A Multicenter Evaluation of Different Chemotherapy Regimens in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Chemoradiation.

PURPOSE: The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiation therapy is considered the standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older patients with HNSCC. METHODS AND MATERIALS: The SENIOR study is an international multicenter cohort study including older patients (≥65 years) with HNSCC treated with definitive radiation therapy at 13 academic centers in the United States and Europe. Patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) via Kaplan-Meier analyses. Fine-Gray competing risk regressions were performed regarding the incidence of locoregional failures and distant metastases. RESULTS: Six hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n = 310; 44%), followed by cisplatin plus 5-fluorouracil (n = 137; 20%), carboplatin (n = 73; 10%), and mitomycin C plus 5-fluorouracil (n = 64; 9%). Carboplatin-based regimens were associated with diminished PFS (hazard ratio [HR], 1.39 [1.03-1.89]; P < .05) and a higher incidence of locoregional failures (subdistribution HR, 1.54 [1.00-2.38]; P = .05) compared with single-agent cisplatin, whereas OS (HR, 1.15 [0.80-1.65]; P = .46) was comparable. There were no oncological differences between single-agent and multiagent cisplatin regimens (all P > .05). The median cumulative dose of cisplatin was 180 mg/m2 (IQR, 120-200 mg/m2). Cumulative cisplatin doses ≥200 mg/m2 were associated with increased OS (HR, 0.71 [0.53-0.95]; P = .02), increased PFS (HR, 0.66 [0.51-0.87]; P = .003), and lower incidence of locoregional failures (subdistribution HR, 0.50 [0.31-0.80]; P = .004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR, 0.996 [0.993-0.999]; P = .009). CONCLUSIONS: Single-agent cisplatin can be considered in the standard chemotherapy regimen for older patients with HNSCC who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant in older patients with HNSCC.

Evaluation of a head rest prototype for rotational corrections in three degrees of freedom.

Cranial stereotactic irradiations require accurate reproduction of the planning CT patient position at the time of treatment, including removal of rotational offsets. A device prototype was evaluated for potential clinical use to correct rotational positional offsets in image-guided radiotherapy workflow. Analysis was carried out with a prototype device "RPS head" by gKteso GmbH, rotatable up to 4° in three dimensions by hand wheels. A software tool accounts for the nonrectangular rotation axes and also indicates translational motions to be performed with the standard couch to correct the initial offset and translational shifts introduced by the rotational motion. The accuracy of angular corrections and positioning of an Alderson RANDO head phantom using the prototype device was evaluated for nine treatment plans for cranial targets. Corrections were obtained from cone beam computed tomography (CBCT) imaging. The phantom position was adjusted and the final position was then verified by another CBCT. The long-term stability of the prototype device was evaluated. Attenuation by the device along its three main axes was assessed. A planning study was performed to evaluate if regions of high-density material can be avoided during plan generation. The device enabled the accurate correction of rotational offsets in a clinical setup with a mean residual angular difference of (0.0 ± 0.1)° and a maximum deviation of 0.2°. Translational offsets were less than 1 mm. The device was stable over a period of 20 min, not changing the head support plate position by more than (0.7 ± 0.6) mm. The device contains high-density material in the adjustment mechanism and slightly higher density in the support structures. These can be avoided during planning generation maintaining comparable plan quality. The head positioning device can be used to correct rotational offsets in a clinical setting.

Impact of Radiotherapy on Malfunctions and Battery Life of Cardiac Implantable Electronic Devices in Cancer Patients.

