Oropharyngeal Cancer Staging Health Record Extraction Using Artificial Intelligence.

Importance: Accurate, timely, and cost-effective methods for staging oropharyngeal cancers are crucial for patient prognosis and treatment decisions, but staging documentation is often inaccurate or incomplete. With the emergence of artificial intelligence in medicine, data abstraction may be associated with reduced costs but increased efficiency and accuracy of cancer staging. Objective: To evaluate an algorithm using an artificial intelligence engine capable of extracting essential information from medical records of patients with oropharyngeal cancer and assigning tumor, nodal, and metastatic stages according to American Joint Committee on Cancer eighth edition guidelines. Design, Setting, and Participants: This retrospective diagnostic study was conducted among a convenience sample of 806 patients with oropharyngeal squamous cell carcinoma. Medical records of patients with staged oropharyngeal squamous cell carcinomas who presented to a single tertiary care center between January 1, 2010, and August 1, 2020, were reviewed. A ground truth cancer stage dataset and comprehensive staging rule book consisting of 135 rules encompassing p16 status, tumor, and nodal and metastatic stage were developed. Subsequently, 4 distinct models were trained: model T (entity relationship extraction) for anatomical location and invasion state, model S (numerical extraction) for lesion size, model M (sequential classification) for metastasis detection, and a p16 model for p16 status. For validation, results were compared against ground truth established by expert reviewers, and accuracy was reported. Data were analyzed from March to November 2023. Main Outcomes and Measures: The accuracy of algorithm cancer stages was compared with ground truth. Results: Among 806 patients with oropharyngeal cancer (mean [SD] age, 63.6 [10.6] years; 651 males [80.8%]), 421 patients (52.2%) were positive for human papillomavirus. The artificial intelligence engine achieved accuracies of 55.9% (95% CI, 52.5%-59.3%) for tumor, 56.0% (95% CI, 52.5%-59.4%) for nodal, and 87.6% (95% CI, 85.1%-89.7%) for metastatic stages and 92.1% (95% CI, 88.5%-94.6%) for p16 status. Differentiation between localized (stages 1-2) and advanced (stages 3-4) cancers achieved 80.7% (95% CI, 77.8%-83.2%) accuracy. Conclusion and Relevance: This study found that tumor and nodal staging accuracies were fair to good and excellent for metastatic stage and p16 status, with clinical relevance in assigning optimal treatment and reducing toxic effect exposures. Further model refinement and external validation with electronic health records at different institutions are necessary to improve algorithm accuracy and clinical applicability.

Predictors of Tumor Dynamics Over a 6-Week Course of Concurrent Chemoradiotherapy for Glioblastoma and the Effect on Survival.

PURPOSE: We present the final analyses of tumor dynamics and their prognostic significance during a 6-week course of concurrent chemoradiotherapy for glioblastoma in the Glioblastoma Longitudinal Imaging Observational study. METHODS AND MATERIALS: This is a prospective serial magnetic resonance imaging study in 129 patients with glioblastoma who had magnetic resonance imaging obtained at radiation therapy (RT) planning (F0), fraction 10 (F10), fraction 20 (F20), and 1-month post-RT. Tumor dynamics assessed included gross tumor volume relative to F0 (Vrel) and tumor migration distance (dmigration). Covariables evaluated included: corpus callosum involvement, extent of surgery, O6-methylguanine-DNA-methyltransferase methylation, and isocitrate dehydrogenase mutation status. RESULTS: The median Vrel were 0.85 (range, 0.25-2.29) at F10, 0.79 (range, 0.09-2.22) at F20, and 0.78 (range, 0.13-4.27) at 1 month after completion of RT. The median dmigration were 4.7 mm (range, 1.1-20.4 mm) at F10, 4.7 mm (range, 0.8-20.7 mm) at F20, and 6.1 mm (range, 0.0-45.5 mm) at 1 month after completion of RT. Compared with patients who had corpus callosum involvement (n = 26), those without corpus callosum involvement (n = 103) had significant Vrel reduction at F20 (P = .03) and smaller dmigration at F20 (P = .007). Compared with patients who had biopsy alone (n = 19) and subtotal resection (n = 71), those who had gross total resection (n = 38) had significant Vrel reduction at F10 (P = .001) and F20 (P = .001) and a smaller dmigration at F10 (P = .03) and F20 (P = .002). O6-Methylguanine-DNA-methyltransferase methylation and isocitrate dehydrogenase mutation status were not significantly associated with tumor dynamics. The median progression-free survival and overall survival (OS) were 8.5 months (95% CI, 6.9-9.9) and 20.4 months (95% CI, 17.6-25.2). In multivariable analyses, patients with Vrel ≥ 1.33 at F10 had worse OS (hazard ratio [HR], 4.6; 95% CI, 1.8-11.4; P = .001), and patients with dmigration ≥ 5 mm at 1-month post-RT had worse progression-free survival (HR, 1.76; 95% CI, 1.08-2.87) and OS (HR, 2.2; 95% CI, 1.2-4.0; P = .007). CONCLUSIONS: Corpus callosum involvement and extent of surgery are independent predictors of tumor dynamics during RT and can enable patient selection for adaptive RT strategies. Significant tumor enlargement at F10 and tumor migration 1-month post-RT were associated with poorer OS.

