ABSTRACT
CONTEXT: Prognosis of metastatic pheochromocytoma/paraganglioma following 131-Iodine metaiodobenzylguanidine (MIBG) is incompletely characterized due to small samples and shorter follow-up in these rare, often indolent tumors. OBJECTIVE: To describe long-term survival, frequency, and prognostic impact of imaging, biochemical, and symptomatic response to 131-I MIBG. DESIGN: Retrospective chart and imaging review at a tertiary referral center. PATIENTS: Six hundred sixty-eight person-years of follow-up in 125 patients with metastatic pheochromocytoma/paraganglioma with progression through prior multimodal treatment. INTERVENTION: Median 18 800 MBq 131-I MIBG. MAIN OUTCOME MEASURES: Overall survival, Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) imaging response, symptomatic response per chart review, and biochemical response (20% change over 2 consecutive assays of catecholamines, vanillylmandelic acid, metanephrines, or chromogranin A). RESULTS: Median survival standard deviation [SD] from diagnosis was 11.5 years [2.4]; following metastasis, 6.5 years [0.8]; post treatment, 4.3 years [0.7]. Among 88 participants with follow-up imaging, 1% experienced complete response, 33% partial response, 53% stability, and 13% progression. Fifty-one percent showed subsequent progression, median progression-free survival [SD] of 2.0 years [0.6]. Stability/response vs progression at first imaging follow-up (3-6 months) predicted improved survival, 6.3 vs 2.4 years (P = 0.021). Fifty-nine percent of 54 patients demonstrated biochemical response. Fifty percent of these relapsed, with median time to laboratory progression [SD] of 2.8 years [0.7]. Biochemical response did not predict extended survival. Seventy-five percent of 83 patients reported improvement in pretreatment symptoms, consisting primarily of pain (42%), fatigue (27%), and hypertension (14%). Sixty-one percent of these patients experienced subsequent symptomatic progression at median [SD] 1.8 years [0.4]. Symptomatic response did not predict extended survival. CONCLUSIONS: Imaging, symptomatic, and laboratory response to multimodal treatment including high-dose 131-I MIBG were achieved on long-term follow-up in metastatic pheochromocytoma or paraganglioma. Imaging response at 3 to 6 months was prognostic.
Subject(s)
3-Iodobenzylguanidine/therapeutic use , Adrenal Gland Neoplasms/radiotherapy , Iodine Radioisotopes/therapeutic use , Paraganglioma/radiotherapy , Pheochromocytoma/radiotherapy , Radiopharmaceuticals/therapeutic use , Adrenal Gland Neoplasms/secondary , Adult , Disease Progression , Female , Follow-Up Studies , Humans , Male , Middle Aged , Paraganglioma/pathology , Pheochromocytoma/pathology , Prognosis , Retrospective Studies , Survival RateABSTRACT
This retrospective analysis identifies predictors of survival in a cohort of patients with meta-iodobenzylguanidine (MIBG)-positive stage IV pulmonary and gastroenteropancreatic neuroendocrine tumor (P/GEP-NET) treated with 131I-MIBG therapy, to inform treatment selection and posttreatment monitoring. Methods: Survival, symptoms, imaging, and biochemical response were extracted via chart review from 211 P/GEP-NET patients treated with 131I-MIBG between 1991 and 2014. For patients with CT follow-up (n = 125), imaging response was assessed by RECIST 1.1 if images were available (n = 76) or by chart review of the radiology report if images could not be reviewed (n = 49). Kaplan-Meier analysis and Cox multivariate regression estimated survival and progression-free survival benefits predicted by initial imaging, biochemical response, and symptomatic response. Results: All patients had stage IV disease at the time of treatment. Median survival was 29 mo from the time of treatment. Symptomatic response was seen in 71% of patients, with the median duration of symptomatic relief being 12 mo. Symptomatic response at the first follow-up predicted a survival benefit of 30 mo (P < 0.001). Biochemical response at the first clinical follow-up was seen in 34% of patients, with stability of laboratory values in 48%; response/stability versus progression extended survival by 40 mo (P < 0.03). Imaging response (20% of patients) or stability (60%) at the initial 3-mo follow-up imaging extended survival by 32 mo (P < 0.001). Additionally, multiple 131I-MIBG treatments were associated with 24 mo of additional survival (P < 0.05). Conclusion: Therapeutic 131I-MIBG for metastatic P/GEP-NETs appears to be an effective means of symptom palliation. Imaging, biochemical, and symptomatic follow-up help prognosticate expected survival after 131I-MIBG therapy. Multiple rounds of 131I-MIBG are associated with prolonged survival.
