CLINICAL PAPER
Superficial or Cutaneous Malignant Peripheral Nerve Sheath Tumor—Clinical Experience at Taipei Veterans General Hospital Chin-Jung Feng, MD,*† Hsu Ma, MD, PhD,*† and Wen-Chieh Liao, MD*† Background: Primary malignant peripheral nerve sheath tumors (MPNSTs) with a cutaneous or subcutaneous origin represent a small subset of MPNSTs thought to be derived from cutaneous neurofibromas or small peripheral nerves. Few cases of superficial MPNSTs originating from the skin have been reported in the literature. Materials and Methods: From October 1999 to February 2014, 13 patients were diagnosed with superficial or cutaneous MPNSTs and received treatment at Taipei Veterans General Hospital. Clinical data were collected via retrospective chart review. A retrospective study was performed to compare superficial and deep-seated lesions in terms of local recurrence, distal metastasis, and survival analysis. The relevant literature is also briefly reviewed. Results: The most frequent initial symptoms were local swelling and pain. Ten tumors were found in the extremities, and 3 tumors were located on the trunk. All patients underwent surgery with curative intent. Four patients developed local recurrence, and 3 developed distant metastasis. Three of 13 patients died after a follow-up period of 11 to 180 months (mean, 53.4). Compared to deep-seated MPNSTs, superficial MPNSTs had a lower histopathological grading and better survival rate. Conclusions: Superficial MPNSTs are a rare variant of MPNST. The relatively frequent lack of associated neurofibromatosis and superficial location within the dermis and subcutis may result in this entity being overlooked. According to our clinical experience, superficial MPNSTs might have better prognosis, but similar recurrence and metastasis rates compared with deep-seated lesions. Hence, awareness of this entity should prompt its consideration in the differential diagnosis of cutaneous sarcomas. Key Words: malignant peripheral nerve sheath tumor, superficial, cutaneous, deep, neurofibromatosis type 1 (Ann Plast Surg 2015;74: S85–S88)
M
alignant peripheral nerve sheath tumor (MPNST) is a rare type of sarcoma that accounts for 5% to 10% of all soft tissue sarcomas. Malignant peripheral nerve sheath tumor is strongly associated with neurofibromatosis type 1 (NF-1 or von Recklinghausen disease), with about 25% to 50% of MPNST cases occurring in association with NF-1. Patients with NF-1 are at increased risk of developing MPNST. The incidence of MPNST is estimated to be 0.001% in the general population and approximately 3% to 4.6% in patients with NF-1.1,2 In some cases (10%), MPNST may also be related to previous radiation at that site.1 Malignant peripheral nerve sheath tumor is a malignant spindle cell tumor of the soft tissues thought to be derived from components of the nerve sheath, such as perineural fibroblasts or Schwann cells.1 Malignant peripheral nerve sheath tumor can develop in pre-existing neurofibromas and de novo from peripheral nerve sheaths. Malignant peripheral nerve sheath tumors are highly aggressive, with rapid Received September 12, 2014, and accepted for publication, after revision, December 17, 2014. From the *Division of Plastic Surgery, Taipei Veterans General Hospital, and †School of Medicine, National Yang Ming University, Taipei, Taiwan. Conflicts of interest and sources of funding: none declared. Reprints: Wen-Chieh Liao, MD, Division of Plastic Surgery, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Rd, Taipei 112, Taiwan. E-mail: [email protected]. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0148-7043/15/7402–S085 DOI: 10.1097/SAP.0000000000000465
Annals of Plastic Surgery • Volume 74, Supplement 2, May 2015
invasive growth and early hematogenous dissemination.1 Even after radical surgical treatment, MPNSTs have a dismal prognosis, with reported 5-year survival rates of less than 50%.3 Classically, MPNSTs arise in the deep soft tissue and have a propensity to occur in the proximal limbs and trunk. They typically affect the large nerves of the neck and proximal extremities (including the sciatic nerve, brachial plexus, and sacral plexus), as well as the retroperitoneum, mediastinum, and viscera. However, there have been a limited number of case reports and small series describing superficial or cutaneous MPNST.3–17 Superficial primary MPNSTs with a cutaneous or subcutaneous origin represent a small subset of MPNSTs thought to be derived from cutaneous neurofibromas or small peripheral nerves. Fewer than 30 cases of superficial MPNSTs originating from the skin have been reported in the literature.3 In contrast to classic MPNSTs of deep anatomic origin, which are mostly found on the extremities and trunk, more than half of cutaneous MPNSTs are located on the head and neck.12 Here, we describe the clinicopathological features of 13 cases of superficial MPNSTs arising in cutaneous or subcutaneous tissue at Taipei Veterans General Hospital. A retrospective study was performed to compare MPNSTs with deep-seated lesions in terms of local recurrence and distal metastasis rates and survival analysis. The relevant literature is also briefly reviewed.