Evolving concepts in margin strategies and adaptive radiotherapy for glioblastoma: A new future is on the horizon.

Chemoradiotherapy is the standard treatment after maximal safe resection for glioblastoma (GBM). Despite advances in molecular profiling, surgical techniques, and neuro-imaging, there have been no major breakthroughs in radiotherapy (RT) volumes in decades. Although the majority of recurrences occur within the original gross tumor volume (GTV), treatment of a clinical target volume (CTV) ranging from 1.5 to 3.0 cm beyond the GTV remains the standard of care. Over the past 15 years, the incorporation of standard and functional MRI sequences into the treatment workflow has become a routine practice with increasing adoption of MR simulators, and new integrated MR-Linac technologies allowing for daily pre-, intra- and post-treatment MR imaging. There is now unprecedented ability to understand the tumor dynamics and biology of GBM during RT, and safe CTV margin reduction is being investigated with the goal of improving the therapeutic ratio. The purpose of this review is to discuss margin strategies and the potential for adaptive RT for GBM, with a focus on the challenges and opportunities associated with both online and offline adaptive workflows. Lastly, opportunities to biologically guide adaptive RT using non-invasive imaging biomarkers and the potential to define appropriate volumes for dose modification will be discussed.

Stereotactic body radiation therapy for spinal metastases: A new standard of care.

Advancements in systemic therapies for patients with metastatic cancer have improved overall survival and, hence, the number of patients living with spinal metastases. As a result, the need for more versatile and personalized treatments for spinal metastases to optimize long-term pain and local control has become increasingly important. Stereotactic body radiation therapy (SBRT) has been developed to meet this need by providing precise and conformal delivery of ablative high-dose-per-fraction radiation in few fractions while minimizing risk of toxicity. Additionally, advances in minimally invasive surgical techniques have also greatly improved care for patients with epidural disease and/or unstable spines, which may then be combined with SBRT for durable local control. In this review, we highlight the indications and controversies of SBRT along with new surgical techniques for the treatment of spinal metastases.

Utility of molecular markers in predicting local control specific to lung cancer spine metastases treated with stereotactic body radiotherapy.

