Lymphatic fistulas secondary to vascular surgery of the groin can be treated with conservative therapy, surgery, or radiation therapy. Persistent lymphatic fistulas can cause delayed wound healing, infection of deeper layers including the vascular graft, and a prolonged hospital stay. Immobility is associated with increased morbidity, wound infections and arterial bleeding, possibly leading to leg amputation.
Our study suggests a high efficacy and tolerability of low-dose irradiation for the treatment of lymphatic fistulas. This is in accordance with a trial from Mayer et al. from Graz10. They were the first to demonstrate lymphatic obliteration with low dose radiation therapy. In their analysis, 13 of 17 patients had a complete response to low dose radiation. There was a clinical response with total doses of ≤ 3 Gy and with fraction sizes ranging from 0.3 to 0.5 Gy 10. Our results are consistent with this data. Mayer et al used electrons or kV radiation therapy4,10 because that was standard of practice in the early 2000 and easy to apply. We used IMAT and MV photons with 6–15 MV which allowed to apply the smallest therapeutic dose to the target with minimal side effects to the surrounding tissue. In our cohort, successful obliteration of all the lymphatic vessels occurred after a median cumulative dose of 1.2 Gy, which is much lower of what reported in the literature. We think this is probably related to the direct application of the radiation to the clinical target volume of the lymph node area at the surgical site.
Different doses of radiation have been proposed to treat lymphatic fistulas7,8,12,13. In the largest study to date, Hautmann et al., reported the use of 3 x 3 Gy at the start of the treatment 7 with an increase to 3 additional fractions of 3 Gy for persistent fistulas. The radiation treatment is usually stopped when the fistula output is less than 50 ml/ 24 hours. In this cohort of 206 patients, 40.8% of individuals were irradiated with 9 Gy while 18 Gy were used in 46% of the individuals. In a large proportion of patients, a dose of 9 Gy in 3 Gy per fraction was not able to close the fistula. These doses are higher than what reported by Mayer et al., who suggested that a median dose of 2.4 Gy led to the fistula obliteration 7.
Our data is consistent with what reported by Graz, Kazan and Zaporozhy. Low fraction doses of 0.3–0.5 Gy do not seem to be inferior to higher doses10,12,14. The “As low as reasonably achievable” (ALARA) fundamental principle of radioprotection is very well applicable to this clinical use of radiation. It has been postulated that low dose radiation leads to functional changes in the vessels, as well as decreased expression of E-selectin in the endothelial cells, decreased leukocyte adhesion, and reduced L-selectin expression.
Irradiating with electrons or low energy (kV) X-rays provides the benefit of deep tissue doses. If the clinical target volume incorporates deep inguinal lymphatic structures, the rotational intensity modulated high energy (MV) photon therapy could deliver the optimal dose coverage for the clinical target volume with the best healthy tissue protection. The research groups from Regensburg II, Santander and Düsseldorf worked with this technique.
The novelty of our treatment is the use of low dose radiation at the site of the fistula in the immediate postoperative period. Hautmann et al. investigated the time sequence for starting radiation therapy after lymph node dissection (< 10 and more > 10 days), without finding a time correlation15. We believe that if radiation therapy is effective, the procedure should be performed as soon as possible to improve clinical outcomes, reduce costs, expedite discharge and improve the overall quality of life.
The radiation treatment of lymphatic fistulas has a very low carcinogenic risk. The lifetime risk of leukaemia is ≤ 0.2%2, while the risk of developing basal cell carcinoma is approximately 0.006%2. On the other hand, people who undergo vascular surgery usually are elderly and with multiple co-morbidities, like coronary heart disease, dementia, and diabetes mellitus. Their life expectancy is reduced when compared to the younger counterpart, making the long-term radiogenic side effects negligible in this patient population.
Due to a large proportion of fistulas closing spontaneously, the benefits of prompt irradiation must be weighed against the risk of unnecessary treatment4. Prospective randomized trials are needed to answer this question.