PURPOSE: This study analyses a large number of cancer patients with CIEDs for device malfunction and premature battery depletion by device interrogation after each radiotherapy fraction and compares different guidelines in regard to patient safety. METHODS: From 2007 to 2022, a cohort of 255 patients was analyzed for CIED malfunctions via immediate device interrogation after every RT fraction. RESULTS: Out of 324 series of radiotherapy treatments, with a total number of 5742 CIED interrogations, nine device malfunctions (2.8%) occurred. Switching into back-up/safety mode and software errors occurred four times each. Once, automatic read-out could not be performed. The median prescribed cumulative dose at planning target volume (PTV) associated with CIED malfunction was 45.0 Gy (IQR 36.0-64.0 Gy), with a median dose per fraction of 2.31 Gy (IQR 2.0-3.0 Gy). The median maximum dose at the CIED at time of malfunction was 0.3 Gy (IQR 0.0-1.3 Gy). No correlation between CIED malfunction and maximum photon energy (p = 0.07), maximum dose at the CIED (p = 0.59) nor treatment localization (p = 0.41) could be detected. After excluding the nine malfunctions, premature battery depletion was only observed three times (1.2%). Depending on the national guidelines, 1-9 CIED malfunctions in this study would have been detected on the day of occurrence and in none of the cases would patient safety have been compromised. CONCLUSION: Radiation-induced malfunctions of CIEDs and premature battery depletion are rare. If recommendations of national safety guidelines are followed, only a portion of the malfunctions would be detected directly after occurrence. Nevertheless, patient safety would not be compromised.

Hydration Status of Geriatric Patients Is Associated with Changes in Plasma Proteome, Especially in Proteins Involved in Coagulation.

Due to multifactorial reasons, such as decreased thirst and decreased total body water, elderly patients are vulnerable to dehydration. The study aims to investigate whether moderate dehydration or hyperhydration affects the blood proteome. Blood samples, medication, and bioelectrical impedance analysis (BIA) details were collected from 131 geriatric patients (77 women and 54 men aged 81.1 ± 7.2 years). Based on an evaluation by Bioelectrical Impedance Vector Analyses (BIVAs) of this cohort, for each hydration status (dehydrated, hyperhydrated, and control), five appropriate blood plasma samples for both males and females were analyzed by liquid chromatography-mass spectrometry (LC-MS). Overall, 262 proteins for female patients and 293 proteins for male patients could be quantified. A total of 38 proteins had significantly different abundance, showing that hydration status does indeed affect the plasma proteome. Protein enrichment analysis of the affected proteins revealed "Wound Healing" and "Keratinization" as the two main biological processes being dysregulated. Proteins involved in clot formation are especially affected by hydration status.

External validation of three prognostic scores for brain metastasis velocity in patients treated with intracranial stereotactic radiotherapy.

BACKGROUND AND INTRODUCTION: Brain metastasis velocity (BMV) has been proposed as a prognostic factor for overall survival (OS) in patients with brain metastases (BMs). In this study, we conducted an external validation and comparative assessment of the performance of all three BMV scores. MATERIALS AND METHODS: Patients treated with intracranial stereotactic radiotherapy (SRT) for BM at a single center between 2014 and 2018 were identified. Where possible, all three BMV scores were calculated. Log-rank tests and linear, logistic and Cox regression analysis were used for validation and predictor identification of OS. RESULTS: For 333 of 384 brain metastasis patients, at least one BMV score could be calculated. In a sub-group of 187 patients, "classic" BMV was validated as categorical (p < 0.0001) and continuous variable (HR 1.02; 95% CI 1.02-1.03; p < 0.0001). In a sub-group of 284 patients, "initial" BMV was validated as categorical variable (high-risk vs. low-risk; p < 0.01), but not as continuous variable (HR 1.02; 95% CI 0.99-1.04; p = 0.224). "Volume-based" BMV could not be validated in a sub-group of 104 patients. On multivariable Cox regression analysis, iBMV (HR 1.85; 95% CI 1.01-3.38; p < 0.05) and cBMV (HR 2.32; 95% CI 1.15 4.68; p < 0.05) were predictors for OS for intermediate-risk patients after first SRT and first DBFs, respectively. cBMV proved to be the dominant predictor for OS for high-risk patients (HR 2.99; 95% CI 1.30-6.91; p < 0.05). CONCLUSION: This study externally validated cBMV and iBMV as prognostic scores for OS in patients treated with SRT for BMs whereas validation of vBMV was not achieved.

Assessment of dual-energy computed tomography derived virtual monoenergetic imaging for target volume delineation of brain metastases.

