Impact of clinical target volume margin reduction in glioblastoma patients treated with concurrent chemoradiation.

Background: Glioblastoma (GBM) is widely treated using large radiotherapy margins, resulting in substantial irradiation of the surrounding cerebral structures. In this context, the question arises whether these margins could be safely reduced. In 2018, clinical target volume (CTV) expansion was reduced in our institution from 20 to 15 mm around the gross target volume (GTV) (ie, the contrast-enhancing tumor/cavity). We sought to retrospectively analyze the impact of this reduction. Methods: All adult patients with GBM treated between January 2015 and December 2020 with concurrent chemoradiation (60Gy/2Gy or 59.4Gy/1.8Gy) were analyzed. Patients treated using a 20 (CTV20, n = 57) or 15 mm (CTV15, n = 56) CTV margin were compared for target volumes, dose parameters to the surrounding organs, pattern of recurrence, and survival outcome. Results: Mean GTV was similar in both groups (ie, CTV20: 39.7cm3; CTV15: 37.8cm3; P = .71). Mean CTV and PTV were reduced from 238.9cm3 to 176.7cm3 (P = .001) and from 292.6cm3 to 217.0cm3 (P < .001), for CTV20 and CTV15, respectively. As a result, average brain mean dose (Dmean) was reduced from 25.2Gy to 21.0Gy (P = .002). Significantly lower values were also observed for left hippocampus Dmean, brainstem D0.03cc, cochleas Dmean, and pituitary Dmean. Pattern of recurrence was similar, as well as patient outcome, ie, median progression-free survival was 8.0 and 7.0 months (P = .80), and median overall survival was 11.0 and 14.0 months (P = .61) for CTV20 and CTV15, respectively. Conclusions: In GBM patients treated with chemoradiation, reducing the CTV margin from 20 to 15 mm appears to be safe and offers the potential for less treatment toxicity.

Dose rate conversion coefficients for ocular contamination in nuclear medicine: A Monte Carlo simulation with experimental validation.

BACKGROUND: Since 2011, the International Commission on Radiological Protection (ICRP) has recommended an annual eye lens dose limit of 20 mSv for radiation workers, averaged over 5 years, with no year exceeding 50 mSv. However, limited research has been conducted on dose rate conversion coefficients (DCCs) for direct contamination of the eye. PURPOSE: This study aimed to accurately determine DCCs for the eye lens and cornea for ocular contamination with radionuclides used in nuclear medicine. METHODS: DCCs for 37 radionuclides used in nuclear medicine were determined using two different methods. Method 1 involved conducting Monte Carlo (MC) simulations of an ICRU cylinder to determine the absorbed dose at a depth of 3 mm resulting from a point source. The accuracy of this simulation approach was validated by experimental thermoluminescent dosimeter (TLD) measurements for 18F, 68Ga, 99mTc, and 177Lu. In method 2, average DCCs were calculated for the eye lens (complete and radiosensitive parts) and the cornea for both a point source and thin surface contamination centered on the cornea using MC simulations on the adult mesh-type reference computational phantom of the eye from the ICRP (MRCP). RESULTS: DCCs determined from TLD measurements showed excellent agreement (deviations: +1.4%, +4.7%, -3.1%, and -2.5% for 18F, 68Ga, 99mTc, and 177Lu, respectively) compared to MC simulations of the experimental set-up. For the 37 radionuclides, DCCs of the complete eye-lens for a point source ranged from 2.53 × 10-7 to 4.15 × 10-2 mGy MBq-1 s-1 for the adult MRCPs, being substantially smaller compared to DCCs determined via MC simulations of a ICRU cylinder. In general, point source and surface contamination showed comparable DCCs for the eye lens. Radionuclides emitting low-energy beta radiation or conversion electrons (e.g., 177Lu, 99mTc) showed low DCCs as the radiation does not penetrate to the depth of the eye lens, while radionuclides emitting high-energy beta radiation (e.g., 90Y) showed high DCCs. Overall, DCCs for the radiosensitive part of the eye lens were larger (up to a factor of 3) compared to the complete eye lens. DCCs for the cornea were larger than for the eye lens with a factor that strongly depended on the emitted radiation type. Especially alpha emitters (e.g., 211At, 223Ra) showed high DCCs for the cornea because of the short range of alpha radiation, leading to local maxima in the cornea and not reaching the eye lens. CONCLUSION: DCCs at a depth of 3 mm in an ICRU cylinder and adult MRCP DCCs for both the complete and sensitive parts of the eye lens and cornea were determined for 37 radionuclides having applications in nuclear medicine. These DCCs are highly useful in radiation safety assessments and radiation dose calculations in ocular contamination incidents.

