Survival after resection of malignant peripheral nerve sheath tumors: Introducing and validating a novel type-specific prognostic model.

Background: This study aimed to assess the performance of currently available risk calculators in a cohort of patients with malignant peripheral nerve sheath tumors (MPNST) and to create an MPNST-specific prognostic model including type-specific predictors for overall survival (OS). Methods: This is a retrospective multicenter cohort study of patients with MPNST from 11 secondary or tertiary centers in The Netherlands, Italy and the United States of America. All patients diagnosed with primary MPNST who underwent macroscopically complete surgical resection from 2000 to 2019 were included in this study. A multivariable Cox proportional hazard model for OS was estimated with prespecified predictors (age, grade, size, NF-1 status, triton status, depth, tumor location, and surgical margin). Model performance was assessed for the Sarculator and PERSARC calculators by examining discrimination (C-index) and calibration (calibration plots and observed-expected statistic; O/E-statistic). Internal-external cross-validation by different regions was performed to evaluate the generalizability of the model. Results: A total of 507 patients with primary MPNSTs were included from 11 centers in 7 regions. During follow-up (median 8.7 years), 211 patients died. The C-index was 0.60 (95% CI 0.53-0.67) for both Sarculator and PERSARC. The MPNST-specific model had a pooled C-index of 0.69 (95%CI 0.65-0.73) at validation, with adequate discrimination and calibration across regions. Conclusions: The MPNST-specific MONACO model can be used to predict 3-, 5-, and 10-year OS in patients with primary MPNST who underwent macroscopically complete surgical resection. Further validation may refine the model to inform patients and physicians on prognosis and support them in shared decision-making.

Preoperative Classification of Peripheral Nerve Sheath Tumors on MRI Using Radiomics.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue tumors prevalent in neurofibromatosis type 1 (NF1) patients, posing a significant risk of metastasis and recurrence. Current magnetic resonance imaging (MRI) imaging lacks decisiveness in distinguishing benign peripheral nerve sheath tumors (BPNSTs) and MPNSTs, necessitating invasive biopsies. This study aims to develop a radiomics model using quantitative imaging features and machine learning to distinguish MPNSTs from BPNSTs. Clinical data and MRIs from MPNST and BPNST patients (2000-2019) were collected at a tertiary sarcoma referral center. Lesions were manually and semi-automatically segmented on MRI scans, and radiomics features were extracted using the Workflow for Optimal Radiomics Classification (WORC) algorithm, employing automated machine learning. The evaluation was conducted using a 100× random-split cross-validation. A total of 35 MPNSTs and 74 BPNSTs were included. The T1-weighted (T1w) MRI radiomics model outperformed others with an area under the curve (AUC) of 0.71. The incorporation of additional MRI scans did not enhance performance. Combining T1w MRI with clinical features achieved an AUC of 0.74. Experienced radiologists achieved AUCs of 0.75 and 0.66, respectively. Radiomics based on T1w MRI scans and clinical features show some ability to distinguish MPNSTs from BPNSTs, potentially aiding in the management of these tumors.

Local recurrence in malignant peripheral nerve sheath tumours: multicentre cohort study.

BACKGROUND: Malignant peripheral nerve sheath tumours (MPNSTs) have high local recurrence (LR) rates. Literature varies on LR risk factors and treatment. This study aimed to elucidate treatment options and risk factors for first and second LRs (LR1 and LR2) in a large multicentre cohort. METHOD: Surgically treated primary MPNSTs between 1988 and 2019 in the MONACO multicentre cohort were included. Cox regression analysed LR1 and LR2 risk factors and overall survival (OS) after LR1. Treatment of LR1 and LR2 was evaluated. RESULTS: Among 507 patients, 28% developed LR1. Median follow-up was 66.9 months, and for survivors 111.1 months. Independent LR1 risk factors included high-grade tumours (HR 2.63; 95% c.i. 1.15 to 5.99), microscopically positive margins (HR 2.19; 95% c.i. 1.51 to 3.16) and large tumour size (HR 2.14; 95% c.i. 1.21 to 3.78). Perioperative radiotherapy (HR 0.62; 95% c.i. 0.43 to 0.89) reduced the risk. LR1 patients had poorer OS. Synchronous metastasis worsened OS (HR 1.79; 95% c.i. 1.02 to 3.14) post-LR1, while surgically treated LR was associated with better OS (HR 0.38; 95% c.i. 0.22 to 0.64) compared to non-surgical cases. Two-year survival after surgical treatment was 71% (95% c.i. 63 to 82%) versus 28% (95% c.i. 18 to 44%) for non-surgical LR1 patients. Most LR1 (75.4%) and LR2 (73.7%) patients received curative-intent treatment, often surgery alone (64.9% versus 47.4%). Radiotherapy combined with surgery was given to 11.3% of LR1 and 7.9% of LR2 patients. CONCLUSION: Large, high-grade MPNSTs with R1 resections are at higher LR1 risk, potentially reduced by radiotherapy. Surgically treated recurrences may provide improved survival in highly selected cases.