Subject(s)
3-Iodobenzylguanidine/metabolism , Intestinal Neoplasms/metabolism , Intestinal Neoplasms/radiotherapy , Iodine Radioisotopes/therapeutic use , Lung Neoplasms/metabolism , Lung Neoplasms/radiotherapy , Neuroendocrine Tumors/metabolism , Neuroendocrine Tumors/radiotherapy , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/radiotherapy , Radiopharmaceuticals/therapeutic use , Stomach Neoplasms/metabolism , Stomach Neoplasms/radiotherapy , Aged , Cohort Studies , Female , Humans , Intestinal Neoplasms/secondary , Kaplan-Meier Estimate , Lung Neoplasms/secondary , Male , Middle Aged , Neuroendocrine Tumors/secondary , Pancreatic Neoplasms/secondary , Progression-Free Survival , Proportional Hazards Models , Retrospective Studies , Stomach Neoplasms/secondaryABSTRACT
INTRODUCTION: Meningiomas of the anterior clinoid process are uncommon tumors, acknowledged by most experienced surgeons to be among the most challenging meningiomas to completely remove. In this article, we summarize our institutional experience removing these uncommon and challenging skull base meningiomas. METHODS: We analyzed the clinical outcomes of patients undergoing surgical removal of anterior at our institution over an 18-year period. We characterized the radiographic appearance of these tumors and related tumor features to symptoms and ability to obtain a gross total resection. We also analyzed visual outcomes in these patients, focusing on visual outcomes with and without optic canal unroofing. RESULTS: We identified 29 patients with anterior clinoid meningiomas who underwent surgical resection at our institution between 1991 and 2007. The median length of follow-up was 7.5 years (range: 2.0 to 18.6 years). Similar to others, we found gross total resection was seldom safely achievable in these patients. Despite this, only 1/20 of patients undergoing subtotal resection without immediate postoperative radiosurgery experienced tumor progression. The optic canal was unroofed in 18/29 patients in this series, while in 11/29 patients it was not. Notably, all five patients experiencing visual improvement underwent optic canal unroofing, while three of four patients experiencing visual worsening did not. CONCLUSIONS: These data provide some evidence suggesting that unroofing the optic canal in anterior clinoid meningiomas might improve visual outcomes in these patients.
ABSTRACT
Venous malformations (VMs) are congenital anomalies of the venous vasculature, but not all are evident at birth. The factors that lead to presentation later in life are not well understood. The objective of this retrospective cohort study of patients with VMs evaluated at the University of California at San Francisco Birthmarks and Vascular Anomalies Center from 2005 to 2009 was to investigate the clinical presentation of VMs and correlate these features with different types of tissues (e.g., skin, subcutis, intramuscular). Main outcomes included the age at which lesions were first noticed, tissue type involved, presenting signs and symptoms, aggravating factors, and morbidities. A total of 115 subjects was included. The mean age when VM was first noted was 6.7 ± 0.9 years. Tissue types involved included skin/subcutaneous (46%); intramuscular (40%); and bone, tendon, or joint (14%). Presenting signs/symptoms included soft tissue swelling (44%), discrete mass (34%), pain (33%), and skin discoloration (26%). When compared with VMs limited to the skin or subcutis, those restricted to the intramuscular compartment were less likely to present at birth (27% vs 53%, p < 0.05) but were more frequently painful (79% vs 60%, p < 0.05) and contained more phleboliths (28% vs 11%, p < 0.05), and were associated with more exercise limitation (35% vs 16%, p < 0.05). VMs differ in age of onset, clinical features, and complications based on differing tissues and sites of involvement, with isolated intramuscular involvement associated with later presentation and greater morbidity.
Subject(s)
Skin/blood supply , Vascular Malformations/epidemiology , Vascular Malformations/pathology , Veins/abnormalities , Adolescent , Adult , Age Distribution , Aged , Child , Child, Preschool , Disease Progression , Female , Humans , Infant , Male , Middle Aged , Morbidity , Muscle, Skeletal/blood supply , Muscle, Skeletal/pathology , Phlebitis/epidemiology , Phlebitis/pathology , Retrospective Studies , Skin/pathology , Subcutaneous Tissue/blood supply , Subcutaneous Tissue/pathology , Young AdultABSTRACT
OBJECT: Cushing and Eisenhardt were the first to describe sphenoid wing meningiomas in detail, categorizing globoid tumors into 3 groups: 1) medial; 2) middle; and 3) lateral. The authors review their experience with resection of sphenoid wing meningiomas at a single center, to examine whether this classification predicts clinical presentation and postsurgical outcome. METHODS: All patients undergoing resection of sphenoid wing meningioma at the authors' institution over a 9-year period were identified. Clinical data were compared from patients with tumors arising at different points along the sphenoid wing to determine if these tumors behaved differently in terms of symptoms, radiographic characteristics, and postsurgical outcome. RESULTS: A total of 56 patients underwent microsurgical resection for sphenoid wing meningioma during this period. The rates of optic canal invasion (medial 50% vs middle 5% vs lateral 0%; p<0.0001, chi-square test), supraclinoid internal carotid artery encasement (medial 32% vs middle 5% vs lateral 0%; p<0.01, chi-square test), and middle cerebral artery encasement (medial 45% vs middle 24% vs lateral 0%; p<0.01, chi-square test) were all highest with medial-third tumors. New or worsened neurological deficits occurred in 10 (19%) of 56 patients. Of all the imaging characteristics studied, only location of the tumor along the medial third of the sphenoid wing significantly predicted an increased rate of new or worsened neurological deficit (OR 2.7, p<0.05). CONCLUSIONS: The authors report outcomes in a large series of sphenoid wing meningiomas that were treated using modern surgical techniques.