MATERIALS AND METHODS We identified 13 cases of superficially located primary MPNSTs with a cutaneous or subcutaneous origin from the surgical pathology files at the Taipei Veterans General Hospital from October 1999 to February 2014. These cases were all diagnosed as superficial or cutaneous MPNSTs and received treatment at Taipei Veterans General Hospital. Superficial MPNST was defined as a lesion with its predominant and primary mass located in the dermis or subcutaneous tissue and not in contact with the fascia. All available diagnostic reports and medical records were reviewed retrospectively. Patient data including sex, age at diagnosis, first symptom, site and size of the tumor, associated history of NF-1 or radiation exposure, treatment, surgical margin, histopathological grading, adjuvant therapy, local recurrence, distal metastasis, and survival time were analyzed. The observed survival time was calculated from the date of diagnosis to death or last follow-up. The clinicopathological features of 13 cases of superficial MPNSTs were compared with those of deep-seated lesions (n = 29) treated at the same hospital in the same period. Statistical analysis was performed using SPSS software (Chicago, IL). Pearson chisquared test and independent t test were used to assess differences between these 2 groups. Survival analysis was based on the Kaplan-Meier method and log-rank test.
RESULTS Among the 13 patients with superficial MPNST, 8 were men, 5 were women, and no sex predominance was noted. The mean age at diagnosis was 62.7 ± 18.6 years (range, 32–82 years). The most common initial symptom was pain, reported by 6 patients (42.6%), but most were asymptomatic. The average tumor diameter was 7.0 ± 2.6 cm (range, 3– 10 cm). Three patients (23.1%) had a history of NF-1, and 1 case www.annalsplasticsurgery.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
S85
Annals of Plastic Surgery • Volume 74, Supplement 2, May 2015
Feng et al
developed in a patient with pre-existing neurofibroma (Fig. 1). No patients had a history of radiation exposure before diagnosis. Ten (76.9%) tumors were found in the extremities, and 3 (23.1%) tumors were located on the trunk. All patients underwent surgery with curative intent. Ten patients received adjuvant therapy (76.9%). According to the Fédération Nationale des Centres de Lutte Contre le Cancer grading, nine tumors (81.8%) were classified as grade 2. Four (30.8%) of 13 patients developed local recurrence, and 3 (23.1%) developed distant metastasis. Three
of 13 patients died after a mean follow-up time of 53.4 months (range, 11–180 months). The disease-free 5-year survival rate was 64.2%. Compared with the 29 cases of deep-seated MPNSTs (Table 1), the age at diagnosis of superficial MPNSTs was significantly older than that of deep-seated lesions (62.7 ± 18.6 vs 33.9 ± 14.7 years; P < 0.001). The histopathological grading of superficial MPNSTs was significantly lower than that of deep-seated lesions, the majority of which were grade 3 (P = 0.021). Although 76.9% of superficial MPNSTs were found in the extremities, 58.6% of deep-seated MPNSTs were located in the trunk (Fig. 2). However, the tumor size, associated history of NF-1 or radiation, local recurrence rate, and distal metastasis rate did not significantly differ between the 2 groups. In survival analysis, the disease-free 5-year survival rate of patients with deep-seated lesions (32.6%) tended to be worse than that of patients with superficial MPNSTs (64.2%, P = 0.055), although the difference was not significant (Fig. 3).
