Karnofsky Performance Index Research Articles

IMMU-11. CLINICAL EXPERIENCE WITH THE CONCEPT OF MULTIPHASE COMBINED TREATMENT FOR ADULTS WITH GBM

Abstract BACKGROUND We published survival data of 50 adults with GBM treated with individualized multimodal immunotherapy (IMI) as part of a multiphase combined treatment (Van Gool et al, https://doi:org/10.1016/bs.mcb.2023.06.001). Analysis was repeated with new observation data. METHODS Patient definition for retrospective analysis: start IMI between 27/05/2015 and 31/10/2023, >18y, newly diagnosed, IDH1 wild-type, MGMT promoter-methylation status documented, survival known, no second malignancy. RESULTS Forty (14 female, 26 male) GBM patients were MGMT-promoter-unmethylated (unmeth), while 31 (15 female, 16 male) were MGMT-promoter-methylated (meth). Comparing the molecular subgroups, both respective median age; 48 years (range 18-65) and 54 years (range 26-72), and respective Karnofsky performance index; 70 (range 50-100) and 80 (range 60-100), were equal. Patient distribution (< complete resection, complete resection, not documented) was equal: 17/15/8 (unmeth) versus 17/11/3 (meth). Both groups were treated similarly: in median 37 (range 0-147) sessions of modulated electrohyperthermia, in median 37 (range 5-147) bolus injections of Newcastle Disease Virus, in median 2 (range 0-6) IO-Vac® vaccines with a median total number of 30.7x10e6 DCs (range 0-158x10e6). The median overall survival (mOS) for the total group was 27 months. The 2-year overall survival (OS) was 57.9 % and the 3-year OS 37.1 %. The mOS for unmeth patients was 22.1 month, with a 2-year OS of 42.7%. The mOS for meth patients was 37.7 months, with a 2-year OS of 75.5%. Sampling five control arms of contemporary RCTs as external control arm (Liau et al, JAMA Oncol 2023) showed for unmeth and meth patients a mOS of 14.6 resp. 21.3 months with a 2-year OS of 21% resp. 42%, which reflects the current prognosis for these patients. CONCLUSIONS Our analysis confirms that the integration of IMI during and after standard of care improves the OS. Similar multiphase combined treatment strategy, including IMI, should be considered to treat childhood GBM.

Validation of the Internal Coherence Scale (ICS) in Healthy Geriatric Individuals and Patients Suffering from Diabetes Mellitus Type 2 and Cancer.

With increased life expectancy, the coexistence of functional impairment and multimorbidity can negatively impact life quality and coherence in geriatric individuals. The self-report 10-item Internal Coherence (ICS) measures how individuals cope with and make sense of disease-specific life challenges. The aim of this study was to validate the ICS in a sample of geriatric individuals. In a cross-sectional study, geriatric individuals with and without chronic diseases were recruited. A factor analysis with principal component extraction (PCA) and a structural equation model (SEM) was conducted to assess the ICS factor structure in a geriatric sample. To measure convergent validity, the following scales were used: Short Health Survey (SF-12), Karnofsky Performance Index (KPI), Trait autonomic regulation (Trait aR), Sense of Coherence Scale (SOC), and Geriatric Depression Scale (GDS). A sample of n = 104 (70-96 years of age) patients with Diabetes Mellitus Type 2 (n = 22), cancer diseases (n = 31) and healthy controls (n = 51) completed the ICS. PCA and SEM yielded the original two-factor solution: 1. Inner resilience and coherence and 2. Thermo coherence. Overall internal consistency for this cohort was satisfying (Cronbach's α with rα = 0.72), and test-retest reliability was moderate (rrt = 0.53). ICS scores were significantly correlated to all convergent criteria ranging between r = 0.22 * and 0.49 ** (p < 0.05 *; p < 0.01 **). Study results suggest that the ICS appears to be a reliable and valid tool to measure internal coherence in a geriatric cohort (70-96 years). However, moderate test-retest reliability prompts the consideration of potential age-effects that may bias the reliability for this specific cohort.

