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An observational-phase clinical trial for intralesional radiofrequency ablation in the treatment of slow-flow vascular malformations
*Corresponding author: Somesh Gupta, Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi, India. someshgupta@aiims.edu
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Received: ,
Accepted: ,
How to cite this article: Jain A, Ahuja R, Vyas S, Sahni K, Gupta S. An observational-phase clinical trial for intralesional radiofrequency ablation in the treatment of slow-flow vascular malformations. J Cutan Aesthet Surg. doi: 10.25259/JCAS_125_2025
Abstract
Objectives:
Current treatments for vascular malformations, such as sclerotherapy, laser ablation, and surgery, often result in suboptimal outcomes with high recurrence rates. This study aimed to evaluate intralesional radiofrequency ablation (RFA) as a potential treatment for slow-flow vascular malformations.The objective is to assess the efficacy and safety of intralesional RFA in treating slow-flow vascular malformations.
Material and Methods:
In this self-controlled observational study, 28 patients (ages 6–54) with slow-flow vascular malformations underwent two intralesional RFA sessions, spaced 4 weeks apart. An initial 16-week observational period served as the control phase. Outcomes included lesion volume (measured by ultrasound and clinical evaluation), Visual Analog Scale (VAS), dermatology life quality index (DLQI), patient satisfaction, and physician assessment.
Results:
Post-RFA, lesion volume decreased by 48.84% clinically and 25.99% by ultrasound, contrasting with volume increases of 6.02% and 10.04% during the control phase (P < 0.01). VAS scores dropped from 7.71 to 3.96, and DLQI from 13.89 to 7.75 (P < 0.001). Patient satisfaction was favorable (median score of 6), with mild transient adverse effects.
Conclusion:
Intralesional RFA significantly reduced lesion volume and improved patient-reported outcomes compared to the control phase.
Keywords
Intralesional radiofrequency
Slow-flow
Vascular malformations
Volume reduction
INTRODUCTION
Vascular malformations are congenital anomalies characterized by abnormal development of blood and lymphatic vessels. They are categorized into venous, arterial, capillary, lymphatic, or mixed types, with slow-flow malformations primarily encompassing venous malformations (VMs) and lymphatic malformations (LMs).1 These malformations typically grow proportionately with individual development.2
The management of vascular malformations remains complex due to associated soft-tissue hypertrophy, inconsistent treatment response, and high recurrence rates. Current treatment modalities, including sclerotherapy, laser ablation, and surgical excision, often yield suboptimal outcomes,3 particularly for larger lesions or those that involve deep tissue structures. These limitations necessitate the exploration of alternative treatment options that can provide effective and lasting results.
Intralesional radiofrequency ablation (RFA) is a minimally invasive technique for slow-flow vascular malformations.4 By delivering focused thermal energy, RFA induces coagulative necrosis of target tissues while minimizing collateral damage to surrounding structures. This technique offers several distinct advantages over traditional methods. RFA is associated with reduced hemorrhage due to its ability to coagulate blood vessels, which enhances safety during procedures. Furthermore, the minimally invasive nature of RFA results in smaller incision sizes, leading to reduced post-operative pain, shorter recovery, and improved cosmetic outcomes. Hence, this study aims to evaluate the efficacy and safety of intralesional RFA in slow-flow vascular malformations.
MATERIAL AND METHODS
Study design and participants
This observational-phase clinical trial was conducted at a tertiary care hospital in New Delhi, India, from September 2023 to May 2025. The protocol was registered (CTRI/2023/09/057170) and approved by the Institute Ethics Committee (1ECPG-674/25.08.2022). This study included patients aged 5 years and older who were clinically diagnosed with slow-flow vascular malformations, confirmed on ultrasonography (USG) Doppler. Patients with high-flow malformations, flat capillary malformations, uncontrolled hypertension, or a history of bleeding disorders were excluded from participation. In addition, pregnant and lactating women were excluded.
The study design incorporated an observational phase lasting 16 weeks, which served as a self-control comparator arm for each patient.3 During this period, lesion size and symptoms were closely monitored. Following the observational phase, patients transitioned to the interventional period, where they underwent two sessions of RFA, scheduled 4 weeks apart.
