Differences in chemosensitivity between primary and paired metastatic lung cancer tissues: In vitro analysis based on the collagen gel droplet embedded culture drug test (CD-DST)

Abstract

Background: To elucidate the differences in chemosensitivity to anticancer drugs between primary and metastatic lesions in non-small cell lung cancer (NSCLC) patients, we examined the in vitro chemosensitivities of surgically resected NSCLC tissues.

Methods: A total of 32 specimens were enrolled: 26 specimens of primary lesions paired with metastases in the lymph node, 3 specimens of primary lesions paired with metastases in the adrenal gland, and 3 specimens of primary lesions paired with metastases in the lung. The collagen gel droplet embedded culture drug test (CD-DST) was applied to examine the sensitivity of the tissues to anticancer drugs, including cisplatin, gemcitabine, vinorelbine, docetaxel and 5-fluorouracil.

Results: The degree of in vitro sensitivity to each anticancer drug varied between the primary and metastatic lesions. The sensitivity of the paired metastatic lesions was significantly lower than that of the primary lesions only for gemcitabine (P=0.029), vinorelbine (P=0.012), and docetaxel (P=0.009). The incidence of cases diagnosed as CD-DST-sensitive among the paired metastatic lesions was significantly lower than that for the primary lesions for vinorelbine (P=0.035) or docetaxel (P=0.022). The difference in the sensitivity to gemcitabine between the primary and paired non-lymphatic metastases was clearer than that between the primary lesion and paired lymph node metastases.

Conclusions: The sensitivities of the paired metastatic lesions to some anticancer drugs were significantly lower than those of the primary lesions. When performing chemotherapy based on CD-DST data using primary tumors from patients with postoperative recurrence, an appropriate regimen can be selected by carefully considering these differences.

Keywords: Non-small cell lung cancer (NSCLC); chemosensitivity test; chemotherapy; collagen gel droplet embedded culture drug test (CD-DST); metastatic tissue.

Figure 1.. Comparison of the in vitro chemosensitivities (T/C ratio, %) of primary lesions and their paired metastatic NSCLC lesions.

P: primary lesions, M: paired metastatic lesions. The cases surrounded with dotted-line frames were diagnosed as being in vitro-sensitive. The P value for each anticancer drug was calculated using the Paired T test. Fig 1. shows a comparison of CD-DST data between each primary lesion and its paired metastatic lesion for each anticancer drug. For GEM, VNR, and TXT, the T/C ratio of the metastatic lesions was significantly higher than that of the primary lesions. In contrast, for CDDP and 5-FU, no significant differences in chemosensitivity were observed.

Figure 2.. Differences in the T/C ratio (%) between the primary lesions and their paired metastatic lesions.

Differences in the T/C ratio (%) between the primary lesions and their paired metastatic lesions are shown by waterfall plots. The black columns show the difference between primary lesions and their paired lymph node lesion. The white columns show the difference between primary lesions and their paired non-lymphatic lesions. Although the cases involving a non-lymphatic route (white column) were widely distributed, 4 cases (67%) treated with GEM showed a 30% or greater increase in in vitro resistance in the paired metastatic lesions compared with the primary tissue. Three cases (50%) showed similar results for CDDP.