Vitamin D deficiency and its associated factors in active TB patients at a tertiary hospital and three primary health care level facilities in Lusaka, Zambia: A cross sectional analytical study

Background: Tuberculosis (TB) remains a leading infectious cause of morbidity and mortality in Zambia. Vitamin D deficiency has been associated with increased TB incidence and severity but data for the Zambian setting is lacking, inclusive of the general population. We sought to determine the prevalence of vitamin D deficiency and its associated factors in active TB patients in comparison to matched adults from the general population without TB, and to compare clinical and radiological severity of TB based on vitamin D status.&#x0D; Methods: We enrolled 89 TB patients and 78 matched adults from the general population. Demographic and clinical data was collected. The key findings on physical examination were body mass index (BMI), mid upper arm circumference (MUAC), and signs of undernutrition. Clinical severity was assessed using the TB I Score and the Karnofsky Performance Index (KPI).Chest x-ray and measurement of serum vitamin D levels were done. Radiological severity was assessed using the Timika chest x-ray score. Vitamin D was measured using the Cobas® E411 analyser from Roche Diagnostics (Germany) with vitamin D deficiency defined as &lt;30 ng/ml and chi square used to analyse vitamin D deficiency as a categorical variable.&#x0D; Results: The median (IQR) age was 27.5 (24-38) years in the TB patients and 32 (25-37) years in the non-TB adults (p=0.30).Sixty-nine (77.53%) of the TB patients and 57 (73.08%) of the comparison group were male (p=0.51). The prevalence of vitamin D deficiency was 33.71 % in the TB patients and 15.38% in the comparison group (p &lt;0.01). Associations with vitamin D deficiency were active TB (AOR =2.27; 95% CI = 1.04- 4.95; p=0.04) and undernutrition (AOR 14.5; 95% CI 1.65-126.97; p=0.02). Median (IQR) KPI was 70 (60-80) in the vitamin D deficient patients compared to 80 (70-90) in non- vitamin D deficient patients (p=0.01). Median (IQR) Timika chest x-ray score was 75 (45-115) in the vitamin D deficient TB patients compared to 42.5 (20-75) in the non- vitamin D deficient patients (p&lt;0.01).&#x0D; Conclusions: We found a significant difference in the prevalence of vitamin D deficiency in active TB patients compared with matched non-TB adults. Vitamin D deficiency was associated with active TB and under nutrition. TB patients with vitamin D deficiency had more clinical and radiological severe disease than those with normal vitamin D levels. These findings warrant further studies on the role of vitamin D supplementation in TB in Zambia.&#x0D;

Reevaluating age restrictions of spinal metastasis surgery in elderly groups with over 2-year follow-up

This study aimed to compare and assess clinical outcomes of spinal metastasis with epidural spinal cord compression (MESCC) in patients aged 65–79 years and ≥ 80 years with an acute onset of neurological illness who underwent laminectomy. A second goal was to determine morbidity rates and potential risk factors for mortality. This retrospective review of electronic medical records at a single institution was conducted between September 2005 and December 2020. Data on patient demographics, surgical characteristics, complications, hospital clinical course, and 90-day mortality were also collected. Comorbidities were assessed using the age-adjusted Charlson comorbidity index (CCI). A total of 99 patients with an overall mean age of 76.2 ± 3.4 years diagnosed with MESCC within a 16-year period, of which 65 patients aged 65–79 years and 34 patients aged 80 years and older were enrolled in the study. Patients aged 80 and over had higher age-adjusted CCI (9.2 ± 2.1) compared to those aged 65–79 (5.1 ± 1.6; p < 0.001). Prostate cancer was the primary cause of spinal metastasis. Significant neurological and functional decline was more pronounced in the older group, evidenced by Karnofsky Performance Index (KPI) scores (80+ years: 47.8% ± 19.5; 65–79 years: 69.0% ± 23.9; p < 0.001). Despite requiring shorter decompression duration (148.8 ± 62.5 min vs. 199.4 ± 78.9 min; p = 0.004), the older group had more spinal levels needing decompression. Median survival time was 14.1 ± 4.3 months. Mortality risk factors included deteriorating functional status and comorbidities, but not motor weakness, surgical duration, extension of surgery, hospital or ICU stay, or complications. Overcoming age barriers in elderly surgical treatment in MSCC patients can reduce procedural delays and has the potential to significantly improve patient functionality. It emphasizes that age should not be a deterrent for spine surgery when medically necessary, although older MESCC patients may have reduced survival.