BACKGROUND: Objective and subjective assessment of image quality of brain metastases on dual-energy computed tomography (DECT) virtual monoenergetic imaging (VMI) and its impact on target volume delineation. MATERIALS AND METHODS: 26 patients with 37 brain metastases receiving Magnetic Resonance Imaging (MRI) and DECT for stereotactic radiotherapy planning were included in this retrospective analysis. Lesion contrast (LC), contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were assessed for reconstructed VMI at 63 keV and artificial 120 kV Computed Tomography (CT). Image contrast and demarcation of metastases between 120 kV CT, VMI and MRI were subjectively assessed. Brain metastases were delineated by four radiation oncologists on VMI with a fixed or free brain window and contours were compared to solely MRI-based delineation using the Dice similarity coefficient. RESULTS: LC, CNR and SNR were significantly higher in VMI than in 120 kV CT (p < 0.0001). Image contrast and lesion demarcation were significantly better on VMI compared to 120 kV CT (p < 0.0001). Mean gross tumor volume (GTV)/planning target volume (PTV) Dice similarity coefficients were 0.87/0.9 for metastases without imaging uncertainties (no artifacts, calcification or impaired visibility with MRI) but worse for metastases with imaging uncertainties (0.71/0.74). Target volumes delineated on VMI were around 5-10% smaller compared to MRI. CONCLUSION: Image quality of VMI is objectively and subjectively superior to conventional CT. VMI provides significant advantages in stereotactic radiotherapy planning with improved visibility of brain metastases and geometrically distortion-free representation of brain metastases. Beside a plausibility check of MRI-based target volume delineation, VMI might improve reliability and accuracy in target volume definition particularly in cases with imaging uncertainties with MRI.

Obesity-Related Pitfalls of Virtual versus True Non-Contrast Imaging-An Intraindividual Comparison in 253 Oncologic Patients.

OBJECTIVES: Dual-source dual-energy CT (DECT) facilitates reconstruction of virtual non-contrast images from contrast-enhanced scans within a limited field of view. This study evaluates the replacement of true non-contrast acquisition with virtual non-contrast reconstructions and investigates the limitations of dual-source DECT in obese patients. MATERIALS AND METHODS: A total of 253 oncologic patients (153 women; age 64.5 ± 16.2 years; BMI 26.6 ± 5.1 kg/m2) received both multi-phase single-energy CT (SECT) and DECT in sequential staging examinations with a third-generation dual-source scanner. Patients were allocated to one of three BMI clusters: non-obese: <25 kg/m2 (n = 110), pre-obese: 25-29.9 kg/m2 (n = 73), and obese: >30 kg/m2 (n = 70). Radiation dose and image quality were compared for each scan. DECT examinations were evaluated regarding liver coverage within the dual-energy field of view. RESULTS: While arterial contrast phases in DECT were associated with a higher CTDIvol than in SECT (11.1 vs. 8.1 mGy; p < 0.001), replacement of true with virtual non-contrast imaging resulted in a considerably lower overall dose-length product (312.6 vs. 475.3 mGy·cm; p < 0.001). The proportion of DLP variance predictable from patient BMI was substantial in DECT (R2 = 0.738) and SECT (R2 = 0.620); however, DLP of SECT showed a stronger increase in obese patients (p < 0.001). Incomplete coverage of the liver within the dual-energy field of view was most common in the obese subgroup (17.1%) compared with non-obese (0%) and pre-obese patients (4.1%). CONCLUSION: DECT facilitates a 30.8% dose reduction over SECT in abdominal oncologic staging examinations. Employing dual-source scanner architecture, the risk for incomplete liver coverage increases in obese patients.

Evaluation of Concomitant Systemic Treatment in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Radiotherapy.