BACKGROUND AND PURPOSE: We report outcomes following spine stereotactic body radiotherapy (SBRT) in metastatic non-small cell lung cancer (NSCLC) and the significance of programmed death-ligand 1 (PD-L1) status, epidermal growth factor receptor (EGFR) mutation and timing of immune check point inhibitors (ICI) on local failure (LF). MATERIALS AND METHODS: 165 patients and 389 spinal segments were retrospectively reviewed from 2009 to 2021. Baseline patient characteristics, treatment and outcomes were abstracted. Primary endpoint was LF and secondary, overall survival (OS) and vertebral compression fracture (VCF). Multivariable analysis (MVA) evaluated factors predictive of LF and VCF. RESULTS: The median follow-up and OS were: 13.0 months (range, 0.5-95.3 months) and 18.4 months (95% CI 11.4-24.6). 52.1% were male and 76.4% had adenocarcinoma. Of the 389 segments, 30.3% harboured an EGFR mutation and 17.0% were PD-L1 ≥ 50%. The 24 months LF rate in PD-L1 ≥ 50% vs PD-L1 < 50% was 10.7% vs. 38.0%, and in EGFR-positive vs. negative was 18.1% vs. 30.0%. On MVA, PD-L1 status of ≥ 50% (HR 0.32, 95% CI 0.15-0.69, p = 0.004) significantly predicted for lower LF compared to PD-L1 < 50%. Lower LF trend was seen with ICI administration peri and post SBRT (HR 0.41, 95% CI 0.16-1.05, p = 0.062). On MVA, polymetastatic disease (HR 3.28, 95% CI 1.84-5.85, p < 0.0001) and ECOG ≥ 2 (HR 1.87, 95% CI 1.16-3.02, p = 0.011) significantly predicted for worse OS and absence of baseline VCF predicted for lower VCF rate (HR 0.20, 95% CI 0.10-0.39, p < 0.0001). CONCLUSION: We report a significant association of PD-L1 ≥ 50% status on improved LC rates from spine SBRT in NSCLC patients.

Magnetic Resonance Imaging Frequency After Stereotactic Body Radiation Therapy for Spine Metastases.

PURPOSE: Stereotactic body radiation therapy (SBRT) is increasingly being used to treat spine metastases. Current post-SBRT imaging surveillance strategies in this patient population may benefit from a more data-driven and personalized approach. The objective of this study was to develop risk-stratified post-SBRT magnetic resonance imaging (MRI) surveillance strategies using quantitative methods. METHODS AND MATERIALS: Adult patients with bony spine metastases treated with SBRT between 2008 and 2021 and who had at least 2 follow-up spine MRIs were reviewed retrospectively. A recursive partitioning analysis model was developed to separate patients into different risk categories for post-SBRT progression anywhere within the spine. Imaging intervals were derived for each risk category using parametric survival regression based on multiple expected spine progression rates per scan. RESULTS: A total of 446 patients and 1039 vertebral segments were included. Cumulative incidence of spine progression was 19.2% at 1 year, 26.7% at 2 years, and 35.3% at 4 years. The internally validated risk stratification model was able to divide patients into 3 risk categories based on epidural disease, paraspinal disease, and Spinal Instability Neoplastic Score category. The 4-year risk of spine progression was 23.4%, 39.0%, and 51.8%, respectively, for the low-, intermediate-, and high-risk groups. Using an expected per-scan spine progression rate of 3.75%, the low-risk group would require follow-up scans every 6.0 months (95% CI, 4.9-7.6) and the intermediate-risk group would require surveillance every 3.1 months (95% CI, 2.6-3.7). At an expected spine progression rate of 5%, the high-risk group would require surveillance every 1.3 months (95% CI, 1.1-1.6) during the first 13.2 months after SBRT and every 5.9 months thereafter (95% CI, 2.8-12.3). CONCLUSIONS: Data-driven follow-up MRI surveillance intervals at a range of expected spine progression rates have been determined for patients at different risks of spine progression based on an internally validated, single-institution risk stratification model.

Stereotactic Body Radiation Therapy for Sacral Metastases: Deviation From Recommended Target Volume Delineation Increases the Risk of Local Failure.

