Novel Functional Radiomics for Prediction of Cardiac Positron Emission Tomography Avidity in Lung Cancer Radiotherapy.

PURPOSE: Traditional methods of evaluating cardiotoxicity focus on radiation doses to the heart. Functional imaging has the potential to provide improved prediction for cardiotoxicity for patients with lung cancer. Fluorine-18 (18F) fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging is routinely obtained in a standard cancer staging workup. This work aimed to develop a radiomics model predicting clinical cardiac assessment using 18F-FDG PET/CT scans before thoracic radiation therapy. METHODS: Pretreatment 18F-FDG PET/CT scans from three study populations (N = 100, N = 39, N = 70) were used, comprising two single-institutional protocols and one publicly available data set. A clinician (V.J.) classified the PET/CT scans per clinical cardiac guidelines as no uptake, diffuse uptake, or focal uptake. The heart was delineated, and 210 novel functional radiomics features were selected to classify cardiac FDG uptake patterns. Training data were divided into training (80%)/validation (20%) sets. Feature reduction was performed using the Wilcoxon test, hierarchical clustering, and recursive feature elimination. Ten-fold cross-validation was carried out for training, and the accuracy of the models to predict clinical cardiac assessment was reported. RESULTS: From 202 of 209 scans, cardiac FDG uptake was scored as no uptake (39.6%), diffuse uptake (25.3%), and focal uptake (35.1%), respectively. Sixty-two independent radiomics features were reduced to nine clinically pertinent features. The best model showed 93% predictive accuracy in the training data set and 80% and 92% predictive accuracy in two external validation data sets. CONCLUSION: This work used an extensive patient data set to develop a functional cardiac radiomic model from standard-of-care 18F-FDG PET/CT scans, showing good predictive accuracy. The radiomics model has the potential to provide an automated method to predict existing cardiac conditions and provide an early functional biomarker to identify patients at risk of developing cardiac complications after radiotherapy.

Evaluation of variables predicting PFT changes for lung cancer patients treated on a prospective 4DCT-ventilation functional avoidance clinical trial.

PURPOSE: Functional avoidance radiotherapy uses functional imaging to reduce pulmonary toxicity by designing radiotherapy plans that reduce doses to functional regions of the lung. A phase-II, multi-center, prospective study of 4DCT-ventilation functional avoidance was completed. Pre and post-treatment pulmonary function tests (PFTs) were acquired and assessed pulmonary function change. This study aims to evaluate which clinical, dose and dose-function factors predict PFT changes for patients treated with 4DCT-ventilation functional avoidance radiotherapy. MATERIALS AND METHODS: 56 patients with locally advanced lung cancer receiving radiotherapy were accrued. PFTs were obtained at baseline and three months following radiotherapy and included forced expiratory volume in 1-second (FEV1), forced vital capacity (FVC), and FEV1/FVC. The ability of patient, clinical, dose (lung and heart), and dose-function metrics (metrics that combine dose and 4DCT-ventilation-based function) to predict PFT changes were evaluated using univariate and multivariate linear regression. RESULTS: Univariate analysis showed that only dose-function metrics and the presence of chronic obstructive pulmonary disease (COPD) were significant (p<0.05) in predicting FEV1 decline. Multivariate analysis identified a combination of clinical (immunotherapy status, presence of thoracic comorbidities, smoking status, and age), along with lung dose, heart dose, and dose-function metrics in predicting FEV1 and FEV1/FVC changes. CONCLUSION: The current work evaluated factors predicting PFT changes for patients treated in a prospective functional avoidance radiotherapy study. The data revealed that lung dose- function metrics could predict PFT changes, validating the significance of reducing the dose to the functional lung to mitigate the decline in pulmonary function and providing guidance for future clinical trials.

Consensus Quality Measures and Dose Constraints for Lung Cancer From the Veterans Affairs Radiation Oncology Quality Surveillance Program and ASTRO Expert Panel.

