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Da Li and Jun-Ting Zhang

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Cheng-Bei Li, Lai-Rong Song, Da Li, Jian-Cong Weng, Li-Wei Zhang, Jun-Ting Zhang, and Zhen Wu

OBJECTIVE

The overall survival and pertinent adverse factors for primary intracranial malignant melanoma (PIMM) have not been previously determined. This aim of this study was to determine the rates of progression-free survival (PFS) and overall survival (OS) and identify the adverse factors for PIMM.

METHODS

This study included 15 cases from the authors’ own series and 100 cases with detailed clinical data that were obtained from the literature from 1914 to 2018 using the Ovid Medline, EMBASE, PubMed, Cochrane, and EBSCO databases. Patient demographics, treatment (surgery, chemotherapy, and radiotherapy [RT]), PFS, and OS were reviewed. Data from prior publications were processed and used according to PRISMA guidelines.

RESULTS

Diffuse lesions were identified in 24 (20.9%) patients, who had a younger age (p < 0.001). The mean follow-up time was 16.6 months, and 76 (66.1%) deaths occurred. The 6-month, 1-year, 3-year, and 5-year OS rates of the whole cohort were 62.8%, 49.9%, 28.9%, and 17.2%, respectively, with an estimated median survival time (EMST) of 12.0 months. The multivariate analysis revealed that gross-total resection (GTR) (HR 0.299, 95% CI 0.180–0.497, p < 0.001), radiotherapy (HR 0.577, 95% CI 0.359–0.929, p = 0.024), and chemotherapy (HR 0.420, 95% CI 0.240–0.735, p = 0.002) predicted a better OS. The EMST was 5.0 months in patients with diffuse-type PIMM and 13.0 months in patients with the solitary type. Patients receiving GTR with adjuvant RT and/or chemotherapy (GTR + [RT and/or chemo]) had significantly higher 1-year and 5-year OS rates (73.0% and 40.1%, respectively) and a longer EMST (53 months) than patients who underwent GTR alone (20.5 months) or RT and/or chemotherapy without GTR (13.0 months).

CONCLUSIONS

Optimal outcomes could be achieved by radical resection plus postoperative radiotherapy and/or chemotherapy. Patients with diffuse PIMM have a more severe clinical spectrum and poorer survival than patients with solitary PIMM. Immunotherapy and targeted therapy show promise as treatment options for PIMM based on results in patients with brain metastases from extracranial melanoma.

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Da Li, Shu-Yu Hao, Zhen Wu, Li-Wei Zhang, and Jun-Ting Zhang

Medulla oblongata teratomas are rare. The authors report 2 new cases of teratomas that occurred exclusively in the medulla oblongata. The first case was in a 9-year-old boy who presented with a 6-month history of neck pain and repeated paroxysmal vomiting. Based on preoperative radiographic findings, the initial diagnosis was of an intraaxial medulla oblongata hemangioblastoma. Intraoperatively, the cystic component of the tumor was gray, gelatinous, and soft in consistency. The solid component was light pink, rubbery, and nodular in appearance, with an identifiable boundary. The lesion was completely removed. Histopathological investigation revealed a mature teratoma. Postoperatively, the patient was supported with ventilator assistance and received a tracheotomy, but died of intracranial infection. The second case was in a 10-year-old boy with intermittent headache for 1 month. Radiographs revealed an exophytic cystic and solid lesion with dorsal involvement of the medulla oblongata. The lesion was predominantly solid, pinkish gray, tenacious, and moderately vascularized, with clearly delineated surgical dissection planes. The histopathological examination confirmed a diagnosis of immature teratoma. Total resection was achieved, followed by postoperative chemotherapy. He was alive without recurrence of the lesion or symptoms at 59 months after surgery.

Resection of medulla oblongata teratoma is challenging, with inherent surgical risks that are contingent on the tumor growth pattern. Teratomas should be considered in the differential diagnosis of brainstem lesions. Chemotherapy has been suggested for immature teratomas. Long-term follow-up and larger studies of teratomas in unusual locations are required to improve practitioners' understanding of this disease's treatment and outcomes.