PURPOSE: Although spine stereotactic body radiation therapy (SBRT) is considered a standard of care in the mobile spine, mature evidence reporting outcomes specific to sacral metastases is lacking. Furthermore, there is a need to validate the existing sacral SBRT international consensus contouring guidelines to define the optimal contouring approach. We report mature rates of local failure (LF), adverse events, and the effect of contouring deviations in the largest experience to date specific to sacrum SBRT. METHODS AND MATERIALS: Consecutive patients who underwent sacral SBRT from 2010 to 2021 were retrospectively reviewed. The primary endpoint was magnetic resonance imaging-based LF with a focus on adherence to target volume contouring recommendations. Secondary endpoints included vertebral compression fracture and neural toxicity. RESULTS: Of the 215 sacrum segments treated in 112 patients, most received 30 Gy/4 fractions (51%), 24 Gy/2 fractions (31%), or 30 Gy/5 fractions (10%). Sixteen percent of segments were nonadherent to the consensus guideline with a more restricted target volume (undercontoured). The median follow-up was 21.4 months (range, 1.5-116.9 months). The cumulative incidence of LF at 1 and 2 years was 18.4% and 23.1%, respectively. In those with guideline adherent versus nonadherent contours, the LF rate at 1 year was 15.1% versus 31.4% and at 2 years 18.8% versus 40.0% (hazard ratio [HR], 2.5; 95% CI, 1.4-4.6; P = .003), respectively. On multivariable analysis, guideline nonadherence (HR, 2.4; 95% CI, 1.3-4.7; P = .008), radioresistant histology (HR, 2.4; 95% CI, 1.4-4.1; P < .001), and extraosseous extension (HR, 2.5; 95% CI, 1.3-4.7; P = .005) predicted for an increased risk of LF. The cumulative incidence of vertebral compression fracture was 7.1% at 1 year and 12.3% at 2 years. Seven patients (6.3%) developed peripheral nerve toxicity, of whom 4 had been previously radiated. CONCLUSIONS: Sacral SBRT is associated with high efficacy rates and an acceptable toxicity profile. Adhering to consensus guidelines for target volume delineation is recommended to reduce the risk of LF.

Brain Tumor Imaging in Adolescents and Young Adults: 2021 WHO Updates for Molecular-based Tumor Types.

Published in 2021, the fifth edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) introduced new molecular criteria for tumor types that commonly occur in either pediatric or adult age groups. Adolescents and young adults (AYAs) are at the intersection of adult and pediatric care, and both pediatric-type and adult-type CNS tumors occur at that age. Mortality rates for AYAs with CNS tumors have increased by 0.6% per year for males and 1% per year for females from 2007 to 2016. To best serve patients, it is crucial that both pediatric and adult radiologists who interpret neuroimages are familiar with the various pediatric- and adult-type brain tumors and their typical imaging morphologic characteristics. Gliomas account for approximately 80% of all malignant CNS tumors in the AYA age group, with the most common types observed being diffuse astrocytic and glioneuronal tumors. Ependymomas and medulloblastomas also occur in the AYA population but are seen less frequently. Importantly, biologic behavior and progression of distinct molecular subgroups of brain tumors differ across ages. This review discusses newly added or revised gliomas in the fifth edition of the CNS WHO classification, as well as other CNS tumor types common in the AYA population.

Practice and principles of stereotactic body radiation therapy for spine and non-spine bone metastases.

Radiotherapy is the dominant treatment modality for painful spine and non-spine bone metastases (NSBM). Historically, this was achieved with conventional low dose external beam radiotherapy, however, stereotactic body radiotherapy (SBRT) is increasingly applied for these indications. Meta-analyses and randomized clinical trials have demonstrated improved pain response and more durable tumor control with SBRT for spine metastases. However, in the setting of NSBM, there is limited evidence supporting global adoption and large scale randomized clinical trials are in need. SBRT is technically demanding requiring careful consideration of organ at risk tolerance, and strict adherence to technical requirements including immobilization, simulation, contouring and image-guidance procedures. Additional considerations include follow up practices after SBRT, with appropriate imaging playing a critical role in response assessment. Finally, there is renewed research into promising new technologies that may further refine the use of SBRT in both spinal and NSBM in the years to come.

Dose-Escalated Radiation Therapy Is Associated With Improved Outcomes for High-Grade Meningioma.