PURPOSE: For patients with lung cancer, it is critical to provide evidence-based radiation therapy to ensure high-quality care. The US Department of Veterans Affairs (VA) National Radiation Oncology Program partnered with the American Society for Radiation Oncology (ASTRO) as part of the VA Radiation Oncology Quality Surveillance to develop lung cancer quality metrics and assess quality of care as a pilot program in 2016. This article presents recently updated consensus quality measures and dose-volume histogram (DVH) constraints. METHODS AND MATERIALS: A series of measures and performance standards were reviewed and developed by a Blue-Ribbon Panel of lung cancer experts in conjunction with ASTRO in 2022. As part of this initiative, quality, surveillance, and aspirational metrics were developed for (1) initial consultation and workup; (2) simulation, treatment planning, and treatment delivery; and (3) follow-up. The DVH metrics for target and organ-at-risk treatment planning dose constraints were also reviewed and defined. RESULTS: Altogether, a total of 19 lung cancer quality metrics were developed. There were 121 DVH constraints developed for various fractionation regimens, including ultrahypofractionated (1, 3, 4, or 5 fractions), hypofractionated (10 and 15 fractionations), and conventional fractionation (30-35 fractions). CONCLUSIONS: The devised measures will be implemented for quality surveillance for veterans both inside and outside of the VA system and will provide a resource for lung cancer-specific quality metrics. The recommended DVH constraints serve as a unique, comprehensive resource for evidence- and expert consensus-based constraints across multiple fractionation schemas.

Predictors and characteristics of Rib fracture following SBRT for lung tumors.

BACKGROUND: The utilization of stereotactic body radiation therapy (SBRT) is increasing for primary and secondary lung neoplasms. Despite encouraging results, SBRT is associated with an increased risk of osteoradionecrosis-induced rib fracture. We aimed to (1) evaluate potential clinical, demographic, and procedure-related risk factors for rib fractures and (2) describe the radiographic features of post-SBRT rib fractures. METHODS: We retrospectively identified 106 patients who received SBRT between 2015 and 2018 for a primary or metastatic lung tumor with at least 12 months of follow up. Exclusion criteria were incomplete records, previous ipsilateral thoracic radiation, or relevant prior trauma. Computed tomography (CT) images were reviewed to identify and characterize rib fractures. Multivariate logistic regression modeling was employed to determine clinical, demographic, and procedural risk factors (e.g., age, sex, race, medical comorbidities, dosage, and tumor location). RESULTS: A total of 106 patients with 111 treated tumors met the inclusion criteria, 35 (32%) of whom developed at least one fractured rib (60 total fractured ribs). The highest number of fractured ribs per patient was five. Multivariate regression identified posterolateral tumor location as the only independent risk factor for rib fracture. On CT, fractures showed discontinuity between healing edges in 77% of affected patients. CONCLUSIONS: Nearly one third of patients receiving SBRT for lung tumors experienced rib fractures, 34% of whom experienced pain. Many patients developed multiple fractures. Post-SBRT fractures demonstrated a unique discontinuity between the healing edges of the rib, a distinct feature of post-SBRT rib fractures. The only independent predictor of rib fracture was tumor location along the posterolateral chest wall. Given its increasing frequency of use, describing the risk profile of SBRT is vital to ensure patient safety and adequately inform patient expectations.

Characterizing Pulmonary Function Test Changes for Patients With Lung Cancer Treated on a 2-Institution, 4-Dimensional Computed Tomography-Ventilation Functional Avoidance Prospective Clinical Trial.