Patient-reported outcomes after free muscle flap coverage for therapy-resistant neuropathic pain from the ulnar nerve.

Extensive microsurgical neurolysis followed by free gracilis muscle flap coverage can be performed as a last resort for patients with persistent neuropathic pain of the ulnar nerve. All patients who had this surgery between 2015 and 2021 were identified. Data were collected from the medical records of 21 patients and patient-reported outcomes were collected from 18 patients, with a minimum follow-up of 12 months. The median visual analogue pain score decreased significantly 8 months postoperatively from 8.0 to 6.0 and stabilized to 5.4 at the 3-year follow-up. Health-related quality-of-life scores remained diminished compared to normative data. In the treatment of therapy-resistant neuropathic pain of the ulnar nerve, extensive neurolysis with a subsequent free gracilis muscle flap coverage shows a promising reduction of pain that persists at long-term follow-up.Level of evidence: IV.

Sonographic normal values for the cross-sectional area of the ulnar nerve: a systematic review and meta-analysis.

PURPOSE: Nerve size is a commonly used sonographic parameter when assessing suspected entrapment of the ulnar nerve. We aimed to create a robust set of normal values, based on a critical review of published normal values. METHODS: We performed a systematic evaluation of studies on normal ulnar nerve sizes, identified in PubMed, Embase, and Cochrane databases. Using meta-analyses, we determined pooled mean cross-sectional area (CSA) values for different anatomical locations of the ulnar nerve throughout the arm. Subgroup analyses were performed for gender, probe frequency, in- or exclusion of diabetic patients, position of the elbow and Asian versus other populations. RESULTS: We identified 90 studies of which 77 studies were included for further analyses after quality review, resulting in data from 5772 arms of 3472 participants. Subgroup analyses show lower CSA values at at the wrist crease and proximal to the wrist crease when using low frequency probes (< 15 MHz) and at the wrist crease, proximal to the wrist crease, proximal forearm and the distal upper arm in Asians. CSA values were lower when in flexed position compared to extended position for the cubital tunnel inlet only. No difference was found for gender. CONCLUSIONS: Our systematic review provides a comprehensive set of normal values at sites along the entire length of the ulnar nerve. This provides a foundation for clinical practise and upon which future studies could be more systematically compared.

Diagnostic value of 18F-FDG PET-CT in detecting malignant peripheral nerve sheath tumors among adult and pediatric neurofibromatosis type 1 patients.

PURPOSE: Detecting malignant peripheral nerve sheath tumors (MPNSTs) remains difficult. 18F-FDG PET-CT has been shown helpful, but ideal threshold values of semi-quantitative markers remain unclear, partially because of variation among scanners. Using EU-certified scanners diagnostic accuracy of ideal and commonly used 18F-FDG PET-CT thresholds were investigated and differences between adult and pediatric lesions were evaluated. METHODS: A retrospective cohort study was performed including patients from two hospitals with a clinical or radiological suspicion of MPNST between 2013 and 2019. Several markers were studied for ideal threshold values and differences among adults and children. A diagnostic algorithm was subsequently developed. RESULTS: Sixty patients were included (10 MPNSTs). Ideal threshold values were 5.8 for SUVmax (sensitivity 0.70, specificity 0.92), 5.0 for SUVpeak (sensitivity 0.70, specificity 0.97), 1.7 for TLmax (sensitivity 0.90, specificity 0.86), and 2.3 for TLmean (sensitivity 0.90, specificity 0.79). The standard TLmean threshold value of 2.0 yielded a sensitivity of 0.90 and specificity of 0.74, while the standard SUVmax threshold value of 3.5 yielded a sensitivity of 0.80 and specificity of 0.63. SUVmax and adjusted SUV for lean body mass (SUL) were lower in children, but tumor-to-liver ratios were similar in adult and pediatric lesions. Using TLmean > 2.0 or TLmean < 2.0 and SUVmax > 3.5, a sensitivity and specificity of 1.00 and 0.63 can be achieved. CONCLUSION: 18F-FDG PET-CT offers adequate accuracy to detect MPNSTs. SUV values in pediatric MPNSTs may be lower, but tumor-to-liver ratios are not. By combining TLmean and SUVmax values, a 100% sensitivity can be achieved with acceptable specificity.

