Incidence and prognosis of distant metastasis in malignant peripheral nerve sheath tumors.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are a type of soft tissue sarcomas (STS) with recurrence and metastatic potential. We aimed to investigate the risk factors for developing distant metastases (DM) and to identify the prognostic factors in patients with DM. METHODS: Based on the Surveillance, Epidemiology, and End Result (SEER) database, MPNST patients diagnosed between 2010 and 2016 were extracted in our study. The logistic regression model was performed for predicting DM development while the Cox proportional hazard regression model was conducted for revealing the prognostic factors. RESULTS: Eventually, 764 patients diagnosed with MPNSTs were included with 109 cases presenting with metastases at initial diagnosis. Larger tumor size and lymph node metastases were independent risk factors for developing DM. The median overall survival (OS) for patients with metastases was 8.0 (95% CI: 6.1-9.9) months. Multiple metastatic sites and no surgical treatment were prognostic factors for worse survival. Tumors located in non-head and neck region were related with better survival. CONCLUSIONS: The incidence of DM was 14.3% with a dismal median OS of 8.0 months for metastatic MPNSTs. More evaluation should be applied for patients with large tumor size and lymph metastases. Tumors located in head and neck region and the presence of multiple metastases predicted worse survival outcome. Surgical treatment can significantly improve the survival of MPNST patients with distant metastasis.

Personal and Familial Malignancy History in Patients with Malignant Peripheral Nerve Sheath Tumors with a Focus on Sporadic Tumors.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) occur sporadically, in patients with neurofibromatosis 1, and in patients with prior radiation therapy. The incidence of unrelated prior malignancies and family history of malignancy in patients with MPNSTs has not been previously described. METHODS: A retrospective search for cases of MPNSTs at our institution for the years 1994-2019 was performed. The electronic medical record was reviewed for documentation of personal and family history of malignancies. RESULTS: The study included 331 patients. Of patients, 301 had documentation of their personal history of prior unrelated malignancies; 70 (23.3%) of these patients had a personal history of an unrelated previous malignancy. Of patients, 285 had information in the chart regarding family history of cancer; 210 (73.7%) of these patients had a family history of malignancy. Of patients, 145 had sporadic MPNSTs, 118 had neurofibromatosis 1-associated MPNSTs, 31 had radiation-induced MPNSTs, and 37 were missing this information. Among the sporadic cases, 29 had a personal history of an unrelated prior malignancy, and 10 developed an unrelated malignancy following diagnosis of MPNST. A family history of malignancy was present in 109 patients. There was a trend toward longer time to recurrence, time to metastasis, and overall survival in patients with sporadic MPNSTs and negative personal and family histories compared with patients with positive personal or family histories or both. CONCLUSIONS: Patients with sporadic MPNSTs had a high incidence of personal and family history of malignancy. The genetics associated with sporadic MPNSTs include RAS and p53 mutations, which are found in multiple oncologic processes and tumor-forming syndromes. This suggests an underlying genetic predisposition to formation of malignancies, including MPNSTs.

Incidence of second malignancies in individuals diagnosed with malignant peripheral nerve sheath tumors.

BACKGROUND: The incidence of malignant peripheral nerve sheath tumors (MPNSTs) is low in the general population, although individuals with Neurofibromatosis Type I (NF1) are particularly susceptible. These tumors generally have a high probability of metastasis. The rate and types of second malignancies (SMNs) after a primary diagnosis of MPNST are not well characterized. We aimed to quantify the rate of SMNs among individuals with a first primary MPNST using population-based data. METHODS: We estimated age-standardized incidence rates (SIRs) for SMNs among 1,579 primary MPNST cases between ages 0-85+ using SEER 18 (2000-2015). We estimated incidence rate ratios (IRRs) and 95% confidence intervals (95% CI) for SMNs in MPNST cases compared with general population rates. We conducted sex-stratified and age-restricted analyses (< 30 years at diagnosis). RESULTS: Seven percent (108/1579) of MPNST cases developed a SMN (SIR of 4635 cases/million). Compared to the general population, MPNST cases were more likely to develop SMNs (IRR: 29.3; 95% CI 23.8-34.8) and had a much higher rate of second MPNSTs (IRR: 15,992.9; 95% CI 9594.5-22,391.3). Aside from a second MPNST, second cancers were frequently diagnosed in the breast, lung, skin, and soft tissue in females and were myeloid and skin malignancies in males. When restricted to < 30 years of age, second MPNSTs were the most common cancers diagnosed. CONCLUSIONS: The rate of SMNs among MPNST cases is tremendously higher than that observed among individuals with other cancers, particularly for second MPNSTs. These findings suggest rates of SMNs may also be higher in NF1 individuals.