Subject(s)
Meningeal Neoplasms/surgery , Meningioma/surgery , Microsurgery , Neurosurgical Procedures , Sphenoid Bone/surgery , Adult , Aged , Aged, 80 and over , Carotid Artery, Internal/surgery , Databases, Factual , Female , Humans , Male , Middle Aged , Middle Cerebral Artery/surgery , Postoperative Complications , Treatment OutcomeABSTRACT
Despite the relatively low-grade of most central neurocytomas (CN), evidence suggests the existence of an aggressive subset with a propensity for recurrence. Recent studies have found the MIB-1 labeling index to be a prognostic indicator in CN. Here we review our experience with CN to analyze the relationships between extent of resection, adjuvant therapy, tumor histology, and clinical outcomes based on aggressive histology, as defined by MIB-1 labeling. A retrospective review was performed on histologically proven CN surgically resected from 1993 to 2009 at the University of California at San Francisco. Recurrence rates were analyzed using the Kaplan-Meier method with respect to MIB-1 labeling and extent of resection. All MIB-1 labeling indices were analyzed. A total of 18 patients were identified with a mean age of 30 years (range 17-58 years) and median follow-up of 40 months (5-173 months). The treatments were: gross total resection (GTR) alone (17% of patients), subtotal resection (STR) alone (50% of patients), STR plus radiotherapy (XRT: external beam or stereotactic radiosurgery: 28% of patients), or STR plus chemotherapy (5% of patients). The extent of resection and a MIB-1 labeling index >4% was predictive of recurrence (p<0.01). In the 33% of the patients in whom the tumor recurred, all had STR with MIB-1 labeling >4% with median time to recurrence of 23.5 months. The 2-year and 4-year recurrence rates in patients with MIB-1 labeling >4% were 50% and 75% respectively. No patient with a MIB-1 labeling index <4% who received STR alone had a recurrence. Thus, in patients with CN who were treated with STR, histology demonstrating a MIB-1 labeling index >4% can be a clinically useful prognostic indicator and can help guide adjuvant treatment.
Subject(s)
Cerebral Ventricle Neoplasms/diagnosis , Ki-67 Antigen/metabolism , Neoplasm Recurrence, Local/diagnosis , Neurocytoma/diagnosis , Adolescent , Adult , Antineoplastic Agents/therapeutic use , Cerebral Ventricle Neoplasms/metabolism , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Magnetic Resonance Imaging , Male , Middle Aged , Morbidity , Neurocytoma/metabolism , Postoperative Complications/epidemiology , Radiotherapy/methods , Retrospective Studies , Young AdultABSTRACT
Esthesioneuroblastoma (EN) is a rare sinonasal tumor with varied aggressiveness and potential for intracranial invasion. EN is staged anatomically with radiographic evaluation using the Kadish staging system (stages A, B, and C) and histologically by using Hyam's criteria (grades 1-4). Here we show that despite radiographic evidence of aggressive features, the prognosis of patients with Kadish stage C EN is best predicted by tumor histology using Hyam's criteria. We retrospectively analyzed patients with EN with Kadish stage C who were evaluated and treated at our institution between 1995 and 2009. Clinical information was collected using patient medical records, imaging, and review of pathological specimens. Twenty patients with Kadish stage C EN were identified with mean age of 51 years (31-70 years) with a median follow-up of 41.4 months (1.3-175 months). Upon pathological review, 44.4% of patients had low-grade (1/2) and 55.6% had high-grade (3/4) histology. About 37.5% of patients with low-grade EN had undergone gross total resection (GTR) and the remaining 62.5% had GTR and adjuvant radiation, whereas 50% of patients with high-grade ER had undergone GTR, 20% had undergone GTR and adjuvant radiation, and 30% had been treated with a subtotal resection (STR) and adjuvant radiation. The 5-year and 10-year survival in patients with low-grade EN was 86% in comparison to 56% and 28% with high-grade EN, respectively. In patients with low-grade EN, the 2-year progression free survival (PFS) was 86% and the 5-year PFS was 65% in comparison to 73% and 49% in patients with high-grade EN, respectively. The patient's tumor histology (Hyam's criteria) appeared to be the best way of predicting the prognosis and for selecting patients for adjuvant radiotherapy.
Subject(s)
Esthesioneuroblastoma, Olfactory/diagnosis , Nasal Cavity/pathology , Nose Neoplasms/diagnosis , Adult , Aged , Esthesioneuroblastoma, Olfactory/epidemiology , Esthesioneuroblastoma, Olfactory/surgery , Female , Follow-Up Studies , Humans , Male , Middle Aged , Nasal Cavity/surgery , Neoplasm Staging/trends , Nose Neoplasms/epidemiology , Nose Neoplasms/surgery , Prognosis , Retrospective StudiesABSTRACT
We retrospectively reviewed the records of 153 patients with breast cancer undergoing serial abdominal computed tomography (CT). During a median follow-up of 40 months, 2 (1.4%) of 153 patients developed bilateral hydronephrosis in the absence of radiologically visible obstructing pathology. Surgery confirmed malignant infiltration of the ureters by metastatic lobular carcinoma in both patients, suggesting that new unexplained bilateral hydronephrosis on serial CT in patients with breast cancer is likely to reflect infiltrative retroperitoneal involvement of the ureters by metastatic lobular carcinoma.
