Tumoral cavitation in patients with non-small-cell lung cancer treated with antiangiogenic therapy using bevacizumab

Abstract

Rationale and objectives: To investigate the frequency and radiographic patterns of tumoral cavitation in patients with non-small cell lung cancer (NSCLC) treated with bevacizumab, and correlate the imaging findings with the pathology, clinical characteristics and outcome.

Materials and methods: Seventy-two patients with NSCLC treated with bevacizumab therapy were identified retrospectively. Baseline and follow-up chest computed tomography scan were reviewed to identify tumoral cavitation and subsequent filling in of cavitation. Radiographic cavitation patterns were classified into 3 groups. The clinical and outcome data were correlated with cavity formation and patterns.

Results: Out of 72 patients, 14 patients developed cavitation after the initiation of bevacizumab therapy (19%; median time to event, 1.5 months; range 1.0-24.8 months). Three radiographic patterns of tumoral cavitation were noted: (1) development of cavity within the dominant lung tumor (n = 8); (2) development of non-dominant cavitary nodules (n = 3); and (3) development of non-dominant cavitary nodules with adjacent interstitial abnormalities (n = 3). Eleven patients (79%) demonstrated subsequent filling in of cavitation (the time from the cavity formation to filling in; median 3.7 months; range 1.9-22.7 months). No significant difference was observed in the clinical characteristics, including smoking history, or in the survival between patients who developed cavitation and those who did not. Smoking history demonstrated a significant difference across 3 radiographic cavitation patterns (P = 0.006). Hemoptysis was noted in 1 patient with cavity formation and 4 patients without, with no significant difference between the 2 groups.

Conclusion: Tumoral cavitation occurred in 19% in patients with NSCLC treated with bevacizumab and demonstrated 3 radiographic patterns. Subsequent filling in of cavitation was noted in the majority of cases.

Figure 1

A 64-year-old man with stage IV adenocarcinoma of the lung treated with bevacizumab, carboplatin and paclitaxel. (a) Baseline contrast-enhanced CT of the chest prior to therapy demonstrated a solid dominant mass in the left lower lobe (arrow), without cavitation. A smaller nodule was also noted in the right lower lobe (arrowhead). (b) Follow-up CT scan at 1.5 months after the initiation of therapy demonstrated a cavity developed within the dominant mass (arrow) demonstrating pattern 1 cavitation, with decrease in size of the mass. (c) Further follow-up CT performed 16 months after the initiation of therapy demonstrated filling in of cavitation (arrow) with regrowth of the mass. The bevacizumab was completed 3 weeks prior to this CT scan.

Figure 2

A 53-year-old woman with stage IA adenocarcinoma of the lung who underwent right lower lobectomy 3 years ago, presenting with histologically confirmed recurrent disease in the pleura and lung nodules. (a,b) Baseline contrast-enhanced CT of the chest prior to therapy demonstrated pleural nodularity along the right lung (arrowheads, a) and small faint nodules in the left lower lobe (arrows, a,b). Bevacizumab, carboplatin and paclitaxel therapy was initiated to treat recurrent disease. (c,d) Follow-up CT scan at 13 months of therapy demonstrated development cavitary nodules in both lungs (arrowheads, c), representing pattern 2 cavitation. In some nodules, cavitation developed within the existing solid nodules (arrow, d). The findings were thought to represent disease progression, and the bevacizumab therapy was discontinued at 14 months. The patient was then treated with pemetrexed. (e,f) While on pemetrexed therapy, the patient continued to develop cavitary nodules, which have increased in size and number. Chest CT scan 2 years since the baseline scan demonstrated multiple cavitary nodules in both lungs (arrowheads, e,f), with increase in size and number compared with the prior scans. Based on the findings, pemetrexed was discontinued and docetaxel therapy was initiated. (g,h) CT scan 4 years after the baseline scan demonstrated further increase in size and number of cavitary nodules, with faint opacities surrounding the cavitary nodules representing interstitial abnormalities (arrowheads, h) (pattern 3). Some cavities showed an elongated and tubular appearance at the peripheral and basilar lung (arrows, h). Some of the cavitary nodules are in centrilobular distribution, mimicking the appearance of Langerhans cell histiocytosis (arrowheads, g).

Figure 3

A 46-year-old woman with stage IV adenocarcinoma of the lung treated with bevacizumab, carboplatin and paclitaxel therapy. (a) Baseline CT scan prior to therapy demonstrated a dominant spiculated lesion in the left upper lobe with preexisting cavitation (arrow). Innumerable small metastatic nodules without cavitation were also noted in both lungs (arrowheads). Bevacizumab, carboplatin and paclitaxel therapy was started and response to therapy was noted initially with a decrease in the size of the dominant lesion as well as the metastatic nodules. However, the therapy was discontinued after 8 months due to recurrent and increased pulmonary nodules. The patient was then treated with pemetrexed. (b,c) CT scan 11 months after the baseline scan demonstrated development of cavitation within multiple lung nodules (arrowheads, b,c), demonstrating pattern 2 cavitation. The dominant lesion has decreased in size since the baseline, the preexisting cavitation at baseline is no longer present, without development of new cavitation (arrow, b). (d,e) Follow-up CT scan 17 months after the baseline scan demonstrated an increase in size and number of innumerable cavitary nodules throughout the lungs, with adjacent interstitial abnormalities (pattern 3). The cavitary nodules were seen mostly along the bronchovascular bundles and had a coalescent appearance with adjacent interstitial opacities. Some of the cavities were tubular and branching (arrowheads, d,e). (f,g,h) Left upper and lower lobe wedge resections were performed 3 weeks after the CT scan shown in (d)–(f). On pathology, metastatic tumor (arrowhead, f) is present adjacent to a terminal bronchiole and its paired arteriole (f; 100× magnification). Air is trapped (**, f) between the tumor and uninvolved lung, which shows atelectasis, airspace macrophages, and interstitial chronic inflammation consistent with endogenous/obstructive pneumonia (arrow, f). Metastatic tumor present in the subpleural lung shows central air trapping (g; 200× magnification). Lung uninvolved by tumor shows moderate lymphocyte-predominant interstitial infiltrates (h; 100× magnification).

Figure 4

Progression-free survival (a) and overall survival (b) were compared between patients who developed cavitation versus those who did not.