Purpose: Four-dimensional computed tomography (4DCT)-ventilation-based functional avoidance uses 4DCT images to generate plans that avoid functional regions of the lung with the goal of reducing pulmonary toxic effects. A phase 2, multicenter, prospective study was completed to evaluate 4DCT-ventilation functional avoidance radiation therapy. The purpose of this study was to report the results for pretreatment to posttreatment pulmonary function test (PFT) changes for patients treated with functional avoidance radiation therapy. Methods and Materials: Patients with locally advanced lung cancer receiving chemoradiation were accrued. Functional avoidance plans based on 4DCT-ventilation images were generated. PFTs were obtained at baseline and 3 months after chemoradiation. Differences for PFT metrics are reported, including diffusing capacity for carbon monoxide (DLCO), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC). PFT metrics were compared for patients who did and did not experience grade 2 or higher pneumonitis. Results: Fifty-six patients enrolled on the study had baseline and posttreatment PFTs evaluable for analysis. The mean change in DLCO, FEV1, and FVC was -11.6% ± 14.2%, -5.6% ± 16.9%, and -9.0% ± 20.1%, respectively. The mean change in DLCO was -15.4% ± 14.4% for patients with grade 2 or higher radiation pneumonitis and -10.8% ± 14.1% for patients with grade <2 radiation pneumonitis (P = .37). The mean change in FEV1 was -14.3% ± 22.1% for patients with grade 2 or higher radiation pneumonitis and -3.9% ± 15.4% for patients with grade <2 radiation pneumonitis (P = .09). Conclusions: The current work is the first to quantitatively characterize PFT changes for patients with lung cancer treated on a prospective functional avoidance radiation therapy study. In comparison with patients treated with standard thoracic radiation planning, the data qualitatively show that functional avoidance resulted in less of a decline in DLCO and FEV1. The presented data can help elucidate the potential pulmonary function improvement with functional avoidance radiation therapy.

Definitive radiotherapy for meningeal brainstem melanocytoma: a case report.

Meningeal melanocytomas are rare, benign tumours of the central nervous system arising from the melanocytes of the leptomeninges. First-line treatment consists of either gross or subtotal resection with or without radiotherapy. However, given the sensitive locations of these tumours, alternative treatment options such as definitive radiotherapy may be warranted in patients deemed high-risk or without accessible tumours. A 67-year-old male presenting with spastic gait, frequent falls, and vertical gaze palsy was diagnosed with a 2.4 cm primary meningeal melanocytoma arising from the interpeduncular fossa. Given the critical tumour position within the brainstem, definitive radiotherapy was recommended. He received fractionated stereotactic radiotherapy (FSRT) to a total dose of 54 Gy in 27 fractions, resulting in a gradual improvement in gait and ocular range of motion. Follow-up imaging over the next three years revealed largely stable disease and an increase in edema with mild upper extremity weakness that improved with steroids. He was followed for three years and expired four years after treatment due to pneumonia. For patients unable to receive surgical resection, definitive RT may provide local control with minimal morbidity.

Creating and Implementing a Principal Investigator Tool Kit for Enhancing Accrual to Late Phase Clinical Trials: Development and Usability Study.

BACKGROUND: Accrual to oncology clinical trials remains a challenge, particularly during the COVID-19 pandemic. For late phase clinical trials funded by the National Cancer Institute, the development of these research protocols is a resource-intensive process; however, mechanisms to optimize patient accrual after trial activation are underdeveloped across the National Clinical Trial Network (NCTN). Low patient accrual can lead to the premature closure of clinical trials and can ultimately delay the availability of new, potentially life-saving therapies in oncology. OBJECTIVE: The purpose of this study is to formally create an easily implemented tool kit of resources for investigators of oncology clinical trials within the NCTN, specifically the NRG Oncology cooperative group, in order to optimize patient accrual. METHODS: NRG Oncology sought to formally develop a tool kit of resources to use at specific time points during the lifetime of NRG Oncology clinical trials. The tools are clearly described and involve the facilitation of engagement of the study principal investigator with the scientific and patient advocate community during the planning, activation, and accrual periods. Social media tools are also leveraged to enhance such engagement. The principal investigator (PI) tool kit was created in 2019 and thereafter piloted with the NRG Oncology/Alliance NRG-LU005 phase II or III trial in small-cell lung cancer. The PI tool kit was developed by the NRG Oncology Protocol Operations Management committee and was tested with the NRG/Alliance LU005 randomized trial within the NCTN. RESULTS: NRG Oncology/Alliance NRG-LU005 has seen robust enrollment, currently 127% of the projected accrual. Importantly, many of the tool kit elements are already being used in ongoing NRG Oncology trials, with 56% of active NRG trials using at least one element of the PI tool kit and all in-development trials offered the resource. This underscores the feasibility and potential benefits of deploying the PI tool kit across all NRG Oncology trials moving forward. CONCLUSIONS: While clinical trial accrual can be challenging, the PI tool kit has been shown to augment accrual in a low-cost and easily implementable fashion. It could be widely and consistently deployed across the NCTN to improve accrual in oncology clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT03811002; https://clinicaltrials.gov/ct2/show/NCT03811002.