Subject(s)
Breast Neoplasms/pathology , Carcinoma, Lobular/secondary , Hydronephrosis/diagnostic imaging , Hydronephrosis/etiology , Radiographic Image Interpretation, Computer-Assisted , Retroperitoneal Neoplasms/secondary , Adult , Age Distribution , Aged , Aged, 80 and over , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Carcinoma, Lobular/mortality , Carcinoma, Lobular/therapy , Databases, Factual , Female , Humans , Hydronephrosis/epidemiology , Incidence , Longitudinal Studies , Middle Aged , Prognosis , Retroperitoneal Neoplasms/diagnostic imaging , Retroperitoneal Neoplasms/mortality , Retrospective Studies , Risk Assessment , Survival Analysis , Tomography, X-Ray Computed/methodsABSTRACT
Sphenoid wing meningiomas (SWMs) typically are histologically benign, insidious lesions, but the propensity of these tumors for local invasion makes disease control very challenging. In this review, we assess whether the degree of resection and extent of cavernous sinus invasion affects morbidity, mortality, and recurrence in patients with SWM. A comprehensive search of the English-language literature was performed. Patients were stratified according to extent of resection and extent of cavernous sinus invasion, and tumor recurrence rate, morbidity, and mortality were analyzed. A total of 23 studies and 131 patients were included. Overall recurrence and surgical mortality rate were 11% and 2%, respectively (average follow-up = 65 months). Cranial nerve III palsy was significantly associated with incompletely versus completely resected SWMs (7 to 0%) as well as meningiomas with cavernous sinus invasion versus no sinus invasion (14 vs. 0%). No significant difference in tumor recurrence rate was noted between these groups. In conclusion, complete excision of SWMs is always recommended whenever possible, but surgeons should acknowledge that there is nonetheless a chance of recurrence and should weigh this against the risk of causing cranial nerve injuries.
ABSTRACT
BACKGROUND: For this report, the authors comprehensively summarized the existing literature on patients with pineoblastoma and identified the variables and treatments that had an impact patient on outcomes. METHODS: A comprehensive search identified 109 studies that collectively described the outcomes of patients with pineoblastoma. Individual patient data were classified based on treatment and were subjected to univariate comparisons. Cox regression analysis included comparisons of survival outcomes controlling for age, extent of resection, and treatment group, and between-group survival comparisons were performed using the Kendall tau (rank correlation) statistic. RESULTS: Two hundred ninety-nine patients met inclusion criteria. The overall survival rate was 54% (175 of 299 patients) at a mean follow-up of 31 ± 1.9 months (range, 1-159 months). The analyses demonstrated a markedly worse prognosis for children aged ≤ 5 years compared with older patients (5-year survival rate: 15% for children aged ≤ 5 years vs 57% for children aged ≥ 5 years; log-rank P < .00001). In addition, a graded increase in survival was observed with increasing degrees of resection (5-year survival rate: 84% for patients who underwent gross total resection vs 53% for patients who underwent subtotal resection vs 29% for patients who underwent debulking; log-rank P < .0001). Multivariate analysis indicated that not achieving gross total resection markedly worsened patient survival (subtotal resection: hazard ratio, 6.47; 95% confidence interval, 2.3-19; P = .001. debulking: hazard ratio, 9.27; 95% confidence interval, 3.2-27; P < .0001). CONCLUSIONS: The current findings emphasize the importance of aggressive surgical resection in the treatment of pineoblastoma. In addition, the authors conclude that clinical trials should not mix young patients with older patients or patients who undergo subtotal resection with patients who undergo gross total resection, because such heterogeneity may alter the variability of responses to treatment and reduce the likelihood of success.
