Glioblastoma, a high-grade glial infiltrating tumor, is the most frequent malignant brain tumor in adults and carries a dismal prognosis. External beam radiotherapy (EBRT) increases overall survival ...but this is still low due to local relapses, mostly occurring in the irradiation field. As the ratio of spectra of choline/N acetyl aspartate> 2 (CNR2) on MR spectroscopic imaging has been described as predictive for the site of local relapse, we hypothesized that dose escalation on these regions would increase local control and hence global survival.
In this multicenter prospective phase III trial for newly diagnosed glioblastoma, 220 patients having undergone biopsy or surgery are planned for randomization to two arms. Arm A is the Stupp protocol (EBRT 60 Gy on contrast enhancement + 2 cm margin with concomitant temozolomide (TMZ) and 6 months of TMZ maintenance); Arm B is the same treatment with an additional simultaneous integrated boost of intensity-modulated radiotherapy (IMRT) of 72Gy/2.4Gy delivered on the MR spectroscopic imaging metabolic volumes of CHO/NAA > 2 and contrast-enhancing lesions or resection cavity. Stratification is performed on surgical and MGMT status.
This is a dose-painting trial, i.e. delivery of heterogeneous dose guided by metabolic imaging. The principal endpoint is overall survival. An online prospective quality control of volumes and dose is performed in the experimental arm. The study will yield a large amount of longitudinal multimodal MR imaging data including planning CT, radiotherapy dosimetry, MR spectroscopic, diffusion and perfusion imaging.
NCT01507506 , registration date December 20, 2011.
•Helical tomotherapy is effective for craniospinal irradiation of several CNS tumours.•HT-CSI is delivered more often but there are few data about late effects.•Tomotherapy offers technical ...advantages when compared to other radiation techniques.•HT-CSI provides good organ-at-risk sparing with no additional acute or late toxicities.
As craniospinal irradiation (CSI) is delivered more frequently by helical tomotherapy (HT) with few reports about late effects, we analysed all patients treated in our centre over an 11-year period.
Our study included all patients that underwent CSI by HT, between September 2009 and January 2020, in the Department of Radiation Oncology of the Toulouse Cancer Institute. Acute radiotherapy toxicities were reported and medium- to long-term outcomes analysed.
Among the 79 patients included, 70.9 % were younger than 18 years at diagnosis, the median age was 13 (range: 1–52) at the time of radiation therapy, 67.1 % of patients had medulloblastoma. Half of them (49.4 %) had a metastatic disease at diagnosis. The median dose of CSI was 36 Gy (range, 18–36). Seventy-seven patients received a radiation boost to the original location of the primary tumour (97.5 %), 32 patients also received a boost to their metastatic sites (40.5 %). Median follow-up was 55.5 months (95 %CI = 41.2; 71.8). The 3-year event-free survival rate was 66.3 % (95 %CI = 54.2; 75.9). Most patients presented with acute haematological toxicities during CSI (85.9 %), predominantly severe thrombocytopenia (39.7 %). Among the 64 patients assessed for medium- and long-term outcomes, 52 survived and 47 were alive and disease-free at the latest follow-up visit on record. There were 3.8 % secondary tumours: two meningiomas and one diffuse intrinsic pontine glioma. Adult and paediatric patients respectively presented with secondary cataract (4.3 % vs 22.0 %), persistent hearing disorders (26.1 % vs 29.3 %), pulmonary or cardiac late effects (4.3 % vs 2.4 %), hormonal pituitary gland deficiencies (30.0 % vs 56.8 %) and psycho-cognitive disorders (56.5 % vs 53.7 %).
CSI dispensed by HT, did not result in any additional acute or late toxicities when compared to 3D-CSI. There was no increase in the secondary tumour rate compared to that reported in the literature.