Scalp-Sparing Radiation With Concurrent Temozolomide and Tumor Treating Fields (SPARE) for Patients With Newly Diagnosed Glioblastoma.

Introduction: Standard-of-care treatment for patients with newly diagnosed glioblastoma (GBM) after surgery or biopsy includes concurrent chemoradiation followed by maintenance temozolomide (TMZ) with tumor treating fields (TTFields). Preclinical studies suggest TTFields and radiotherapy work synergistically. We report the results of our trial evaluating the safety of TTFields used concurrently with chemoradiation. Methods: This is a single-arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Adult patients (age ≥ 18 years) with newly diagnosed glioblastoma and a Karnofsky performance score (KPS) of ≥ 60 were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions) with TMZ (75 mg/m2 daily) and TTFields (200 kHz). Maintenance therapy included TMZ and continuation of TTFields. Scalp-sparing radiation treatment was used to reduce radiation dermatitis. Radiation treatment was delivered through the TTFields arrays. The primary endpoint was safety and toxicity of tri-modality treatment within 30 days of completion of chemoradiation treatment. Results: There were 30 patients enrolled, including 20 (66.7%) men and 10 (33.3%) women, with a median age of 58 years (range 19 to 77 years). Median KPS was 90 (range 70 to 100). A total of 12 (40%) patients received a gross total resection and 18 (60%) patients had a subtotal resection. A total of 12 (40%) patients had multifocal disease at presentation. There were 20 (66.7%) patients who had unmethylated O(6)-methylguanine-DNA-methyltransferase (MGMT) promotor status and 10 (33.3%) patients who had methylated MGMT promoter status. Median follow-up was 15.2 months (range 1.7 to 23.6 months). Skin adverse events were noted in 83.3% of patients, however, these were limited to Grade 1 or 2 events, which resolved spontaneously or with topical medications. The primary end point was met; no TTFields discontinuation occurred during the evaluation period due to high grade scalp toxicity. A total of 27 (90%) patients had progression, with a median progression-free survival (PFS) of 9.3 months (95% confidence interval (CI): 8.5-11.6 months). The 1-year progression-free survival was 23% (95% CI: 12%-45%). The median overall survival (OS) was 15.8 months (95% CI: 12.5 months-infinity). The 1-year overall survival was 66% (95% CI: 51%-86%). Conclusions: Concurrent TTFields with scalp-sparing chemoradiation is a feasible and well-tolerated treatment option with limited toxicity. A phase 3, randomized clinical trial (EF-32, clinicaltrials.gov Identifier: NCT04471844) investigating the clinical benefit of concurrent TTFields with chemoradiation treatment is currently enrolling. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT03477110.

How to Respond to a Ransomware Attack? One Radiation Oncology Department's Response to a Cyber-Attack on Their Record and Verify System.