Nomograms for predicting the overall and cause-specific survival in patients with malignant peripheral nerve sheath tumor: a population-based study.

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is extremely rare in soft tissue sarcoma, with a high rate of recurrence and metastasis. Due to its rarity, the epidemiological features and prognostic factors are still uncertain. Moreover, nomograms for patients with MPNST have not been constructed and validated until now. PATIENTS AND METHODS: Patients diagnosed with MPNST between 1973 and 2014 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Survival analysis, machine learning and Lasso regression were used to identify the prognostic factors for overall survival (OS) and cause-specific survival (CSS). Significant prognostic factors were integrated to construct nomograms and then the nomograms were validated externally with a separate cohort from our own institution. RESULTS: A total of 689 patients were included in the training set and 42 patients in the validation set. Multivariate analysis suggested that age, histology, historic stage and chemotherapy were independent prognostic factors for OS and primary site, surgery, historic stage and chemotherapy for CSS. The nomograms based on multivariate models were developed and validated for predicting 3- and 5-year OS and CSS, with a C-index of 0.686 and 0.707, respectively. In the external validation set, the C-index was 0.700 for OS and 0.722 for CSS. CONCLUSION: ICD-O-3 histology, historic stage and chemotherapy were independent prognostic factors for OS and primary site, surgery, historic stage and chemotherapy for CSS. The constructed nomograms could provide individual prediction for MPNST patients and assist oncologists in making accurate survival evaluation.

Comments on the US National Toxicology Program technical reports on toxicology and carcinogenesis study in rats exposed to whole-body radiofrequency radiation at 900 MHz and in mice exposed to whole-body radiofrequency radiation at 1,900 MHz.

During the use of handheld mobile and cordless phones, the brain is the main target of radiofrequency (RF) radiation. An increased risk of developing glioma and acoustic neuroma has been found in human epidemiological studies. Primarily based on these findings, the International Agency for Research on Cancer (IARC) at the World Health Organization (WHO) classified in May, 2011 RF radiation at the frequency range of 30 kHz­300 GHz as a 'possible' human carcinogen, Group 2B. A carcinogenic potential for RF radiation in animal studies was already published in 1982. This has been confirmed over the years, more recently in the Ramazzini Institute rat study. An increased incidence of glioma in the brain and malignant schwannoma in the heart was found in the US National Toxicology Program (NTP) study on rats and mice. The NTP final report is to be published; however, the extended reports are published on the internet for evaluation and are reviewed herein in more detail in relation to human epidemiological studies. Thus, the main aim of this study was to compare earlier human epidemiological studies with NTP findings, including a short review of animal studies. We conclude that there is clear evidence that RF radiation is a human carcinogen, causing glioma and vestibular schwannoma (acoustic neuroma). There is some evidence of an increased risk of developing thyroid cancer, and clear evidence that RF radiation is a multi­site carcinogen. Based on the Preamble to the IARC Monographs, RF radiation should be classified as carcinogenic to humans, Group 1.

Epidemiological Analysis of Major Complications Requiring Medical Intervention in Patients with Neurofibromatosis 1.