DISCUSSION
FIGURE 1. A, A 70-year-old woman initially presented with a recurrent neurofibroma, approximately 8 5 cm in size, over the upper back, with a solitary itching and painful reddish nodule. Tumor-wide excision with a safe margin of 3 cm (dashed line) was performed. B, Histopathological examination revealed sheets of neoplastic polygonal to spindle cells (histological score 3) with increased cellularity and cellular pleomorphic nuclei. Myxoid changes and neurofibroma-like low grade areas were also are noted. These findings were compatible with a malignant peripheral nerve sheath tumor. The surgical margin was clear (hematoxylin-eosin stain, original magnification 100). C, Postoperative 1 year follow-up showed unremarkable change. S86
Superficial or cutaneous MPNST is a rare entity. A review of 230 cutaneous malignant spindle cell lesions found that superficial MPNSTs account for approximately 2% of cases.5 By definition, superficial or cutaneous MPNSTs are predominantly located in the dermis or subcutis. They typically arise in association with a pre-existing neurofibroma or small cutaneous nerves. Evans et al17 reviewed 13 cases of superficial MPNSTs arising in sporadic superficial neurofibroma. One case in our series involved a superficial MPNST developed in a preexisting neurofibroma over the upper back with no associated history of NF-1 (Fig. 1). All cases in this study were diagnosed with superficial MPNST based on histopathological examination. The classical findings are histological spindle-shaped cells with hyperchromatic nuclei and numerous mitotic figures. Immunohistochemical studies demonstrating reactivity to S-100 protein also indicate tumor cells of nerve sheath origin. Although MPNSTs do not have specific imaging features, CT scans and MRI assessment are useful tools to detect their relationship with surrounding tissues. Clinically, MPNSTs are reported to undergo a prolonged period of slow growth, followed by rapid proliferation. In sporadic cases of superficial MPNST, there is no age predilection. Cases associated with NF typically occur in younger patients. Deep MPNSTs are strongly associated with NF-1, with approximately 50% of cases linked with the syndrome.3 This association appears to be less common in superficial MPNST, with 10 of 27 (37%) of reported cases associated with NF-1 in a previous study.3 Similarly, in our series, association with NF-1 was less common among superficial MPNSTs (23.1%) than in deepseated MPNSTs (31.0%). Tumors arising in the head and neck account for the majority (56%) of superficial MPNSTs, but a wide variety of sites have been reported.12 For superficial MPNSTs of the head and neck, the scalp seems to be a common site, with 11 reported cases to date.15 However, in our series, the extremities were the most common location of superficial MPNSTs. This discrepancy should be evaluated in future studies. Surgical excision remains the mainstay of treatment for MPNSTs because this malignancy demonstrates a limited response to both chemotherapy and radiotherapy. The International Consensus Group has recommended that the current management of MPNST should be identical to that of any other soft tissue tumors. The goal is to achieve complete surgical excision of the tumor with negative margins. Wide surgical excision (at least 3–5 cm) has been reported as paramount to local control: even amputation should be considered.18 Because of the limited number of cases in the literature, the safe surgical margins of superficial MPNSTs require further evaluation. Adjuvant radiotherapy should be considered for all intermediateand high-grade lesions as well as low-grade tumors with positive
www.annalsplasticsurgery.com Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Annals of Plastic Surgery • Volume 74, Supplement 2, May 2015
Superficial MPNST Experience
TABLE 1. Comparison of Clinical Features of Deep (n = 29) and Superficial (n = 13) MPNSTs Treated at the Taipei Veterans General Hospital from October 1999 to February 2014*
Sex M F Age Symptom Size, cm Hx of NF-1 Hx of radiation Grade 1 2 3 Recurrence Metastasis Survival, mo Mean 5y
Deep MPNSTs (n = 29)
Superficial MPNSTs (n = 13)
14 (48.3) 15 (51.7) 33.9 ± 14.7 21 (72.4) 10.1 ± 6.2 9 (31.0) 3 (10.3)
8 (61.5) 5 (38.5) 62.7 ± 18.6 6 (42.6) 7.0 ± 2.6 3 (23.1) 0 (0)
4 (14.8) 9 (33.3) 14 (51.9) 14 (48.3) 11 (37.9)
1 (9.1) 9 (81.8) 1 (9.1) 4 (30.8) 3 (23.1)
54.0 ± 10.1 32.6%
129.4 ± 24.3 64.2%
P
0.426
