was given 5 weeks and 19 weeks after chemotherapy, respectively. We do not know if the pulmonary function was reduced before irradiation since spirometry was not performed. We cannot rule out that our two patients, who succumbed, had a genetic predisposition of an individual vulnerability for an abnormal lung toxicity of radiotherapy. A blood test was performed in Case 2 to look for a mutation in the ataxia telangiectasia mutated gene, which is associated with a higher sensitivity to radiation . The mutation was not found. Obviously, we cannot leave out the possibility of other mutations associated with side-effects of irradiation [27,28].
Conclusion Lung metastases remain the most common cause of death in osteosarcoma and Ewing\'s sarcoma patients. The two cases presented here demonstrate that lethal lung toxicity may occur following TLI. In any multimodal treatment regiments, pulmonary function should be evaluated before TLI. Impairment of pulmonary function before radiotherapy seems to be a risk factor for higher grade of late toxicity to the lung [24,29]. Hence, if reduced lung function is observed, this indicates that TLI probably should be omitted.
Conflicts of interest statement