Intervention
For the treatment procedure, an 18G intravenous (IV) cannula was utilized, with the luer lock plug removed. A small window was created at the proximal end of the outer plastic sheath using a surgical blade to facilitate contact between the radiofrequency probe and the inner metallic needle. The IV cannula was then carefully introduced into the bulk of the vascular malformation. We employed the KLS Martin maXium® electrosurgery machine using a monopolar loop radiofrequency probe in coagulation mode at a power setting of 10–20 watts, depending on the thickness of the vascular malformation . The probe was brought into contact with the metallic needle through the created window to ablate the tissue. The IV cannula was slightly withdrawn after each application, allowing for systematic treatment of the entire lesion4 [Supplementary Video 1].
Hence, the treatment comprised two sessions spaced 4 weeks apart (weeks 16 and 20) or until complete flattening of the lesion was achieved, whichever occurred first. Patients were followed up at 24, 28, and 32week post-treatment to assess outcomes and recurrence.
Outcome measures
Primary outcomes
Reduction in volume of vascular malformations: This was assessed through both ultrasound imaging and clinical evaluation. The three-dimensional volume of the target lesion was calculated based on orthogonal diameters using the formula: Volume = width × height × length × 0.524.5,6
Adverse effects of treatment: Monitoring and documenting any adverse effects that occurred as a result of the treatment.
Secondary outcomes
Reduction in dermatology life quality index (DLQI): This questionnaire comprises 10 questions addressing various aspects of daily life affected by the skin condition. Each question is scored from 0–3, resulting in a total score out of 30.
Symptom reduction: Symptoms such as pain and bleeding were graded on a scale of 0–3, with 0 indicating no symptoms, 1 representing mild symptoms, 2 for moderate symptoms, and 3 for severe symptoms.
Patient satisfaction score: This was assessed using a subjective tool (Visual Analog patient satisfaction scale) with score ranging from 0–10, where 0 means not satisfied at all, and 10 means fully satisfied with the treatment provided.7
Physician global assessment: At the conclusion of the study, a physician’s assessment was conducted to evaluate changes in the lesions. The assessment was rated on a scale from −2 (markedly exacerbated) to 3 (markedly improved), with 0 indicating no change.
Statistical analysis
Statistical analysis was conducted using Stata 16 software (StataCorp, 2019, College Station, TX: StataCorp LLC). A per-protocol analysis was performed to evaluate the primary outcome–the mean reduction in the volume of the vascular malformation–using the paired t-test. In addition, subgroup analyses were carried out to identify which types of vascular malformations (lymphatic, venous, or mixed) exhibited greater volume reductions. Secondary outcomes, including the DLQI and symptom reduction, were assessed using the Wilcoxon signed-rank test. A P < 0.05 was considered statistically significant.
RESULTS
Baseline characteristics
The study enrolled 35 patients diagnosed with vascular malformations, out of which 28 completed at least 1 session. Six patients were excluded as they were lost to follow-up during the observational phase, and one patient with a LM was excluded due to significant fluctuations in swelling that nearly resolved before any intervention. The mean age was 19.50 ± 10.77 years, and the cohort predominantly consisted of males (67.8%, n = 19), while females accounted for 32.2% (n = 9). No patient had any systemic involvement or syndromic malformation. One patient (3.5%) with glomuvenous malformation had a family history, in which her brother also had a similar lesion [Table 1].
| Diagnosis | n=28 (%) |
|---|---|
| Diagnosis | |
| Venous | 11 (39.3) |
| Lymphatic | 4 (14.3) |
| Mixed | 13 (46.4) |
| Diagnosis subtype | |
| Capillary lymphatic malformation | 1 (3.6) |
| Capillary venous malformation | 5 (17.9) |
| Glomuvenous malformation | 1 (3.6) |
| Lymphangioma circumscriptum | 4 (14.3) |
| Venolymphatic malformation | 6 (21.4) |
| Pure venous malformation | 7 (25.0) |
| Verrucous hemangioma | 4 (14.3) |
| Location | |
| Head and neck | 7 (25.0) |
| Upper limb | 4 (14.3) |
| Lower limb | 7 (25.0) |
| Trunk | 8 (28.6) |
| Genitals | 2 (7.1) |
Patients presented with a variety of symptoms, with the most common being pain, reported by 20 patients (71.4%). Other symptoms included bleeding or oozing in 10 patients (35.7%), cosmetic concerns and swelling reported by 3 patients (10.7%) each, difficulty speaking by 2 patients (7.1%), and itching experienced by 1 patient (3.5%). These symptoms were either primary or co-existing concerns among patients.