Superficial or Cutaneous Malignant Peripheral Nerve Sheath Tumor—Clinical Experience at Taipei Veterans General Hospital Chin-Jung Feng, MD,*† Hsu Ma, MD, PhD,*† and Wen-Chieh Liao, MD*† Background: Primary malignant peripheral nerve sheath tumors (MPNSTs) with a cutaneous or subcutaneous origin represent a small subset of MPNSTs thought to be derived from cutaneous neurofibromas or small peripheral nerves. Few cases of superficial MPNSTs originating from the skin have been reported in the literature. Materials and Methods: From October 1999 to February 2014, 13 patients were diagnosed with superficial or cutaneous MPNSTs and received treatment at Taipei Veterans General Hospital. Clinical data were collected via retrospective chart review. A retrospective study was performed to compare superficial and deep-seated lesions in terms of local recurrence, distal metastasis, and survival analysis. The relevant literature is also briefly reviewed. Results: The most frequent initial symptoms were local swelling and pain. Ten tumors were found in the extremities, and 3 tumors were located on the trunk. All patients underwent surgery with curative intent. Four patients developed local recurrence, and 3 developed distant metastasis. Three of 13 patients died after a follow-up period of 11 to 180 months (mean, 53.4). Compared to deep-seated MPNSTs, superficial MPNSTs had a lower histopathological grading and better survival rate. Conclusions: Superficial MPNSTs are a rare variant of MPNST. The relatively frequent lack of associated neurofibromatosis and superficial location within the dermis and subcutis may result in this entity being overlooked. According to our clinical experience, superficial MPNSTs might have better prognosis, but similar recurrence and metastasis rates compared with deep-seated lesions. Hence, awareness of this entity should prompt its consideration in the differential diagnosis of cutaneous sarcomas. Key Words: malignant peripheral nerve sheath tumor, superficial, cutaneous, deep, neurofibromatosis type 1 (Ann Plast Surg 2015;74: S85–S88)
M
alignant peripheral nerve sheath tumor (MPNST) is a rare type of sarcoma that accounts for 5% to 10% of all soft tissue sarcomas. Malignant peripheral nerve sheath tumor is strongly associated with neurofibromatosis type 1 (NF-1 or von Recklinghausen disease), with about 25% to 50% of MPNST cases occurring in association with NF-1. Patients with NF-1 are at increased risk of developing MPNST. The incidence of MPNST is estimated to be 0.001% in the general population and approximately 3% to 4.6% in patients with NF-1.1,2 In some cases (10%), MPNST may also be related to previous radiation at that site.1 Malignant peripheral nerve sheath tumor is a malignant spindle cell tumor of the soft tissues thought to be derived from components of the nerve sheath, such as perineural fibroblasts or Schwann cells.1 Malignant peripheral nerve sheath tumor can develop in pre-existing neurofibromas and de novo from peripheral nerve sheaths. Malignant peripheral nerve sheath tumors are highly aggressive, with rapid Received September 12, 2014, and accepted for publication, after revision, December 17, 2014. From the *Division of Plastic Surgery, Taipei Veterans General Hospital, and †School of Medicine, National Yang Ming University, Taipei, Taiwan. Conflicts of interest and sources of funding: none declared. Reprints: Wen-Chieh Liao, MD, Division of Plastic Surgery, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Rd, Taipei 112, Taiwan. E-mail: [email protected]. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0148-7043/15/7402–S085 DOI: 10.1097/SAP.0000000000000465
Annals of Plastic Surgery • Volume 74, Supplement 2, May 2015
invasive growth and early hematogenous dissemination.1 Even after radical surgical treatment, MPNSTs have a dismal prognosis, with reported 5-year survival rates of less than 50%.3 Classically, MPNSTs arise in the deep soft tissue and have a propensity to occur in the proximal limbs and trunk. They typically affect the large nerves of the neck and proximal extremities (including the sciatic nerve, brachial plexus, and sacral plexus), as well as the retroperitoneum, mediastinum, and viscera. However, there have been a limited number of case reports and small series describing superficial or cutaneous MPNST.3–17 Superficial primary MPNSTs with a cutaneous or subcutaneous origin represent a small subset of MPNSTs thought to be derived from cutaneous neurofibromas or small peripheral nerves. Fewer than 30 cases of superficial MPNSTs originating from the skin have been reported in the literature.3 In contrast to classic MPNSTs of deep anatomic origin, which are mostly found on the extremities and trunk, more than half of cutaneous MPNSTs are located on the head and neck.12 Here, we describe the clinicopathological features of 13 cases of superficial MPNSTs arising in cutaneous or subcutaneous tissue at Taipei Veterans General Hospital. A retrospective study was performed to compare MPNSTs with deep-seated lesions in terms of local recurrence and distal metastasis rates and survival analysis. The relevant literature is also briefly reviewed.
