To the best of our knowledge, this is the first nasopharyngeal cancer-specific series to document that PICC-VTE correlate with poorer survival. PSM was performed to balance the characteristics between the VTE group and non-VTE group.
VTE is a common complication in cancer patients and is regarded as a leading cause of death. The incidence of VTE in NPC patients in our analysis was 7.20%, which was in accordance with studies with previous documented of 1~20% . VTE has been reported to be a significant predictor of decreased survival in several malignant diseases, including lung, gastrointestinal, prostate and breast cancer, with HRs ranging from 1.9 to 5 [15, 16]. Chew et al. conducted a large cohort of 235,149 cases s to investigate the incidence of VTE and its effect on survival among patients with common cancers including prostate, breast, lung, melanoma, non-Hodgkin lymphoma, gastrointestinal and urogenital cancer. VTE maintained a significant predictor of decreased survival in all cancer types in the first year with adjustment for age, race, and stage of cancer in the multivariate analysis (HRs, 1.6–4.2; P < 0.01, ). M Mandala and colleagues investigated the survival of 227 irresectable pancreatic cancer patients and compared PFS and OS between these patients with and without VTE during chemotherapy. Patients with occurrence of VTE during chemotherapy were reported to have significantly worse PFS and OS compared to patients without, with HRs of 3.04 and 1.95. At multivariate assessment with adjustment for age, tumor stage and chemotherapy, VTE during chemotherapy continued to be a significant predictor of decreased PFS with a 2.62-fold HR .
Consistently, in our study, developing symptomatic VTE associated with PICC was a prognostic parameter for shorter survival and led to increased risk of progression. With a median follow-up of 5 years, the HR of PFS in NPC patients with development of PICC-VTE in the well-balanced cohort was 2.92-fold (p < 0.001) higher than patients without. The 5-year PFS rate of NPC patients who developed PICC-VTE was 77.5%, which was significantly lower than that of patients without (87.6%, P < 0.001). Similar results were observed in the secondary endpoints, with 5-year DMFS, LRRFS, and OS rates of 85.0% vs 91.2% (p < 0.001), 93.9% vs 97.7% (p < 0.001), 85.4% vs 87.6% (p < 0.001) in the VTE group and non-VTE group respectively.
In our study, age, tumor stage, UICC clinical stage, BMI, EBV DNA, CRP and PICC-VTE were found to be associated with PFS in univariable analysis. After adjustment, multivariate analysis revealed that age, BMI, EBV DNA, UICC clinical stage and PICC-VTE were still significant independent factors for PFS in nonmetastatic NPC patients. Older patients had poorer progression free survival, which could theoretically be interpreted by more comorbidities and decreased physical function. The American Joint Committee on Cancer (AJCC) TNM classification is the most widely used cancer staging system and aims to provide reference of treatment regimens and prognosis in clinical. BMI and EBV DNA had been demonstrated to be correlated with survival in NPC patients .
Moreover, we discovered that PICC-VTE was a significant risk factor for survival, which has not been studied in NPC patients before. This effect was independent of age, EBV DNA level, UICC clinical staging and BMI. Taken together, we could completely confirm that PICC-VTE was an independent risk factor for survival in nonmetastatic NPC patients.
No significant survival difference was found between the PICC-related superficial venous thrombosis and deep vein involved thrombosis in NPC patients. Additionally, in spite of the lack of direct evidence on catheter-related thrombosis in cancer patients, the fundamental of anticoagulation therapy is to relieve acute symptoms, maintain PICC function and prevent post-thrombotic syndrome or even pulmonary embolism. Common treatment modalities include removal of catheter and anticoagulation [20, 21]. In our study, different treatment methods have no significant impact on survival in NPC patients. With regard to VTE, risk factors associated were patient-, provider-, and device-related characteristics. General items include stage of carcinoma, thrombosis history, age, comorbidities, catheter insertion, chemotherapy, surgery and others [22,23,24]. We previously have reported that VTE history, BMI, ECOG performance score and metastasis stage were significantly associated with symptomatic PICC-VTE in NPC patients . In our study, the values of pre-treatment Plt and FDP were significantly higher in the VTE group. In addition, we also discovered that NPC patients developing VTE induced by PICC had a higher probability of progression and mortality rate. There are a few biological explanations that support our results. Previous studied have reported: (i) that NPC interacts with both the hemostatic system and coagulation system; (ii) that VTE is caused by prothrombotic factors produced by the malignancies, which can be exaggerated by cancer treatment modalities and exists persistently; (iii) that mechanisms involved in cancer associated hypercoagulability can lead to tumor progression and MP-enriched prothrombotic and proangiogenic factors play vital roles in supporting tumor growth [18, 25,26,27].
However, this study is not devoid of limitations. First, this retrospective study is suspected of selection bias, although we tried to eliminated selection biases by performing a propensity score matching analysis. Next, the incidence and influence of asymptomatic VTE were not taken into consideration in our study.