Assessment of change in volume over time (clinical measurements)
At baseline, the mean volume was 31.10 cm3 ± 51.48, which decreased to 18.20 cm3 ± 29.28 by week 32, indicating a substantial reduction (P < 0.001).
In the observational phase (0–16 weeks), the mean volume increase was +1.27 cm3 ± 10.82. During the interventional phase (16–32 weeks), the mean volume decrease was −14.70 cm3 ± 28.60, with a statistically significant difference between these two phases (P = 0.003). These results highlight a marked reduction in lesion volume over time, particularly during the interventional phase, reflecting the efficacy of the intervention.
The mean percentage change in volume during the observational phase (0–16 weeks) was +6.02% ± 48.37, while the mean percentage change in volume during the interventional phase (16–32 weeks) was −48.84% ± 37.36, with a statistically significant difference observed (P < 0.001) [Table 2 and Figures 1-3].
| Time point/ Phase | Clinical measurements | USG measurements |
|---|---|---|
| Volume (cm3) | ||
| • Baseline | 31.10±51.48 cm3 | 17.25±25.32 cm3 |
| • At 16 weeks | 32.37±44.84 cm3 | 18.47±28.28 cm3 |
| • At 20 weeks | 23.60±27.44 cm3 | |
| • At 24 weeks | 17.13±24.65 cm3 | |
| • At 28 weeks | 15.70±22.75 cm3 | |
| • At 32 weeks | 18.20±29.28 cm3 | 8.96±14.96 cm3 |
| Change during observational phase (0–16 weeks) | ||
| • Absolute change (range, cm3) | +1.27 cm3(−41.41–21.21) | +1.22 % (−7.94–16.55) |
| • Percentage change (range, %) |
+6.02 % (38.24–224.90) | +10.40 % (−29.81–111.32) |
| Change during interventional phase (16–32 weeks) | ||
| • Absolute change (range, cm3) | −14.70 cm3(−130.06–5.55) | −8.41 cm3 (−77.03–7.80) |
| • Percentage change (range, %) |
−48.84% (−100.00–34.02) | −25.99 % (−100.00–168.12) |
USG: Ultrasonography
- Graph showing the change in the mean volumes of the vascular malformations.
- (a) Venous malformation over tongue at baseline (6.82 cm3); (b) Minimal change in volume after observational phase at 16 weeks (6 cm3); (c) Marked reduction in volume post intervention at 32 weeks (0.85 cm3).
- (a) Lymphatic malformation over the flank at baseline (247cm3); (b) Minimal change in volume after observational phase at 16 weeks (206.17 cm3); (c) Marked reduction in volume post intervention at 32 weeks (76.11 cm3).
When comparing the three groups (venous, lymphatic, and mixed), the venous group showed a statistically significant decrease in volume over time, with a reduction from +0.46 cm3 ± 4.01 at 0–16 weeks to −4.91 cm3 ± 5.55 at 16–32 weeks (P = 0.027). In contrast, the changes in volume for the lymphatic and mixed groups were not statistically significant.
At the end of the interventional phase, the mean change in volume was highest in the Trunk group: −39.99 ± 60.77, followed by the lower limb: −11.98 ± 7.99, genitals: −9.48 ± 13.04, upper limb: −9.09 ± 7.90, and head and neck: −7.74 ± 15.63. Most of the patients who had the lesions over the trunk had a lymphatic component in their malformations (6/8 patients).
Recurrence was rare, with only 1 patient (3.5%) experiencing recurrence within 3 months after the procedure. The remaining 27 patients (96.5%) showed no signs of recurrence during the follow-up.
Assessment of change in volume (ultrasound measurements) over time
USG assessments of volume showed similar reductions. At baseline, the mean volume was 17.25 cm3 ± 25.32, which increased slightly to 18.47 cm3 ± 28.28 at week 16, and it decreased to 8.96 cm3 ± 14.96 by week 32 (P = 0.010).
Changes in USG-measured volume between the observational and interventional phases were significant, with a mean increase in volume of +1.22 cm3 ± 5.41 in the observational phase compared to a decrease of volume by −8.41 cm3 ± 19.33 in the interventional phase (P = 0.025).
The mean standard deviation percentage increase in volume (USG) during the observational phase (0–16 weeks) was 10.40 ± 34.24, while the decrease in the interventional phase (16–32 weeks) was −25.99 ± 54.34. The difference observed was statistically significant (P = 0.007) [Table 2].