Predicting the risk of neurocognitive decline after brain irradiation in adult patients with a primary brain tumor.

BACKGROUND: Deterioration of neurocognitive function in adult patients with a primary brain tumor is the most concerning side effect of radiotherapy. This study was aimed to develop and evaluate Normal-Tissue Complication Probability (NTCP) models using clinical and dose-volume measures for 6-month, 1-year and 2-year Neurocognitive Decline (ND) post-radiotherapy. METHODS: A total of 219 patients with a primary brain tumor treated with radical photon and/or proton radiotherapy (RT) between 2019 and 2022 were included. Controlled Oral Word Association (COWA) test, Hopkins Verbal Learning Test-Revised (HVLTR) and Trail Making Test (TMT) were used to objectively measure ND. A comprehensive set of potential clinical and dose-volume measures on several brain structures were considered for statistical modelling. Clinical, dose-volume and combined models were constructed and internally tested in terms of discrimination (Area Under the Curve, AUC), calibration (Mean Absolute Error, MAE) and net benefit. RESULTS: 50%, 44.5% and 42.7% of the patients developed ND at 6-month, 1-year and 2-year timepoints, respectively. Following predictors were included in the combined model for 6-month ND: age at radiotherapy>56 years (OR=5.71), overweight (OR=0.49), obesity (OR=0.35), chemotherapy (OR=2.23), brain V20Gy≥20% (OR=3.53), brainstem volume≥26cc (OR=0.39) and hypothalamus volume≥0.5cc (OR=0.4). Decision curve analysis showed that the combined models had the highest net benefits at 6-month (AUC=0.79, MAE=0.021), 1-year (AUC=0.72, MAE=0.027) and 2-year (AUC=0.69, MAE=0.038) timepoints. CONCLUSION: The proposed NTCP models use easy-to-obtain predictors to identify patients at high-risk of ND after brain RT. These models can potentially provide a base for RT-related decisions and post-therapy neurocognitive rehabilitation interventions.

The existence of cranial bone flap displacement during brain radiotherapy.

This retrospective study examined bone flap displacement during radiotherapy in 25 post-operative brain tumour patients. Though never exceeding 2.5 mm, the sheer frequency of displacement highlights the need for future research on larger populations to validate its presence and assess the potential clinical impact on planning tumour volume margins.

Skull-Base Chondrosarcoma: A Systematic Review of the Role of Postoperative Radiotherapy.

Surgery and radiotherapy are key elements to the treatment of skull-base chondrosarcomas; however, there is currently no consensus regarding whether or not adjuvant radiotherapy has to be administered. This study searched the EMBASE, Cochrane, and PubMed databases for clinical studies evaluating the long-term prognosis of surgery with or without adjuvant radiotherapy. After reviewing the search results, a total of 22 articles were selected for this review. A total of 1388 patients were included in this cohort, of which 186 received surgery only. With mean follow-up periods ranging from 39.1 to 86 months, surgical treatment provided progression-free survival (PFS) rates ranging from 83.7 to 92.9% at 3 years, 60.0 to 92.9% at 5 years, and 58.2 to 64.0% at 10 years. Postoperative radiotherapy provides PFS rates ranging between 87 and 96.2% at 3 years, 57.1 and 100% at 5 years, and 67 and 100% at 10 years. Recurrence rates varied from 5.3% to 39.0% in the surgery-only approach and between 1.5% and 42.90% for the postoperative radiotherapy group. When considering prognostic variables, higher age, brainstem/optic apparatus compression, and larger tumor volume prior to radiotherapy were found to be significant factors for local recurrence.