The digitization of healthcare for patient safety and efficiency introduced third party networks into closed hospital systems increasing the probability of cyberattacks and their consequences(1). In April 2021, a major vendor of a Radiation Oncology (RO) record and verify system (RVS) suffered a ransomware attack, affecting our department and many others across the United States. This article summarizes our response to the ransomware event including workflows, team member roles, responsibilities, communications and departmental recovery. The RVS created or housed accurate patient dose records for 6 locations. The immediate response to the ransomware attack was to shut down the system including the ability to treat patients. With the utilization of the hospital EMR and pre-existing interfaces with RVS, the department was able to safely continue patient radiotherapy treatments innovatively utilizing a direct Digital Imaging and Communications in Medicine (DICOM) transfer of patient data to the linear accelerators and implementing paper charting. No patients were treated in the first 24 hours of the attack. Within 48 hours of the ransomware event, 50% of patients were treated, and within 1 week, 95% of all patients were treated using direct DICOM transfer and paper charts. The RVS was completely unavailable for 2.5 weeks and full functionality was not restored for 4.5 weeks. A phased approach was adopted for re-introduction of patient treatments back into the RVS. Human capital costs included communication, outreach, workflow creation, quality assurance and extended clinical hours. Key lessons learned were to have a back-up of essential information, employ 'dry run' emergency training, having consistent parameter requirements across different vendor hardware and software, and having a plan for the recovery effort of restoring normal operations once software is operational. The provided report presents valuable information for the development of cyber-attack preparedness for RO departments.

Independently validated sex-specific nomograms for predicting survival in patients with newly diagnosed glioblastoma: NRG Oncology RTOG 0525 and 0825.

BACKGROUND/PURPOSE: Glioblastoma (GBM) is the most common primary malignant brain tumor. Sex has been shown to be an important prognostic factor for GBM. The purpose of this study was to develop and independently validate sex-specific nomograms for estimation of individualized GBM survival probabilities using data from 2 independent NRG Oncology clinical trials. METHODS: This analysis included information on 752 (NRG/RTOG 0525) and 599 (NRG/RTOG 0825) patients with newly diagnosed GBM. The Cox proportional hazard models by sex were developed using NRG/RTOG 0525 and significant variables were identified using a backward selection procedure. The final selected models by sex were then independently validated using NRG/RTOG 0825. RESULTS: Final nomograms were built by sex. Age at diagnosis, KPS, MGMT promoter methylation and location of tumor were common significant predictors of survival for both sexes. For both sexes, tumors in the frontal lobes had significantly better survival than tumors of multiple sites. Extent of resection, and use of corticosteroids were significant predictors of survival for males. CONCLUSIONS: A sex specific nomogram that assesses individualized survival probabilities (6-, 12- and 24-months) for patients with GBM could be more useful than estimation of overall survival as there are factors that differ between males and females. A user friendly online application can be found here- https://npatilshinyappcalculator.shinyapps.io/SexDifferencesInGBM/ .

Long-Term Report of a Comprehensive Molecular and Genomic Analysis in NRG Oncology/RTOG 0424: A Phase II Study of Radiation and Temozolomide in High-Risk Grade II Glioma.

PURPOSE: This study sought to determine the prognostic significance of the WHO-defined glioma molecular subgroups along with additional alterations, including MGMT promoter methylation and mutations in ATRX, CIC, FUBP1, TERT, and TP53, in NRG/RTOG 0424 using long-term follow-up data. METHODS: Mutations were determined using an Ion Torrent sequencing panel. 1p/19q co-deletion and MGMT promoter methylation were determined by Affymetrix OncoScan and Illumina 450K arrays. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and tested using the log-rank test. Hazard ratios were calculated using the Cox proportional hazard model. Multivariable analyses (MVAs) included patient pretreatment characteristics. RESULTS: We obtained complete molecular data to categorize 80/129 eligible patients within the WHO subgroups. Of these, 26 (32.5%) were IDHmutant/co-deleted, 28 (35%) were IDHmutant/non-co-deleted, and 26 (32.5%) were IDHwild-type. Upon single-marker MVA, both IDHmutant subgroups were associated with significantly better OS and PFS (P values < .001), compared with the IDHwild-type subgroup. MGMT promoter methylation was obtained on 76 patients, where 58 (76%) were methylated and 18 (24%) were unmethylated. Single-marker MVAs demonstrated that MGMT promoter methylation was statistically significant for OS (P value < .001) and PFS (P value = .003). In a multimarker MVA, one WHO subgroup comparison (IDHmutant/co-deleted v IDHwild-type) was significant for OS (P value = .045), whereas MGMT methylation did not retain significance. CONCLUSION: This study reports the long-term prognostic effect of the WHO molecular subgroups, MGMT promoter methylation, and other mutations in NRG/RTOG 0424. These results demonstrate that the WHO molecular classification and MGMT both serve as strong prognostic indicators, but that MGMT does not appear to add statistically significant prognostic value to the WHO subgrouping, above and beyond IDH and 1p/19q status.