Impact of Surgical Timing on Motor Level Lowering in Motor Complete Traumatic Spinal Cord Injury Patients.

Patients with complete traumatic spinal cord injury (tSCI) have a low potential to recover ambulation. Motor level recovery, adjacent to the level of injury, could influence functional independency. This study addresses whether surgical timing influences motor level recovery in patients with motor complete (American Spinal Injury Association [ASIA] Impairment Scale A [AIS A]) and motor incomplete (AIS B) tSCI. A retrospective cohort study was performed in the Netherlands in patients with AIS A/B tSCI (C2-L2), who consecutively underwent surgery between January 2010 and April 2020. Neurological examination was performed directly at presentation to the emergency room and at discharge from the rehabilitation facility. Motor level lowering, AIS grade, and upper and lower extremity motor score recovery were calculated for patients who underwent early (< 24 h) and late (24 h+) surgery. A total of 96 patients met the inclusion criteria. In the multi-variate analysis, late surgical decompression (24 h+) was negatively associated with ≥1 motor level lowering and ≥2 AIS grade improvement [odds ratio (OR) 0.11 [95% confidence interval (CI): 0.01, 0.67], p = 0.046, and OR 0.06 [95% CI: 0.00, 047], p = 0.030. respectively). The presence of sacral sparing (AIS B) at initial examination, and cervical level of the tSCI were associated with ≥1 motor level lowering. In addition, AO Spine C-type injuries were negatively associated with any type of neurological recovery, except motor level lowering. Although sensorimotor complete injuries as well as thoracolumbar injuries negatively influence neurological recovery, early surgical decompression (< 24 h) appears independently associated with enhanced neurological recovery in patients with traumatic spinal cord injury despite level and severity of injury.

Morbidity and Function Loss After Resection of Malignant Peripheral Nerve Sheath Tumors.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas. Their resection may lead to serious morbidity. Incidence of postoperative motor and sensory deficits is unknown, and reconstruction aimed at restoring such deficits is infrequently carried out. OBJECTIVE: To identify the incidence and risk factors of postoperative morbidity in MPNST as well as the use and outcomes of functional reconstructions in these patients. METHODS: Postoperative function and treatment of MPNSTs diagnosed from 1988 to 2019 in 10 cancer centers was obtained. Two models were constructed evaluating factors independently associated with postoperative motor (

The Association of Metastasis Pattern and Management of Metastatic Disease with Oncological Outcomes in Patients with Malignant Peripheral Nerve Sheath Tumors: A Multicenter Cohort Study.

PURPOSE: This multicenter cohort study aimed to identify clinicopathologic and treatment-related factors associated with the development of distant metastasis (DM) and with overall survival (OS) after DM diagnosis in patients with malignant peripheral nerve sheath tumors (MPNST). METHODS: All patients diagnosed with primary MPNST from 1988 to 2019 who were surgically treated for the primary tumor were included. Multivariable Cox regression analyses were performed to identify factors associated with DM and OS after DM diagnosis. RESULTS: A total of 383 patients were included in this analysis, of which 150 developed metastatic disease. No differences in clinicopathologic characteristics and clinical outcome were found between patients with synchronous and metachronous DM. Neurofibromatosis type 1 (NF1), high grade, tumor size, triton and R2 resections were independent risk factors for the development of DM. NF1 and more than two metastasis sites were independently associated with worse OS after DM diagnosis. Metastasectomy, chemotherapy and the metastatic site category 'other' were associated with prolonged survival after DM diagnosis. CONCLUSIONS: This analysis provides important insights into clinicopathologic and treatment factors associated with outcomes in metastatic MPNST. Moreover, NF1-status is associated with a higher risk of DM; it is also independently associated with worse survival in metastatic MPNST.

Prevalence of residual limb pain and symptomatic neuromas after lower extremity amputation: a systematic review and meta-analysis.