Anatomical changes in resection cavity during brain radiotherapy.

BACKGROUND AND PURPOSE: Brain tumors are in general treated with a maximal safe resection followed by radiotherapy of remaining tumor including the resection cavity (RC) and chemotherapy. Anatomical changes of the RC during radiotherapy can have impact on the coverage of the target volume. The aim of the current study was to quantify the potential changes of the RC and to identify risk factors for RC changes. MATERIALS AND METHODS: Sixteen patients treated with pencil beam scanning proton therapy between October 2019 and April 2020 were retrospectively analyzed. The RC was delineated on pre-treatment computed tomography (CT) and magnetic resonance imaging, and weekly CT-scans during treatment. Isotropic expansions were applied to the pre-treatment RC (1-5 mm). The percentage of volume of the RC during treatment within the expanded pre-treatment volumes was quantified. Potential risk factors (volume of RC, time interval surgery-radiotherapy and relationship of RC to the ventricles) were evaluated using Spearman's rank correlation coefficient. RESULTS: The average variation in relative RC volume during treatment was 26.1% (SD 34.6%). An expansion of 4 mm was required to cover > 95% of the RC volume in > 90% of patients. There was a significant relationship between the absolute volume of the pre-treatment RC and the volume changes during treatment (Spearman's ρ = - 0.644; p = 0.007). CONCLUSION: RCs are dynamic after surgery. Potentially, an additional margin in brain cancer patients with an RC should be considered, to avoid insufficient target coverage. Future research on local recurrence patterns is recommended.

Patient-derived glioblastoma organoids reflect tumor heterogeneity and treatment sensitivity.

Background: Treatment resistance and tumor relapse are the primary causes of mortality in glioblastoma (GBM), with intratumoral heterogeneity playing a significant role. Patient-derived cancer organoids have emerged as a promising model capable of recapitulating tumor heterogeneity. Our objective was to develop patient-derived GBM organoids (PGO) to investigate treatment response and resistance. Methods: GBM samples were used to generate PGOs and analyzed using whole-exome sequencing (WES) and single-cell karyotype sequencing. PGOs were subjected to temozolomide (TMZ) to assess viability. Bulk RNA sequencing was performed before and after TMZ. Results: WES analysis on individual PGOs cultured for 3 time points (1-3 months) showed a high inter-organoid correlation and retention of genetic variants (range 92.3%-97.7%). Most variants were retained in the PGO compared to the tumor (range 58%-90%) and exhibited similar copy number variations. Single-cell karyotype sequencing demonstrated preservation of genetic heterogeneity. Single-cell multiplex immunofluorescence showed maintenance of cellular states. TMZ treatment of PGOs showed a differential response, which largely corresponded with MGMT promoter methylation. Differentially expressed genes before and after TMZ revealed an upregulation of the JNK kinase pathway. Notably, the combination treatment of a JNK kinase inhibitor and TMZ demonstrated a synergistic effect. Conclusions: Overall, these findings demonstrate the robustness of PGOs in retaining the genetic and phenotypic heterogeneity in culture and the application of measuring clinically relevant drug responses. These data show that PGOs have the potential to be further developed into avatars for personalized adaptive treatment selection and actionable drug target discovery and as a platform to study GBM biology.

Geometric and dosimetric analysis of CT- and MR-based automatic contouring for the EPTN contouring atlas in neuro-oncology.