Addition of Metformin to Concurrent Chemoradiation in Patients With Locally Advanced Non-Small Cell Lung Cancer: The NRG-LU001 Phase 2 Randomized Clinical Trial.

IMPORTANCE: Non-small cell lung cancer (NSCLC) has relatively poor outcomes. Metformin has significant data supporting its use as an antineoplastic agent. OBJECTIVE: To compare chemoradiation alone vs chemoradiation and metformin in stage III NSCLC. DESIGN, SETTING, AND PARTICIPANTS: The NRG-LU001 randomized clinical trial was an open-label, phase 2 study conducted from August 24, 2014, to December 15, 2016. Patients without diabetes who were diagnosed with unresectable stage III NSCLC were stratified by performance status, histology, and stage. The setting was international and multi-institutional. This study examined prespecified endpoints, and data were analyzed on an intent-to-treat basis. Data were analyzed from February 25, 2019, to March 6, 2020. INTERVENTIONS: Chemoradiation and consolidation chemotherapy with or without metformin. MAIN OUTCOMES AND MEASURES: The primary outcome was 1-year progression-free survival (PFS), designed to detect 15% improvement in 1-year PFS from 50% to 65% (hazard ratio [HR], 0.622). Secondary end points included overall survival, time to local-regional recurrence, time to distant metastasis, and toxicity per Common Terminology Criteria for Adverse Events, version 4.03. RESULTS: A total of 170 patients were enrolled, with 167 eligible patients analyzed after exclusions (median age, 64 years [interquartile range, 58-72 years]; 97 men [58.1%]; 137 White patients [82.0%]), with 81 in the control group and 86 in the metformin group. Median follow-up was 27.7 months (range, 0.03-47.21 months) among living patients. One-year PFS rates were 60.4% (95% CI, 48.5%-70.4%) in the control group and 51.3% (95% CI, 39.8%-61.7%) in the metformin group (HR, 1.15; 95% CI, 0.77-1.73; P = .24). Clinical stage was the only factor significantly associated with PFS on multivariable analysis (HR, 1.79; 95% CI, 1.19-2.69; P = .005). One-year overall survival was 80.2% (95% CI, 69.3%-87.6%) in the control group and 80.8% (95% CI, 70.2%-87.9%) in the metformin group. There were no significant differences in local-regional recurrence or distant metastasis at 1 or 2 years. No significant difference in adverse events was observed between treatment groups. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the addition of metformin to concurrent chemoradiation was well tolerated but did not improve survival among patients with unresectable stage III NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02186847.

Stereotactic body radiation therapy (SBRT) for patients with stage I non-small cell lung cancer is applicable to more tumors than sublobar resection.

