European Journal of Obstetrics & Gynecology and Reproductive Biology 182 (2014) 247–251
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Safety and five-year re-intervention following magnetic resonanceguided focused ultrasound (MRgFUS) for uterine fibroids S.D. Quinn a,*, J. Vedelago b,1, W. Gedroyc b,2, L. Regan a,2 a b
Department of Obstetrics and Gynaecology, St. Mary’s Hospital, Praed Street, London W2 1NY, United Kingdom Department of Radiology, St. Mary’s Hospital, Praed Street, London W2 1NY, United Kingdom
A R T I C L E I N F O
A B S T R A C T
Article history: Received 11 April 2014 Received in revised form 19 September 2014 Accepted 29 September 2014
Objective: To examine the safety and re-intervention rates following magnetic resonance-guided focused ultrasound (MRgFUS) for uterine fibroids at 5 years. To assess how the non-perfused volume (NPV), fibroid signal intensity and use of gonadotrophin-releasing hormone analogues (GnRHa) affect the re-intervention rates. Study design: Cohort study of women undergoing MRgFUS for treatment of their uterine fibroids between 2003 and 2010. Results: Of 280 women undergoing MRgFUS the rate of minor complications was 3.9% and there were 3 serious complications (1.1%) including one skin burn, a fibroid expulsion and one case of persistent neuropathy. The NPVs achieved following MRgFUS have increased as the experience with this treatment has grown. In a 5-year follow-up study of 162 women, the overall re-intervention rate was 58.64%, but in those treatments with greater than 50% NPV the re-intervention rate was 50%. Conclusion: MRgFUS treatment of uterine fibroids is a safe treatment for uterine fibroids. The reintervention rate at 5 years is high, but the improvements in NPVs achieved may further improve the long term results. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Magnetic resonance-guided focused ultrasound (MRgFUS) Fibroids Treatment’ follow-up
Introduction Magnetic resonance-guided focused ultrasound (MRgFUS) uses MR imaging-guidance to direct high-intensity focused ultrasound (HiFU) into a uterine fibroid (UF) resulting in coagulative necrosis of the fibroid tissue. This treatment was first performed in 2002 [1] and received approval from the US Food and Drug Administration (FDA) in 2004. Since then this treatment has been associated with favorable pregnancy outcomes [2,3], and encouraging short to medium term results [4–6]. Since its introduction, increasing experience of this treatment has led to a refinement of patient selection, with a tendency toward treating women with fewer fibroids and smaller uteri [7]. A recent retrospective study of women undergoing uterine artery embolization (UAE) and
* Corresponding author. Tel.: +44 2033126666. E-mail addresses: [email protected], [email protected], [email protected] (S.D. Quinn), [email protected], [email protected] (J. Vedelago), [email protected] (W. Gedroyc), [email protected] (L. Regan). 1 Tel.: +44 7796 284 834/2033126666; fax: +44 20331 21123. 2 Tel.: +44 2033126666. http://dx.doi.org/10.1016/j.ejogrb.2014.09.039 0301-2115/ß 2014 Elsevier Ireland Ltd. All rights reserved.