PURPOSE: Atlas-based and deep-learning contouring (DLC) are methods for automatic segmentation of organs-at-risk (OARs). The European Particle Therapy Network (EPTN) published a consensus-based atlas for delineation of OARs in neuro-oncology. In this study, geometric and dosimetric evaluation of automatically-segmented neuro-oncological OARs was performed using CT- and MR-models following the EPTN-contouring atlas. METHODS: Image and contouring data from 76 neuro-oncological patients were included. Two atlas-based models (CT-atlas and MR-atlas) and one DLC-model (MR-DLC) were created. Manual contours on registered CT-MR-images were used as ground-truth. Results were analyzed in terms of geometrical (volumetric Dice similarity coefficient (vDSC), surface DSC (sDSC), added path length (APL), and mean slice-wise Hausdorff distance (MSHD)) and dosimetrical accuracy. Distance-to-tumor analysis was performed to analyze to which extent the location of the OAR relative to planning target volume (PTV) has dosimetric impact, using Wilcoxon rank-sum tests. RESULTS: CT-atlas outperformed MR-atlas for 22/26 OARs. MR-DLC outperformed MR-atlas for all OARs. Highest median (95 %CI) vDSC and sDSC were found for the brainstem in MR-DLC: 0.92 (0.88-0.95) and 0.84 (0.77-0.89) respectively, as well as lowest MSHD: 0.27 (0.22-0.39)cm. Median dose differences (ΔD) were within ± 1 Gy for 24/26(92 %) OARs for all three models. Distance-to-tumor showed a significant correlation for ΔDmax,0.03cc-parameters when splitting the data in ≤ 4 cm and > 4 cm OAR-distance (p < 0.001). CONCLUSION: MR-based DLC and CT-based atlas-contouring enable high-quality segmentation. It was shown that a combination of both CT- and MR-autocontouring models results in the best quality.

Difficult medical encounters in oncology: What physicians need. An exploratory study.

Objective: The objective of this study was to assess how often-medical oncology professionals encounter difficult consultations and if they desire support in the form of training. Methods: In February 2022, a survey on difficult medical encounters in oncology, training and demographics was set up. The survey was sent to 390 medical oncology professionals part of the OncoZON network of the Southeast region of the Netherlands. Results: Medical oncology professionals perceive a medical encounter as difficult when there is a dominant family member (n = 27), insufficient time (n = 24), or no agreement between medical professional and patient (n = 22). Patients involved in these encounters are most often characterized with low health literacy (n = 12) or aggressive behavior (n = 10). The inability to comprehend difficult medical information or perceived difficult behavior complicates encounters. Of the medical oncology professionals, 27-44% preferred a training as a physical group meeting (24%) or an individual virtual meeting (19%). Conclusion: Medical oncology professionals consider dominant or aggressive behavior and the inability to comprehend medical information by patients during consultations as difficult encounters for which they would appreciate support. Innovation: Our results highlight concrete medical encounters in need of specific education programs within daily oncology practice.

Epidemiology of adult meningioma: Report from the Dutch Brain Tumour Registry (2000-2019).

BACKGROUND AND PURPOSE: Meningiomas are the most common primary tumours of the central nervous system. This study aimed to provide comprehensive nationwide estimates on the incidence, prevalence and prognostic impact of meningioma diagnosis in the Netherlands. METHODS: Adult patients diagnosed with meningioma in 2000-2019 were selected from the Dutch Brain Tumour Registry (DBTR), part of the Netherlands Cancer Registry (NCR). Time trends in age-adjusted incidence and prevalence rates were evaluated using the estimated annual percentage change (EAPC). Relative survival rates were calculated using the Pohar Perme estimator. Case completeness of the DBTR/NCR was estimated through record linkage with one of the Dutch neuro-oncology centres. RESULTS: From a total of 23,454 cases of meningioma, 11,306 (48.2%) were histologically confirmed and 12,148 (51.8%) were radiological diagnoses. Over time, the incidence of diagnosis increased from 46.9 per 1,000,000 inhabitants (European Standardized Rate [ESR]) to 107.3 (EAPC 4.7%, p < 0.01), with an increase in the incidence of radiological diagnoses from 14.0 to 70.2 per 1,000,000 ESR (EAPC 9.1%, p < 0.01). The prevalence of meningioma was estimated at 1012/1,000,000 on 1 January 2020, with almost 17,800 individuals having had a diagnosis of meningioma. Relative survival rate at 10 years for grade 1 meningiomas was 91.0% (95% confidence interval [CI] 89.4%-92.3%), 71.3% (95% CI 66.8%-75.2%) for grade 2 meningiomas and 36.4% (95% CI 27.3%-45.6%) for grade 3 meningiomas. Local case completeness was estimated at 97.6% for histologically confirmed meningiomas and 84.5% for radiological diagnoses. CONCLUSION: With a near-complete registry, meningioma prevalence was estimated at over 1000 per 1,000,000 inhabitants.

