The Safety And Efficacy Of High-intensity Focused Ultrasound Ablation For Desmoid Tumors And The Factors Influencing Ablation Outcome

Desmoid tumors(DTs)are rare soft tissue tumors characterized by local invasion and non-metastasis.While surgical resection used to be the mainstay of treatment for DTs,high recurrence rate,more aggressive recurrence,and associated postoperative functional impairment became major concerns.Systemic treatments such as toxic chemotherapy and target therapy resulted in limited efficacy.At present,there is still a lack of repeatable and effective treatment methods to control the progression of DTs.Several small-sample studies have reported the feasibility of high-intensity focused ultrasound(HIFU)ablation for DTs,showing the prospect of HIFU ablation.However,clinical evidence is insufficient to confirm the safety,efficacy and reliability of current clinical programs.ObjectiveTo evaluate the safety and efficacy of HIFU ablation in the treatment of DTs,and to explore the factors influencing the HIFU ablation outcome.MethodsFrom August 2012 to December 2018,a total of 85 patients with histologically-proven DTs were treated by HIFU ablation in Chongqing Haifu Hospital and the First Affiliated Hospital of Chongqing Medical University.Adverse events were recorded during the procedure and after treatment.The differences of adverse events in patients with extra-abdominal,abdominal wall and intra-abdominal DTs,and the differences of adverse events between patients who received a single session of HIFU treatment and those who received multiple sessions of HIFU treatment were analyzed.Non-perfused volume rate(NPVR)was evaluated using contrast-enhanced MRI before and one week after the procedure.Symptom improvement was evaluated by comparing pain score and limb motor function before and after treatment.The end point was the date of tumor progression or the last follow-up,and the deadline for follow-up was December 31,2020.The change of tumor volume was observed according to modified response evaluation criteria in solid tumors(m RECIST)v1.1 guidelines.Progression-free survival(PFS)was evaluated using Kaplan-Meier and multivariate Cox regression,and PFS curves were compared.ROC curve was used to assess NPVR threshold through analyzing the correlation between tumor outcome two years after HIFU ablation treatment and NPVR.From August 2012 to December 2020,a total of 90 patients with histologically-proven DTs(extra-abdominal and abdominal wall)were included from Chongqing Haifu Hospital and the First Affiliated Hospital of Chongqing Medical University.NPVR was evaluated using contrast-enhanced MRI before and one week after the procedure.Then,DTs were divided into two groups(high-NPVR group and low-NPVR group)according to the NPVR threshold.NPVR was the dependent variable.The independent variables included gender,age,body mass index,tumor status(primary/recurrent),tumor location(trunk/limbs),tumor depth,the maximum diameter of tumor,distance from tumor to a major nerve,the acoustic pathway through bone,types of T2WI,and types of contrast-enhanced MRI.The factors influencing ablation results(NPVR)were assessed using logistic regression.ResultsEighty-five patients underwent 137 sessions of HIFU ablation.The total incidence of adverse events was 27.0%(37/137),of which CTCAE grade 1-2 adverse events accounted for 97.5%and CTCAE grade 3 adverse events accounted for 2.5%.No CTCAE grade 4-5 adverse event was observed.There was no significant difference in the incidence of adverse events in patients with extra-abdominal,abdominal wall and intra-abdominal DTs(x~2=0.308,P=0.922).There was no significant difference in the incidence of adverse events between patients who received a session of HIFU treatment and those who received multiple sessions of HIFU treatment(x~2=0.095,P=0.843).Of the 85 patients included,83 patients successfully completed 135sessions of HIFU ablation.The non-perfused area was observed in each treated lesion,and the median NPVR was 85.0%(interquartile range:59.8-99.3%).Pain symptoms improved in the majority(30/41,73.2%)of patients with pain,and limb motor function improved in the minority(3/44,6.8%)of patients with limb dysfunction.The mean follow-up time was 33.3±2.2months(range:24-100),and the overall survival rate was 96.5%(82/85).Median PFS time was 30 months,and the PFS for 1 year,2 years,3 years,and 5 years was 85.1%,75.1%,67.5%,and 63.9%,respectively.NPVR was related to the outcome of tumor progression,and the NPVR threshold was around 70%.NPVR was an independent factor affecting the progression of DTs.The risk of tumor progression in the high-NPVR group(NPVR>70%)was lower than that in the low-NPVR group(NPVR≤70%),HR=0.064(95%CI:0.027-0.152).The included 90 patients with 123 extra-abdominal and abdominal wall DTs successfully underwent the first session of HIFU ablation.Univariate analysis showed that the factors including tumor depth,the maximum diameter of tumor,and distance from tumor to the major nerve affected NPVR of extra-abdominal and abdominal wall DTs(P<0.05).Subsequently,multivariate logistic regression analysis showed that distance from tumor to the major nerve was significantly correlated with NPVR(P=0.028).The incidence of high-NPVR(>70%)in DTs with a distance of 0.1-1.0 cm from a major nerve was 2.8 times that in DTs without distance from a major nerve(OR=2.8,95%CI:1.1-7.1).The incidence of high-NPVR in DTs with a distance of more than 1.0 cm from a major nerve was 4.2 times that in DTs without distance from a major nerve(OR=4.2,95%CI:1.1-16.1).ConclusionsHIFU ablation,as a noninvasively local treatment,is a promising treatment for desmoid tumors.NPVR can be used to predict the outcome of tumor progression after HIFU ablation of DTs,and distance from tumor to a major nerve is a factor influencing the ablation outcome(NPVR).