Subject(s)
Brain Neoplasms/diagnosis , Pinealoma/mortality , Adult , Brain Neoplasms/surgery , Chemotherapy, Adjuvant , Child , Child, Preschool , Combined Modality Therapy , Female , Humans , Male , Pinealoma/diagnosis , Pinealoma/surgery , Pinealoma/therapy , Prognosis , Radiotherapy, Adjuvant , Survival Analysis , Treatment OutcomeABSTRACT
OBJECT: The literature, at present, provides limited information about extraventricular neurocytomas (EVNs) and is almost exclusively composed of case reports or small case series. Treatment for EVNs has largely been guided by results from central neurocytoma outcome studies. The authors present an analysis of all reported intracranial EVN cases to establish if tumor histopathological features can substratify EVN into groups with differing prognosis and help guide treatment decisions. METHODS: The authors identified studies reporting histology, treatment modality, and outcomes for patients with intracranial EVN. The rates of recurrence and survival for patients were compared using Kaplan-Meier analysis. Atypical tumors, defined by MIB-1 labeling index exceeding 3% or atypical histological features, were compared with typical tumors, and patients 50 years of age or older were compared with those younger than 50 years of age. RESULTS: Eighty-five patients met the inclusion criteria, and 27% of them had an atypical histology. Typical EVNs had a better prognosis than atypical EVNs after primary treatment, with a 5-year recurrence rate of 36% compared with 68% (p < 0.001), and a 5-year mortality rate of 4% compared with 44%, respectively (p < 0.001). Age younger 50 years was associated with a better prognosis than age equal to or greater than 50 years, with a 5-year recurrence rate of 33% and 74%, respectively (p < 0.001), and a 5-year mortality rate of 4% and 52%, respectively (p < 0.001). Multivariate analysis demonstrated that atypical EVNs carried significantly increased risk for recurrence (hazard ratio [HR] 4.91, p < 0.001) and death (HR 22.91, p < 0.01). Gross-total resection was superior to subtotal resection (STR) alone in tumor control rates for typical EVNs (95% and 68%, p < 0.05), and there was a trend for adjuvant external-beam radiotherapy to benefit STR. There was suggestion of similar trends in patients with atypical EVNs. CONCLUSIONS: There are at least 2 distinct histological subtypes of EVN, with different prognostic significances. Atypia or MIB-1 labeling index greater than 3% is a significant predictor of poor prognosis for EVNs. Complete resection or more aggressive attempts at providing adjuvant therapy following STR appear to improve the prognosis for patients with EVNs. Although the authors' results are informative, there are limitations to their analysis. Given the relatively modest total number of cases reported, as well as the nature of the disaggregated analysis, the authors were not able to use formal meta-analytical methods to limit the impact of between center heterogeneity. Additionally, they were not able to control for individual differences in data analysis and presentation across the different studies included in their analysis.
Subject(s)
Brain Neoplasms/mortality , Brain Neoplasms/therapy , Neurocytoma/mortality , Neurocytoma/therapy , Adolescent , Adult , Aged , Brain Neoplasms/pathology , Child , Child, Preschool , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neurocytoma/pathology , Predictive Value of Tests , Prognosis , Recurrence , Young AdultABSTRACT
We retrospectively reviewed 24 patients with cerebellopontine angle (CPA) meningioma from our institution to describe the clinical and surgical significance of extensions into the internal auditory canal (IAC). Of these patients, 62% had invasion of the IAC, which was associated with high rates of unilateral hearing loss at presentation (67% versus [vs.] 22%, p<0.05). A retrosigmoid approach was used in 22/24 patients, of whom 13 had an IAC extension. In five patients, IAC drilling was needed to achieve a more complete resection and 20 patients of the 22 (91%) had improved or stable hearing postoperatively, and one patient had permanent facial paralysis. Cranial nerve IX and X were the most common complications (17% and 33% respectively), and were almost exclusively associated with resection of tumor extensions into the jugular foramen (p<0.01). We conclude that CPA meningiomas can be removed with excellent rates of hearing and facial nerve preservation. Caution must be used when attempting to resect tumor extensions into the jugular foramen given the high rates of lower CN complications.
Subject(s)
Cerebellopontine Angle/pathology , Meningeal Neoplasms/pathology , Meningeal Neoplasms/surgery , Meningioma/pathology , Meningioma/surgery , Neurosurgical Procedures/methods , Adult , Aged , Female , Follow-Up Studies , Hearing/physiology , Humans , Magnetic Resonance Imaging , Male , Meningioma/physiopathology , Middle Aged , Neoplasm Invasiveness , Postoperative Complications , Retrospective Studies , Young AdultABSTRACT
Astroblastoma is a rare tumor, and thus experience with these lesions is very limited. The prognosis and appropriate treatment is not well understood, as few individual centers have enough experience with astroblastoma to guide treatment recommendations. We performed a systematic comprehensive search of the published English language literature on patients undergoing surgery for astroblastoma to summarize what is known about these tumors, and to provide some framework for future efforts in this area. A total of 62 references met our inclusion criteria, and contained individual patient data on 116 patients with astroblastoma. Determination of overall survival rates was performed using Kaplan-Meier analysis. This analysis suggests that the distribution is bimodal, with a prominent peak in young adulthood. Astroblastomas are generally amenable to complete tumor resection, even when very large, with gross total resection (GTR) achieved in 71/85 (84%) of reported patients, including both 9cm tumors reported. Patients undergoing GTR experienced a significant improvement in survival compared to patients who underwent subtotal resection (STR) (5-year progression-free survival: GTR 83% versus [vs.] STR 55%, log rank p=0.011). Although patients receiving external beam radiotherapy or fractionated three-dimensional conformal radiotherapy (XRT) seemed to have lower survival rates, this was not statistically significant (5-year survival: GTR 94% vs. GTR+XRT 73%, log rank p=0.463). Thus, we have reported the results of a summary of the literature on astroblastomas and have accurately described outcome characteristics using a data set that would be difficult to accumulate at a single center treating this tumor.
