Radiation therapy And VTE Risk

Thromboembolic events are often the primary cause of complications in malignancies. They also have a major effect on the morbidity and mortality of cancer patients. Compared to chemotherapy and other kinds of systemic therapies, there’s not enough data about the impact of ionizing radiation on the incidence of venous thromboembolism (VTE) in cancer patients.

Thrombosis is a key cause of mortality and morbidity in cancer patients. They affect the treatment, prognosis, and quality of life of cancer patients. Thrombotic events manifest in the form of arterial or venous thromboembolism to disseminated intravascular coagulation. Data also shows that the onset rate of VTE (including pulmonary thromboembolism and deep vein thrombosis) is 47x higher in cancer patients than in patients who don’t have cancer. Epidemiologic studies have shown that 20%– 30% of all first VTE events are cancer-associated and that the cumulative incidence of VTE in cancer patients may reach 8%.

The pathobiology of cancer-associated VTE is multifactorial and mainly implies the activation of coagulation and inflammatory pathways. Various risk factors have been described as contributing to VTE. It’s important to note that VTE incidence also varies due to patient-related factors (e.g. age, sex, comorbidities, and prior history of venous disease), tumor-related factors (e.g. cancer localization, histology, stage), and treatment-related factors (e.g. surgery, systemic chemotherapy, anti-angiogenic treatment, hormonal and supportive therapies). Discerning factors associated with increased thrombosis in cancer is crucial in order to adequately identify patients who might benefit from thromboprophylaxis.

Methods

The current prospective study’s goal is to investigate the incidence, management, and outcome of VTE in newly diagnosed cancer patients who were treated with curative radiotherapy. The RIT (for radiation-induced thrombosis) study was an investigator-initiated multicenter prospective trial, which started in June 2016 at the Institut de Cancérologie Lucien Neuwirth and at the Centre Hospitalier de Roanne (France).

The study was approved by the institutional review board and was conducted in compliance with the international standards, including the International Conference on Harmonization (ICH) and the principles of the Declaration of Helsinki (NCT02696447).

Adult patients (18 years and above) with a newly diagnosed malignancy or progressive disease requiring treatment by RT or brachytherapy with curative intent were eligible for inclusion. Patients were not included if they presented a metastatic disease or if their follow-up was not possible within the 6 months post inclusion.

Furthermore, patients with an indication for long-term therapeutic anticoagulation were excluded, but temporary treatment with low molecular weight heparin (LMWH) was allowed. In addition, patients on acetylsalicylic acid or other platelet inhibitors were not excluded. All patients gave their written consent and were prospectively followed for a maximum of 6 months, until loss of follow-up, withdrawal of consent, or death.

Until December 2019, 450 patients were included in this study. After re-evaluation of the inclusion and exclusion criteria as well as the completion of at least one day of RT, 49 patients had to be excluded, because: (1) they did not fulfill inclusion or exclusion criteria (n = 2); (2) patients withdrew consent (n = 20); (3) no RT treatment was administered (n = 12); (4) no complete follow up during RT treatment was available (n = 13); (5) other reasons (n = 2). Thus, overall 401 patients were included in the analysis.

Results

VTE was found in 8 patients, out of 401 patients at a median time of 80 days after radiotherapy initiation. The incidence rate of VTE at 6 months posttreatment was 2% (95% CI, 0.9– 3.7), with 50% of cases occurring during the radiotherapy course and 50% of cases in patients who received or were receiving chemotherapy.

As none of the patients harbored a personal history of VTE, no prophylactic measure was initiated during cancer therapy. Most patients received monotherapy with low molecular weight heparin and were still on surveillance at the end of the study. No specific clinical risk factor was identified that might systematically indicate the need for thromboprophylaxis in the context of curative radiotherapy. The study cohort included 450 patients with a wide range of different cancer types. The researchers analyzed data from 401 subjects who received at least one fraction of ionizing radiations; 66% (n = 265) were women, and 34% (n = 134) were men, with a median age of 65 years (range 33– 88) and a median BMI of 25.4 kg/m2 (range 15.6– 42.8).

The most common primary tumor site was breast (59.9%), followed by prostate (19.2%), and head and neck (10.2%) cancer (Table 2). Most participants (70.1%) had an early disease and 83% had at least one comorbidity. Of note, less than 15% of patients had chronic respiratory disease or cardiac issues (n = 49 [12.2%] and n = 56 [14%], respectively); around 5% of patients had renal impairment or were diabetic (n = 18 [4.5%] and n = 26 [6.5%], respectively). While half of the population (n = 203) was active or ex-smokers, a quarter of participants (n = 105) presented varicose veins and only 7.2% of patients (n = 29) had a personal history of VTE.

At baseline, 30 patients (7.5%) were receiving thromboprophylaxis, with 28 patients treated with prophylactic intensity anticoagulation and 2 patients with LMWH. Most patients (78.8%) underwent cancer surgery before radiation. The number of radiotherapy treatment cancer patients included in RIT study = 450; Excluded = 49; Consent withdrawn before = 20; No treatment = 12; Incomplete visit procedure before and during = 13; Included in another study = 1; Deceased before RT = 1; Population for analysis = 401 total patients.

Conclusion

The study provides important insight as a basis for future studies with subcategories of cancer. It will also produce a fine guide and further recommendations for frail patients. Clinical trial registration number present study shows that in pooled cancer patient populations, curative RT was not associated with an increased risk of VTE when compared to other therapeutic strategies such as immunosuppressive or cytotoxic chemotherapy.

During a follow-up period of up to 6 months, 2.0% of patients developed VTE, essentially with a DVT presentation. These patients were not considered high-risk individuals, given that no thromboprophylaxis was initiated despite relevant medical history and/or the presence of VTE risk factors. Yet, the incidence in this study is much higher in comparison to the general population for which the estimated annual incidence of VTE was 184.0 per 100,000 subjects.

Importantly, it is estimated that approximately 4%– 20% of cancer patients will experience VTE at some stage during the disease course. The observations of the RIT study should be balanced to estimated annual incidences in which 0.5% of cancer patients will experience thrombosis compared with a 0.1% incidence rate in the general population.

One might also consider that the long-term incidence could be underestimated given that around 8% of patients were lost to follow-up at 6 months post-treatment. Although this study did not show an increased risk of VTE during the therapy course, it still demonstrates that a careful assessment has to be done before RT to determine whether prophylactic measures are needed.

Radiation therapy And VTE Risk