Importance: The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and these patients are underrepresented in clinical trials. It is unclear whether the addition of chemotherapy or cetuximab to radiotherapy is associated with improved survival in older adults with HNSCC. Objective: To examine whether the addition of chemotherapy or cetuximab to definitive radiotherapy is associated with improved survival in patients with locoregionally advanced (LA) HNSCC. Design, Setting, and Participants: The Special Care Patterns for Elderly HNSCC Patients Undergoing Radiotherapy (SENIOR) study is an international, multicenter cohort study including older adults (≥65 years) with LA-HNSCCs of the oral cavity, oropharynx/hypopharynx, or larynx treated with definitive radiotherapy, either alone or with concomitant systemic treatment, between January 2005 and December 2019 at 12 academic centers in the US and Europe. Data analysis was conducted from June 4 to August 10, 2022. Interventions: All patients underwent definitive radiotherapy alone or with concomitant systemic treatment. Main Outcomes and Measures: The primary outcome was overall survival. Secondary outcomes included progression-free survival and locoregional failure rate. Results: Among the 1044 patients (734 men [70.3%]; median [IQR] age, 73 [69-78] years) included in this study, 234 patients (22.4%) were treated with radiotherapy alone and 810 patients (77.6%) received concomitant systemic treatment with chemotherapy (677 [64.8%]) or cetuximab (133 [12.7%]). Using inverse probability weighting to attribute for selection bias, chemoradiation was associated with longer overall survival than radiotherapy alone (hazard ratio [HR], 0.61; 95% CI, 0.48-0.77; P < .001), whereas cetuximab-based bioradiotherapy was not (HR, 0.94; 95% CI, 0.70-1.27; P = .70). Progression-free survival was also longer after the addition of chemotherapy (HR, 0.65; 95% CI, 0.52-0.81; P < .001), while the locoregional failure rate was not significantly different (subhazard ratio, 0.62; 95% CI, 0.30-1.26; P = .19). The survival benefit of the chemoradiation group was present in patients up to age 80 years (65-69 years: HR, 0.52; 95% CI, 0.33-0.82; 70-79 years: HR, 0.60; 95% CI, 0.43-0.85), but was absent in patients aged 80 years or older (HR, 0.89; 95% CI, 0.56-1.41). Conclusions and Relevance: In this cohort study of older adults with LA- HNSCC, chemoradiation, but not cetuximab-based bioradiotherapy, was associated with longer survival compared with radiotherapy alone.

Predicting Adverse Radiation Effects in Brain Tumors After Stereotactic Radiotherapy With Deep Learning and Handcrafted Radiomics.

Introduction: There is a cumulative risk of 20-40% of developing brain metastases (BM) in solid cancers. Stereotactic radiotherapy (SRT) enables the application of high focal doses of radiation to a volume and is often used for BM treatment. However, SRT can cause adverse radiation effects (ARE), such as radiation necrosis, which sometimes cause irreversible damage to the brain. It is therefore of clinical interest to identify patients at a high risk of developing ARE. We hypothesized that models trained with radiomics features, deep learning (DL) features, and patient characteristics or their combination can predict ARE risk in patients with BM before SRT. Methods: Gadolinium-enhanced T1-weighted MRIs and characteristics from patients treated with SRT for BM were collected for a training and testing cohort (N = 1,404) and a validation cohort (N = 237) from a separate institute. From each lesion in the training set, radiomics features were extracted and used to train an extreme gradient boosting (XGBoost) model. A DL model was trained on the same cohort to make a separate prediction and to extract the last layer of features. Different models using XGBoost were built using only radiomics features, DL features, and patient characteristics or a combination of them. Evaluation was performed using the area under the curve (AUC) of the receiver operating characteristic curve on the external dataset. Predictions for individual lesions and per patient developing ARE were investigated. Results: The best-performing XGBoost model on a lesion level was trained on a combination of radiomics features and DL features (AUC of 0.71 and recall of 0.80). On a patient level, a combination of radiomics features, DL features, and patient characteristics obtained the best performance (AUC of 0.72 and recall of 0.84). The DL model achieved an AUC of 0.64 and recall of 0.85 per lesion and an AUC of 0.70 and recall of 0.60 per patient. Conclusion: Machine learning models built on radiomics features and DL features extracted from BM combined with patient characteristics show potential to predict ARE at the patient and lesion levels. These models could be used in clinical decision making, informing patients on their risk of ARE and allowing physicians to opt for different therapies.

Comprehensive summary and retrospective evaluation of prognostic scores for patients with newly diagnosed brain metastases treated with upfront radiosurgery in a modern patient collective.