Subclassification of the Koos grade 2 vestibular schwannoma into 2a and 2b for individualized patient care: A validity and reliability study.

OBJECTIVE: Vestibular schwannoma (VS) growth of ≥2 mm during serial MRI observation, irrespective of size, is the benchmark for treatment initiation in almost all centers. Although the probability of less optimal outcomes significantly increases in VS closer to the brainstem, early intervention does not improve long-term quality of life. Moving beyond the recommendation of definitive treatment for all VS after detected growth, we subclassified Koos 2 tumors based on extrameatal extension and relation to the brainstem. The aim of the current study was to evaluate the Koos 2 subclassification's validity and the inter-and intra-rater reliability of the entire Koos classification. METHODS: Six experts, including neurosurgeons, otorhinolaryngologists and radiologists from two tertiary referral centers, classified 43 VS MRI scans. Validity of the Koos 2 subclassification was evaluated by the percentage agreement against the multidisciplinary skull base tumor board management advice. Inter- and intra-rater reliability were calculated using the intraclass correlation coefficient (ICC). RESULTS: Validity was almost perfect in Koos 2a VSs with a 100% agreement and 87.5% agreement for Koos 2b. Inter-rater reliability for all Koos grades was significantly excellent (ICC 0.91; 95%CI 0.866 to 0.944, p= <0.001). Five raters had an excellent intra-rater reliability (ICC > 0.90; p= <0.01) and one rater had a good intra-rater reliability (ICC 0.88; 95% CI 0.742 to 0.949). CONCLUSIONS: Although multiple factors influence decision-making, the classification of Koos 2a and 2b with excellent inter- and intra-rater reliability, can aid in recommending treatment initiation, moving beyond detected tumor growth, aiming to optimize patient centered care.

Long-term results of upfront, single-session Gamma Knife radiosurgery for large cystic vestibular schwannomas.