PURPOSE: The optimal modern radiation therapy (RT) approach after surgery for atypical and malignant meningioma is unclear. We present results of dose escalation in a single-institution cohort spanning 2000 to 2021. METHODS AND MATERIALS: Consecutive patients with histopathologic grade 2 or 3 meningioma treated with RT were reviewed. A dose-escalation cohort (≥66 Gy equivalent dose in 2-Gy fractions using an α/ß = 10) was compared with a standard-dose cohort (<66 Gy). Outcomes were progression-free survival (PFS), cause-specific survival, overall survival (OS), local failure (LF), and radiation necrosis. RESULTS: One hundred eighteen patients (111 grade 2, 94.1%) were identified; 54 (45.8%) received dose escalation and 64 (54.2%) standard dose. Median follow-up was 45.4 months (IQR, 24.0-80.0 months) and median OS was 9.7 years (Q1: 4.6 years, Q3: not reached). All dose-escalated patients had residual disease versus 65.6% in the standard-dose cohort (P < .001). PFS at 3, 4, and 5 years in the dose-escalated versus standard-dose cohort was 78.9%, 72.2%, and 64.6% versus 57.2%, 49.1%, and 40.8%, respectively, (P = .030). On multivariable analysis, dose escalation (hazard ratio [HR], 0.544; P = .042) was associated with improved PFS, whereas ≥2 surgeries (HR, 1.989; P = .035) and older age (HR, 1.035; P < .001) were associated with worse PFS. The cumulative risk of LF was reduced with dose escalation (P = .016). Multivariable analysis confirmed that dose escalation was protective for LF (HR, 0.483; P = .019), whereas ≥2 surgeries before RT predicted for LF (HR, 2.145; P = .008). A trend was observed for improved cause-specific survival and OS in the dose-escalation cohort (P < .1). Seven patients (5.9%) developed symptomatic radiation necrosis with no significant difference between the 2 cohorts. CONCLUSIONS: Dose-escalated RT with ≥66 Gy for high-grade meningioma is associated with improved local control and PFS with an acceptable risk of radiation necrosis.

Tumor volumes in T3 supraglottic cancers treated with radiotherapy in the modern era: A study of the Canadian Head & Neck Collaborative Research Initiative.

PURPOSE: To evaluate the association of primary tumor volume (TV) with overall survival (OS) and disease-free survival (DFS) in T3 N0-3M0 supraglottic cancers treated with intensity-modulated radiotherapy (IMRT). METHODS: This was a retrospective cohort study involving 239 patients diagnosed with T3 N0-3M0 supraglottic cancers between 2002 and 2018 from seven regional cancer centers in Canada. Clinical data were obtained from the patient records. Supraglottic TV was measured by neuroradiologists on diagnostic imaging. Kaplan-Meier method was used for survival probabilities, and a restricted cubic spline Cox proportional hazards regression analysis was used to analyze TV associations with OS and DFS. RESULTS: Mean (SD) of participants was 65.2 (9.4) years; 176 (73.6%) participants were male. 90 (38%) were N0, and 151 (64%) received concurrent systemic therapy. Mean TV (SD) was 11.37 (12.11) cm3 . With mean follow up (SD) of 3.28 (2.60) years, 2-year OS was 72.7% (95% CI 66.9%-78.9%) and DFS was 53.6% (47.4%-60.6%). Increasing TV was associated (per cm3 increase) with worse OS (HR, 1.01, 95% CI 1.00-1.02, p < 0.01) and DFS (HR, 1.01, 95% CI 1.00-1.02, p = 0.02). CONCLUSIONS: Increasing primary tumor volume is associated with worse OS and DFS in T3 supraglottic cancers treated with IMRT, with no clear threshold. The findings suggest that patients with larger tumors and poor baseline laryngeal function may benefit from upfront laryngectomy with adjuvant radiotherapy.

Chemical Exchange Saturation Transfer MRI: What Neuro-Oncology Clinicians Need To Know.