BACKGROUND: Numerous prognostic scores (PS) for patients with brain metastases (BM) have been developed. Recently, PS based on laboratory parameters were introduced to better predict overall survival (OS). A comprehensive comparison of the wide range of scores in a modern patient collective is still missing. MATERIALS AND METHODS: Twelve PS considering clinical parameters only at the time of BM diagnosis were calculated for 470 patients receiving upfront SRS between January 2014 and March 2020. In a subcohort of 310 patients where a full laboratory dataset was available five additional prognostic scores were compared. Restricted mean survival time (RMST), partial likelihood and c-index were calculated as metrics for performance evaluation. Univariable and multivariable analysis were used to identify prognostic factors for OS. RESULTS: The median OS of the whole cohort was 15.8 months (95% C.I.: 13.4-20.1). All prognostic scores performed well in separating patients into different prognostic groups. RPA achieved the highest c-index, whereas GGS achieved highest partial likelihood with evaluation in the total cohort. With incorporation of the laboratory scores the recently suggested EC-GPA achieved highest c-index and highest partial likelihood. A prognostic score solely based on the assessment of performance status achieved considerable high performance as either 3- or 4-tiered score. Multivariable analysis revealed performance status, systemic disease status and laboratory parameters to be significantly associated with OS among variates included in prognostic scores. CONCLUSION: Although recent PS incorporating laboratory parameters show convincing performance in predicting overall survival, older scores relying on clinical parameters only are still valid and appealing as they are easier to calculate, and as overall performance is almost equal. Moreover, a score just based on performance status is not significantly inferior and should at least be assessed for informed decision making.

Two-Weekly High-Dose-Rate Brachytherapy Boost After External Beam Radiotherapy for Localized Prostate Cancer: Long-Term Outcome and Toxicity Analysis.

PURPOSE: Evaluation of clinical outcome of two-weekly high-dose-rate brachytherapy boost after external beam radiotherapy (EBRT) for localized prostate cancer. METHODS: 338 patients with localized prostate cancer receiving definitive EBRT followed by a two-weekly high-dose-rate brachytherapy boost (HDR-BT boost) in the period of 2002 to 2019 were analyzed. EBRT, delivered in 46 Gy (DMean) in conventional fractionation, was followed by two fractions HDR-BT boost with 9 Gy (D90%) two and four weeks after EBRT. Androgen deprivation therapy (ADT) was added in 176 (52.1%) patients. Genitourinary (GU)/gastrointestinal (GI) toxicity was evaluated utilizing the Common Toxicity Criteria for Adverse Events (version 5.0) and biochemical failure was defined according to the Phoenix definition. RESULTS: Median follow-up was 101.8 months. 15 (4.4%)/115 (34.0%)/208 (61.5%) patients had low-/intermediate-/high-risk cancer according to the D`Amico risk classification. Estimated 5-year and 10-year biochemical relapse-free survival (bRFS) was 84.7% and 75.9% for all patients. The estimated 5-year bRFS was 93.3%, 93.4% and 79.5% for low-, intermediate- and high-risk disease, respectively. The estimated 10-year freedom from distant metastasis (FFM) and overall survival (OS) rates were 86.5% and 70.0%. Cumulative 5-year late GU toxicity and late GI toxicity grade ≥ 2 was observed in 19.3% and 5.0% of the patients, respectively. Cumulative 5-year late grade 3 GU/GI toxicity occurred in 3.6%/0.3%. CONCLUSIONS: Two-weekly HDR-BT boost after EBRT for localized prostate cancer showed an excellent toxicity profile with low GU/GI toxicity rates and effective long-term biochemical control.

Comparison of treatment plans for hypofractionated high-dose prostate cancer radiotherapy using the Varian Halcyon and the Elekta Synergy platforms.