ABSTRACT: Residual limb pain (RLP) is associated with (partial) extremity amputations and is defined as pain felt in the remaining part of the amputated limb. A common cause of RLP is neuroma formation after nerve transections. Neuromas can be very painful and severely debilitating pathologies, preventing prosthetic use, reducing quality of life, and requiring medication. Residual limb pain and symptomatic neuromas are often not properly recognized by physicians explaining the varying prevalence in the literature. This systematic review and meta-analysis aim to provide a comprehensive overview of published literature on the prevalence of RLP and symptomatic neuroma after lower extremity amputation. Studies reporting the prevalence of RLP and symptomatic neuroma pain in patients who have had a lower extremity amputation published between 2000 and 2020 were identified in PubMed and Embase. Random-effects meta-analyses of proportions were performed to quantify the prevalence of RLP and symptomatic neuroma. Subgroups were identified and analysed. For RLP, the pooled prevalence was 59% (95% CI: 51-67). For symptomatic neuromas, the pooled prevalence was 15% (95% CI: 7-28). Residual limb pain subgroup analysis showed statistically significant higher prevalence in patients aged >50 years, follow-up >2 years, and in studies using a self-administered questionnaire for data collection. The prevalence of RLP and symptomatic neuroma in patients who have had a lower extremity amputation is 59% and 15%, respectively. Knowledge of their high prevalence may result in better awareness among physicians, in turn providing timely and adequate management.

A Bayesian approach for diagnostic accuracy of malignant peripheral nerve sheath tumors: a systematic review and meta-analysis.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) carry a dismal prognosis and require early detection and complete resection. However, MPNSTs are prone to sampling errors and biopsies or resections are cumbersome and possibly damaging in benign peripheral nerve sheath tumor (BPNST). This study aimed to systematically review and quantify the diagnostic accuracy of noninvasive tests for distinguishing MPNST from BPNST. METHODS: Studies on accuracy of MRI, FDG-PET (fluorodeoxyglucose positron emission tomography), and liquid biopsies were identified in PubMed and Embase from 2000 to 2019. Pooled accuracies were calculated using Bayesian bivariate meta-analyses. Individual level-patient data were analyzed for ideal maximum standardized uptake value (SUVmax) threshold on FDG-PET. RESULTS: Forty-three studies were selected for qualitative synthesis including data on 1875 patients and 2939 lesions. Thirty-five studies were included for meta-analyses. For MRI, the absence of target sign showed highest sensitivity (0.99, 95% CI: 0.94-1.00); ill-defined margins (0.94, 95% CI: 0.88-0.98); and perilesional edema (0.95, 95% CI: 0.83-1.00) showed highest specificity. For FDG-PET, SUVmax and tumor-to-liver ratio show similar accuracy; sensitivity 0.94, 95% CI: 0.91-0.97 and 0.93, 95% CI: 0.87-0.97, respectively, specificity 0.81, 95% CI: 0.76-0.87 and 0.79, 95% CI: 0.70-0.86, respectively. SUVmax ≥3.5 yielded the best accuracy with a sensitivity of 0.99 (95% CI: 0.93-1.00) and specificity of 0.75 (95% CI: 0.56-0.90). CONCLUSIONS: Biopsies may be omitted in the presence of a target sign and the absence of ill-defined margins or perilesional edema. Because of diverse radiological characteristics of MPNST, biopsies may still commonly be required. In neurofibromatosis type 1, FDG-PET scans may further reduce biopsies. Ideal SUVmax threshold is ≥3.5.

Eosinophilic Myocarditis: Is Endomyocardial Biopsy Essential for Diagnosis in the Era of Advanced Cardiac Imaging?

A 60-year-old female presented with dyspnea and chest pressure. Clinical presentation, laboratory data, echocardiography, and cardiac magnetic resonance (CMR) imaging findings confirmed diagnosis of eosinophilic myocarditis and obviated unnecessary invasive endomyocardial biopsy. She was treated with oral steroid and oral anticoagulation. Follow-up CMR imaging showed resolution of the left ventricle thrombus with improvement in endomyocardial inflammation.

