The Long-Term Outcome of CyberKnife-Based Stereotactic Radiotherapy for Intra/ Extracranial Non-Vestibular Schwannomas: A Single-Center Experience

The long-term outcomes of CyberKnife-based hypofractionated stereotactic radiotherapy (SRT) for intra/ extracranial non-vestibular schwannomas (nVS) need to be accumulated. Patients who received SRT by CyberKnife for nVS from 2010 to 2019 were retrospectively reviewed. A total of 45 patients with nVS were identified. The mean age was 53 (± 18) years old, and 23 patients (51%) were female. Twenty-nine patients (64%) had previous procedures. As for the tumor extension, 22 (49%) nVS were classified as primary intracranial, five (11%) were classified as intra/ extracranial (dumbbell shape), and 18 (40%) were classified as primary extracranial. The median prescribed dose, covering 95% of the planning target volume, was 21 (IQR 21 – 25) Gy, and the median target volume was 7 (IQR 3.6-13.1) cm3. The local control rate of nVS for patients without neurofibromatosis type 2 (NF2) was 100%. Old age (OR 0.92, p-value 0.03) and previous surgery (OR 0.02, p-value 0.02) were significant risk factors for no symptomatic improvement. The progression-free survival was 74 (±33) months clinically and 69 (IQR 36 – 94) months radiologically. During follow-up, two cases (4%) with NF2 resulted in treatment failure, 13 cases (41%) resulted in transient tumor expansion (TTE), 10 (22%) suffered from transient adverse radiation effect (ARE), and two (4%) resulted in permanent ARE. Hypofractionated SRT by CyberKnife for head, neck, and spine nVS was an effective treatment regardless of tumor extension relative to the cranium. Although the risk of permanent ARE was low, some patients experienced transient clinical worsening due to TTE.

The Long-term Outcome of CyberKnife-Based Stereotactic Radiotherapy for Intra/ Extracranial Non-Vestibular Schwannomas: A Single-Center Experience

Background The long-term outcomes of CyberKnife-based hypofractionated stereotactic radiotherapy (SRT) for intra/ extracranial non-vestibular schwannomas (nVS) need to be accumulated. Method Patients who received SRT by CyberKnife for nVS from 2010 to 2019 were retrospectively reviewed. Results A total of 45 patients with nVS were identified. The mean age was 53 (± 18) years old, and 23 patients (51%) were female. Twenty-nine patients (64%) had previous procedures. As for the tumor extension, 22 (49%) nVS were classified as primary intracranial, five (11%) were classified as intra/ extracranial (dumbbell shape), and 18 (40%) were classified as primary extracranial. The median prescribed dose, covering 95% of the planning target volume, was 21 (IQR 21 – 25) Gy, and the median target volume was 7 (IQR 3.6-13.1) cm3. The local control rate of nVS for patients without neurofibromatosis type 2 (NF2) was 100%. Old age (OR 0.92, p-value 0.03) and previous surgery (OR 0.02, p-value 0.02) were significant risk factors for no symptomatic improvement. The progression-free survival was 74 (±33) months clinically and 69 (IQR 36 – 94) months radiologically. During follow-up, two cases (4%) with NF2 resulted in treatment failure, 13 cases (41%) resulted in transient tumor expansion (TTE), 10 (22%) suffered from transient adverse radiation effect (ARE), and two (4%) resulted in permanent ARE. Conclusions Hypofractionated SRT for head, neck, and spine nVS was an effective treatment regardless of tumor extension relative to the cranium. Although the risk of permanent ARE was low, some patients experienced transient clinical worsening due to TTE.

Clinicopathologic analysis of microscopic tumor extension in glioma for external beam radiotherapy planning