Abstract The outcomes of adolescents/young adults with osteosarcoma have not improved in decades. The chaotic karyotype of this rare tumor has precluded the identification of prognostic biomarkers ...and patient stratification. We reasoned that transcriptomic studies should overcome this genetic complexity. RNA sequencing (RNA-seq) of 79 osteosarcoma diagnostic biopsies identified stable independent components that recapitulate the tumor and microenvironment cell composition. Unsupervised classification of the independent components stratified this cohort into favorable (G1) and unfavorable (G2) prognostic tumors in terms of overall survival. Multivariate survival analysis ranked this stratification as the most influential variable. Functional characterization associated G1 tumors with innate immunity and G2 tumors with angiogenic, osteoclastic, and adipogenic activities as well as PPARγ pathway upregulation. A focused gene signature that predicted G1/G2 tumors from RNA-seq data was developed and validated within an independent cohort of 82 osteosarcomas. This signature was further validated with a custom NanoString panel in 96 additional osteosarcomas. This study thus proposes new biomarkers to detect high-risk patients and new therapeutic options for osteosarcoma. Significance: These findings indicate that the osteosarcoma microenvironment composition is a major feature to identify hard-to-treat patient tumors at diagnosis and define the biological pathways and potential actionable targets associated with these tumors.
In an attempt to gain a better understanding of the cerebral functions represented in the angular gyrus and to spare them during surgery, the authors studied patients with brain tumors located close ...to the angular gyrus and mapped cortical sites by using electrostimulation.
Before undergoing tumor removal, six right-handed patients (five with left and one with right hemisphere tumors) were studied using cortical mapping with the aid of calculating, writing, finger-recognition, and color-naming tasks in addition to standard reading and object-naming tasks (for a total of 36 brain mapping studies). Strict conditions of functional site validation were applied to include only those cortical sites that produced repetitive interferences in the function tested. Preoperatively, four of the patients exhibited discrete symptoms related to Gerstmann syndrome while performing very specific tasks, whereas the other two patients presented with no symptoms of the syndrome. No patient had significant language or apraxic deficits. Distinct or shared cortical sites producing interferences in calculating, finger recognition, and writing were repeatedly found in the angular gyrus. Object- or color-naming sites and reading-interference sites were also found in or close to the angular gyrus; although frequently demonstrated, these latter results were variable and unpredictable in the group of patients studied. Finger agnosia and acalculia sites were also found elsewhere, such as in the supramarginal gyrus or close to the intraparietal sulcus. Mechanisms involved in acalculia, agraphia, or finger agnosia (either complete interferences or hesitations) during stimulation were various, from an aphasia-like form (for instance, the patient did not understand the numbers or words given for calculating or writing tasks) to an apparently pure interference in the function tested (patients understood the numbers, but were unable to perform a simple addition).
Symptoms of Gerstmann syndrome can be found during direct brain mapping in the angular gyrus region. In this series of patients, sites producing interferences in writing, calculating, and finger recognition were demonstrated in the angular gyrus, which may or may not have been associated with object-naming, color-naming, or reading sites.
Reversible cerebral vasoconstriction syndrome (RCVS) is a rare cause of intracerebral hemorrhage (ICH) causing intracranial hypertension.
Case report.
We report a case of RCVS-related ICH leading to ...refractory intracranial hypertension. A decompressive craniectomy was performed to control intracranial pressure. We discuss here the management of RCVS with intracranial hypertension. Decompressive craniectomy was preformed to avoid the risky option of high cerebral perfusion pressure management with the risk of bleeding, hemorrhagic complications, and high doses of norepinephrine. Neurological outcome was good.
RCVS has a complex pathophysiology and can be very difficult to manage in cases of intracranial hypertension. Decompressive craniectomy should probably be considered.
Purpose
To highlight the changes in the management of vestibular schwannoma (VS) since 2004 with a focus on small- to middle-size VS.
Methods
Retrospective analysis of the decisions made in skull ...base tumor board between 2004 and 2021.