Chemical exchange saturation transfer (CEST) is a relatively novel magnetic resonance imaging (MRI) technique with an image contrast designed for in vivo measurement of certain endogenous molecules with protons that are exchangeable with water protons, such as amide proton transfer commonly used for neuro-oncology applications. Recent technological advances have made it feasible to implement CEST on clinical grade scanners within practical acquisition times, creating new opportunities to integrate CEST in clinical workflow. In addition, the majority of CEST applications used in neuro-oncology are performed without the use gadolinium-based contrast agents which are another appealing feature of this technique. This review is written for clinicians involved in neuro-oncologic care (nonphysicists) as the target audience explaining what they need to know as CEST makes its way into practice. The purpose of this article is to (1) review the basic physics and technical principles of CEST MRI, and (2) review the practical applications of CEST in neuro-oncology.

Segmentation of Brain Metastases Using Background Layer Statistics (BLAST).

BACKGROUND AND PURPOSE: Accurate segmentation of brain metastases is important for treatment planning and evaluating response. The aim of this study was to assess the performance of a semiautomated algorithm for brain metastases segmentation using Background Layer Statistics (BLAST). MATERIALS AND METHODS: Nineteen patients with 48 parenchymal and dural brain metastases were included. Segmentation was performed by 4 neuroradiologists and 1 radiation oncologist. K-means clustering was used to identify normal gray and white matter (background layer) in a 2D parameter space of signal intensities from postcontrast T2 FLAIR and T1 MPRAGE sequences. The background layer was subtracted and operator-defined thresholds were applied in parameter space to segment brain metastases. The remaining voxels were back-projected to visualize segmentations in image space and evaluated by the operators. Segmentation performance was measured by calculating the Dice-Sørensen coefficient and Hausdorff distance using ground truth segmentations made by the investigators. Contours derived from the segmentations were evaluated for clinical acceptance using a 5-point Likert scale. RESULTS: The median Dice-Sørensen coefficient was 0.82 for all brain metastases and 0.9 for brain metastases of ≥10 mm. The median Hausdorff distance was 1.4 mm. Excellent interreader agreement for brain metastases volumes was found with an intraclass correlation coefficient = 0.9978. The median segmentation time was 2.8 minutes/metastasis. Forty-five contours (94%) had a Likert score of 4 or 5, indicating that the contours were acceptable for treatment, requiring no changes or minor edits. CONCLUSIONS: We show accurate and reproducible segmentation of brain metastases using BLAST and demonstrate its potential as a tool for radiation planning and evaluating treatment response.

Relationship between apparent diffusion coefficient and survival as a function of distance from gross tumor volume on radiation planning MRI in newly diagnosed glioblastoma.

PURPOSE: To investigate the changes in apparent diffusion coefficient (ADC) within incrementally-increased margins beyond the gross tumor volume (GTV) on post-operative radiation planning MRI and their prognostic utility in glioblastoma. METHODS: Radiation planning MRIs of adult patients with newly diagnosed glioblastoma from 2017 to 2020 were assessed. The ADC values were normalized to contralateral normal white matter (nADC). Using 1 mm isotropic incremental margin increases from the GTV, the nADC values were calculated at each increment. Age, ECOG performance status, extent of resection and MGMT promoter methylation status were obtained from medical records. Using univariate and multivariable Cox regression analysis, association of nADC to progression-free and overall survival (PFS, OS) was assessed at each increment. RESULTS: Seventy consecutive patients with mean age of 53.6 ± 10.3 years, were evaluated. The MGMT promoter was methylated in 31 (44.3%), unmethylated in 36 (51.6%) and unknown in 3 (4.3%) patients. 11 (16%) underwent biopsy, 41 (44%) subtotal resection and 18 (26%) gross total resection. For each 1 mm increase in distance from GTV, the nADC decreased by 0.16% (p < 0.0001). At 1-5 mm increment, the nADC was associated with OS (p < 0.01). From 6 to 11 mm increment the nADC was associated with OS with the p-value gradually increasing from 0.018 to 0.046. nADC was not associated with PFS. CONCLUSION: The nADC values at 1-11 mm increments from the GTV margin were associated with OS. Future prospective multicenter studies are needed to validate the findings and to pave the way for the utilization of ADC for margin reduction in radiation planning.

