The management of brain tumors developed in adolescents and young adults (AYAs) is challenging because of their histological heterogeneity and low incidence. The brain tumor and its treatment ...interventions can negatively affect neurological, neurocognitive, and endocrinological function, and dramatically affect the circumstances of AYA patients progressing to further education, employment, and marriage. Specific support is thus necessary to maintain the quality of life (QOL) of AYA brain tumor patients. AYA patients and survivors require active intervention and support for returning to school or work, progressing to further education, finding employment, and preserving fertility. Recent cancer genome profiling revealed that AYA gliomas include pediatric- and adult-type genetic alteration. Insights into the biology underlying the distribution of tumors in AYAs may influence the development of prospective trials. A more individualized view of brain tumors may influence stratification of patients’ in future clinical studies as well as selection for molecular targeted therapy. Here I review strategies for achieving a better outcome to decrease late effects and improve QOL.
Recovery from adult growth hormone deficiency (AGHD) after transsphenoidal surgery (TSS) has not been well discussed because of the lack of examinations including pituitary provocation tests (PPTs) ...before and after the procedure. This study aimed to evaluate the growth hormone (GH) axis function of patients with nonfunctioning pituitary adenoma (NFPA) via pre- and postoperative PPTs. Moreover, the predictive factors for recovery from AGHD after TSS were validated to facilitate surgery for AGHD in patients with NFPA.
In total, 276 patients (median age 60.0 years) who underwent TSS for NFPA were included in this study. PPTs were performed before and 3 months after TSS. Then, the relationships between recovery from AGHD after TSS and clinical, surgical, and hormonal factors, including peak GH level based on PPTs, were evaluated statistically.
In this study, 114 patients were diagnosed with preoperative AGHD. Approximately 25.4% recovered from AGHD after TSS. In contrast, among the 162 patients without preoperative AGHD, 13 (8.0%) had newly developed postoperative AGHD. The predictive factors for recovery from AGHD were younger age, female sex, initial TSS, and high peak GH level based on preoperative PPT. According to the receiver operating characteristic curve analysis, patients who were aged ≤ 62.2 years and had a peak GH level of ≥ 0.74 μg/L based on preoperative PPT were likely to recover from AGHD (sensitivity: 82.8%, specificity: 72.9%, and area under the curve: 0.8229).
AGHD caused by NFPA can improve after initial TSS among young patients with certain peak GH levels assessed by preoperative PPT. Whether TSS for NFPA can promote recovery from AGHD is worth considering in some patients.
Rathke's cleft cysts (RCCs) are relatively common and often detected incidentally. They are usually asymptomatic and managed conservatively. However, little is known about their natural history. ...Thus, the authors aimed to examine the natural course of RCCs and identify the risk factors for their progression.
This retrospective study examined 229 patients (median age 43.0 years) diagnosed with RCCs by MRI and followed up without surgery (median period 36.6 months). The median cyst height on the initial MRI was 10 mm. Progression or regression of RCC was defined as cyst height changes of ≥ 1 mm.
In total, 23 (10.0%) RCCs progressed, whereas 73 (31.9%) RCCs spontaneously regressed. The remaining 133 were noted to be stable throughout the follow-up period. Patients with progressed RCCs were significantly older than those with stable RCCs. In patients with acute headache as an initial symptom, RCCs were significantly more likely to spontaneously regress. New symptoms occurred in 6 patients, 5 of whom underwent surgery for RCC progression. Of these 6 patients, 1 patient had persistent adrenocorticotropic hormone deficiency and 1 patient developed diabetes insipidus. Kaplan-Meier analysis results showed RCC progression and new symptom development rates to be 12.0% and 4.1% at 5 years and 13.7% and 5.7% at 10 years, respectively.
RCCs rarely progress or cause new symptoms in the long term. Patients with asymptomatic RCC should be followed up for at least 5 years to ensure RCC inactivity. RCCs in older adults may require greater surveillance.
Purpose
Diabetes insipidus (DI) following transsphenoidal surgery (TSS) is a common complication. Although postoperative DI often occurs in patients with craniopharyngioma and Rathke’s cleft cyst, ...postoperative DI in patients with non-functioning pituitary adenoma (NFPA) has not been fully examined. We clarified the clinical characteristics and magnetic resonance imaging (MRI) findings predicting postoperative DI in NFPAs.
Methods
A total of 333 patients undergoing initial TSS for NFPA were included in this retrospective study. Hyperintensity (HI) in the posterior pituitary lobe was evaluated on preoperative T1-weighted MRI. Based on the findings of HI patients were divided into three groups as follows: HI was not detected (Disappearance group), HI located intrasellarly (Intrasellar group), and HI located suprasellarly (Suprasellar group).