BACKGROUND: Virtually all patients with medically inoperable stage I non-small cell lung cancer (NSCLC) can receive stereotactic body radiation therapy. However, the percentage of such patients in whom sublobar resection is technically feasible is unknown. This discrepancy can confound clinical trial eligibility and designs comparing stereotactic body radiation therapy vs. sublobar resection. METHODS: A total of 137 patients treated with stereotactic body radiation therapy for lung lesions (3/2013-11/2017) underwent retrospective review. Diagnostic CT chest and PET/CT images, stereotactic body radiation therapy dates, and demographic data were collected on 100 of 137 patients. Two experienced board-certified thoracic surgeons independently reviewed anonymized patients' pre-stereotactic body radiation therapy diagnostic imaging and completed a custom survey about the technical feasibility of sublobar resection for each patient. Interrater agreement was measured using Cohen's kappa coefficient by bootstrap methodology. Summary statistics were performed for baseline demographics and tumor characteristics. RESULTS: Of the 100 patients, 57% were female, with median age of 75 years (range, 52-95 years) and Karnofsky Performance Status of 80 (range, 40-100). Most patients (61%) had Stage IA1, T1a tumors. For interrater agreement analysis, one patient was removed from each cohort due to inability to locate tumor on images, leaving 98 patients analyzed. Comparing Surgeon #1 vs. Surgeon #2, 64 (65.3%) vs. 69 (70.3%) of tumors were thought eligible for sublobar resection, respectively (κ=0.414). CONCLUSIONS: Stereotactic body radiation therapy for stage I NSCLC is applicable to more tumors than sublobar resection, with ~30-35% of stereotactic body radiation therapy patients unable to undergo sublobar resection assessed by pretreatment diagnostic imaging based on technical grounds. This study illustrates that clinical trials comparing stereotactic body radiation therapy vs. sublobar resection are limited to only a subpopulation of patients with stage I NSCLC.

Initial Clinical Experience of MR-Guided Radiotherapy for Non-Small Cell Lung Cancer.

Curative-intent radiotherapy plays an integral role in the treatment of lung cancer and therefore improving its therapeutic index is vital. MR guided radiotherapy (MRgRT) systems are the latest technological advance which may help with achieving this aim. The majority of MRgRT treatments delivered to date have been stereotactic body radiation therapy (SBRT) based and include the treatment of (ultra-) central tumors. However, there is a move to also implement MRgRT as curative-intent treatment for patients with inoperable locally advanced NSCLC. This paper presents the initial clinical experience of using the two commercially available systems to date: the ViewRay MRIdian and Elekta Unity. The challenges and potential solutions associated with MRgRT in lung cancer will also be highlighted.

Phase Ib Clinical Trial of IGV-001 for Patients with Newly Diagnosed Glioblastoma.

PURPOSE: Despite standard of care (SOC) established by Stupp, glioblastoma remains a uniformly poor prognosis. We evaluated IGV-001, which combines autologous glioblastoma tumor cells and an antisense oligonucleotide against IGF type 1 receptor (IMV-001), in newly diagnosed glioblastoma. PATIENTS AND METHODS: This open-label protocol was approved by the Institutional Review Board at Thomas Jefferson University. Tumor cells collected during resection were treated ex vivo with IMV-001, encapsulated in biodiffusion chambers with additional IMV-001, irradiated, then implanted in abdominal acceptor sites. Patients were randomized to four exposure levels, and SOC was initiated 4-6 weeks later. On the basis of clinical improvements, randomization was halted after patient 23, and subsequent patients received only the highest exposure. Safety and tumor progression were primary and secondary objectives, respectively. Time-to-event outcomes were compared with the SOC arms of published studies. RESULTS: Thirty-three patients were enrolled, and median follow-up was 3.1 years. Six patients had adverse events (grade ≤3) possibly related to IGV-001. Median progression-free survival (PFS) was 9.8 months in the intent-to-treat population (vs. SOC, 6.5 months; P = 0.0003). In IGV-001-treated patients who met Stupp-eligible criteria, PFS was 11.6 months overall (n = 22; P = 0.001) and 17.1 months at the highest exposure (n = 10; P = 0.0025). The greatest overall survival was observed in Stupp-eligible patients receiving the highest exposure (median, 38.2 months; P = 0.044). Stupp-eligible patients with methylated O6-methylguanine-DNA methyltransferase promoter (n = 10) demonstrated median PFS of 38.4 months (P = 0.0008). Evidence of immune activation was noted. CONCLUSIONS: IGV-001 was well tolerated, PFS compared favorably with SOC, and evidence suggested an immune-mediated mechanism (ClinicalTrials.gov: NCT02507583).

