Incidence and clinical implication of tumor cavitation in patients with advanced non-small cell lung cancer induced by Endostar, an angiogenesis inhibitor

Abstract

Background: Antiangiogenesis plays a key role in the treatment of non-small lung cancer (NSCLC). We observed the cavitation of lesions in patients with stage IIIB/IV NSCLC treated with Endostar and vinorelbine-cisplatin (NP) chemotherapy, and evaluated the imaging characteristics and clinical outcome of patients who developed tumor cavitation.

Methods: Our study included 105 untreated NSCLC patients who received Endostar in combination with NP chemotherapy at the Tianjin Lung Cancer Center. Chest computed tomography (CT) was performed to evaluate the efficacy every two cycles. The number of activated circulating endothelial cells (aCECs) was measured by flow cytometry. Rates of tumor cavitation were documented and their clinical CT imaging data were analyzed.

Results: Tumor cavitation occurred in 11 of the 105 (10.5%) patients treated with Endostar and NP. The response rates were 37.2% (35/94) in patients without cavitation, 27.3% (3/11) evaluated by Response Evaluation Criteria in Solid Tumors, and 100.0% (11/11) if evaluated by an alternate method in patients who developed cavitation. Three of the 11 cases with cavitation had a centrally located tumor. No patients had hemoptysis or any other severe side effects. Compared with patients not developing cavitation, cavity formation resulted in a longer median survival time (13.6 vs. 11.8 months, P = 0.011) and an increase in the number of aCECs (244.4/10(5) vs. 23.3/10(5), P = 0.000).

Conclusions: Intratumoral cavitation induced by Endostar is common in NSCLC patients, and is not correlated with squamous histology, tumor location or pulmonary hemorrhage. Cavitation might have a significant effect on the number of aCECs and overall prognosis.

Keywords: Activated circulating endothelial cells; Endostar; angiogenesis; cavitation; non-small cell lung cancer.

Figure 1

Tumor cavitation of four patients. (a) Case 1 – a 54-year old man with lung adenocarcinoma. Pulmonary cavitation in the left superior lobe mass near the aortic arch occurred after two cycles of Endostar and vinorelbine-cisplatin chemotherapy. The patient died of progressive disease (PD) 13.6 months after initiation of treatment. (b) Case 2 – a 74-year old man with lung adenosquamous carcinoma. Pulmonary cavitation in the right superior lobe mass near the chest wall occurred after two cycles of therapy. The patient died of PD 14.5 months after initiation of treatment. (c) Case 3 – a 44-year old woman with lung adenocarcinoma. Pulmonary cavitation in the right inferior lobe mass occurred after two cycles of therapy. The patient survived for 38 months after the initiation of treatment. (d) Case 4 – a 56-year old woman with lung adenocarcinoma. Pulmonary cavitation in the left inferior lobe mass near the aorta descendens occurred after two cycles of therapy. The patient died of PD 13.5 months after initiation of treatment.

Figure 2

Circulating endothelial cell enumeration by flow cytometry. (a) Panels show the gate used to exclude CD45-positive cells; (b) Negative control; (c) Panels show the gate used to count activated circulating endothelial cells (aCECs) (defined as CD45⁻ CD146+ CD105+) pre-therapeutically; (d) Panels show the gate used to count aCECs (defined as CD45- CD146+ CD105+) post-therapeutically.