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Da Li, Shu-Yu Hao, Gui-Jun Jia, Zhen Wu, Li-Wei Zhang, and Jun-Ting Zhang

Object

Cerebral cavernous malformations have been studied widely, but the natural history of brainstem cavernous malformations (CMs) is not well defined, and hemorrhages caused by brainstem CMs are devastating. The goal of this study was to quantify the hemorrhage risks and functional outcomes of patients with brainstem CMs.

Methods

This prospective, longitudinal, cohort study included patients with brainstem CMs diagnosed between 1985 and 2012. The clinical courses of all patients were recorded. Predictors of hemorrhage and the overall untreated outcomes were evaluated.

Results

A total of 331 patients (46.5% female) were included, with a mean follow-up duration of 6.5 years. The annual hemorrhage rates in patients initially presenting with hemorrhage with (n = 215) or without (n = 34) focal neurological deficits were 15.9% and 12.4%, respectively. However, the annual hemorrhage rate was 8.7% in patients initially presenting without hemorrhage (n = 82). The risk factors for hemorrhage were female sex (hazard ratio [HR] 1.445, p = 0.041), prior hemorrhage (HR 1.277, p = 0.029), and perilesional edema (HR 1.830, p = 0.002). Overall, neurological function at the most recent assessment was improved compared with neurological function at diagnosis. Additionally, 307 patients (92.7%) improved or stabilized, 268 (81.0%) lived independently, and 95 (28.7%) completely recovered. Predictors favoring complete recovery were no prospective hemorrhage (HR 1.958, p = 0.001), younger age (HR 1.268, p = 0.001), and small lesion size (HR 1.578, p = 0.004).

Conclusions

Patients' initial presentation predicts their prospective annual hemorrhage rate. This study suggests that several strong risk factors for hemorrhage and predictors of brainstem CM outcomes may enable clinicians to evaluate the potential hemorrhage risks of their patients and design personalized treatments.

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Jing-Jie Zheng, Gui-Jun Zhang, Xu-Lei Huo, Liang Wang, Shu-Yu Hao, Li-Wei Zhang, Zhen Wu, Yu-Mei Wu, Jun-Ting Zhang, and Da Li

OBJECTIVE

Primary intracranial rhabdomyosarcoma (PIRMS) is rare, and the effects of the treatment strategy on overall survival (OS) are unclear. This study aimed to evaluate risk factors pertinent to OS and to propose an optimal treatment strategy.

METHODS

Clinical data of patients with PIRMS treated at Beijing Tiantan Hospital and from the English-language literature between 1946 and 2018 were reviewed. A literature review was performed via Ovid, MEDLINE, Embase, PubMed, Web of Science, and Cochrane databases using the terms “rhabdomyosarcoma,” “intracranial,” “cerebral,” and “brain.” Previously published data were processed and used according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

RESULTS

There were 8 males (66.7%) and 4 females with PIRMS at our institution, with a mean age of 24.3 years. Gross-total resection was achieved in 4 patients (33.3%), and adjuvant radiation and chemotherapy were administered in 5 (45.5%) and 3 (27.3%) patients, respectively. After a mean follow-up period of 13.7 months, all patients developed local-regional recurrence and died of the disease. Twenty-nine cases (14 female and 15 male) were reported in the literature with a median age of 9.0 years. After a mean follow-up duration of 18.6 months, 13 patients (44.8%) developed recurrences, 7 patients (24.1%) had extracranial metastasis, and 14 patients (48.3%) died. In the pooled cases, adjuvant radiation (hazard ratio [HR] 0.089, 95% confidence interval [CI] 0.027–0.288, p < 0.001) and age < 10 years (HR 0.227, 95% CI 0.077–0.666, p = 0.007) were independent predictors of good local-regional progression-free survival (LR-PFS). Adjuvant radiation therapy (HR 0.301, 95% CI 0.110–0.828, p = 0.020) and age < 10 years (HR 0.359, 95% CI 0.131–0.983, p = 0.046) were significant predictors for favorable OS in the multivariate model.