MRgFUS found a re-intervention rate of 66.7% at five years following a mean non-perfused volume (NPV) of fibroid tissue of 36.4% [8]. It is expected that as experience with this novel treatment increases the outcomes achieved will improve, both in terms of overall volume of fibroid ablated and reduction of adverse events [9]. At present no randomized controlled trials have been performed comparing MRgFUS with other treatment modalities, and the current published data regarding outcomes is from cohort studies [4]. Materials and methods This was a cohort study of 280 women undergoing MRgFUS for treatment of their uterine fibroids between 2003 and 2010. Data were obtained from patient records and patient questionnaires, including the uterine fibroid symptom and quality of life (UFS-QoL) questionnaire [10]. In addition, telephone consultation was attempted for all women, during which a standardized questionnaire was completed to assess their personal experience of the treatment and outcomes. The MRI images of the MRgFUS procedure were retrieved where possible, and the T1 and T2 images were reviewed. From these,
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S.D. Quinn et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 182 (2014) 247–251
uterine volume, volume of fibroids treated and non-perfused volume following contrast agent were calculated using the parallel planimetric area method [11]. In addition to re-intervention for their uterine fibroids, women were asked whether they would recommend this treatment to friend, stratifying their responses into yes, no or not sure. Treated fibroids were also described in terms of their pixel signal intensity on T2-weighted MR imaging, in relation to both the adjacent myometrium and skeletal muscle. The overall intensity for the treated uterus was described in terms of the largest fibroid treated. Type 1 were those uterine fibroids which appeared hypointense in relation to skeletal muscle, type 2 had signal intensity equal to that of skeletal muscle (iso-intensity) and type 3 appeared hyper-intense in relation to skeletal muscle. This additional categorization of signal intensity has been used in other studies examining the effects of fibroid signal intensity on MRgFUS outcomes [4]. For the cohort study of those subjects undergoing treatment with the ExAblate 2000 system the outcomes measured were reintervention by surgical means, embolization or repeat MRgFUS at three and five years. Treatments were stratified according to the degree of NPV achieved. An NPV of 0–25% was for the purposes of this study classified as a failed treatment. Treatments were then classified as 25–50% NPV and >50% NPV. In addition to NPV, the effects of age, parity and body mass index (BMI) on re-intervention were tested, to assess for possible confounding variables. A logistic regression model was used, and the model was tested for goodness-of-fit by the Hosmer–Lemeshow test and Le Cessie– Van Houwe–Copas–Hosmer un-weighted sum of squares test [12]. The statistical package R version 2.15.0 [13] was used to check the fit of the logistical regression model and calculate the odds ratio of requiring further treatment at five years compared with those with less than 25% NPV. Other statistical calculations were performed using SPSS version 19 (BM SPSS Statistics for Windows, Version 19.0. Armonk, NY: IBM Corp). All distributions of continuous data were tested for normality and where the data were not normally distributed means were compared using the Mann–Whitney test, to test the differences between medians in these two groups. Results Notes and patient records were reviewed for all 280 women undergoing MRgFUS between January 2003 and January 2011. At the time of this study, 239 women had undergone their MRgFUS three or more years earlier and were therefore able to contribute to the three-year outcomes data, and of these 181 were successfully contacted (75.7%). In additional, a total of 187 women had their MRgFUS treatments over five years before the study and were therefore eligible to be included in the 5-year outcomes study. Of these 187 women, 162 were successfully contacted (87.17%). Details on ethnicity were available for 248 of the 280 women and are given in Table 1. Mean age was 42.2 years, mean BMI 25.1, and mean UFS-QOL symptom severity score (SSS) was 62.4/100. MRI images were successfully located for 241 of the 280 women. Mean uterine volume was 795.5 cm3 (SD 408.89), and the mean total volume of fibroid tissue attempted was 396.3 cm3 (SD 265.0). Total non-perfused volume (NPV) following contrast was 165.0 cm3 (SD 137.23). This gave a mean percentage NPV of the total fibroid volume attempted as 44.2%. Between 2003 and 2011 the mean uterine volume fell from 809.73 ml (SD 445.48) to 658.38 (SD 296.37) (p = 0.015), the mean %NPV increased from 41.22 (SD 25.66) to 50.49 (SD 18.23) by 2010 (p = 0.038) and significantly fewer treated UF were hyper-intense on T2-weighted imaging (13.78% vs 29.2% p = 0.049). The overall
Table 1 Demographics of women undergoing ExAblate 2000 treatment. Age Mean (years) Range (years) BMI Mean Standard deviation
Race White Black Asian Arabic Other Not stated/declined Parity P0 P1 P2 >P2 Previous treatment Nil Myomectomy UFE TCRF IUS
42.2 25–84 25.1 4.6 Numbers
Percentage
Valid percentage
135 76 17 7 13 32
48.2 27.1 6.1 2.5 4.6 11.4
54.4 30.6 6.9 2.8 5.2
198 42 35 5
70.7 15.0 12.5 1.8
202 12 7 12 47
72.1 4.3 2.5 4.3 16.8