Anecdotally, cystic vestibular schwannomas (cVSs) are regarded to have unpredictable biologic activity with poorer clinical results, and most studies showed a less favorable prognosis following surgery. While stereotactic radiosurgery (SRS) is a well-established therapeutic option for small- to medium-sized VSs, cVSs are often larger, thus making upfront SRS more complicated. The purpose of this retrospective study was to assess the efficacy and safety of upfront SRS for large cVSs. The authors reviewed the data of 54 patients who received upfront, single-session Gamma Knife radiosurgery (GKRS) with a diagnosis of large cVS (> 4 cm3). Patients with neurofibromatosis type 2, multiple VSs, or recurrent VSs and < 24 months of clinical and neuroimaging follow-up were excluded. Hearing loss (48.1%) was the primary presenting symptom. The majority of cVSs were Koos grade IV (66.7%), and the most prevalent cyst pattern was "mixed pattern of small and big cysts" (46.3%). The median time between diagnosis and GKRS was 12 months (range, 1-147 months). At GKRS, the median cVS volume was 6.95 cm3 (range, 4.1-22 cm3). The median marginal dose was 12 Gy (range, 10-12 Gy). The mean radiological and clinical follow-up periods were 62.2 ± 34.04 months (range, 24-169 months) and 94.9 ± 45.41 months (range, 24-175 months), respectively. At 2, 6, and 12 years, the tumor control rates were 100%, 95.7%, and 85.0%, respectively. Tumor shrinkage occurred in 92.6% of patients (n = 50), tumor volume remained stable in 5.6% of patients (n = 3), and tumor growth occurred in 1.9% of patients (n = 1). At a median follow-up of 53.5 months, the pre-GKRS tumor volume significantly decreased to 2.35 cm3 (p < 0.001). While Koos grade 3 patients had a greater possibility of attaining higher volume reduction, "multiple small thick-walled cyst pattern" and smaller tumor volumes decreased the likelihood of achieving higher volume reduction. Serviceable hearing (Gardner-Robertson Scale I-II) was present in 16.7% of patients prior to GKRS and it was preserved in all of these patients following GKRS. After GKRS, 1.9% of patients (n = 1) had new-onset trigeminal neuralgia. There was no new-onset facial palsy, hemifacial spasm, or hydrocephalus. Contrary to what was believed, our findings suggest that upfront GKRS seems to be a safe and effective treatment option for large cVSs.

Performance and usability evaluation of a mobile health data capture application in clinical cancer trials follow-up.

Mobile health data capture applications (mHDA's) may improve communication between healthcare providers and patients. However, there is limited literature about the use of mHDA's facilitating clinical trials. In this study, the effectiveness of an application, supporting follow-up visits of cancer trial participants was investigated. Twenty participants were provided with an e-questionnaire via the mHDA. Participants rated the usability of the application as high performing (mean Systems Usability Scale 87 points). The research team rated the mHDA as highly applicable and efficient in preparing visits. Anamnesis, physical examination and agreement on further policy were performed within an average of 31 min.

Correlation of reduced temporal muscle thickness and systemic muscle loss in newly diagnosed glioblastoma patients.

PURPOSE: Reduced temporal muscle thickness (TMT) has recently been postulated as a prognostic imaging marker and an objective tool to assess patients frailty in glioblastoma. Our aim is to investigate the correlation of TMT and systemic muscle loss to confirm that TMT is an adequate surrogate marker of sarcopenia in newly diagnosed glioblastoma patients. METHODS: TMT was assessed on preoperative MR-images and skeletal muscle area (SMA) was assessed at the third lumbar vertebra on preoperative abdominal CT-scans. Previous published TMT sex-specific cut-off values were used to classify patients as 'patient at risk of sarcopenia' or 'patient with normal muscle status'. Correlation between TMT and SMA was assessed using Spearman's rank correlation coefficient. RESULTS: Sixteen percent of the 245 included patients were identified as at risk of sarcopenia. The mean SMA of glioblastoma patients at risk of sarcopenia (124.3 cm2, SD 30.8 cm2) was significantly lower than the mean SMA of patients with normal muscle status (146.3 cm2, SD 31.1 cm2, P < .001). We found a moderate association between TMT and SMA in the patients with normal muscle status (Spearman's rho 0.521, P < .001), and a strong association in the patients at risk of sarcopenia (Spearman's rho 0.678, P < .001). CONCLUSION: Our results confirm the use of TMT as a surrogate marker of total body skeletal muscle mass in glioblastoma, especially in frail patients at risk of sarcopenia. TMT can be used to identify patients with muscle loss early in the disease process, which enables the implementation of adequate intervention strategies.

Neurocognition in adults with intracranial tumors: does location really matter?