INNV-18. MULTIPHASE COMBINED TREATMENT, INCLUDING INDIVIDUALIZED MULTIMODAL IMMUNOTHERAPY FOR ADULTS WITH GBM: SINGLE INSTITUTE REAL WORLD MEDICAL DATA IN THE LIGHT OF CLINICAL TRIAL RESEARCH DATA

Abstract A phase III prospective externally controlled cohort trial recently demonstrated beneficial effects of DCVax®-L for adults with GBM. The beneficial effect of TTF was demonstrated in a RCT. We designed a multiphase combined treatment using subsequentially 1/ modulated electrohyperthermia and Newcastle Disease Virus therapy to induce immunogenic cell death (ICD) during temozolomide maintenance chemotherapy, 2/ two autologous DC vaccinations (IO-Vac®), and 3/ ICD immunotherapy, long-peptide vaccines and one boost IO-Vac® vaccine. During phase 2 + 3, individualized modulatory immunotherapy was provided. Fifty adults with first-line IDH1wt GBM were retrospectively analysed: MGMT promoter-unmethylated (unmeth, 10 f, 18 m); -methylated (meth, 12 f, 10 m). Median age was 48y, median Karnofsky performance index was 80. More than half of the patients had less than complete resection. Dynamics in tumor biology and immune response were demonstrated during treatment (e.g. mRNA expression for PDL1 in circulating tumor cells), and required treatment adaptations (checkpoint inhibitors). The median OS of unmeth and meth patients were 22m (2y-OS: 42%) resp. 38m (2y-OS: 81%, p=0.0414). There were no considerable treatment-related adverse reactions. The (external) control arms in the DCVax®-L and TTF trials, which reflect the current standard-of-care clinical results, showed median OS and 2y-OS of 15m/21% in unmeth and 21m/42% in meth patients. TTF improved the OS in both unmeth and meth patients (17m/27% and 32m/59%), while DCvax®-L improved OS only in meth patients (15m/19% and 30m/58%). These real world data support to prospectively explore the addition of individualized multimodal immunotherapy during and after standard of care, and the role of treatment adaptations during treatment.

QOL-02. MONITORING GBM PATIENT HEALTH-RELATED QUALITY OF LIFE AND QUALITY ADJUSTED LIFE MONTHS DURING INDIVIDUALIZED MULTIMODAL IMMUNOTHERAPY USING EQ-5D-5L

Abstract DC vaccination emerges as effective treatment for patients with GBM. Besides overall survival, Health-Related Quality of Life (HRQoL) during and after treatment is an important qualitative assessment. We explored the usability of the self-reporting EQ-5D-5L instrument (), available in 14 languages, to determine the Health Utility Index (HUI) and calculate Quality Adjusted Life Months (QALM) in GBM patients during individualized multimodal immunotherapy (IMI). Selection criteria for this retrospective analysis were the start of IMI between 15 October 2021 and May 2023, and availability of at least 5 HRQoL measurements with EQ-5D-5L. Nineteen GBM patients (9 females, 10 males) met these criteria. Median age at diagnosis was 52 years (range 21-67). Median Karnofsky performance index was 80 (60-100). The HUI at time of first diagnosis was unknown. The median HUI at start of immunotherapy was 0.868 (1-0.346). Fifteen patients received IMI as part of first-line treatment. Four patients were treated at time of relapse. Patients received in median 2 IO-Vac® vaccines (0-3) and 6 immunogenic cell death immunotherapy courses (4-12). Sixteen patients were still alive in median 11 months (6-48) after first diagnosis. Three patients died respectively 11, 16, 34 months after diagnosis. The patient response rate to the EQ-5D-5L instrument was high. A median of 7 HRQoL measurements were registered per patient (5-15). One patient did not appropriately answer the EQ-5D-5L questionnaire due to active refusal. The median life time between start of IMI and last time point for measurement of HRQoL was 12.5 months (7.8-47.5). The Quality Adjusted life time between each time point was calculated based on the HUI for each patient. The life time reduction was -0.9 months (-4.2-0), resulting in a median QALM of 12 months (6.3-45.9). EQ-5D-5L can be used to determine the QALMs as qualitative basis for cost-effectiveness calculations for innovative treatments like IMI.

