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Kaneko et al. Hyperostosis of metastatic adenocarcinoma by gefitinib

Figure 2: Osteolytic metastatic lesions of the left fourth rib (A) and the fourth thoracic spine (B); hyperostosis of the lesions was seen by
gefitinib treatment (C, D)

have seldom been demonstrated previously. Although
osteosclerotic changes within the metastatic lesions
were depicted in these studies, [4,5] our patient showed
excessive calcification including metastatic lesions as
shown in Figure 2. There has been no similar description
of such hyperostosis in English literature. We
hypothesized that radiographically latent tumor tissue
around the bone metastasis might also be calcified
by EGFR-TKI therapy, resulting in hyperostosis. On
the other hand, radiographic osteoblastic change of
metastasis before treatment was also regarded as a
favorable prognostic marker for NSCLC treated with
Figure 3: Transient ALP flare after the initiation of gefitinib is EGFR-TKI. It is suggested that osteoblastic reaction
[10]
shown. CEA continued to decrease. ALP: alkaline phosphatase;
CEA: carcinoembryonic antigen regardless before or after the initiation of treatment
might influence tumor reduction, as well as ALP flare
induce ALP flare in various malignancies with bone phenomenon.
lesions. It is also intriguing that NSCLC patients even
without definite bone metastasis who experienced ALP Moreover, drug-induced liver injury might cover ALP
flare showed better survival. Bone-derived ALP flare flare if liver transaminases or biliary tract markers also
[6]
that might represent osteoblastic reaction is supposed markedly elevate as well as ALP. Drug-induced liver
to predict a response to EGFR-TKI, although a precise damage was reported to be seen in 5 of 41 (12.5%)
mechanism is to be elucidated. A previous investigation patients with NSCLC who were treated with EGFR-
referred to the reduction of osteoclast differentiation in TKI. Thus, the frequency of ALP flare is supposed to
[11]
the bone marrow caused by gefitinib, suggesting a be much higher than practically observed. Negativity of
[9]
relation between therapeutic response and osteoblastic hepatitis viral markers or outstandingly elevated ALP
reaction. It is notable that ALP flare has mainly been among liver function markers might help detecting ALP
found in Japanese patients. There might be racial flare. Physicians should pay more attention to ALP
differences among biological responses to EGFR-TKI. flare as well as therapeutic response of radiographic
findings of bone metastasis to elucidate the significance
To our knowledge, CT findings of improvement of of osteoblastic reactions in the outcome of lung cancer.
bone metastatic lesions accompanied by ALP flare At least, ALP flare strongly suggests that EGFR-TKI
36 Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ February 23, 2017