Treatment of malignant peripheral nerve sheath tumors in pediatric NF1 disease.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are rare yet highly aggressive soft tissue sarcomas. Children with neurofibromatosis type 1 (NF1) have a 10% lifetime risk for development of MPNST. Prognosis remains poor and survival seems worse for NF1 patients. METHODS: This narrative review highlights current practices and pitfalls in the management of MPNST in pediatric NF1 patients. RESULTS: Preoperative diagnostics can be challenging, but PET scans have shown to be useful tools. More recently, functional MRI holds promise as well. Surgery remains the mainstay treatment for these patients, but careful planning is needed to minimize postoperative morbidity. Functional reconstructions can play a role in improving functional status. Radiotherapy can be administered to enhance local control in selected cases, but care should be taken to minimize radiation effects as well as reduce the risk of secondary malignancies. The exact role of chemotherapy has yet to be determined. Reports on the efficacy of chemotherapy vary as some report lower effects in NF1 populations. Promisingly, survival seems to ameliorate in the last few decades and response rates of chemotherapy may increase in NF1 populations when administering it as part of standard of care. However, in metastasized disease, response rates remain poor. New systemic therapies are therefore desperately warranted and multiple trials are currently investigating the role of drugs. Targeted drugs are nevertheless not yet included in first line treatment. CONCLUSION: Both research and clinical efforts benefit from multidisciplinary approaches with international collaborations in this rare malignancy.

Oncological Treatment Considerations Differ across Surgical Subspecialties Treating Malignant Peripheral Nerve Sheath Tumors: An International Survey.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are rare and aggressive soft tissue sarcomas (STS) that, because of their origin, are operated by several surgical subspecialties. This may cause differences in oncologic treatment recommendations based on presentation. This study investigated these differences both within and between subspecialties. METHODS: A survey was distributed among several (inter)national surgical societies. Differences within and between subspecialties were analyzed by χ 2-tests. RESULTS: In total, 30 surgical oncologists, 30 neurosurgeons, 85 plastic surgeons, and 29 "others" filled out the survey. Annual caseload, tumor sites operated, and fellowship training differed significantly between subspecialties. While most surgeons agreed upon preoperative use of MRI, the use of radiological staging and FDG-PET use differed between subspecialties. Surgical oncologists agreed upon core needle biopsies as an ideal type of biopsy while other subspecialties differed in opinion. On average, 53% of surgeons always consider preservation of function preoperatively, but 42% would never perform less extensive resections for function preservation. Respondents agreed that radiotherapy should be considered in tumor sizes >10 cm, microscopic, and macroscopic positive margins. A preferred sequence of radiotherapy administration differed between subspecialties. There was no consensus on indications and sequence of administration of chemotherapy in localized disease. CONCLUSION: Surgical oncologists generally agree on preoperative diagnostics; other subspecialties do not. Considering the preservation of function differed among all subspecialties. Surgeons do agree on some indications for radiotherapy, yet the use of chemotherapy in localized MPNSTs lacks consensus. A preferred sequence of multimodal therapy differs between and within surgical subspecialties, but surgical oncologists prefer neoadjuvant radiotherapy.

Neurological recovery after traumatic spinal cord injury: what is meaningful? A patients' and physicians' perspective.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: Most studies on neurological recovery after traumatic spinal cord injury (tSCI) assess treatment effects using the American Spinal Injury Association Impairment Scale (AIS grade) or motor points recovery. To what extent neurological recovery is considered clinically meaningful is unknown. This study investigated the perceived clinical benefit of various degrees of neurological recovery one year after C5 AIS-A tSCI. SETTING: The Netherlands. METHODS: By means of a web-based survey SCI patients and physicians evaluated the benefit of various scenarios of neurological recovery on a scale from 0 to 100% (0% no benefit to 100% major benefit). Recovery to AIS-C and D, was split into C/C+ and D/D+, which was defined by the lower and upper limit of recovery for each grade. RESULTS: A total of 79 patients and 77 physicians participated in the survey. Each AIS grade improvement from AIS-A was considered significant benefit (all p < 0.05), ranging from 47.8% (SD 26.1) for AIS-B to 86.8% (SD 24.3) for AIS-D+. Motor level lowering was also considered significant benefit (p < 0.05), ranging from 66.1% (SD 22.3) for C6 to 81.7% (SD 26.0) for C8. CONCLUSIONS: Meaningful recovery can be achieved without improving in AIS grade, since the recovery of functional motor levels appears to be as important as improving in AIS grade by both patients and physicians. Moreover, minor neurological improvements within AIS-C and D are also considered clinically meaningful. Future studies should incorporate more detailed neurological outcomes to prevent potential underestimation of neurological recovery by only using the AIS grade.