Background There is no consensus regarding the clinical target volume (CTV) margins in radiotherapy for glioma. In this study, we aimed to perform a complete macropathologic analysis examining microscopic tumor extension (ME) to more accurately define the CTV in glioma. Methods Thirty-eight supra-total resection specimens of glioma patients were examined on histologic sections. The ME distance, defined as the maximum linear distance from the tumor border to the invasive tumor cells, was measured at each section. We defined the CTV based on the relationships between ME distance and clinicopathologic features. Results Between February 2016 and July 2020, a total of 814 slides were examined, corresponding to 162 slides for low-grade glioma (LGG) and 652 slides for high-grade glioma (HGG). The ME value was 0.69 ± 0.43 cm for LGG and 1.29 ± 0.54 cm for HGG (P < 0.001). After multivariate analysis, tumor grade, O6-methylguanine-DNA-methyltransferase promoter methylated status (MGMTm), isocitrate dehydrogenase wild-type status (IDHwt), and 1p/19q non-co-deleted status (non-codel) were positively correlated with ME distance (all P < 0.05). We defined the CTV of glioma based on tumor grade. To take into account approximately 95% of the ME, a margin of 1.00 cm, 1.50 cm, and 2.00 cm were chosen for grade II, grade III, and grade IV glioma, respectively. Paired analysis of molecularly defined patients confirmed that tumors that had all three molecular alterations (i.e., MGMTm/IDHwt/non-codel) were the most aggressive subgroups (all P < 0.05). For these patients, the margin could be up to 1.50 cm, 2.00 cm, and 2.50 cm for grade II, grade III, and grade IV glioma, respectively, to cover the subclinical lesions in 95% of cases. Conclusions The ME was different between the grades of gliomas. It may be reasonable to recommend 1.00 cm, 1.50 cm, and 2.00 cm CTV margins for grade II, grade III, and grade IV glioma, respectively. Considering the highly aggressive nature of MGMTm/IDHwt/non-codel tumors, for these patients, the margin could be further expanded by 0.5 cm. These recommendations would encompass microscopic disease extension in 95% of cases. Trial registration The trial was registered with Chinese Clinical Trial Registry (ChiCTR2100049376).

Trends in Intracranial Glioma Incidence and Mortality in the United States, 1975-2018

PurposeGlioma incidence in the US seems to have stabilized over the past 20 years. It’s also not clear whether changes in glioblastoma incidence are associated with glioma mortality trends. Our study investigated trends in glioma incidence and mortality according to tumor characteristics.MethodsThis study obtained data from the Surveillance, Epidemiology, and End Results-9 (SEER-9) registries to calculate glioma incidence and mortality trends. Annual percent changes (APC) and 95% CIs were calculated using the Joinpoint program.Results62,159 patients (34,996 males and 55,424 whites) were diagnosed with glioma during 1975-2018, and 31,922 deaths occurred from 1995-2018. Glioblastoma (32,893 cases) and non-glioblastoma astrocytoma (17,406 cases) were the most common histologic types. During the study period, the incidence of glioma first experienced a significant increase (APC=1.8%, [95% CI, 1.3% to 2.3%]) from 1975 to 1987, and then experienced a slight decrease (APC=-0.4%, [95% CI, -0.5% to -0.3%]) from 1987 to 2018, while the APC was 0.8% for glioblastoma, -2.0% for non-glioblastoma astrocytoma, 1.1% for oligodendroglial tumors, 0.7% for ependymoma and -0.3% for glioma NOS during the study period. Glioblastoma incidence increased for all tumor size and tumor extension except for distant. From 1995 to 2018, glioma mortality declined 0.4% per year (95% CI: -0.6% to -0.2%) but only increased in patients older than 80 years [APC=1.0%, (95% CI, 0.4% to 1.6%)].ConclusionSignificant decline in glioma incidence (1987-2018) and mortality (1995-2018) were observed. Epidemiological changes in non-glioblastoma astrocytoma contributed the most to overall trends in glioma incidence and mortality. These findings can improve understanding of risk factors and guide the focus of glioma therapy.

EXPRESSION OF THE VASCULAR ENDOTHELIAL GROWTH FACTOR AND ITS RECEPTORS (VEGFR-1 AND VEGFR-2) IN PRIMARY TUMOR CELLS IN PATIENTS WITH RENAL CANCER