CONCLUSIONS

Due to the rarity of the disease, a poor outcome of PIRMS was demonstrated based on the pooled cohort. Use of radiation was associated with improved outcomes and should be considered to improve OS/LR-PFS. Further study is required to identify the optimal treatment regimen.

Systematic review no.: CRD42019121249 (crd.york.ac.uk/PROSPERO/)

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Jian-Cong Weng, Da Li, Liang Wang, Zhen Wu, Jun-Mei Wang, Gui-Lin Li, Wang Jia, Li-Wei Zhang, and Jun-Ting Zhang

OBJECTIVE

Intracranial giant cell tumors (GCTs) are extremely rare neoplasms with dismal survival and recurrence rates. The authors aimed to confirm independent adverse factors for progression-free survival (PFS) and to propose an optimal treatment algorithm.

METHODS

The authors reviewed the clinical data of 43 cases of intracranial GCTs in their series. They also reviewed 90 cases of previously reported GCTs in the English language between 1982 and 2017 using Ovid MEDLINE, Embase, PubMed, and Cochrane databases with keywords of “giant cell tumor” or “osteoclastoma” and “skull,” “skull base,” “temporal,” “frontal,” “sphenoid,” or “occipital.” These prior publication data were processed and used according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Aforementioned risk factors for the authors’ series and the pooled cases were evaluated in patients not lost to follow-up (m = 38 and n = 128, respectively).

RESULTS

The authors’ cohort included 28 males and 15 females with a mean age of 30.5 years. Gross-total resection (GTR) was achieved in 15 (34.9%) patients. Fifteen patients (39.5%) who did not undergo GTR received postoperative radiotherapy with a mean total dose of 54.7 ± 4.1 Gy. After a mean follow-up of 71.3 months, 12 (31.6%) patients experienced recurrence, and 4 (10.5%) died of disease. The actuarial 5-year PFS and overall survival (OS) were 68.6% and 90.0% in the authors’ cohort, respectively. A multivariate Cox regression analysis verified that partial resection (HR 7.909, 95% CI 2.296–27.247, p = 0.001), no radiotherapy (HR 0.114, 95% CI 0.023–0.568, p = 0.008), and Ki-67 ≥ 10% (HR 7.816, 95% CI 1.584–38.575, p = 0.012) were independent adverse factors for PFS. Among the 90 cases in the literature, GTR was achieved in 49 (54.4%) cases. Radiotherapy was administered to 33 (36.7%) patients with a mean total dose of 47.1 ± 5.6 Gy. After a mean follow-up of 31.5 months, recurrence and death occurred in 17 (18.9%) and 5 (5.6%) cases, respectively. Among the pooled cases, the 5-year PFS and OS were 69.6% and 89.2%, respectively. A multivariate model demonstrated that partial resection (HR 4.792, 95% CI 2.909–7.893, p < 0.001) and no radiotherapy (HR 0.165, 95% CI 0.065–0.423, p < 0.001) were independent adverse factors for poor PFS.

CONCLUSIONS

GTR and radiotherapy were independent favorable factors for PFS of intracranial GCTs. Based on these findings, GTR alone or GTR plus radiotherapy was advocated as an optimal treatment; otherwise, partial resection plus radiotherapy with a dose ≥ 45 Gy, if tolerable, was a secondary alternative. Lack of randomized data of the study was stressed, and future studies with larger cohorts are necessary to verify these findings.

Systematic review no.: CRD42018090878 (crd.york.ac.uk/PROSPERO/)

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Kai-Bing Tian, Jing-Jie Zheng, Jun-Peng Ma, Shu-Yu Hao, Liang Wang, Li-Wei Zhang, Zhen Wu, Jun-Ting Zhang, and Da Li

OBJECTIVE

The natural history of cerebral cavernous malformations (CMs) has been widely studied, but the clinical course of untreated thalamic CMs is largely unknown. Hemorrhage of these lesions can be devastating. The authors undertook this study to obtain a prospective hemorrhage rate and provide a better understanding of the prognosis of untreated thalamic CMs.