Subject(s)
Neoplasms, Neuroepithelial/mortality , Neoplasms, Neuroepithelial/surgery , Databases, Factual/statistics & numerical data , Disease-Free Survival , Humans , Kaplan-Meier Estimate , Neurosurgical Procedures/methods , Prognosis , Radiotherapy, Adjuvant , Treatment OutcomeABSTRACT
Epidermal growth factor (EGF) module-containing mucin-like receptor 2 (EMR2) is a member of the seven span transmembrane (TM7) adhesion G-protein coupled receptor subclass. It is abundantly expressed in immune cells of myeloid origin and appears to mediate cellular adhesion, migration, and signaling. Based on an analysis showing earlier mortality among glioblastoma patients whose tumors highly express EMR2, we studied its expression patterns in glioblastoma and potential to mediate cellular proliferation and invasion. We performed univariate analysis of overall survival in GBM patients expressing low, moderate, and high amounts of EMR2 based on publicly available microarray data in the Cancer Genome Atlas (TCGA). Using RT-PCR and western blotting, we studied mRNA and protein expression patterns of EMR2, respectively. We then employed siRNA knockdown of EMR2 in two human glioblastoma cell lines expressing high levels of EMR2 to assess functional effects on cellular proliferation and invasion, in vitro. Kaplan-Meier analysis of TCGA survival data for GBM demonstrated that EMR2 levels are inversely correlated with overall time until mortality (log rank, P < 0.01). EMR2 mRNA and protein is variably expressed in primary glioblastoma samples and human glioblastoma cell lines. When comparing cells transfected with siRNA targeting EMR2 to those transfected with a negative, scramble control, there was no difference in proliferation over 72 h in the SF767 and G55 glioblastoma cell lines. However, EMR2 knockout cells demonstrated an almost 3-fold reduction in migration compared to their negative controls (P < 0.05) in the SF767 cell line, and an almost 2-fold reduction (P < 0.05) in migration in the G55 cell line. We provide evidence that EMR2 is expressed in glioblastoma and has significant functional consequences on cellular invasion, but not proliferation. In light of its ability to promote adhesion and migration in immune cells, our data suggest that EMR2 may mediate similar phenomena in glioblastoma. The invasive phenotype conferred by EMR2 correlates with clinical data demonstrating poor survival in glioblastoma patients who express high levels of EMR2 in their tumor.
Subject(s)
Brain Neoplasms/mortality , Brain Neoplasms/pathology , Cell Movement , Glioblastoma/mortality , Glioblastoma/pathology , Receptors, G-Protein-Coupled/metabolism , Blotting, Western , Brain Neoplasms/metabolism , Cell Adhesion , Cell Proliferation , Glioblastoma/metabolism , Humans , Neoplasm Invasiveness , Phenotype , Prognosis , RNA, Messenger/genetics , RNA, Small Interfering/genetics , Receptors, G-Protein-Coupled/antagonists & inhibitors , Receptors, G-Protein-Coupled/genetics , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, CulturedABSTRACT
BACKGROUND: Grade II and III meningiomas have higher rates of tumor recurrence than grade I meningiomas after surgery and/or external irradiation. As the utility of noninvasive treatments for brain tumors increases, it is becoming increasingly important to assess the likelihood that a tumor is not benign before treatment initiation. Hence, the authors have reviewed a large series of their patients to determine risk factors for higher-grade pathology, with particular interest paid to tumor location. METHODS: The authors reviewed 378 patients presenting at their institution from 2000 to 2007 with histologically confirmed meningioma, central pathology grading according to the World Health Organization 2000 guidelines, and tumor location confirmed with preoperative imaging. They performed univariate and multivariate logistic regression on potential risk factors for high-grade pathology. RESULTS: Risk factors for grade II/III pathology included nonskull base location (2-fold) and male sex (2-fold). Patients with prior surgery had a 3-fold increased incidence of higher-grade meningiomas at presentation at the authors' center. The authors controlled for this referral bias by performing a multivariate regression, and analysis without patients receiving prior treatment. Ninety-seven percent of operations were performed for tumor size and clinical symptoms, whereas <3% were performed for interval growth or features concerning higher-grade pathology. CONCLUSIONS: Nonskull-base meningiomas, male sex, and prior surgery impart increased risk for grade II or III pathology. This increased risk translates to probable poorer prognosis and increased likelihood of recurrence after treatment. Thus, it is prudent to take these specific variables into consideration in conjunction with the complete clinical presentation when advising patients regarding their prognosis.