PURPOSE: To compare radiotherapy plans between an O-ring and a conventional C-arm linac for hypofractionated high-dose prostate radiotherapy in terms of plan quality, dose distribution, and quality assurance in a multi-vendor environment. METHODS: Twenty prostate cancer treatment plans were irradiated on the O-ring Varian Halcyon linac and were re-optimized for the C-arm Elekta Synergy Agility linac. Dose-volume histogram metrics for target coverage and organ at risk dose, quality assurance, and monitor units were retrospectively compared. Patient-specific quality assurance with ion chamber measurements, gamma index analysis, and portal dosimetry was performed using the Varian Portal Dosimetry system and the ArcCHECK® phantom (Sun Nuclear Corporation). Prostate-only radiotherapy was delivered with simultaneous integrated boost (SIB) volumetric modulated arc therapy (VMAT) in 20 fractions of 2.5/3.0 Gy each. RESULTS: For both linacs, target coverage was excellent and plan quality comparable. Homogeneity in PTVBoost was high for Synergy as well as Halcyon with a mean homogeneity index of 0.07 ± 0.01 and 0.05 ± 0.01, respectively. Mean dose for the organs at risk rectum and bladder differed not significantly between the linacs but were higher for the femoral heads and penile bulb for Halcyon. Quality assurance showed no significant differences in terms of ArcCHECK gamma pass rates. Median pass rate for 3%/2 mm was 99.3% (96.7 to 99.8%) for Synergy and 99.8% (95.6 to 100%) for Halcyon. Agreement between calculated and measured dose was high with a median deviation of -0.6% (-1.7 to 0.8%) for Synergy and 0.2% (-0.6 to 2.3%) for Halcyon. Monitor units were higher for the Halcyon by approximately 20% (p < 0.001). CONCLUSION: Hypofractionated high-dose prostate cancer SIB VMAT on the Halcyon system is feasible with comparable plan quality in reference to a standard C-arm Elekta Synergy linac.

Association of Drug Application and Hydration Status in Elderly Patients.

Due to multifactorial reasons, such as decreased thirst and decreased total body water, elderly patients are vulnerable to dehydration. Mild cognitive impairment (MCI) or dementia increase the risk of dehydration and, in turn, dehydration decreases cognitive performance. The study aims to identify and assess differences in hydration status, taking into account patients' drug treatment and diseases, using bioelectrical impedance vector analysis (BIVA), thereby revealing unfavorable aspects of prognosis. 447 geriatric patients (241 women, 206 men) including information on medication and bioelectrical impedance analysis (BIA) were investigated, which allowed studying the association between 40 drugs and the hydration status. First, patients were divided into disease groups. Renal disease and diuretic treatment were significantly different in both sexes, whereas cardiovascular patients differed exclusively for females. Next, drug enrichment was examined in either hyperhydrated or dehydrated patients. Simvastatin, candesartan, bisoprolol, amlodipine, olmesartan, furosemide, torasemide, allopurinol, mirtazapine, pantoprazole, cholecalciferol, and resveratrol showed enrichment depending on hydration status. This study demonstrated that patients can be differentiated and stratified by BIVA, taking into account medication and disease associated with hydration status. Although patients diagnosed with MCI and therefore treated with resveratrol, BIVA still showed evaluated dehydration. This is unfavorable in terms of prognosis and requires special attention.

Radiomic Analysis to Predict Outcome in Recurrent Glioblastoma Based on Multi-Center MR Imaging From the Prospective DIRECTOR Trial.

BACKGROUND: Based on promising results from radiomic approaches to predict O6-methylguanine DNA methyltransferase promoter methylation status (MGMT status) and clinical outcome in patients with newly diagnosed glioblastoma, the current study aimed to evaluate radiomics in recurrent glioblastoma patients. METHODS: Pre-treatment MR-imaging data of 69 patients enrolled into the DIRECTOR trial in recurrent glioblastoma served as a training cohort, and 49 independent patients formed an external validation cohort. Contrast-enhancing tumor and peritumoral volumes were segmented on MR images. 180 radiomic features were extracted after application of two MR intensity normalization techniques: fixed number of bins and linear rescaling. Radiomic feature selection was performed via principal component analysis, and multivariable models were trained to predict MGMT status, progression-free survival from first salvage therapy, referred to herein as PFS2, and overall survival (OS). The prognostic power of models was quantified with concordance index (CI) for survival data and area under receiver operating characteristic curve (AUC) for the MGMT status. RESULTS: We established and validated a radiomic model to predict MGMT status using linear intensity interpolation and considering features extracted from gadolinium-enhanced T1-weighted MRI (training AUC = 0.670, validation AUC = 0.673). Additionally, models predicting PFS2 and OS were found for the training cohort but were not confirmed in our validation cohort. CONCLUSIONS: A radiomic model for prediction of MGMT promoter methylation status from tumor texture features in patients with recurrent glioblastoma was successfully established, providing a non-invasive approach to anticipate patient's response to chemotherapy if biopsy cannot be performed. The radiomic approach to predict PFS2 and OS failed.