Resected WHO grade I meningioma and predictors of local control.

INTRODUCTION: Despite optimal surgical resection, meningiomas may recur, with increasing grade and the degree of resection being predictive of risk. We hypothesize that an increasing Ki67 correlates with a higher risk of recurrence of resected WHO grade I meningiomas. METHODS: The study population consisted of patients with resected WHO grade 1 meningiomas in locations outside of the base of skull. Digitally scanned slides stained for Ki67 were analyzed using automatic image analysis software in a standardized fashion. RESULTS: Recurrence was observed in 53 (17.7%) of cases with a median follow up time of 25.8 months. Ki67 ranged from 0 to 30%. Median Ki67 was 5.1% for patients with recurrence and 3.5% for patients without recurrence. In unadjusted analyses, high Ki-67 (≥ 5 vs. < 5) vs. ≥ 5) was associated with over a twofold increased risk of recurrence (13.1% vs. 27% respectively; HR 2.1731; 95% CI [1.2534, 3.764]; p = 0.006). After Adjusting for patient or tumor characteristics, elevated Ki-67 remained significantly correlated with recurrence. Grade 4 Simpson resection was noted in 71 (23.7%) of patients and it was associated with a significantly increased risk of recurrence (HR 2.56; 95% CI [1.41, 4.6364]; p = 0.002). CONCLUSIONS: WHO grade 1 meningiomas exhibit a significant rate of recurrence following resection. While Ki-67 is not part of the WHO grading criteria of meningiomas, a value greater than 5% is an independent predictor for increased risk of local recurrence following surgical resection.

Impact of Sarcopenia on Survival in Patients With Early-Stage Lung Cancer Treated With Stereotactic Body Radiation Therapy.

Background Sarcopenia has been associated with poor survival among cancer patients. Normalized total psoas area (NTPA) has been used as a surrogate for defining sarcopenia. Few data exist characterizing the impact of sarcopenia and other metrics of fitness on clinical outcomes in patients with early-stage non-small cell lung cancer (NSCLC) treated non-invasively with stereotactic body radiotherapy (SBRT). Methods To assess the association between sarcopenia and clinical outcomes, we conducted a retrospective analysis of consecutive patients treated with SBRT from 2013 to 2019 . Overall survival (OS), local failure free survival (LFS), distant failure free survival (DFS), NTPA, body mass index (BMI), and Charlson comorbidity index (CCI) were included for analysis. NTPA was calculated by measuring the psoas volume at the L3 vertebra and normalizing for patient height and gender. Survival functions were evaluated using the Kaplan-Meier method. Log-rank test and Cox-proportional hazards were performed for categorical and continuous variables, respectively. Significance was set as p < 0.05. Results A total of 91 patients met the criteria. The median age was seven years and Karnofsky Performance Status score (KPS) was 80 (range: 60-100). Approximately 79% of patients had T1 tumors. Median radiation dose and number of fractions were 60 Gy (range: 45-60) and 5 fractions (range: 3-5). Median NTPA was 531.16 mm2/m2 (range: 90.4-1356.2). After normalization (sarcopenia: <385 mm2/m2, female; <585 mm2/m2, male), 39 patients (42.8%) had sarcopenia. NTPA had no association with OS (p = 0.7), LFS (p = 0.9), or DFS (p = 0.5). Increasing BMI was associated with improved OS (HR 0.90, 95% CI 0.83-0.98). With a median follow-up of 23.4 months, median OS was 60, 60, and 45.9 months (p = 0.37) in all patients, non-sarcopenic patients, and sarcopenic patients, respectively. Conclusion Sarcopenia was not associated with OS, LFS, or DFS. Increasing BMI is associated with improved OS. Future, prospective work is needed to define the impact of sarcopenia and other fitness metrics on clinical outcomes among NSCLC patients treated non-invasively with SBRT.