MATERIALS AND METHODS We identified 13 cases of superficially located primary MPNSTs with a cutaneous or subcutaneous origin from the surgical pathology files at the Taipei Veterans General Hospital from October 1999 to February 2014. These cases were all diagnosed as superficial or cutaneous MPNSTs and received treatment at Taipei Veterans General Hospital. Superficial MPNST was defined as a lesion with its predominant and primary mass located in the dermis or subcutaneous tissue and not in contact with the fascia. All available diagnostic reports and medical records were reviewed retrospectively. Patient data including sex, age at diagnosis, first symptom, site and size of the tumor, associated history of NF-1 or radiation exposure, treatment, surgical margin, histopathological grading, adjuvant therapy, local recurrence, distal metastasis, and survival time were analyzed. The observed survival time was calculated from the date of diagnosis to death or last follow-up. The clinicopathological features of 13 cases of superficial MPNSTs were compared with those of deep-seated lesions (n = 29) treated at the same hospital in the same period. Statistical analysis was performed using SPSS software (Chicago, IL). Pearson chisquared test and independent t test were used to assess differences between these 2 groups. Survival analysis was based on the Kaplan-Meier method and log-rank test.
RESULTS Among the 13 patients with superficial MPNST, 8 were men, 5 were women, and no sex predominance was noted. The mean age at diagnosis was 62.7 ± 18.6 years (range, 32–82 years). The most common initial symptom was pain, reported by 6 patients (42.6%), but most were asymptomatic. The average tumor diameter was 7.0 ± 2.6 cm (range, 3– 10 cm). Three patients (23.1%) had a history of NF-1, and 1 case www.annalsplasticsurgery.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
S85
Annals of Plastic Surgery • Volume 74, Supplement 2, May 2015
Feng et al
developed in a patient with pre-existing neurofibroma (Fig. 1). No patients had a history of radiation exposure before diagnosis. Ten (76.9%) tumors were found in the extremities, and 3 (23.1%) tumors were located on the trunk. All patients underwent surgery with curative intent. Ten patients received adjuvant therapy (76.9%). According to the Fédération Nationale des Centres de Lutte Contre le Cancer grading, nine tumors (81.8%) were classified as grade 2. Four (30.8%) of 13 patients developed local recurrence, and 3 (23.1%) developed distant metastasis. Three
of 13 patients died after a mean follow-up time of 53.4 months (range, 11–180 months). The disease-free 5-year survival rate was 64.2%. Compared with the 29 cases of deep-seated MPNSTs (Table 1), the age at diagnosis of superficial MPNSTs was significantly older than that of deep-seated lesions (62.7 ± 18.6 vs 33.9 ± 14.7 years; P < 0.001). The histopathological grading of superficial MPNSTs was significantly lower than that of deep-seated lesions, the majority of which were grade 3 (P = 0.021). Although 76.9% of superficial MPNSTs were found in the extremities, 58.6% of deep-seated MPNSTs were located in the trunk (Fig. 2). However, the tumor size, associated history of NF-1 or radiation, local recurrence rate, and distal metastasis rate did not significantly differ between the 2 groups. In survival analysis, the disease-free 5-year survival rate of patients with deep-seated lesions (32.6%) tended to be worse than that of patients with superficial MPNSTs (64.2%, P = 0.055), although the difference was not significant (Fig. 3).