Results
The overall rate of DI was 21.9%, including permanent DI in 0.6%. DI occurred at postoperative day 1 (72.6%) or day 2 (19.2%) and improved within 7 days in most cases (87.7%). Univariable and multivariable analyses showed that the predictive factors of DI were a younger age (odds ratio OR 0.97, 95% confidence interval CI 0.95–0.99,
P
= 0.0037) and larger tumor diameter (OR 1.04, 95% CI 1.01–1.08,
P
= 0.0155). The rate of DI was highest in the Disappearance group (43.8%) followed by the Intrasellar group (26.0%). The OR was 2.17 in the Intrasellar group compared with the Suprasellar group (95% CI 1.17–4.02,
P
= 0.0141).
Conclusions
Factors predicting DI following TSS for NFPA were a younger age, larger tumor size, and the location of intrasellar HI on preoperative T1-weighted MRI.
Purpose
Thyrotropin-secreting pituitary adenomas (TSPA) are extremely rare pituitary adenomas; their perioperative thyroid hormone dynamics have not been completely elucidated. Here, we investigated ...the clinical characteristics, perioperative findings, and thyroid hormone dynamics of TSPA at a single institution.
Methods
We enrolled 11 patients who underwent transsphenoidal surgery (TSS) for TSPA during 2005–2019 at Hiroshima University Hospital (TSPA group) and 24 patients who underwent TSS for nonfunctioning pituitary adenomas (NFPA) in 2019 (NFPA group; for comparison). Their clinical characteristics, operative findings, and thyroid hormone dynamics, including serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were retrospectively analyzed.
Results
The NFPA group demonstrated a slight temporary decrease in serum TSH/ FT3/ FT4 levels on day 1 postoperatively and improvement in the levels on day 4 postoperatively. In contrast, the serum TSH level in the TSPA group demonstrated a marked decrease on day 1 postoperatively but improved on day 7 postoperatively. The serum FT3 level was also markedly decreased on day 1 postoperatively but remained within the normal range. The serum FT4 level revealed a gradual decrease until day 21 postoperatively and then recovered within the normal range 3 months postoperatively. There was no significant difference in the frequency of decline in serum FT4 level between the two groups; no patients required thyroid hormonal replacement 3 months postoperatively.
Conclusions
Despite a variable degree of transient hypothyroidism, all patients had a normal thyroid function after 3 months follow-up.
Abstract Objective Glioblastoma (GBM) relapses locally or in a disseminated pattern, and is highly resistant to chemo-radiotherapy. Although dissemination is associated with poor prognosis for GBM ...patients, the clinico-pathological factors that promote dissemination have not been elucidated. Glypican-1 (GPC-1) is a heparin sulfate proteoglycan that is attached to the extracytoplasmic surface of the cell membrane and regulates cell motility. The aim of this study was to determine whether GPC-1 expression correlated with GBM dissemination and patient prognosis. Methods GPC-1 expression was examined by immunohistochemistry in 53 patients with GBM who received radiotherapy and temozolomide (TMZ) treatment. We assessed the relationship between dissemination and clinico-pathological factors, including GPC-1 expression. Additionally, we evaluated the relationship between GPC-1 expression and overall survival (OS) by uni- and multivariate analyses of a range of clinico-pathological factors, including age, Karnofsky Performance Status (KPS), extent of resection, and O6-methylguanine-DNA methyltransferase (MGMT) status. Results Logistic regression analysis revealed that GPC-1 expression correlated with dissemination ( P = 0.0116). Log-rank tests revealed that age, KPS, extent of resection, MGMT status, dissemination ( P = 0.0008) and GPC-1 expression ( P = 0.0011) were significantly correlated with OS. Multivariate analysis indicated that age, MGMT status, and GPC-1 expression were significantly correlated with OS. GPC-1 expression had the highest hazard ratio (2.392) among all regressors. Conclusions GPC-1 expression significantly correlated with OS in GBM patients who received radiotherapy and TMZ treatment. GPC-1 expression can help predict the occurrence of dissemination and shorter OS in GBM patients.