OBJECTIVE: As preservation of cognitive functioning increasingly becomes important in the light of ameliorated survival after intracranial tumor treatments, identification of eloquent brain areas would enable optimization of these treatments. METHODS: This cohort study enrolled adult intracranial tumor patients who received neuropsychological assessments pre-irradiation, estimating processing speed, verbal fluency and memory. Anatomical magnetic resonance imaging scans were used for multivariate voxel-wise lesion-symptom predictions of the test scores (corrected for age, gender, educational level, histological subtype, surgery, and tumor volume). Potential effects of histological and molecular subtype and corresponding WHO grades on the risk of cognitive impairment were investigated using Chi square tests. P-values were adjusted for multiple comparisons (p < .001 and p < .05 for voxel- and cluster-level, resp.). RESULTS: A cohort of 179 intracranial tumor patients was included [aged 19-85 years, median age (SD) = 58.46 (14.62), 50% females]. In this cohort, test-specific impairment was detected in 20-30% of patients. Higher WHO grade was associated with lower processing speed, cognitive flexibility and delayed memory in gliomas, while no acute surgery-effects were found. No grading, nor surgery effects were found in meningiomas. The voxel-wise analyses showed that tumor locations in left temporal areas and right temporo-parietal areas were related to verbal memory and processing speed, respectively. INTERPRETATION: Patients with intracranial tumors affecting the left temporal areas and right temporo-parietal areas might specifically be vulnerable for lower verbal memory and processing speed. These specific patients at-risk might benefit from early-stage interventions. Furthermore, based on future validation studies, imaging-informed surgical and radiotherapy planning could further be improved.

Prediction Models for Radiation-Induced Neurocognitive Decline in Adult Patients With Primary or Secondary Brain Tumors: A Systematic Review.

Purpose: Although an increasing body of literature suggests a relationship between brain irradiation and deterioration of neurocognitive function, it remains as the standard therapeutic and prophylactic modality in patients with brain tumors. This review was aimed to abstract and evaluate the prediction models for radiation-induced neurocognitive decline in patients with primary or secondary brain tumors. Methods: MEDLINE was searched on October 31, 2021 for publications containing relevant truncation and MeSH terms related to "radiotherapy," "brain," "prediction model," and "neurocognitive impairments." Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool. Results: Of 3,580 studies reviewed, 23 prediction models were identified. Age, tumor location, education level, baseline neurocognitive score, and radiation dose to the hippocampus were the most common predictors in the models. The Hopkins verbal learning (n = 7) and the trail making tests (n = 4) were the most frequent outcome assessment tools. All studies used regression (n = 14 linear, n = 8 logistic, and n = 4 Cox) as machine learning method. All models were judged to have a high risk of bias mainly due to issues in the analysis. Conclusion: Existing models have limited quality and are at high risk of bias. Following recommendations are outlined in this review to improve future models: developing cognitive assessment instruments taking into account the peculiar traits of the different brain tumors and radiation modalities; adherence to model development and validation guidelines; careful choice of candidate predictors according to the literature and domain expert consensus; and considering radiation dose to brain substructures as they can provide important information on specific neurocognitive impairments.

Ectopic Recurrence of Skull Base Chordoma after Proton Therapy.

BACKGROUND: Chordoma are rare tumors of the axial skeleton. The treatment gold standard is surgery, followed by particle radiotherapy. Total resection is usually not achievable in skull base chordoma (SBC) and high recurrence rates are reported. Ectopic recurrence as a first sign of treatment failure is considered rare. Favorable sites of these ectopic recurrences remain unknown. METHODS: Five out of 16 SBC patients treated with proton therapy and surgical resection developed ectopic recurrence as a first sign of treatment failure were critically analyzed regarding prior surgery, radiotherapy, and recurrences at follow-up imaging. RESULTS: Eighteen recurrences were defined in five patients. A total of 31 surgeries were performed for primary tumors and recurrences. Seventeen out of eighteen (94%) ectopic recurrences could be related to prior surgical tracts, outside the therapeutic radiation dose. Follow-up imaging showed that tumor recurrence was difficult to distinguish from radiation necrosis and anatomical changes due to surgery. CONCLUSIONS: In our cohort, we found uncommon ectopic recurrences in the surgical tract. Our theory is that these recurrences are due to microscopic tumor spill during surgery. These cells did not receive a therapeutic radiation dose. Advances in surgical possibilities and adjusted radiotherapy target volumes might improve local control and survival.