volume of fibroid tissue treated increased from the initial treatments in 2003 of 333.8 ml (SD 209.75) to a peak of 544.23 ml (SD 276.52) by 2005, before falling to 319.2 ml (SD 241.88) by 2010. This is likely to reflect the anecdotal experience of the MRgFUS operators in terms of improving clinical outcomes, with relatively small uterine fibroids being easier to treat successfully, and a shorter associated treatment time being more tolerable to patients. No adverse events and no significant pain were reported in 249 of the 280 women (88.9%). Mild to moderate pain, lasting up to five days post procedure was reported by 18 of 280 women (6.4%) in the absence of any other significant complications. Minor complications (urinary tract infection, urinary retention, vaginal bleeding, and transient buttock pain) were experienced by 11 of 280 women (3.9%). Only three subjects (1.1% of the total cohort) experienced severe complications. These included one case of fibroid expulsion, one major skin burn requiring surgical repair, and one case of persistent neuropathy. No emergency hysterectomies were required following MRgFUS therapy. One woman required hospital admission for urinary retention, which resolved after three days. Six subjects described moderate abdominal pain in addition to other stated complications. The percentage NPV achieved during these treatments is included in Table 2. There is no significant increase in adverse events seen with increasing NPV, but numbers are small. Of the 280 subjects who had undergone their MRgFUS, 229 were successfully contacted (81.8%). Those subjects were asked whether they would recommend this treatment to a friend. Of these, 124 (54.2%) answered yes, they would recommend this treatment to a friend, 23 (10%) said they would not recommend this treatment, and 82 were not sure (35.8%). One hundred and eighty seven subjects had their MRgFUS treatments over five years before the study and were therefore eligible to be included in the five-year outcomes study. Of these 187 subjects, 162 were successfully contacted (87.17%). Overall reintervention rates by NPV are described in Table 3 and Fig. 1. At three years there was a significant reduction of the re-intervention rate for treatments achieving a greater than 25% NPV posttreatment. At five years there was a decreased re-intervention rate for those treatments with a greater than 50% NPV compared with
S.D. Quinn et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 182 (2014) 247–251
249
Table 2 Adverse events following treatment by ExAblate 2000 system n = 280. Minor complications
Numbers (%)
Mean NPV achieved (%)
Serious complications
Numbers (%)
Mean NPV achieved (%)
Abdominal pain (
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Safety and five-year re-intervention following magnetic resonanceguided focused ultrasound (MRgFUS) for uterine fibroids S.D. Quinn a,*, J. Vedelago b,1, W. Gedroyc b,2, L. Regan a,2 a b
Department of Obstetrics and Gynaecology, St. Mary’s Hospital, Praed Street, London W2 1NY, United Kingdom Department of Radiology, St. Mary’s Hospital, Praed Street, London W2 1NY, United Kingdom
A R T I C L E I N F O
A B S T R A C T
Article history: Received 11 April 2014 Received in revised form 19 September 2014 Accepted 29 September 2014
Objective: To examine the safety and re-intervention rates following magnetic resonance-guided focused ultrasound (MRgFUS) for uterine fibroids at 5 years. To assess how the non-perfused volume (NPV), fibroid signal intensity and use of gonadotrophin-releasing hormone analogues (GnRHa) affect the re-intervention rates. Study design: Cohort study of women undergoing MRgFUS for treatment of their uterine fibroids between 2003 and 2010. Results: Of 280 women undergoing MRgFUS the rate of minor complications was 3.9% and there were 3 serious complications (1.1%) including one skin burn, a fibroid expulsion and one case of persistent neuropathy. The NPVs achieved following MRgFUS have increased as the experience with this treatment has grown. In a 5-year follow-up study of 162 women, the overall re-intervention rate was 58.64%, but in those treatments with greater than 50% NPV the re-intervention rate was 50%. Conclusion: MRgFUS treatment of uterine fibroids is a safe treatment for uterine fibroids. The reintervention rate at 5 years is high, but the improvements in NPVs achieved may further improve the long term results. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Magnetic resonance-guided focused ultrasound (MRgFUS) Fibroids Treatment’ follow-up
Introduction Magnetic resonance-guided focused ultrasound (MRgFUS) uses MR imaging-guidance to direct high-intensity focused ultrasound (HiFU) into a uterine fibroid (UF) resulting in coagulative necrosis of the fibroid tissue. This treatment was first performed in 2002 [1] and received approval from the US Food and Drug Administration (FDA) in 2004. Since then this treatment has been associated with favorable pregnancy outcomes [2,3], and encouraging short to medium term results [4–6]. Since its introduction, increasing experience of this treatment has led to a refinement of patient selection, with a tendency toward treating women with fewer fibroids and smaller uteri [7]. A recent retrospective study of women undergoing uterine artery embolization (UAE) and
* Corresponding author. Tel.: +44 2033126666. E-mail addresses: [email protected], [email protected], [email protected] (S.D. Quinn), [email protected], [email protected] (J. Vedelago), [email protected] (W. Gedroyc), [email protected] (L. Regan). 1 Tel.: +44 7796 284 834/2033126666; fax: +44 20331 21123. 2 Tel.: +44 2033126666. http://dx.doi.org/10.1016/j.ejogrb.2014.09.039 0301-2115/ß 2014 Elsevier Ireland Ltd. All rights reserved.