Subject(s)
Meningeal Neoplasms/etiology , Meningioma/etiology , Neoplasm Recurrence, Local/etiology , Neoplasm Staging/methods , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Meningeal Neoplasms/diagnosis , Meningeal Neoplasms/epidemiology , Meningeal Neoplasms/pathology , Meningeal Neoplasms/surgery , Meningioma/diagnosis , Meningioma/epidemiology , Meningioma/pathology , Meningioma/surgery , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/surgery , Prognosis , Retrospective Studies , Risk Factors , Young AdultABSTRACT
OBJECT: With limited studies available, the correlation between the extent of resection and tumor recurrence in vestibular schwannomas (VSs) has not been definitively established. In this prospective study, the authors evaluated 772 patients who underwent microsurgical resection of VSs to analyze the association between total tumor resection and the tumor recurrence rate. METHODS: The authors selected all cases from a prospectively collected database of patients who underwent microsurgical resection as their initial treatment for a histopathologically confirmed VS. Recurrence-free survival was analyzed using Kaplan-Meier analysis. The authors studied the impact of possible confounders such as patient age and tumor size using stepwise Cox regression to calculate the proportional hazard ratio of recurrence while controlling for other cofounding variables. RESULTS: The authors analyzed data obtained in 571, 89, and 112 patients in whom gross-total, near-total, and subtotal resections, respectively, were performed. A gross-total resection was achieved in 74% of the patients, and the overall recurrence rate in these patients 8.8%. There was no significant relation between the extent of resection and the rate of tumor recurrence (p = 0.58). As expected, the extent of resection was highly correlated with patient age, tumor size, and surgical approach (p < 0.0001). Using Cox regression, the authors found that the approach used did not significantly affect tumor control when the extent of resection was controlled for. CONCLUSIONS: While complete tumor removal is ideal, the results presented here suggest that there is no significant relationship between the extent of resection and tumor recurrence.
Subject(s)
Microsurgery/methods , Neoplasm Recurrence, Local/etiology , Neoplasm, Residual/etiology , Neuroma, Acoustic/surgery , Postoperative Complications/etiology , Adult , Aged , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/surgery , Neoplasm, Residual/epidemiology , Outcome and Process Assessment, Health Care , Postoperative Complications/epidemiology , Postoperative Complications/surgery , Proportional Hazards Models , Reoperation , Retrospective Studies , Risk Assessment/statistics & numerical dataABSTRACT
BACKGROUND: Cystic vestibular schwannomas (VSs) are described as being more aggressive than solid tumors. OBJECTIVE: We examined 468 VS patients to evaluate whether the presence of cystic components in VSs may be an important feature for predicting postoperative outcome. METHODS: We selected all VS patients from a prospectively collected database (1984-2009) who underwent microsurgical resection for VS. Hearing data were analyzed using American Association of Otolaryngology-Head and Neck Surgery. Facial nerve dysfunction was analyzed using the House-Brackmann scale. We used univariate comparisons to determine the clinical impact of cystic changes on preoperative and postsurgical hearing and facial nerve preservation. RESULTS: We identified 58 patients (11%) with cystic changes and 410 patients with solid VSs. In this analysis, cystic VS patients tended to have larger tumors (78% of patients with >2.0 cm extrameatal extension) compared with the solid VS group, which consisted of many smaller and medium-sized tumors (P < .0001). Univariate analyses found that tumors with cystic changes did not lead to worse rates of preoperative hearing loss (χ(2), P = not significant) compared with solid VSs. Cystic changes conferred worse postoperative hearing in patients with medium-sized tumors (P = .035). Cystic changes also did not significantly affect facial nerve outcomes (χ(2), P = not significant). CONCLUSION: Cystic tumors tend to be larger than noncystic tumors and affect outcomes by reducing the rate at which hearing preservation is attempted and by worsening hearing outcome in medium-sized tumors. Further, peripheral cysts cause lower rates of hearing preservation compared with centrally located cysts.
Subject(s)
Central Nervous System Cysts/pathology , Central Nervous System Cysts/surgery , Microsurgery/methods , Neuroma, Acoustic/pathology , Neuroma, Acoustic/surgery , Postoperative Complications/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Central Nervous System Cysts/complications , Databases, Factual , Female , Follow-Up Studies , Humans , Male , Middle Aged , Monitoring, Intraoperative/methods , Neuroma, Acoustic/complications , Postoperative Complications/etiology , Prospective Studies , Treatment Outcome , Young AdultABSTRACT
OBJECT: Because of the rarity of glomus jugulare tumors, a variety of treatment paradigms are currently used. There is no consensus regarding the optimal management to control tumor burden while minimizing treatment-related morbidity. In this study, the authors assessed data collected from 869 patients with glomus jugulare tumors from the published literature to identify treatment variables that impacted clinical outcomes and tumor control rates. METHODS: A comprehensive search of the English-language literature identified 109 studies that collectively described outcomes for patients with glomus jugulare tumors. Univariate comparisons of demographic information between treatment cohorts were performed to detect differences in the sex distribution, age, and Fisch class of tumors among various treatment modalities. Meta-analyses were performed on calculated rates of recurrence and cranial neuropathy after subtotal resection (STR), gross-total resection (GTR), STR with adjuvant postoperative radiosurgery (STR+SRS), and stereotactic radiosurgery alone (SRS). RESULTS: The authors identified 869 patients who met their inclusion criteria. In these studies, the length of follow-up ranged from 6 to 256 months. Patients treated with STR were observed for 72 ± 7.9 months and had a tumor control rate of 69% (95% CI 57%-82%). Those who underwent GTR had a follow-up of 88 ± 5.0 months and a tumor control rate of 86% (95% CI 81%-91%). Those treated with STR+SRS were observed for 96 ± 4.4 months and had a tumor control rate of 71% (95% CI 53%-83%). Patients undergoing SRS alone had a follow-up of 71 ± 4.9 months and a tumor control rate of 95% (95% CI 92%-99%). The authors' analysis found that patients undergoing SRS had the lowest rates of recurrence of these 4 cohorts, and therefore, these patients experienced the most favorable rates of tumor control (p < 0.01). Patients who underwent GTR sustained worse rates of cranial nerve (CN) deficits with regard to CNs IX-XI than those who underwent SRS alone; however, the rates of CN XII deficits were comparable. CONCLUSIONS: The authors' analysis is limited by the quality and accuracy of these studies and may reflect source study biases, as it is impossible to control for the quality of the data reported in the literature. Finally, due to the diverse range of data presentation, the authors found that they were limited in their ability to study and control for certain variables. Some of these limitations should be minimized with their use of meta-analysis methods, which statistically evaluate and adjust for between-study heterogeneity. These results provide the impetus to initiate a prospective study, appropriately controlling for variables that can confound the retrospective analyses that largely comprise the existing literature.