Temporal muscle thickness as an independent prognostic imaging marker in newly diagnosed glioblastoma patients: A validation study.

Background: Previous studies have recognized temporal muscle thickness (TMT) as a prognostic marker in glioblastoma, but clinical implementation is hampered due to studies' heterogeneity and lack of established cutoff values. The aim of this study was to assess the validity of recent proposed sex-specific TMT cutoff values in a real-world population of genotyped primary glioblastoma patients. Methods: We measured TMT in preoperative MR images of 328 patients. Sex-specific TMT cutoff values were used to divide patients into "at risk of sarcopenia" or "normal muscle status". Kaplan-Meier analyses and stepwise multivariate Cox-Regression analyses were used to assess the association with overall survival (OS) and progression-free survival (PFS). The association with occurrence of complications and discontinuation of glioblastoma treatment was investigated using odds ratios (OR). Results: Patients at risk of sarcopenia had a significantly higher risk of progression and death than patients with normal muscle status, which remained significant in the multivariate analyses (OS HR = 1.437; 95%CI: 1.046-1.973; P = .025 and PFS HR = 1.453; 95%CI: 1.037-2.036; P = .030). Patients at risk of sarcopenia also had a significantly higher risk of early discontinuation of treatment (OR = 2.45; 95%CI: 1.011-5.952; P = .042) and a significantly lower chance of receiving second-line treatment (OR = 0.23; 95%CI: 0.09-0.60; P = .001). There was no association with the occurrence of complications. Conclusions: Our study confirms external validity of the use of proposed sex-specific TMT cutoff values as an independent prognostic marker in newly diagnosed glioblastoma patients. This simple, noninvasive marker could improve patient counseling and aid in treatment decision processes or trial stratification.

Pre-treatment visualization of predicted radiation-induced acute alopecia in brain tumour patients.

BACKGROUND AND PURPOSE: Temporary alopecia is a common side-effect in brain tumour patients receiving cranial radiotherapy with a significant psychological burden for the affected patient. The purpose of this study was to generate a method in our treatment planning system (TPS) to visualize the expected radiation-induced alopecia 4 weeks after treatment, in order to inform the patients thereupon before the start of radiotherapy. MATERIAL AND METHODS: A pilot study was conducted in ten patients receiving hypo- (HF) or conventionally fractionated (CF) photon beam Volumetric Modulated Arc Therapy (VMAT) for an intracranial lesion. Dose calculations were correlated to visible alopecia four weeks after the end of treatment to create a structure predictive of alopecia in our TPS. These alopecia structures for both fractionation schedules were validated in two cohorts of 69 HF and 78 CF patients undergoing radiotherapy between 2016 and 2019. RESULTS: In the pilot cohort, a total physical dose of 4 Gy for HF and 12.6 Gy for CF radiotherapy were found to be predictive of alopecia 4 weeks after treatment. Applying these doses to our validation cohort, we found an accurate prediction of alopecia in 59/69 (86%) HF and 73/78 (96%) CF patients. For the total patient group of 147 patients, the predicted amount of alopecia was accurate in 90% of the cases. All inaccurate predictions overestimated the expected extent of alopecia. CONCLUSION: The presented straightforward method to visualize predicted alopecia 4 weeks after treatment has proven to predict the extent alopecia highly accurate in the vast majority of patients. Sharing these results with the patients pre-treatment may result in stress reduction before cranial irradiation.

Development of explanatory movies for the delineation of new organs at risk in neuro-oncology.

Ten new organs at risk (OARs) were recently introduced in the updated European Particle Therapy Network neurological contouring atlas. Despite the use of the illustrated atlas and descriptive text, interindividual contouring variations may persist. To further facilitate the contouring of these OARs, educational films were developed and published on www.cancerdata.org.