Adverse effects
A total of 20 patients (71.4%) experienced mild pain and swelling, which resolved within 3 days following treatment with nonsteroidal anti-inflammatory drugs. Two patients (7.1%) had persistent swelling, whereas 6 patients (21.4%) experienced ulceration, which resolved within 4 weeks with daily dressing and oral antibiotics. No patients developed any secondary bacterial infection. No severe adverse effects or complications were reported, indicating that the procedure was generally well tolerated.
Reduction in DLQI
The mean DLQI score decreased significantly from 13.89 ± 6.81 at baseline to 7.75 ± 6.38 at week 32 (P < 0.001). During the observational phase, the mean change was −0.46 ± 3.92, while in the interventional phase, the mean decrease was −6.00 ± 5.25 (P < 0.001), reflecting an enhanced quality of life post-intervention.
Symptom reduction
Symptom severity was evaluated using a 0–3 scale for both pain and bleeding/oozing, demonstrating significant improvement over the course of the study.
At baseline, pain severity was reported as follows: 8 patients (28.6%) had no pain, 3 patients (10.7%) experienced mild pain, 7 patients (25.0%) reported moderate pain, and 10 patients (35.7%) had severe pain. By week 32, this had improved, with 11 patients (45.8%) reporting no pain, 8 patients (33.3%) with mild pain, 4 patients (16.7%) experiencing moderate pain, and only 1 patient (4.2%) with severe pain. The mean pain score significantly decreased from 1.78 at baseline to 0.80 at week 32 (P = 0.001).
Bleeding and oozing were also assessed on a 0–3 scale. At baseline, 9 patients (32.1%) reported no bleeding, 9 patients (32.1%) experienced mild bleeding, 9 patients (32.1%) had moderate bleeding, and 1 patient (3.6%) reported severe bleeding. By week 32, 20 patients (83.3%) reported no bleeding, 3 patients (12.5%) had mild bleeding, and only 1 patient (4.2%) had severe bleeding. The mean score for bleeding decreased significantly from 1.1 at baseline to 0.3 at week 32 (P < 0.001).
Visual analog patient satisfaction scale
The mean satisfaction score was 5.25 ± 2.8, with a median score of 6.0 (range: 3–8). Six patients reported a score of 6, two patients scored 7, two patients scored 8, and four patients reported a score of 9.
Physician global assessment scale
Physicians assessed patient improvement using the Physician Global Assessment Scale. Five patients (20.8%) were categorized as unchanged, 7 patients (29.2%) as slightly improved, 7 patients (33.3%) as improved, and 4 patients (16.7%) as markedly improved. The mean score was 1.36 ± 1.13, with a median of 1.00 (0.75–2).
DISCUSSION
This study on intralesional RFA for slow-flow vascular malformations demonstrated significant efficacy and safety, with improvements across multiple outcome measures. Objectively, lesion volume demonstrated a significant mean decrease of 48.84% when assessed clinically and a mean 25.99% reduction when measured through ultrasound following two sessions of RFA. The discrepancy between clinical and ultrasound measurements may be attributed to the ultrasound capturing only the volume of vascular channels, while clinical measurements with vernier calipers include both soft-tissue swelling and vascular channels. Quality of life, as measured by the mean DLQI, also improved by 44.2%, underscoring the positive impact of RFA on daily living activities and overall well-being. Patient satisfaction scores were notably high, reflecting the perceived benefits of the intervention.