A Cancer Care Ontario Consensus-Based Organizational Guideline for the Planning and Delivery of Spine Stereotactic Body Radiation Therapy Treatment in Ontario.

The proposed recommendations are primarily based on the consensus opinion and in-field experience of the Ontario Health/Cancer Care Ontario stereotactic body radiation therapy (SBRT) for Spine Metastasis Guideline Development Group and published literature when available. Primary consideration was given to the perceived benefits for patients and the small likelihood of harm arising from recommendation implementation. Apart from the magnetic resonance imaging (MRI) follow-up strategy, all evidence was considered indirect and was provided by the working group in conjunction with their collective expertise in the field of SBRT. The application of an SBRT program requires a multidisciplinary team consisting of a radiation oncologist, spine surgeon, neuroradiologist, medical physicist, medical dosimetrist, and radiation therapist. In Canada, linear accelerators are the most used treatment delivery units and should follow technology-specific quality assurance procedures. Immobilization technique is location dependant. Treatment planning MRI sequences should be acquired no more than 14 days from the date of treatment. In the case of epidural disease, simulation MRI should be completed no more than 7 days from the date of treatment. After treatment, patients should be followed with routine clinical visits every 3 months for the first year, every 3 to 6 months during years 2 and 3, and every 4 to 6 months thereafter. The recommendations enclosed provide a framework for the minimum requirements for a cancer center in Ontario, Canada to offer SBRT for spine metastases.

Diffusion-weighted imaging on an MRI-linear accelerator to identify adversely prognostic tumour regions in glioblastoma during chemoradiation.

BACKGROUND AND PURPOSE: Survival in glioblastoma might be extended by escalating the radiotherapy dose to treatment-resistant tumour and adapting to tumour changes. Diffusion-weighted imaging (DWI) on MRI-linear accelerators (MR-Linacs) could be used to identify a dose escalation target, but its prognostic value must be demonstrated. The purpose of this study was to determine whether MR-Linac DWI can assess treatment response in glioblastoma and whether changes in DWI show greater prognostic value than changes in the contrast-enhancing gross tumour volume (GTV). MATERIALS AND METHODS: Seventy-five patients with glioblastoma were treated with chemoradiotherapy, of which 32 were treated on a 1.5 T MRI-linear accelerator (MR-Linac). Patients were imaged with simulation MRI scanners (MR-sim) at treatment planning and weeks 2, 4, and 10 after treatment start. Twenty-eight patients had additional MR-Linac DWI sequences. Cox modelling was used to evaluate the correlation of overall and progression-free survival (OS and PFS) with clinical variables and volumetric changes in the GTV and low-ADC regions (ADC < 1.25 µm2/ms within GTV). RESULTS: In total, 479 MR-Linac DWI and 289 MR-sim DWI datasets were analyzed. MR-Linac low-ADC changes between weeks 2 and 5 inclusive were prognostic for OS (hazard ratio lower limits ≥ 1.2, p-values ≤ 0.02). MR-sim low-ADC changes showed greater correlation with OS and PFS than GTV changes (e.g., OS hazard ratio at week 2 was 3.4 (p <0.001) for low-ADC versus 2.0 (p = 0.022) for GTV). CONCLUSION: MR-Linac DWI can measure low-ADC tumour volumes that correlate with OS and PFS better than contrast-enhancing GTV. Low-ADC regions could serve as dose escalation targets.

Re-irradiation for recurrent high-grade glioma: an analysis of prognostic factors for survival and predictors of radiation necrosis.