Distance to isocenter is not associated with an increased risk for local failure in LINAC-based single-isocenter SRS or SRT for multiple brain metastases.

PURPOSE: To evaluate the impact of the distance between treatment isocenter and brain metastases on local failure in patients treated with a frameless linear-accelerator-based single-isocenter volumetric modulated arc (VMAT) SRS/SRT for multiple brain metastases. METHODS AND MATERIALS: Patients treated with SRT for brain metastases (BM) between April 2014 and May 2019 were included in this retrospective study. BM treated with a single-isocenter multiple-target (SIMT) SRT were evaluated for local recurrence-free intervals in dependency to their distance to the treatment isocenter. A Cox-regression model was used to investigate different predictor variables for local failure. Results were compared to patients treated with a single-isocenter-single-target (SIST) approach. RESULTS: In total 315 patients with a cumulative number of 1087 BM were analyzed in this study of which 140 patients and 708 BM were treated with SIMT SRS/SRT. Median follow-up after treatment was 13.9 months for SIMT approach and 11.9 months for SIST approach. One-year freedom from local recurrence was 87% and 94% in the SIST and SIMT group, respectively. Median distance to isocenter (DTI) was 4.7 cm (range 0.2-10.5) in the SIMT group. Local recurrence-free interval was not associated with the distance to the isocenter in univariable or multivariable Cox-regression analysis. Multivariable analysis revealed only volume as an independent significant predictor for local failure (p-value <0.05). CONCLUSION: SRS/SRT using single-isocenter VMAT for multiple targets achieved high local metastases control rates irrespective of distance to the isocenter, supporting efficacy of single-isocenter stereotactic radiation therapy for multiple brain metastases.

Management of multiple brain metastases: a patterns of care survey within the German Society for Radiation Oncology.

PURPOSE: The treatment of brain metastases (BM) has changed considerably in recent years and in particular, the management of multiple BM is currently undergoing a paradigm shift and treatment may differ from current guidelines. This survey was designed to analyze the patterns of care in the management of multiple BM. METHODS: An online survey consisting of 36 questions was distributed to the members of the German Society for Radiation Oncology (DEGRO). RESULTS: In total, 193 physicians out of 111 institutions within the German Society for Radiation oncology responded to the survey. Prognostic scores for decision making were not used regularly. Whole brain radiotherapy approaches (WBRT) are the preferred treatment option for patients with multiple BM, although stereotactic radiotherapy treatments are chosen by one third depending on prognostic scores and overall number of BM. Routine hippocampal avoidance (HA) in WBRT is only used by a minority. In multiple BM of driver-mutated non-small cell lung cancer origin up to 30% favor sole TKI therapy as upfront treatment and would defer upfront radiotherapy. CONCLUSION: In multiple BM WBRT without hippocampal avoidance is still the preferred treatment modality of choice regardless of GPA and mutational status, while SRT is only used in patients with good prognosis. Evidence for both, SRS and hippocampal avoidance radiotherapy, is growing albeit the debate over the appropriate treatment in multiple BM is yet not fully clarified. Further prospective assessment of BM management-ideally as randomized trials-is required to align evolving concepts with the proper evidence and to update current guidelines.

Feasibility and Usability Aspects of Continuous Remote Monitoring of Health Status in Palliative Cancer Patients Using Wearables.

BACKGROUND: Mobile health is a promising strategy aiming to anticipate and prevent the deterioration of health status in palliative cancer patients. A prerequisite for successful implementation of this technology into clinical routine is a high level of usability and acceptance of devices. OBJECTIVES: We aimed to evaluate feasibility as well as patients' acceptance of remote monitoring using wearables in palliative cancer patients. METHODS: In this prospective single-center observational feasibility study, 30 cancer patients treated with palliative intent in an inpatient setting with an estimated life expectancy of >8 weeks and <12 months were provided with a smartphone including a pre-installed "Activity Monitoring" app and a sensor-equipped bracelet and monitored over a period of 12 weeks starting at discharge from hospital. We report detailed feasibility and usability aspects and comment on patients' acceptance of the wearables. RESULTS: Between February 2017 and May 2018 a total of 30 patients were included in the study. From these, 25 participants (83%) completed the whole study period. On average, the bracelet was worn on 53% and smartphone used on 85% of the study days. The completion rate of daily digital questionnaires for subjective ratings (pain and distress scale) was 73%, and 28 patients were able to handle the wearables and to operate the app without major problems. Use of the bracelet was low during the night hours, with a wearing time of 1.7% of all night hours (8 p.m. to 8 a.m.). CONCLUSIONS: Remote monitoring of health care status in palliative cancer patients with a limited life expectancy is feasible and patients are able to handle the smartphone and the sensor-equipped bracelet. Feedback towards use of this monitoring system was mostly positive.