The findings of this study are consistent with existing literature. Gao et al. reported that most vascular malformations treated with RFA stopped expanding and decreased in size, with complete resolution (>90% improvement) in two patients and significant improvement (75–90%) in eight out of 16 patients.8 Similarly, Cho et al. used both injectable and non-injectable electrodes for ultrasound-guided RF ablation of facial venolymphatic malformations, achieving a volume reduction ratio of 81%.6 Koo et al. observed moderate volume reduction (50–90%) in four patients with microcystic LMs after 1–4 sessions of ultrasound-guided RFA.5 In another study, five patients with VMs received intralesional bleomycin (0.5 U/kg) every 2 weeks for eight sessions, which resulted in minimal lesion reduction (<50%). However, following 2–4 sessions of RFA (every 2 months), the final lesion size was reduced by approximately 80%.9
In our study, specific symptoms such as pain and bleeding showed significant reductions, with mean scores for bleeding decreasing from 1.1 at baseline to 0.3 at week 32 (P < 0.001). Similarly, Van Der Linden et al. reported complete resolution of pain and bleeding in two out of three patients treated with RFA.10 Sporns et al. demonstrated clinical improvement after RFA, with seven patients (87.5%) becoming completely asymptomatic and one (12.5%) experiencing symptom improvement.11
Compared to other treatment modalities, such as sclerotherapy and sirolimus, RFA may be more efficacious. This study achieved significant results with just two RFA sessions, while sclerotherapy typically requires multiple sessions (more than 2) to yield clinically meaningful outcomes. Van Der Linden et al. reported a 42% rate of clinical inefficacy at the 3-month follow-up with sclerotherapy, even after a mean of 1.6 sessions.12 In the PERFORMUS trial, evaluating the efficacy of sirolimus in slow-flow vascular malformations, the change in the volume of was not significantly different between the interventional (sirolimus) and observational periods at study end, though symptom improvement in pain and bleeding was noted.3 In the vascular anomaly-sirolimus-Europe trial, 33 of 61 patients (54%) who completed a 2-year sirolimus treatment for slow-flow vascular malformations reported symptom recurrence after a median follow-up of 13 months post-treatment.13 Surgical excision also carries a high recurrence risk, with Raveh et al. noting a 22% recurrence rate in 74 children treated with primary surgical excision for LMs.14 However, no head-to-head trial has been done to compare these different modalities.
Recurrence was uncommon in our study, with only one patient (3.5%) experiencing a recurrence within 3 months post-procedure. Garg et al. followed five patients for 1–2 years and reported no recurrences.9 Similarly, Ryu et al., in a study of 11 patients with microcystic LMs of the oral cavity treated with RFA alone, observed no recurrences during a 1-year follow-up.15 Niti and Manish combined sclerotherapy with RFA and found that six out of thirteen patients had a few small vesicles appear at the periphery of the treated area, with recurrence times ranging from 6 to 60 months. In contrast, all three patients treated with sclerotherapy alone experienced recurrences.16
The safety profile of interleukin-RFA in this study compares favorably with previous studies. Although 6 of 28 patients experienced ulceration, it resolved within 4 weeks, and there were no reports of serious complications, such as nerve damage, which can be a risk with surgical excision. This is consistent with the findings of Subhadarshani et al., who reported only mild pain and swelling as adverse effects of intralesional RFA.4
CONCLUSION
Hence, intralesional RFA proves to be a safe, effective, and cosmetically favorable option for treating low-flow vascular malformations. Patients reported significant reductions in lesion size, pain, and bleeding, with minimal side effects. Its adaptability to an outpatient setting and the use of cost-effective IV cannulas as insulated probes make intralesional RFA accessible, especially in resource-limited areas, positioning it as a viable first-line or adjunctive treatment.
While our study supports intralesional RFA’s potential, limitations include its single-center design, small sample size, and short follow-up period. Future studies with larger, multicenter cohorts and extended follow-up, as well as comparative studies with other treatments, are needed to further establish its efficacy, safety, and patient satisfaction outcomes.
Authors’ contributions:
Ayush Jain and Somesh Gupta conceptualized the study. Methodology was developed by Ayush Jain, Somesh Gupta, Rhea Ahuja, and Kanika Sahni. Validation was performed by Ayush Jain, Somesh Gupta, and Kanika Sahni. Formal analysis was conducted by Ayush Jain, Somesh Gupta, Rhea Ahuja.. Resources were provided by Ayush Jain, Somesh Gupta, Surabhi Vyas, and Kanika Sahni. Data curation was carried out by Ayush Jain, Somesh Gupta, and Rhea Ahuja. The original draft was prepared by Ayush Jain and Somesh Gupta, and review and editing were performed by Ayush Jain, Somesh Gupta, Kanika Sahni, and Rhea Ahuja. Visualization was done by Ayush Jain, Somesh Gupta, Surabhi Vyas, and Kanika Sahni.
Ethical approval:
The research/study was approved by the Institutional Review Board at AIIMS Delhi, number 1ECPG-674/25.08.2022, dated August 25, 2022.
Declaration of patients consent:
The authors certify that they have obtained all appropriate patient consent.
Conflicts of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Financial support and sponsorship: Nil.
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