To our knowledge, the present study is the first to investigate the incidence of TEE in H&N cancer patients who underwent CCRT with cisplatin in real-world practice. The observed incidence of TEE was 1.9%, and Khorana score was the only factor associated with the risk of TEE.
In cancer patients, various risk factors increase the incidence of TEE. Among patient-related factors, TEE is known to be associated with age, obesity, thrombocytosis, leukocytosis, hemoglobin < 10g/dL before chemotherapy, and a history of previous TEE (22, 24). Treatment-related factors such as chemotherapy are also associated with risk of TEE (2).
Conflicting results have been reported regarding the incidence of TEE in H&N cancer patients. According to one meta-analysis, the incidence of VTE in H&N cancer patients was 0.16–3.13% (18). Incidence of VTE in H&N cancer patients after surgery is generally low (0 ~ 8%), although one study reported higher rate of 26.3% (18, 20). While one study reported that H&N cancer is the least common type of cancer diagnosed following VTE, another large study identified H&N cancer as the second highest risk for VTE among 18 types of carcinoma (18, 19). In a large population-based study, the incidence of TEE in non-cancer population was 1.4%, which is similar to the rate of occurrence among H&N cancer patients reported in several studies (18, 25).
In the present study, the observed incidence rate of TEE was 1.9%, which is not that dissimilar to the rate in the general population and aligns with previous studies regarding the incidence of TEE in H&N cancer (18). However, most previous studies of TEE in H&N cancer analyzed heterogenous populations consisting mainly of a surgical treatment alone group, with small number of reports about patients who received chemotherapy including various regimens (18, 20). The present study investigated patients who underwent CCRT with cisplatin, which is the essential chemotherapeutic agent for management of H&N cancer. Although the mechanism of cisplatin-induced hypercoagulability is not entirely clear, several studies have proposed possible pathophysiologic processes; these include impaired autoregulation of the vascular system, an altered balance between thrombosis and fibrinolysis, direct endovascular damage, increased procoagulant activity of red blood cells, and modulation of tissue factor on human monocytes (26–28).
There have been several reports of increased TEE incidence in patients treated with cisplatin-based regimens. Among these, Russell et al. reported an 18.1% incidence of TEE related to cisplatin-based chemotherapy in 932 patients with various types of malignancy (8). The reported incidence of TEE in non-small cell lung cancer patients who underwent a cisplatin-based regimen was 8.0 ~ 17.6%, with 10.2% of the 1-year incidence rate of TEE in small cell lung cancer patients treated with cisplatin-based chemotherapy (5–7, 29). In the present study, the incidence of TEE in H&N cancer patients during or after CCRT with cisplatin seems to be low when compared to patients with other types of cancer who received cisplatin-based regimens. A larger-scale study is required to determine the possible explanation for these findings.
In the present study, one interesting result is the significant association between the TEE occurrence and Khorana score despite of the low incidence of TEE itself. As a means of predicting the risk of chemotherapy-associated thrombosis in cancer patients, the Khorana scoring system has some limitations. For example, since BMI > 35kg/m2 is rare among Asian patients, accurate evaluation is difficult (5, 30). In the present study cohort, only one patient (0.4%) had a BMI of > 35 kg/m2, which figure was not significantly different from that of the previous Asian study (5, 30). Nonetheless, Khorana score was the only factor associated with the TEE incidence in present study. Therefore, in cases of H&N cancer patients with high Khorana score receiving cisplatin-CCRT, treating physician should be aware of possible TEE occurrence during or for a period of time after CCRT. In addition, these patients should be informed about the somewhat higher risk of TEE before starting treatment.
The current study has several limitations. As a retrospective study based on a review of medical records, selection bias may occur, resulting in possible underestimation of TEE incidence. The small number of patients with TEE means that statistically significant results are less reliable, especially in terms of the relationship between TEE incidence and clinical characteristics. Finally, the present study cohort comprised patients from a single institution over a fairly long period. Nevertheless, this study seems to be clinically meaningful because it investigated all patients during the defined period who underwent CCRT with cisplatin, which is the mainstay of treatment for locally advanced H&N cancer, reflecting real-world clinical practice in Korea.
In conclusion, while the incidence of TEE in H&N cancer patients who underwent CCRT with cisplatin was relatively low (1.9%) when compared to other types of cancer, patients with a high Khorana score require more careful surveillance for possible occurrence of TEE.