Leukoencephalopathy after prophylactic whole-brain irradiation with or without hippocampal sparing: a longitudinal magnetic resonance imaging analysis.

PURPOSE: Neurocognitive changes are well described after prophylactic or therapeutic whole-brain radiotherapy (WBRT) and have been reported as early as 3 months after radiotherapy (RT). Therefore, WBRT with protection of the hippocampal region (hippocampal avoidance, HA) has been proposed to preserve neurocognition. Our aim was to compare the risk of leukoencephalopathy after prophylactic cranial irradiation (PCI) with or without HA. METHODS: Patients with small-cell lung cancer who received either lateral-opposed field PCI (non-HA-PCI; n = 9) or hippocampus avoidance PCI (HA-PCI; n = 9) with available magnetic resonance imaging (MRI) follow-up were identified and age matched. Pre-therapeutic and follow-up MRI after RT was analysed for leukoencephalopathy based on the Fazekas score. Bilateral cortical and subcortical brain structures were segmented and analysed for alterations in dosimetric parameters and volumes. RESULTS: There was no significant difference of Fazekas scores between groups at baseline. Fazekas score differed in post-treatment with a median of 1 in the HA-PCI group and 2 in the non-HA-PCI group (p = 0.007). Significant increase of Fazekas score over time after RT was observed for HA-PCI patients (p = 0.001) but not for non-HA-PCI patients. Dmax (highest radiation dose) and brain volume receiving doses >25Gy were higher in HA-PCI patients. There were no significant volumetric differences for segmented brain structures between groups. CONCLUSION: Radiological changes are more prominent after HA-PCI than after non-HA-PCI. Although no standardised neurocognitive testing was performed, the significantly increased Fazekas scores after HA-PCI are expected to interfere with neurocognitive function. Prospective long-term neurocognitive studies are warranted before HA-PCI is implemented in routine clinical practice.

Mobile Health Technologies for Continuous Monitoring of Cancer Patients in Palliative Care Aiming to Predict Health Status Deterioration: A Feasibility Study.

Background: Unplanned readmissions or emergency visits (EVs) after discharge from hospital are frequent in patients in palliative care. Strategies to anticipate and prevent rapid deterioration of health are needed. Objective: Assessing feasibility and predictive ability of remote monitoring using wearables. Design: Prospective observational feasibility study in a single center. Setting/Subjects: Thirty cancer patients with an estimated life expectancy of >8 weeks to <12 months, aged >18 years and being discharged from inpatient to outpatient care were included. Measurements: Patients were provided with a smartphone, including the preinstalled "Activity Monitoring" application and a sensor-equipped bracelet. Follow-up was 12 weeks. Both devices recorded several features (e.g., vital signs). Visual analog scale (VAS) for pain and distress was reported once daily and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) once weekly. Statistical methods were applied to explore relationship between sensor data, self-reports, and EVs or readmissions or death. Results: Between February 2017 and May 2018, 30 patients were included. Twenty-five of 30 participants (83%) completed 12 weeks of follow-up. On average, bracelet was worn on 53% and smartphone on 85% of study days. Completion rate of daily digital questionnaires for subjective ratings was 73%. Eight unplanned hospital readmissions occurred. Ratings of pain, distress, and QLQ-C30 scores were not associated with readmission, whereas resting heart rate, resting heart rate variability, as well as speed of steps differed significantly in patients with and without readmission. Conclusions: Monitoring of palliative cancer patients using wearables is feasible. First results indicate that mobile health features might be promising biomarkers to predict unplanned readmissions.