METHODS

This longitudinal cohort study included patients with thalamic CMs who were diagnosed between 2000 and 2015. Clinical data were recorded, radiological studies were extensively reviewed, and follow-up evaluations were performed.

RESULTS

A total of 121 patients were included in the study (56.2% female), with a mean follow-up duration of 3.6 years. The overall annual hemorrhage rate (subsequent to the initial presentation) was calculated to be 9.7% based on the occurrence of 42 hemorrhages over 433.1 patient-years. This rate was highest in patients (n = 87) who initially presented with hemorrhage and focal neurological deficits (FNDs) (14.1%) (χ2 = 15.358, p < 0.001), followed by patients (n = 19) with hemorrhage but without FND (4.5%) and patients (n = 15) without hemorrhage regardless of symptoms (1.2%). The initial patient presentations of hemorrhage with FND (hazard ratio [HR] 2.767, 95% CI 1.336–5.731, p = 0.006) and associated developmental venous anomaly (DVA) (HR 2.510, 95% CI 1.275–4.942, p = 0.008) were identified as independent hemorrhage risk factors. The annual hemorrhage rate was significantly higher in patients with hemorrhagic pres entation at diagnosis (11.7%, p = 0.004) or DVA (15.7%, p = 0.002). Compared with the modified Rankin Scale (mRS) score at diagnosis (mean 2.2), the final mRS score (mean 2.0) was improved in 37 patients (30.6%), stable in 59 patients (48.8%), and worse in 25 patients (20.7%). Lesion size (odds ratio [OR] per 0.1 cm increase 3.410, 95% CI 1.272–9.146, p = 0.015) and mRS score at diagnosis (OR per 1 point increase 3.548, 95% CI 1.815–6.937, p < 0.001) were independent adverse risk factors for poor neurological outcome (mRS score ≥ 2). Patients experiencing hemorrhage after the initial ictus (OR per 1 ictus increase 6.923, 95% CI 3.023–15.855, p < 0.001) had a greater chance of worsened neurological status.

CONCLUSIONS

This study verified the adverse predictors for hemorrhage and functional outcomes of thalamic CMs and demonstrated an overall annual symptomatic hemorrhage rate of 9.7% after the initial presentation. These findings and the mode of initial presentation are useful for clinicians and patients when selecting an appropriate treatment, although the tertiary referral bias of the series should be taken into account.

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Da Li, Shu-Yu Hao, Jie Tang, Xin-Ru Xiao, Gui-Jun Jia, Zhen Wu, Li-Wei Zhang, and Jun-Ting Zhang

Object

The goal of this study was to evaluate surgical outcomes of pediatric brainstem cavernous malformations (CMs) and identify the risk factors associated with postoperative full recovery and rebleeding.

Methods

The clinical charts and radiographs from a series of 52 pediatric patients (37 male and 15 female; mean age 12.2 years; range 1–17 years) who underwent surgery for brainstem CMs between 1996 and 2011 were reviewed. Follow-up evaluation measures were obtained retrospectively. Neurological function was evaluated using the modified Rankin Scale (mRS) score.