DISCUSSION
FIGURE 1. A, A 70-year-old woman initially presented with a recurrent neurofibroma, approximately 8 5 cm in size, over the upper back, with a solitary itching and painful reddish nodule. Tumor-wide excision with a safe margin of 3 cm (dashed line) was performed. B, Histopathological examination revealed sheets of neoplastic polygonal to spindle cells (histological score 3) with increased cellularity and cellular pleomorphic nuclei. Myxoid changes and neurofibroma-like low grade areas were also are noted. These findings were compatible with a malignant peripheral nerve sheath tumor. The surgical margin was clear (hematoxylin-eosin stain, original magnification 100). C, Postoperative 1 year follow-up showed unremarkable change. S86
Superficial or cutaneous MPNST is a rare entity. A review of 230 cutaneous malignant spindle cell lesions found that superficial MPNSTs account for approximately 2% of cases.5 By definition, superficial or cutaneous MPNSTs are predominantly located in the dermis or subcutis. They typically arise in association with a pre-existing neurofibroma or small cutaneous nerves. Evans et al17 reviewed 13 cases of superficial MPNSTs arising in sporadic superficial neurofibroma. One case in our series involved a superficial MPNST developed in a preexisting neurofibroma over the upper back with no associated history of NF-1 (Fig. 1). All cases in this study were diagnosed with superficial MPNST based on histopathological examination. The classical findings are histological spindle-shaped cells with hyperchromatic nuclei and numerous mitotic figures. Immunohistochemical studies demonstrating reactivity to S-100 protein also indicate tumor cells of nerve sheath origin. Although MPNSTs do not have specific imaging features, CT scans and MRI assessment are useful tools to detect their relationship with surrounding tissues. Clinically, MPNSTs are reported to undergo a prolonged period of slow growth, followed by rapid proliferation. In sporadic cases of superficial MPNST, there is no age predilection. Cases associated with NF typically occur in younger patients. Deep MPNSTs are strongly associated with NF-1, with approximately 50% of cases linked with the syndrome.3 This association appears to be less common in superficial MPNST, with 10 of 27 (37%) of reported cases associated with NF-1 in a previous study.3 Similarly, in our series, association with NF-1 was less common among superficial MPNSTs (23.1%) than in deepseated MPNSTs (31.0%). Tumors arising in the head and neck account for the majority (56%) of superficial MPNSTs, but a wide variety of sites have been reported.12 For superficial MPNSTs of the head and neck, the scalp seems to be a common site, with 11 reported cases to date.15 However, in our series, the extremities were the most common location of superficial MPNSTs. This discrepancy should be evaluated in future studies. Surgical excision remains the mainstay of treatment for MPNSTs because this malignancy demonstrates a limited response to both chemotherapy and radiotherapy. The International Consensus Group has recommended that the current management of MPNST should be identical to that of any other soft tissue tumors. The goal is to achieve complete surgical excision of the tumor with negative margins. Wide surgical excision (at least 3–5 cm) has been reported as paramount to local control: even amputation should be considered.18 Because of the limited number of cases in the literature, the safe surgical margins of superficial MPNSTs require further evaluation. Adjuvant radiotherapy should be considered for all intermediateand high-grade lesions as well as low-grade tumors with positive
www.annalsplasticsurgery.com Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Annals of Plastic Surgery • Volume 74, Supplement 2, May 2015
Superficial MPNST Experience
TABLE 1. Comparison of Clinical Features of Deep (n = 29) and Superficial (n = 13) MPNSTs Treated at the Taipei Veterans General Hospital from October 1999 to February 2014*
Sex M F Age Symptom Size, cm Hx of NF-1 Hx of radiation Grade 1 2 3 Recurrence Metastasis Survival, mo Mean 5y
Deep MPNSTs (n = 29)
Superficial MPNSTs (n = 13)
14 (48.3) 15 (51.7) 33.9 ± 14.7 21 (72.4) 10.1 ± 6.2 9 (31.0) 3 (10.3)
8 (61.5) 5 (38.5) 62.7 ± 18.6 6 (42.6) 7.0 ± 2.6 3 (23.1) 0 (0)
4 (14.8) 9 (33.3) 14 (51.9) 14 (48.3) 11 (37.9)
1 (9.1) 9 (81.8) 1 (9.1) 4 (30.8) 3 (23.1)
54.0 ± 10.1 32.6%
129.4 ± 24.3 64.2%
P
0.426