Purpose: to study the expression of vascular endothelial growth factor (vegf-a) and its receptors (vegfr-1 and vegfr-2) in renal cell carcinoma (rcc) cells and assess the effect of the expression levels of these markers on the tumor characteristics and prognosis of patients with rcc.Material and methods. The study included 65 patients with rcc (pt1a-t4n0/+m0/+). All patients underwent radical surgery. Histological tumor tissue samples obtained during surgery were used for the study. Expression of vegfa, vegfr-1, -2 was studied by immunohistochemical staining using appropriate antibodies to receptors and growth factors.Results. Expression of vegf and vegfr-1 and vegfr-2 receptors was ound in the cytoplasm and on the membrane of primary tumor cells of patients with rcc. There was a significant direct correlation of overexpression of the markers with g 3-4 anaplasia (vegfr-1, -2) and signs of significant tumor extension, including high pt category (vegfr-1, -2), larger size of the primary tumor (vegfr-1 , -2), tumor invasion of paranephria (vegf, vegfr-1), tumor venous thrombosis (vegfr-1, -2), multiple metastases (vegf-2), metastases in the adrenal gland (vegf, vegfr-2) and liver (vegfr-1) (p<0.05). There was a trend towards a significant effect of the level of vegf expression on the risk of progression of rcc after cytoreductive nephrectomy (p=0.0821). A tendency towards a significant effect of the level of vegfr-2 expression on the risk of death from rcc was revealed (p=0.089). No other relationships between the expression of vegf-a/vegfr-1, -2 and the prognosis of rcc were found (p>0.05).Conclusion. Expression of vegfa, as well as vegfr-1 and vegfr-2 receptors, was found on the surface and in the cytoplasm of cells of the primary tumor of patients with rcc (pt1a-t4n0/+m0/+). There was a significant correlation between vegf/vegfr overexpression with a high grade (g3-4) tumor anaplasia and significant tumor extension. In univariate analysis, a significant adverse effect on specific survival of vegfr-2 overexpression was observed. In regression analysis, vegfr-2 overexpression tended to independently affect specific survival. These results show the importance of vegf/vegfr expression as biomarkers in renal cell carcinoma.

Prognostic factors and nomogram prediction of survival probability in primary spinal cord astrocytoma patients

OBJECTIVE Knowledge on the management of spinal cord astrocytoma (SCA) remains scarce. Here, the authors constructed and validated a predictive nomogram, often used for individualized prognosis and evaluations, to estimate cancer-specific survival (CSS) and overall survival (OS) for patients with SCA. METHODS Epidemiological characteristics were compared between low-grade SCA (LGSCA) and high-grade SCA (HGSCA) patients from the Surveillance, Epidemiology, and End Results (SEER) database. Risk factors for CSS and OS were determined using univariate and multivariate analyses and Kaplan-Meier curves. A nomogram was developed to individually predict the 3-, 5-, and 10-year CSS and OS rates. The clinical usefulness of the nomogram was assessed using calibration plots, the concordance index (C-index), and time-dependent receiver operating characteristic curves. RESULTS A total of 468 LGSCA and 165 HGSCA patients were eligible for inclusion. LGSCA and HGSCA patients demonstrated differences in age, tumor extension, insurance status, adjuvant treatment, and survival. Multivariate analysis demonstrated that in the LGSCA group, tumor extension, surgery type, and adjuvant therapy were individually associated with CSS. The distance of tumor extension and WHO grade were individually associated with CSS in the HGSCA group. The prognostic variables were further demonstrated using the Kaplan-Meier method, which also suggested that adjuvant treatment provided no advantage to HGSCA patients. A nomogram was constructed, and the C-index for CSS was 0.84 by internal validation (95% CI 0.79–0.90). CONCLUSIONS This research suggests that the distance of tumor extension, type of surgery, and adjuvant therapy are significant risk factors for CSS using multivariate analysis in the LGSCA group. Adjuvant treatment provided no advantages for CSS or OS in patients with HGSCAs. The nomogram may be clinically useful to healthcare providers.

Chondrosarcoma Arising from the Posterior Iliac Crest Extending into the Spinal Canal

Chondrosarcoma is a malignant tumor characterized by the production of a cartilage matrix. Extension into the spinal canal from the extracannular space is seen mainly for neurogenic tumors, but it is rare in nonneurogenic tumors. A 75-year-old woman suffered from sciatic pain and numbness in her lower left extremity. The diagnosis was of a low-grade conventional chondrosarcoma, which originated from the posterior ilium with an intraspinal extension at the level of the sacrum, compressing the cauda equina. The tumor extended further into the S1 sacral anterior foramen, in the shape of a dumbbell. The tumor was resected in several blocks posteriorly, and the dumbbell-shaped tumor in the S1 foramen was resected by widening the S1 foramen from behind. The posterior extension of the iliac tumor seemed prevented by the posterior sacroiliac ligament, and the tumor extended into the canal. Here, we report that the iliac chondrosarcoma extending into the spinal canal is rare for this tumor type. An understating of the tumor extension is important for planning the surgical strategy.