Neurofibromatosis 1 has various complications. To elucidate the frequency of neurofibromatosis 1-related major complications requiring medical intervention, a nationwide retrospective study was conducted of 3,530 patients with neurofibromatosis 1 registered from 2001 to 2014 in Japan. The ratio of certified patients requiring medical intervention (>stage 3) was 82%. Patients classified in the most severe grade experienced dermatological complications (71.8% of patients), neurological complications (38.1%) and bone complications (33.3%). In patients with dermatological manifestations, medical treatment was needed for cutaneous neurofibromas (58%), diffuse plexiform neurofibromas (31%) and malignant peripheral nerve sheath tumours (10%). Patients with neurological manifestations needed medical treatment mainly for brain tumours (53%) and intellectual disability (26%). Patients with bone manifestations needed medical treatment for pseudoarthrosis (9%), scoliosis (55%) and bone defects (16%). It is necessary for physicians to be aware of neurofibromatosis 1-related complications requiring medical intervention in order to provide appropriate care for patients with neurofibromatosis 1.

Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis: Impact of Family History.

OBJECTIVE: The main objective of this study was to determine if family history of malignant peripheral nerve sheath tumor (MPNST) increases risk of developing an MPNST in patients with neurofibromatosis-1 (NF-1). MATERIALS AND METHODS: Individuals with NF-1 registered with the Children's Tumor Foundation's Neurofibromatosis Registry were emailed an anonymous 15-minute survey with regard to personal and family history of NF-1, MPNST, ages of onset, and symptomatology. Participation was voluntary and information was self-reported. RESULTS: The survey was sent to 4801 registrants, 878 responded. Presence of a family history of MPNST was found to be a risk factor for the development of MPNST; 19.4% of respondents confirming a family history of MPNST developed MPNST compared with 7.5% of respondents with no family history (odds ratio, 2.975; 95% confidence interval, 1.232-7.187; P=0.021). NF-1 patients with a positive family history developed MPNST at a younger age than those with no family history (8.3% vs. 0.5% P=0.003 and 13.9% vs. 2.4% P=0.003, for onset before 10 and 20, respectively). In the MPNST population with a known family history, onset prior to age 10 was significantly more prevalent (42.9% vs. 7% P=0.029). CONCLUSIONS: These results suggest a positive family history of MPNST represents a risk factor for the development and early onset of MPNST in individuals with NF-1.

Patterns of recurrence and survival in sporadic, neurofibromatosis Type 1-associated, and radiation-associated malignant peripheral nerve sheath tumors.

OBJECTIVE Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive group of soft tissue sarcomas that can arise sporadically, in the context of neurofibromatosis Type 1 (NF1) or at a site of prior irradiation. Large series profiling the features and outcomes of sporadic, NF1-associated, and radiation-associated MPNSTs are limited. The goal of this study was to elucidate differences between MPNST etiologies in a large single-institution retrospective study. METHODS Patients (n = 317) were identified through the tumor registry of The University of Texas MD Anderson Cancer Center. Clinicopathological features were retrospectively collected. Features were compared among MPNST subtypes for patients who had sufficient clinical history (n = 289), and clinicopathological features were used to identify adverse predictors of recurrence and survival outcomes. RESULTS Five-year local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and disease-specific survival (DSS) estimates were 56.6%, 49.6%, and 53.6%, respectively, for the high-grade MPNST cohort. Five-year DSS was lower in NF1-associated and radiation-associated MPNST than in sporadic MPNST (52%, 47%, and 67%, respectively, p = 0.140). Patients with radiation-associated MPNST had worse 5-year LRFS than those with the sporadic and NF1-associated subtypes (RT-associated vs sporadic, p = 0.010; RT-associated vs NF1-associated, p = 0.232). Truncally located tumors, positive surgical margins, local recurrence, and metastasis were predictors of adverse DSS in multivariate analysis. CONCLUSIONS Radiation-associated MPNSTs are associated with poorer local recurrence-free and disease-specific survival than sporadic and NF1-associated tumors. NF1-associated MPNSTs may have worse survival outcomes owing to large tumor size, compromising truncal location, and lower rate of negative resection margins compared with sporadic tumors.

Neurofibromatosis type 1 in a pediatric population: Ste-Justine's experience.