A systematic review of functional outcomes after nerve reconstruction in extremity soft tissue sarcomas: A need for general implementation in the armamentarium.

Resection of nerves in extremity soft tissue sarcomas (STS) can lead to large functional deficits. Nerve reconstructions are rarely performed and little is known on their outcomes and indications for their use, even though they are essential in restoring sensation in limb salvage procedures. This study investigated current knowledge on functional outcomes and considerations to be taken before performing such reconstructions after sarcoma resection. A systematic search was performed in July 2018 in PubMed and Embase databases according to PRISMA guidelines. Search terms related to "soft tissue sarcoma" and "nerve reconstruction" were used. Studies evaluating functional outcomes after nerve grafting or nerve transfers in extremity STS were included. Qualitative synthesis was performed on all studies. Nineteen studies were included after full-text screening, describing 26 patients. The majority of patients had a nerve reconstruction in the upper extremity (65%). Perioperative radiotherapy was administered in 67% and perioperative chemotherapy in 29% of patients. Nerve grafting was most commonly performed (n = 23) and nerve transfers were performed in six patients. A wide variety of outcome measures were used. Most patients recovered at least some motor function and sensation, but success rates were higher after upper than lower extremity defects. Multimodal treatment did not preclude successful reconstructions. Nerve reconstructions in extremity STS allow the restoration of sensation in limb salvation, even motor nerve function can be restored with satisfactory function. The use of multimodal therapy does not seem to interfere with success. Nerve reconstructions should therefore be considered in STS patients.

Neurofibromatosis-associated malignant peripheral nerve sheath tumors in children have a worse prognosis: A nationwide cohort study.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are rare and aggressive non-rhabdomyoblastic soft-tissue sarcomas (NRSTS) in children. This study set out to investigate clinical presentation, treatment modalities, and factors associated with survival in pediatric MPNST using Dutch nationwide databases. METHODS: Data were obtained from the Netherlands Cancer Registry (NCR) and the Dutch Pathology Database (PALGA) from 1989 to 2017. All primary MPNSTs were collected. Demographic differences were analyzed between adult and pediatric (age ≤18 years) MPNST. In children, demographic and treatment differences between neurofibromatosis type 1 (NF1) and non-NF1 were analyzed. A Cox proportional hazard model was constructed for localized pediatric MPNSTs. RESULTS: A total of 70/784 MPNST patients were children (37.1% NF1). Children did not present differently from adults. In NF1 children, tumor size was more commonly large (> 5 cm, 92.3% vs 59.1%). Localized disease was primarily resected in 90.6%, and radiotherapy was administered in 37.5%. Non-NF1 children tended to receive chemotherapy more commonly (39.5% vs 26.9%). Overall, estimated five-year survival rates of localized NF1-MPNST was 52.4% (SE: 10.1%) compared with 75.8% (SE: 7.1%) in non-NF1 patients. The multivariate model showed worse survival in NF1 patients (HR: 2.98; 95% CI, 1.17-7.60, P = 0.02) and increased survival in patients diagnosed after 2005 (HR: 0.20; 95% CI, 0.06-0.69, P = 0.01). No treatment factors were independently associated with survival. CONCLUSION: Pediatric MPNSTs have presentations similar to adult MPNSTs. In children, NF1 patients present with larger tumors, but are treated similarly to non-NF1 MPNSTs. In localized pediatric MPNST, NF1 is associated with worse survival. Promisingly, survival has increased for pediatric MPNSTs after 2005.

Prognostic Significance of Immunohistochemical Markers and Genetic Alterations in Malignant Peripheral Nerve Sheath Tumors: A Systematic Review.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas with dismal prognosis. Pathological and genetic markers may predict more aggressive behavior in MPNSTs but have uncommonly been investigated, and few are used in daily practice. This study reviews the prognostic value of immunohistochemical markers and genetic alterations in MPNST. METHODS: A systematic search was performed in PubMed and Embase databases according to the PRISMA guidelines. Search terms related to 'MPNST' and 'prognostic' were used. Studies investigating the association of immunohistochemical markers or genetic alterations with prognosis were included. Qualitative synthesis was performed on all studies. A distinction was made between univariable and multivariable associations. RESULTS: Forty-six studies were included after full-text screening. Sixty-seven different immunohistochemical markers were investigated. Absence of S100 and H3K27me3 and high Ki67 and p53 staining was most commonly independently associated with worse survival and disease-free survival. Several genetic alterations were investigated as well with varying association to survival. TP53, CDK4, RASSF1A alterations were independently associated with worse survival, as well as changes in chromosomal length in Xp, 10q, and 16p. CONCLUSIONS: MPNSTs harbor complex and heterogeneous biology. Immunohistochemical markers and genetic alterations have variable prognostic value. Absence of S100 and H3K27me3 and increased Ki67 can be of prognostic value. Alterations in TP53 or increase in p53 staining may distinguish MPNSTs with worse outcomes. Genetic alterations and staining of other cell cycle regulatory and Ras pathway proteins may also help stratifying patients with worse outcomes. A combination of markers can increase the prognostic value.