Subject(s)
Glomus Jugulare Tumor/surgery , Postoperative Complications/etiology , Adult , Cohort Studies , Combined Modality Therapy , Cranial Nerve Diseases/diagnosis , Cranial Nerve Diseases/etiology , Female , Glomus Jugulare Tumor/diagnosis , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/etiology , Neoplasm Recurrence, Local/surgery , Neoplasm, Residual/diagnosis , Neoplasm, Residual/etiology , Neoplasm, Residual/surgery , Postoperative Complications/diagnosis , Postoperative Complications/surgery , Radiosurgery , Reoperation , Tumor BurdenABSTRACT
Avoidance of facial nerve palsy is one of the major goals of vestibular schwannoma (VS) microsurgery. In this study, we examined the significance of previously implicated prognostic factors (age, tumor size, the extent of resection and the surgical approach) on post-operative facial nerve function. We selected all VS patients from prospectively collected database (1984-2009) who underwent microsurgical resection as their initial treatment for histopathologically confirmed VS. The effect of variables such as surgical approach, tumor size, patient age and extent of resection on rates facial nerve dysfunction after surgery, were analyzed using multivariate logistic regression. Patients with preoperative facial nerve dysfunction (House-Brackman [HB] score 3 or higher) were excluded, and HB grade of 1 or 2 at the last follow-up visit was defined as "facial nerve preservation." A total of 624 VS patients were included in this study. Multivariate logistic regression analysis found that only pre-operative tumor size significantly predicted poorer facial nerve outcome for patients followed-up for ≥6 and ≥12 months (OR 1.27, 95% CI 1.09-1.49, p < 0.01; OR 1.35, 95% CI 1.10-1.67, P < 0.01, respectively). We found no significant relationship between facial nerve function and age, extent of resection, surgical approach, or tumor size (when extent of resection and surgical approach were included in the regression analysis). Because facial nerve palsy is a debilitating and psychologically devastating condition for the patient, we suggest altering surgical aggressiveness in patients with unfavorable tumor anatomy, particularly in cases with large tumors where overaggressive resection might subject the patient to unwarranted risk. Residual disease can be followed and controlled with radiosurgery if interval growth is noted.
Subject(s)
Facial Nerve Diseases/prevention & control , Facial Nerve/physiology , Neuroma, Acoustic/surgery , Postoperative Complications , Facial Nerve Diseases/physiopathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm, Residual , Neuroma, Acoustic/physiopathology , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
Craniopharyngiomas are locally aggressive tumors which typically are focused in the sellar and suprasellar region near a number of critical neural and vascular structures mediating endocrinologic, behavioral, and visual functions. The present study aims to summarize and compare the published literature regarding morbidity resulting from treatment of craniopharyngioma. We performed a comprehensive search of the published English language literature to identify studies publishing outcome data of patients undergoing surgery for craniopharyngioma. Comparisons of the rates of endocrine, vascular, neurological, and visual complications were performed using Pearson's chi-squared test, and covariates of interest were fitted into a multivariate logistic regression model. In our data set, 540 patients underwent surgical resection of their tumor. 138 patients received biopsy alone followed by some form of radiotherapy. Mean overall follow-up for all patients in these studies was 54 ± 1.8 months. The overall rate of new endocrinopathy for all patients undergoing surgical resection of their mass was 37% (95% CI = 33-41). Patients receiving GTR had over 2.5 times the rate of developing at least one endocrinopathy compared to patients receiving STR alone or STR + XRT (52 vs. 19 vs. 20%, χ(2) P < 0.00001). On multivariate analysis, GTR conferred a significant increase in the risk of endocrinopathy compared to STR + XRT (OR = 3.45, 95% CI = 2.05-5.81, P < 0.00001), after controlling for study size and the presence of significant hypothalamic involvement. There was a statistical trend towards worse visual outcomes in patients receiving XRT after STR compared to GTR or STR alone (GTR = 3.5% vs. STR 2.1% vs. STR + XRT 6.4%, P = 0.11). Given the difficulty in obtaining class 1 data regarding the treatment of this tumor, this study can serve as an estimate of expected outcomes for these patients, and guide decision making until these data are available.