Results
1819 decisions were analyzed (average age 59.25, 54% females). Overall, 850 (47%) cases were allocated to a Wait and Scan (WS) approach, 416 (23%) received radiotherapy and 553 (30%) were treated surgically (MS). All stages considered WS increased from 39% before 2010 to 50% after 2010. Similarly, Stereotactic Radio Therapy (SRT) increased from 5 to 18%. MS decreased from 46 to 25%. It was more commonly proposed to younger patients and larger tumors,
p
< 0.001. For Koos stages 1, 2, and 3 there was a statistically significant increase in SRT, and a decrease in MS,
p
< 0.001. WS also increased for stages 1 and 2. However, such a trend was not observed for stage 3. MS remained the primary treatment modality for stage 4 tumors throughout the study period,
p
= 0.057. The significance of advanced age as a factor favoring SRT decreased over time. The opposite is true for serviceable hearing. There was also a decrease in the percentage of the justification “young age” in the MS category.
Conclusion
The is a continuing trend towards non-surgical treatment. Small- to medium-sized VS witnessed an increase in both WS and SRT. There is only an increase in SRT for moderately large VS. Physicians are less and less considering young age as a factor favoring MS over SRT. There is a tendency towards favoring SRT when hearing is serviceable.
Craniosynostosis in newborns is caused by the premature closure of the cranial sutures leading to cranial vault deformity. It results in aesthetic imbalance and developmental disabilities and surgery ...is frequent during the first months of growth. Our study focused on scaphocephaly defined as the premature closure of the sagittal suture. We hypothesised that the effective mechanical properties of sutures were altered as compared to those of the parietal adjacent tissue considered as control.
The population consisted of seven males and four females (mean age 4.9 months). Sixteen suture samples and thirty-four parietal tissue samples were harvested during corrective surgery and investigated by using three-point bending tests to obtain the structure-stiffness of specimens. An energy model was used to derive the effective Young's modulus. A histological study complemented the experimental protocol.
Fused sutures were thicker than adjacent bone and the natural curvature of sutures did not influence the static mechanical response. The stiffness of stenotic sutures was significantly higher than that of the parietal bone. The effective Young's modulus of stenotic sutures was significantly lower than that of the parietal adjacent tissue. The parietal tissue showed a parallel bone architecture whereas the central stenotic tissue was disorganised with more vascularisation.
The stenotic suture differed in structural and mechanical terms from the adjacent bone during calvarial growth in the first year of life. Our study emphasised the alteration of effective tissue properties in craniosynostosis.
•Premature closure of sutures causes craniosynostosis and skull deformity.•Fused sutures were stiffer and Young's modules were lower than normality.•Exploration of suture mechanical response may contribute to craniostenosis aetiology.
Glioblastoma (GBM) systematically recurs after a standard 60 Gy radio-chemotherapy regimen. Since magnetic resonance spectroscopic imaging (MRSI) has been shown to predict the site of relapse, we ...analyzed the effect of MRSI-guided dose escalation on overall survival (OS) of patients with newly diagnosed GBM.
In this multicentric prospective phase III trial, patients who had undergone biopsy or surgery for a GBM were randomly assigned to a standard dose (SD) of 60 Gy or a high dose (HD) of 60 Gy with an additional simultaneous integrated boost totaling 72 Gy to MRSI metabolic abnormalities, the tumor bed and residual contrast enhancements. Temozolomide was administered concomitantly and maintained for 6 months thereafter.
One hundred and eighty patients were included in the study between March 2011 and March 2018. After a median follow-up of 43.9 months (95% CI 42.5; 45.5), median OS was 22.6 months (95% CI 18.9; 25.4) versus 22.2 months (95% CI 18.3; 27.8) for HD, and median progression-free survival was 8.6 (95% CI 6.8; 10.8) versus 7.8 months (95% CI 6.3; 8.6), in SD versus HD, respectively. No increase in toxicity rate was observed in the study arm. The pseudoprogression rate was similar across the SD (14.4%) and HD (16.7%) groups. For O(6)-methylguanine-DNA methyltransferase (MGMT) methylated patients, the median OS was 38 months (95% CI 23.2; NR) for HD patients versus 28.5 months (95% CI 21.1; 35.7) for SD patients.
The additional MRSI-guided irradiation dose totaling 72 Gy was well tolerated but did not improve OS in newly diagnosed GBM.
NCT01507506; registration date: December 20, 2011. https://clinicaltrials.gov/ct2/show/NCT01507506?cond=NCT01507506&rank=1.
PDF
