A history of metabolic disorders such as hypertension, diabetes, coronary artery disease, and smoking did not have any statistically significant effect upon the incidence of VTE (Table 1). Univariate and multivariate analyses demonstrated that VTE occurred more frequently in menopausal women than in non-menopausal women OR = 3.55 (95% CI = 0.99–12.78) and P = .04, ages ≥60 with OR = 2.15 (95% CI = 0.83–5.57) but was not statistically significant (P = .13) and in FIGO stages II and III-IV OR = 2.15 (95% CI = 0.82–5.63) but was not statistically significant (P = .12). It should however be noted that ovarian cancer is more common among elderly women who are mostly menopausal.
There were 15/20 events diagnosed in the pre-operative period, 13 at diagnosis of malignancy and 2 associated with NACT administration. The 2 pre-operative VTEs associated with NACT were asymptomatic and all events were DVT. Of these events, 1 patient had received Ci +P/D and 1 received another drug regimen. No association was found between NACT and VTE in comparison with VTE after standard treatment 2/16 (12.5%) vs 5/131 (3.8%) (P = .16). Univariate and multivariate analyses also demonstrated that NACT had no risk of VTE with OR = 0.89 (95% CI = 0.18–4.28) and P = 1. Nonsignificant determinate of VTE comparing different drug combinations occurring both preoperatively (during or after neoadjuvant therapy) versus after standard treatment is shown in Table 3.
There were 13/20 events diagnosed in the pretreatment period, that is, at the time of diagnosis of malignancy with all 7 remaining events associated with treatment modalities (NACT and/or surgery with/without adjuvant chemotherapy administration). Of the 7 post-treatment events, 4 (3 DVT and 1 PE) were symptomatic and the remaining 3 asymptomatic events were DVT.
VTE incidence did not vary by the treatment approach or by the use/no use of NACT. There was no significant difference in the incidence of VTE by individual NACT regimens. However, we noted that ovarian cancer itself acted as an independent risk factor for VTE occurrence in 13/20 (65%).
This study reveals an incidence of 13.6% for VTE in patients receiving multimodal treatment with curative intent for the epithelial type of ovarian cancer. As a routine follow-up scan following surgery with/without adjuvant chemotherapy was not conducted in our patients, this figure is most likely an underestimation. However, as all the patients receiving NACT were scanned prior to surgery, it is likely a very good estimate of VTE incidence at present. This observed level of VTE is lower than previous studies have reported. There was no statistically significant increased risk of VTE occurring with NACT administration compared to surgery with/without adjuvant chemotherapy, that is, standard treatment (P = .16). This lack of significance may be due to the lower sample ratio receiving NACT versus receiving surgery with/without adjuvant chemotherapy: 16/147 (10.9%) vs 131/147 (89.1%). We observed an increased incidence of VTE at the time of diagnosis of malignancy, 13/20 (65%), without any association with the treatment modality. In the present study, univariate and multivariate analyses revealed the risk factors for VTE in patients with EOC in postmenopausal women. Another limitation is the smaller sample size.
VTE is a well-established complication that is being increasingly reported in cancer patients. In 1865, Trousseau first observed an epiphenomenon of “hypercoagulability” and thrombosis in cancer. However, several studies confirmed the strong causative role of malignancy in thromboembolic complications. Interestingly, this risk was particularly high among certain type of malignancies such as ovarian cancer. Thrombin activation, a tumor-induced procoagulant state, and underlying comorbidities[27–30] are thought to be responsible for the hypercoagulable states in malignancy with the clinical VTE incidence ranging from 1% to 11%[3–6,31–33] in patients with cancer. The relationship between VTE and chemotherapy has been widely reported in the literature.[11,34–36] Mereu et al published a retrospective review in 2009 of 203 ovarian cancer patients receiving chemotherapy as primary modality from 1990 to 2004. The risk for symptomatic VTE was 7.8% at 6 months. On multivariate analysis, BMI, histology, single-agent chemotherapy, and FIGO stages were predictive of VTE.
The alterations following chemotherapy have been well described in other tumors such as nonsmall cell lung carcinoma, breast carcinoma,[41,42] carcinoma of the stomach, and malignant bone tumors. As NACT is expected to become a standard treatment for unselected patients with advanced ovarian cancer when favorable results are confirmed by phase III trials, more studies are warranted to scrutinize the chemotherapy-induced changes to confirm the efficacy and safety of NACT before surgery. The primary objective of our study was to determine whether a neoadjuvant chemotherapy regimen carries a risk of incidence of VTE in comparison to treatment with surgery with/without adjuvant chemotherapy for the epithelial type of ovarian cancer, and we found no such association.
In conclusion, this study reports an overall incidence of VTE of 13.6% in patients treated for the epithelial type of ovarian cancer. No association was found between NACT and VTE in comparison with VTE after standard treatment 2/16 (12.5%) vs 5/131 (3.8%), P = .16. Univariate analysis also demonstrated that NACT has no risk for VTE with OR = 0.89 (95% CI = 0.18–4.28) and P = 1. Our study implies that NACT carries minimal risk of VTE and therefore should be considered more often as a pre-operative treatment modality to improve the therapeutic outcome in patients with ovarian cancer; this can be beneficial to both the patient and to the surgeon. We also noted that cancer itself played a causative role in the occurrence of VTE, which is in concordance with previous studies. However, larger studies are warranted to understand the association of NACT with VTE and to evaluate the role of prophylactic anticoagulation in patients receiving chemotherapy for ovarian cancer.
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