Abstract
Primary CNS germ cell tumors (GCTs) are rare neoplasms predominantly observed in the pediatric and young adult populations. In line with the hypothesis that the primordial germ cell is the ...cell-of-origin, histopathological examinations for this pathology involve a diverse range of components mirroring the embryogenic developmental dimensions. Chemotherapy and radiotherapy are the mainstays of treatment, with surgery having a limited role for diagnosis and debulking of residual tissue after treatment. While better management has been achieved over recent decades by modifying radiation coverage and selecting appropriate chemotherapy, standardization of treatment remains challenging, partly due to the low volume of cases encountered in each institution. As the incidence is higher in East Asia, including Japan, the Japan Society for Neuro-Oncology established a multidisciplinary task force to create an evidence-based guideline for CNS GCTs. This guideline provides recommendations for multiple dimensions of clinical management for CNS GCTs, with particular focus on diagnostic measures including serum markers, treatment algorithms including surgery, radiotherapy, and chemotherapy, and under-investigated but important areas such as treatment for recurrent cases, long-term follow-up protocols, and long-term sequelae. This guideline serves the purpose of helping healthcare professionals keep up to date with current knowledge and standards of management for patients with this rare disease in daily clinical practice, as well as driving future translational and clinical research by recognizing unmet needs concerning this tumor.
Abstract
Background
Secondary meningioma after cranial irradiation, so-called radiation-induced meningioma, is one of the important late effects after cranial radiation therapy. In this report, we ...analyzed our case series of secondary meningioma after cranial irradiation and conducted a critical review of literature to reveal the characteristics of secondary meningioma.
Materials and methods
We performed a comprehensive literature review by using Pubmed, MEDLINE and Google scholar databases and investigated pathologically confirmed individual cases. In our institute, we found pathologically diagnosed seven cases with secondary meningioma between 2000 and 2018. Totally, 364 cases were analyzed based on gender, WHO grade, radiation dose, chemotherapy. The latency years from irradiation to development of secondary meningioma were analyzed with Kaplan–Meier analysis. Spearman’s correlation test was used to determine the relationship between age at irradiation and the latency years.
Results
The mean age at secondary meningioma development was 35.6 ± 15.7 years and the mean latency periods were 22.6 ± 12.1 years. The latency periods from irradiation to the development of secondary meningioma are significantly shorter in higher WHO grade group (P = 0.0026, generalized Wilcoxon test), higher radiation dose group (P < 0.0001) and concomitant systemic chemotherapy group (P = 0.0003). Age at irradiation was negatively associated with the latency periods (r = −0.23231, P < 0.0001, Spearman’s correlation test).
Conclusion
Cranial irradiation at older ages, at higher doses and concomitant chemotherapy was associated with a shorter latency period to develop secondary meningiomas. However, even low-dose irradiation can cause secondary meningiomas after a long latency period. Long-term follow-up is necessary to minimize the morbidity and mortality caused by secondary meningioma after cranial irradiation.
Exhaustive research of 364 cases revealed the characteristics of secondary meningioma following cranial irradiation and the factor that associated a shorter latent period of development with secondary meningioma.
Abstract
Background
We conducted a phase III trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA)-A24+ recurrent glioblastoma to develop a new treatment modality.
Methods
...We randomly assigned 88 recurrent glioblastoma patients to receive PPV (n = 58) or the placebo (n = 30) at a 2-to-1 ratio. Four of 12 warehouse peptides selected based on preexisting peptide-specific immunoglobulin G levels or the corresponding placebos were injected 1×/week for 12 weeks.
Results
Our trial met neither the primary (overall survival OS) nor secondary endpoints. Unfavorable factors for OS of 58 PPV patients compared with 30 placebo patients were SART2-93 peptide selection (n = 13 vs 8, hazard ratio HR: 15.9), ≥70 years old (4 vs 4, 7.87), >70 kg body weight (10 vs 7, 4.11), and performance status (PS)3 (8 vs 2, 2.82), respectively. Consequently, the median OS for PPV patients without SART2-93 selection plus one of these 3 favorable factors (<70 y old, ≤70 kg, or PS0–2) was significantly longer than that for the corresponding placebo patients (HR: 0.49, 0.44, and 0.51), respectively. Preexisting immunity against both all 12 warehouse peptides besides SART2-93 and the other cytotoxic T lymphocyte epitope peptides was significantly depressed in the patients with SART2-93 selection (n = 21) compared with that of the patients without SART2-93 selection (n = 67). Biomarkers correlative for favorable OS of the PPV patients were a lower percentage of CD11b+CD14+HLA-DRlow immunosuppressive monocytes and a higher percentage of CD4+CD45RA− activated T cells, the intermediate levels of chemokine C-C ligand 2 (CCL2), vascular endothelial growth factor, interleukin (IL)-6, IL-17, or haptoglobin, respectively.
Conclusion
This phase III trial met neither the primary nor secondary endpoints.
PDF