Functional Outcome and Overall Survival in Patients with Primary or Secondary CNS Lymphoma after Surgical Resection vs. Biopsy

Background: Central nervous system lymphoma (CNSL) is rare form of brain tumour. It manifests either as primary CNS lymphoma (pCNSL) originating within the central nervous system or as secondary CNS lymphoma (sCNSL), arising as cerebral metastases of systemic lymphoma. For a significant period, surgical resection was considered obsolete due to the favourable response to chemotherapy and the associated risk of postoperative deficits. The objective of the present study was to demonstrate the benefits of resection in CNSL patients, including extended survival and improved postoperative function. Methods: A retrospective study involving patients diagnosed with either PCNSL or SCNSL that were surgically approached at our neurosurgical department between 2010 and 2022 was conducted. Patients were categorised into three subgroups based on their neurosurgical approach: (1) stereotactical biopsy, (2) open biopsy, (3) resection. We then performed statistical analyses to assess overall survival (OS) and progression-free survival (PFS). Additionally, we examined various secondary factors such as functional outcome via Karnofsky Performance Index (KPS) and prognosis scoring. Results: 157 patients diagnosed with PCNSL or SCNSL were enclosed in the study. Of these, 101 underwent stereotactic biopsy, 21 had open biopsy, and 35 underwent resection. Mean age of the cohort was 64.94 years, with majority of patients being female (54.1%). The resection group showed longest OS at 44 months (open biopsy = 13 months, stereotactic biopsy = 9 months). Calculated median follow-up was 34.5 months. In the Cox regression model, postoperative KPS 70% (p &lt; 0.001) and resection vs. stereotactic biopsy (p = 0.040) were identified as protective factors, whereas older age at diagnosis was identified as a risk factor (p &lt; 0.001). In the one-way analysis of variance, differences in postoperative KPS were found among all groups (p = 0.021), while there was no difference in preoperative KPS among the groups. Conclusions: Our data show a favourable outcome when resection is compared to either stereotactic or open biopsy. Additionally, the marginally improved postoperative functional status observed in patients who underwent resection, as opposed to in those who underwent biopsy, provides further evidence in favour of the advantages of surgical resection for enhancing neurological deficits.