A nationwide cohort study on treatment and survival in patients with malignant peripheral nerve sheath tumours.

BACKGROUND: Despite curative intents of treatment in localized malignant peripheral nerve sheath tumours (MPNSTs), prognosis remains poor. This study investigated survival and prognostic factors for overall survival in non-retroperitoneal and retroperitoneal MPNSTs in the Netherlands. METHODS: Data were obtained from the Netherlands Cancer Registry and the Dutch Pathology Database. All primary MPNSTs were collected. Paediatric cases (age ≤18 years) and synchronous metastases were excluded from analyses. Separate Cox proportional hazard models were made for retroperitoneal and non-retroperitoneal MPNSTs. RESULTS: A total of 629 localized adult MPNSTs (35 retroperitoneal cases, 5.5%) were included for analysis. In surgically resected patients (88.1%), radiotherapy and chemotherapy were administered in 44.2% and 6.7%, respectively. In retroperitoneal cases, significantly less radiotherapy and more chemotherapy were applied. In non-retroperitoneal MPNSTs, older age (60+), presence of NF1, size >5 cm, and deep-seated tumours were independently associated with worse survival. In retroperitoneal MPNSTs, male sex and age of 60+ years were independently associated with worse survival. Survival of R1 and that of R0 resections were similar for any location, whereas R2 resections were associated with worse outcomes. Radiotherapy and chemotherapy administrations were not associated with survival. CONCLUSION: In localized MPNSTs, risk stratification for survival can be done using several patient- and tumour-specific characteristics. Resectability is the most important predictor for survival in MPNSTs. No difference is present between R1 and R0 resections in both retroperitoneal and non-retroperitoneal MPNSTs. The added value of radiotherapy and chemotherapy is unclear.

Treatment and survival differences across tumor sites in malignant peripheral nerve sheath tumors: a SEER database analysis and review of the literature.

BACKGROUND: Currently, literature is scarce on differences across all possible tumor sites in malignant peripheral nerve sheath tumors (MPNSTs). To determine differences in treatment and survival across tumor sites and assess possible predictors for survival, we used the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: MPNST cases were obtained from the SEER database. Tumor sites were recoded into: intracranial, spinal, head and neck (H&N), limbs, core (thorax/abdomen/pelvis), and unknown site of origin. Patient and tumor characteristics, treatment modalities, and survival were extracted. Overall survival (OS) was assessed using univariable and multivariable Cox regression hazard models. Kaplan-Meier survival curves were constructed per tumor site for OS and disease-specific survival (DSS). RESULTS: A total of 3267 MPNST patients were registered from 1973 to 2013; 167 intracranial (5.1%), 119 spinal (3.6%), 449 H&N (13.7%), 1022 limb (31.3%), 1307 core (40.0%), and 203 unknown (6.2%). The largest tumors were found in core sites (80.0 mm, interquartile range [IQR]: 60.0-115.0 mm) and the smallest were intracranial (37.4 mm, IQR: 17.3-43.5 mm). Intracranial tumors were least frequently resected (58.1%), whereas spinal tumors were most often resected (83.0%). Radiation was administered in 35.5% to 41.8%. Independent factors associated with decreased survival were: older age, male sex, black race, no surgery, partial resection, large tumor size, high tumor grade, H&N site, and core site (all P < .05). Intracranial and pediatric tumors show superior survival (both P < .05). Intracranial tumors show superior OS and DSS curves, whereas core tumors have the worst (P < .001). CONCLUSION: Superior survival is seen in intracranial and pediatric MPNSTs. Core and H&N tumors have a worse prognosis.