Results

The lesion locations among the 52 patients included the midbrain (n = 7, 13.5%), pons (n = 38, 73.1%), and medulla (n = 7, 13.5%). The mean duration of symptoms was 18.5 months, and the preoperative annual hemorrhage and rebleeding rates were 12.3% and 32.5% per patient-year, respectively. The mean lesion size was 2.1 cm. Gross-total resection without surgery-related death was achieved in 49 patients (94.2%). Immediate postoperative reduced neurological function was observed in 17 patients (32.7%). Surgical morbidities developed in 25 patients (48.1%) and remained in 11 patients (21.2%) after 7.9 years of follow-up. The mean mRS scores at admission, discharge after surgery, 3 and 6 months postsurgery, and recent evaluation were 2.0, 2.3, 2.0, 1.5, and 1.0, respectively. The postoperative mRS scores at 6 months (p < 0.001) and on recent evaluation (p < 0.001) were significantly lower than those at admission. Postoperative rebleeding occurred in 2 patients, and the postoperative annual rebleeding rate was 0.5% per patient-year. By the most recent evaluation, 10 patients (19.2%) had achieved full recovery and all patients were either improved (n = 32, 61.5%) or unchanged (n = 20, 38.5%). The adverse predictors for full recovery included age ≥ 12 years (HR 0.230, p = 0.021), ≥ 2 preoperative hemorrhages (HR 0.124, p = 0.048), and poor preoperative status (HR 0.197, p = 0.040). An HR < 1 predicted poor complete recoveries. The single risk factor predicting postoperative rebleeding was incomplete resection (χ2 = 4.340, p = 0.037).

Conclusions

Fair outcomes for pediatric brainstem CMs could be obtained through surgery, but only a few patients achieved full recovery. Thus, to minimize surgical morbidity, surgical planning must be tailored to individual patients in all cases in which an operation is warranted. Complete resection must be attempted to reduce the risk of postoperative rebleeding. The predictors associated with complete postoperative recovery were referential for determining treatment.

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Da Li, Ze-Yu Wu, Pan-Pan Liu, Jun-Peng Ma, Xu-Lei Huo, Liang Wang, Li-Wei Zhang, Zhen Wu, and Jun-Ting Zhang

OBJECTIVE

Given the paucity of data on the natural history of brainstem cavernous malformations (CMs), the authors aimed to evaluate the annual hemorrhage rate and hemorrhagic risk of brainstem CMs.

METHODS

Nine hundred seventy-nine patients diagnosed with brainstem CMs were referred to Beijing Tiantan Hospital from 2006 to 2015; 224 patients were excluded according to exclusion criteria, and 47 patients were lost to follow-up. Thus, this prospective observational cohort included 708 cases (324 females). All patients were registered, clinical data were recorded, and follow-up was completed.

RESULTS

Six hundred ninety (97.5%) of the 708 patients had a prior hemorrhage, 514 (72.6%) had hemorrhagic presentation, and developmental venous anomaly (DVA) was observed in 241 cases (34.0%). Two hundred thirty-seven prospective hemorrhages occurred in 175 patients (24.7%) during 3400.2 total patient-years, yielding a prospective annual hemorrhage rate of 7.0% (95% CI 6.2%–7.9%), which decreased to 4.7% after the 1st year. Multivariate Cox regression analysis after adjusting for sex and age identified hemorrhagic presentation (HR 1.574, p = 0.022), DVA (HR 1.678, p = 0.001), mRS score ≥ 2 on admission (HR 1.379, p = 0.044), lesion size > 1.5 cm (HR 1.458, p = 0.026), crossing the axial midpoint (HR 1.446, p = 0.029), and superficially seated location (HR 1.307, p = 0.025) as independent adverse factors for prospective hemorrhage, but history of prior hemorrhage was not significant. The annual hemorrhage rates were 8.3% and 4.3% in patients with and without hemorrhagic presentation, respectively; the rate was 9.9%, 6.0%, and 1.0% in patients with ≥ 2, only 1, and 0 prior hemorrhages, respectively; and the rate was 9.2% in patients with both hemorrhagic presentation and focal neurological deficit on admission.

CONCLUSIONS

The study reported an annual hemorrhage rate of 7.0% exclusively for brainstem CMs, which significantly increased if patients presented with both hemorrhagic presentation and focal neurological deficit (9.2%), or any other risk factor. Patients with a risk factor for hemorrhage needed close follow-up regardless of the number of prior hemorrhages. It should be noted that the referral bias in this study could have overestimated the annual hemorrhage rate. This study improved the understanding of the natural history of brainstem CMs, and the results are important for helping patients and physicians choose a suitable treatment option based on the risk factors and stratified annual rates.

Clinical trial registration no.: ChiCTR-POC-17011575 (http://www.chictr.org.cn/).