MRgFUS found a re-intervention rate of 66.7% at five years following a mean non-perfused volume (NPV) of fibroid tissue of 36.4% [8]. It is expected that as experience with this novel treatment increases the outcomes achieved will improve, both in terms of overall volume of fibroid ablated and reduction of adverse events [9]. At present no randomized controlled trials have been performed comparing MRgFUS with other treatment modalities, and the current published data regarding outcomes is from cohort studies [4]. Materials and methods This was a cohort study of 280 women undergoing MRgFUS for treatment of their uterine fibroids between 2003 and 2010. Data were obtained from patient records and patient questionnaires, including the uterine fibroid symptom and quality of life (UFS-QoL) questionnaire [10]. In addition, telephone consultation was attempted for all women, during which a standardized questionnaire was completed to assess their personal experience of the treatment and outcomes. The MRI images of the MRgFUS procedure were retrieved where possible, and the T1 and T2 images were reviewed. From these,
248
S.D. Quinn et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 182 (2014) 247–251
uterine volume, volume of fibroids treated and non-perfused volume following contrast agent were calculated using the parallel planimetric area method [11]. In addition to re-intervention for their uterine fibroids, women were asked whether they would recommend this treatment to friend, stratifying their responses into yes, no or not sure. Treated fibroids were also described in terms of their pixel signal intensity on T2-weighted MR imaging, in relation to both the adjacent myometrium and skeletal muscle. The overall intensity for the treated uterus was described in terms of the largest fibroid treated. Type 1 were those uterine fibroids which appeared hypointense in relation to skeletal muscle, type 2 had signal intensity equal to that of skeletal muscle (iso-intensity) and type 3 appeared hyper-intense in relation to skeletal muscle. This additional categorization of signal intensity has been used in other studies examining the effects of fibroid signal intensity on MRgFUS outcomes [4]. For the cohort study of those subjects undergoing treatment with the ExAblate 2000 system the outcomes measured were reintervention by surgical means, embolization or repeat MRgFUS at three and five years. Treatments were stratified according to the degree of NPV achieved. An NPV of 0–25% was for the purposes of this study classified as a failed treatment. Treatments were then classified as 25–50% NPV and >50% NPV. In addition to NPV, the effects of age, parity and body mass index (BMI) on re-intervention were tested, to assess for possible confounding variables. A logistic regression model was used, and the model was tested for goodness-of-fit by the Hosmer–Lemeshow test and Le Cessie– Van Houwe–Copas–Hosmer un-weighted sum of squares test [12]. The statistical package R version 2.15.0 [13] was used to check the fit of the logistical regression model and calculate the odds ratio of requiring further treatment at five years compared with those with less than 25% NPV. Other statistical calculations were performed using SPSS version 19 (BM SPSS Statistics for Windows, Version 19.0. Armonk, NY: IBM Corp). All distributions of continuous data were tested for normality and where the data were not normally distributed means were compared using the Mann–Whitney test, to test the differences between medians in these two groups. Results Notes and patient records were reviewed for all 280 women undergoing MRgFUS between January 2003 and January 2011. At the time of this study, 239 women had undergone their MRgFUS three or more years earlier and were therefore able to contribute to the three-year outcomes data, and of these 181 were successfully contacted (75.7%). In additional, a total of 187 women had their MRgFUS treatments over five years before the study and were therefore eligible to be included in the 5-year outcomes