PURPOSE: Recurrent high-grade glioma (rHGG) is a heterogeneous population, and the ideal patient selection for re-irradiation (re-RT) has yet to be established. This study aims to identify prognostic factors for rHGG patients treated with re-RT. METHODS: We retrospectively reviewed consecutive adults with rHGG who underwent re-RT from 2009 to 2020 from our institutional database. The primary objective was overall survival (OS). Secondary endpoints included prognostic factors for early death (< 6 months after re-RT) and predictors of radiation necrosis (RN). RESULTS: For the 79 patients identified, the median OS after re-RT was 9.9 months (95% CI 8.3-11.6). On multivariate analyses, re-resection at progression (HR 0.56, p = 0.027), interval from primary treatment to first progression ≥ 16.3 months (HR 0.61, p = 0.034), interval from primary treatment to re-RT ≥ 23.9 months (HR 0.35, p < 0.001), and re-RT PTV volume < 112 cc (HR 0.27, p < 0.001) were prognostic for improved OS. Patients who had unmethylated-MGMT tumours (OR 12.4, p = 0.034), ≥ 3 prior systemic treatment lines (OR 29.1, p = 0.022), interval to re-RT < 23.9 months (OR 9.0, p = 0.039), and re-RT PTV volume ≥ 112 cc (OR 17.8, p = 0.003) were more likely to die within 6 months of re-RT. The cumulative incidence of RN was 11.4% (95% CI 4.3-18.5) at 12 months. Concurrent bevacizumab use (HR < 0.001, p < 0.001) and cumulative equivalent dose in 2 Gy fractions (EQD2, α/ß = 2) < 99 Gy2 (HR < 0.001, p < 0.001) were independent protective factors against RN. Re-RT allowed for less corticosteroid dependency. Sixty-six percent of failures after re-RT were in-field. CONCLUSION: We observe favorable OS rates following re-RT and identified prognostic factors, including methylation status, that can assist in patient selection and clinical trial design. Concurrent use of bevacizumab mitigated the risk of RN.

30 Gy in 4 Stereotactic Body Radiotherapy Fractions for Complex Spinal Metastases: Mature Outcomes Supporting This Novel Regimen.

BACKGROUND AND OBJECTIVES: We designed a 30 Gy in 4 fractions stereotactic body radiotherapy protocol, as an alternative option to our standard 2-fraction approach, for primarily large volume, multilevel, or previously radiated spinal metastases. We report imaging-based outcomes of this novel fractionation scheme. METHODS: The institutional database was reviewed to identify all patients who underwent 30 Gy/4 fractions from 2010 to 2021. Primary outcomes were magnetic resonance-based vertebral compression fracture (VCF) and local failure per treated vertebral segment. RESULTS: We reviewed 245 treated segments in 116 patients. The median age was 64 years (range, 24-90). The median number of consecutive segments within the treatment volume was 2 (range, 1-6), and the clinical target volume (CTV) was 126.2 cc (range, 10.4-863.5). Fifty-four percent had received at least 1 previous course of radiotherapy, and 31% had previous spine surgery at the treated segment. The baseline Spinal Instability Neoplastic Score was stable, potentially unstable, and unstable for 41.6%, 51.8%, and 6.5% of segments, respectively. The cumulative incidence of local failure was 10.7% (95% CI 7.1-15.2) at 1 year and 16% (95% CI 11.5-21.2) at 2 years. The cumulative incidence of VCF was 7.3% (95% CI 4.4-11.2) at 1 year and 11.2% (95% CI 7.5-15.8) at 2 years. On multivariate analysis, age ≥68 years ( P = .038), CTV volume ≥72 cc ( P = .021), and no previous surgery ( P = .021) predicted an increased risk of VCF. The risk of VCF for CTV volumes <72 cc/≥72 cc was 1.8%/14.6% at 2 years. No case of radiation-induced myelopathy was observed. Five percent of patients developed plexopathy. CONCLUSION: 30 Gy in 4 fractions was safe and efficacious despite the population being at increased risk of toxicity. The lower risk of VCF in previously stabilized segments highlights the potential for a multimodal treatment approach for complex metastases, especially for those with a CTV volume of ≥72 cc.