BACKGROUND: To date, few pediatric series of neurofibromatosis type 1 (NF-1) have been described in the literature even though it is the most frequently encountered phakomatosis. METHODS: We reviewed 987 charts of pediatric patients with a presumptive diagnosis of NF-1 who were evaluated at Ste-Justine hospital from January 1, 1991 to July 31, 2002. Patients who presented with two or more cardinal criteria were diagnosed with NF-1. Clinical and laboratory data were retrospectively collected, including: demographics, neuroimaging and presence or absence of associated symptoms or signs of NF-1. RESULTS: A total of 279 patients were diagnosed with NF-1. The mean age at diagnosis was 3.4 years. Ninety-nine percent of the patients had café au lait spots and 47% had a first degree relative with NF-1. Almost 60 percent (59.6%) of those seen by an ophthalmologist had Lisch nodules. Optic glioma was found in in 14.7%, cutaneous neurofibromas in 38.4%, plexiform neurofibromas in 24.7%, neurofibrosarcoma in 1.8%, learning disabilities in 39%, attention deficit disorder in 40.5%, osseous dysplasias in 7.2%, pseudoarthrosis in 3.6%, precocious puberty in 3.2% and short stature in 17.9%. Magnetic resonance, when performed, showed hyperintense T2 lesions in 87.1% of cases. The mean period of follow-up was 7.4 years. CONCLUSION: Neurofibromatosis type 1 is a multisystemic disorder associated with increased risk of malignancy. It can be diagnosed at a very young age and clinical follow-up is advised. To our knowledge, this is the largest single center study of NF-1 in a pediatric population.

Pediatric neurofibrosarcoma.

BACKGROUND/PURPOSE: Neurofibrosarcoma is rare in children, and the natural history and prognostic factors are not well described. The authors present a 57-year review of their experience. METHODS: The charts of children with neurofibrosarcoma were reviewed retrospectively. Statistical analysis was performed using the Chi2 and unpaired t tests. RESULTS: From 1944 to 2001, 38 patients under the age of 21 were diagnosed with neurofibrosarcoma. Twenty-two were boys. The average age at diagnosis was 13.8 years (range, 3 to 19.9 years). Nineteen patients (50%) had neurofibromatosis. The tumor site was as follows: extremity, 19 patients; trunk, 9 patients; head and neck, 7 patients; and retroperitoneum, 3 patients. The average tumor size was 10 cm. The margins after resection were as follows: grossly positive, 9; microscopically positive, 5; negative, 21; and unknown, 3. Patients with positive margins had a 22% survival rate, whereas those with negative or unknown margins had a 34% survival rate. Thirty-two patients achieved a complete response, 2 a partial response, and 4 progressed while on therapy. Twenty-six patients relapsed after a complete response (11 local, 10 distant, 5 both). Of the 15 patients with a distant relapse, 73% (11) relapsed in the lung. Twelve (32%) patients survived with an average follow-up of 14 years (range, 0.3 to 28 years). Nine patients were treated with chemotherapy, 9 with radiation, and 9 with both chemotherapy and radiation. Outcome was not significantly affected by gender, presence of neurofibromatosis, site, margin, or use of adjuvant therapy. CONCLUSION: Neurofibrosarcoma remains a rare disease in children with insufficient contemporary numbers to assess efficacy of therapy. Prognosis remains poor with a high incidence of relapse, particularly in the lungs, suggesting that more aggressive therapies to control both local and distant relapses are needed.

Intraspinal tumours in children--clinical presentation.

Intraspinal tumours in children are rare, the estimated average ratio of spinal to intracranial tumour in the paediatric population is 1:10. We reviewed our experience of paediatric spinal tumours over the period 1992-96. Nineteen patients presented during this time, 12 males and 7 females with the mean age of 7.8 years. The main presenting symptoms were pain, limb weakness, ataxia, sensory disturbance and spinal curvature abnormalities with a mean duration of 10 months. There was a wide variety of tumour types. All underwent a laminectomy with 8 having total tumour excision, 5 partial excision, and 6 had biopsies only. Five patients had extradural lesions and fourteen were intra-dural, four of which were extramedullary and six were intramedullary tumours. There were no major complications of surgery and only one patient had a CSF leak which was repaired. The average hospital stay was 15 days. Seven patients underwent radiotherapy and four had chemotherapy. Four patients are disease free and seven are symptom free after a mean follow-up of 2 years. Four patients died in this series with extensive diffuse tumours.