study. Of these 187 women, 162 were successfully contacted (87.17%). Details on ethnicity were available for 248 of the 280 women and are given in Table 1. Mean age was 42.2 years, mean BMI 25.1, and mean UFS-QOL symptom severity score (SSS) was 62.4/100. MRI images were successfully located for 241 of the 280 women. Mean uterine volume was 795.5 cm3 (SD 408.89), and the mean total volume of fibroid tissue attempted was 396.3 cm3 (SD 265.0). Total non-perfused volume (NPV) following contrast was 165.0 cm3 (SD 137.23). This gave a mean percentage NPV of the total fibroid volume attempted as 44.2%. Between 2003 and 2011 the mean uterine volume fell from 809.73 ml (SD 445.48) to 658.38 (SD 296.37) (p = 0.015), the mean %NPV increased from 41.22 (SD 25.66) to 50.49 (SD 18.23) by 2010 (p = 0.038) and significantly fewer treated UF were hyper-intense on T2-weighted imaging (13.78% vs 29.2% p = 0.049). The overall
Table 1 Demographics of women undergoing ExAblate 2000 treatment. Age Mean (years) Range (years) BMI Mean Standard deviation
Race White Black Asian Arabic Other Not stated/declined Parity P0 P1 P2 >P2 Previous treatment Nil Myomectomy UFE TCRF IUS
42.2 25–84 25.1 4.6 Numbers
Percentage
Valid percentage
135 76 17 7 13 32
48.2 27.1 6.1 2.5 4.6 11.4
54.4 30.6 6.9 2.8 5.2
198 42 35 5
70.7 15.0 12.5 1.8
202 12 7 12 47
72.1 4.3 2.5 4.3 16.8
volume of fibroid tissue treated increased from the initial treatments in 2003 of 333.8 ml (SD 209.75) to a peak of 544.23 ml (SD 276.52) by 2005, before falling to 319.2 ml (SD 241.88) by 2010. This is likely to reflect the anecdotal experience of the MRgFUS operators in terms of improving clinical outcomes, with relatively small uterine fibroids being easier to treat successfully, and a shorter associated treatment time being more tolerable to patients. No adverse events and no significant pain were reported in 249 of the 280 women (88.9%). Mild to moderate pain, lasting up to five days post procedure was reported by 18 of 280 women (6.4%) in the absence of any other significant complications. Minor complications (urinary tract infection, urinary retention, vaginal bleeding, and transient buttock pain) were experienced by 11 of 280 women (3.9%). Only three subjects (1.1% of the total cohort) experienced severe complications. These included one case of fibroid expulsion, one major skin burn requiring surgical repair, and one case of persistent neuropathy. No emergency hysterectomies were required following MRgFUS therapy. One woman required hospital admission for urinary retention, which resolved after three days. Six subjects described moderate abdominal pain in addition to other stated complications. The percentage NPV achieved during these treatments is included in Table 2. There is no significant increase in adverse events seen with increasing NPV, but numbers are small. Of the 280 subjects who had undergone their MRgFUS, 229 were successfully contacted (81.8%). Those subjects were asked whether they would recommend this treatment to a friend. Of these, 124 (54.2%) answered yes, they would recommend this treatment to a friend, 23 (10%) said they would not recommend this treatment, and 82 were not sure (35.8%). One hundred and eighty seven subjects had their MRgFUS treatments over five years before the study and were therefore eligible to be included in the five-year outcomes study. Of these 187 subjects, 162 were successfully contacted (87.17%). Overall reintervention rates by NPV are described in Table 3 and Fig. 1. At three years there was a significant reduction of the re-intervention rate for treatments achieving a greater than 25% NPV posttreatment. At five years there was a decreased re-intervention rate for those treatments with a greater than 50% NPV compared with
S.D. Quinn et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 182 (2014) 247–251
249
Table 2 Adverse events following treatment by ExAblate 2000 system n = 280. Minor complications
Numbers (%)
Mean NPV achieved (%)
Serious complications
Numbers (%)
Mean NPV achieved (%)
Abdominal pain (