P11.15.A IMPACT OF PERIOPERATIVE DEXAMETHASONE IN THE CONTEXT OF NEUROSURGICAL BRAIN METASTASIS RESECTION

Abstract BACKGROUND Patients with brain metastases that undergo brain metastasis resection regularly receive perioperative dexamethasone. We sought to evaluate whether perioperative dexamethasone in brain metastases is linked to survival. MATERIAL AND METHODS Retrospective data on perioperative dexamethasone dosage in resected brain metastasis patients at three hospital sites of the Charité from 2010-2022 were collected. Cut-off values for cumulative perioperative dexamethasone dose as a continuous predictor variable for survival were determined using maximally selected rank statistics. Patients were dichotomized based on determined cut-offs of cumulative dexamethasone (pre-operative: &amp;lt; 40 mg vs ≥ 40 mg; post-operative: &amp;lt; 180 mg vs ≥ 180 mg) and pre- and postoperative: &amp;lt; 281 mg vs ≥ 281 mg). Medical records included baseline demographic, radiological, histopathological and treatment-related characteristics. Based on cut-off values for dexamethasone downstream statistical analyses included Kaplan-Meier, Cox proportional hazards regression for overall survival with adjustment for potential confounders including age, gender, Karnofsky performance index and presence of extracranial metastasis via propensity score matching. RESULTS 539 patients were included. Median follow-up time was 58,97 months. After adjusting for age, gender, Karnofsky performance index and presence of extracranial metastasis patients with higher cumulative perioperative dexamethasone (≥281 mg) showed shorter survival (HR: 1.47 (1.20-1.80, p&amp;lt;0.001) as compared to patients with lower cumulative doses (&amp;lt;281 mg). This effect remained significant after correction for patients that died within 3 months after resection and for patients with KPS below 50% and, independently from this approach performing propensity score matched-based analysis of the total cohort of patients, respectively. CONCLUSION Cumulative perioperative dexamethasone is associated with decreased survival in the context of brain metastasis resection. Strict dosage, down taper or methods reducing corticosteroid dependency should be regularly evaluated in clinical practice in patients with brain metastases

Emergency Posterior Decompression for Metastatic Spine Tumors in Octogenarians: Clinical Course and Prognostic Factors for Functional Outcomes

This study aimed to describe the clinical outcome of metastatic epidural spinal cord compression in octogenarians with an acute onset of neurological illness who undergo laminectomy, further assess morbidity and mortality rates, and determine potential risk factors for a nonambulatory outcome. This retrospective review of electronic medical records at a single institution was conducted between September 2005 and December 2020. Patient demographics, surgical characteristics, complications, hospital course, and 90-day mortality were collected. Thirty-four patients aged 80 years and older who posterior decompression via laminectomy were enrolled in the present study. The mean Charlson Comorbidity Index was >6 (9.2 ± 2.1). The thoracic spine was the most common site of metastasis. A potentially unstable spine, determined using the Spinal Instability Neoplastic Score, was identified in 79.4% of the cases. Preoperatively, the neurological condition and functional status exhibited a notable decline (mean Motor Score of the American Spinal Injury Association grading system, 78.2 ± 16.4; mean Karnofsky Performance Index, 47.8 ± 19.5). The Motor Score of the American Spinal Injury Association grading system and Karnofsky Performance Index scores improved significantly after surgery. Motor weakness and comorbidities were unique risk factors for the loss of ambulation. Emergent decompressive laminectomy in patients with acute onset of neurological decline and potentially unstable spines improved functional outcome at discharge. Age should not be a determinant of whether to perform surgery; surgery should be performed in older patients when indicated.

Individualized Multimodal Immunotherapy for Adults with IDH1 Wild-Type GBM: A Single Institute Experience

Synergistic activity between maintenance temozolomide (TMZm) and individualized multimodal immunotherapy (IMI) during/after first-line treatment has been suggested to improve the overall survival (OS) of adults with IDH1 wild-type MGMT promoter-unmethylated (unmeth) GBM. We expand the data and include the OS of MGMT promoter-methylated (meth) adults with GBM. Unmeth (10 f, 18 m) and meth (12 f, 10 m) patients treated between 27 May 2015 and 1 January 2022 were analyzed retrospectively. There were no differences in age (median: 48 y) or Karnofsky performance index (median: 80). The IMI consisted of 5-day immunogenic cell death (ICD) therapies during TMZm: Newcastle disease virus (NDV) bolus injections and sessions of modulated electrohyperthermia (mEHT); subsequent active specific immunotherapy: dendritic cell (DC) vaccines plus modulatory immunotherapy; and maintenance ICD therapy. There were no differences in the number of vaccines (median: 2), total number of DCs (median: 25.6 × 106), number of NDV injections (median: 31), and number of mEHT sessions (median: 28) between both groups. The median OS of 28 unmeth patients was 22 m (2y-OS: 39%), confirming previous results. OS of 22 meth patients was significantly better (p = 0.0414) with 38 m (2y-OS: 81%). There were no major treatment-related adverse reactions. The addition of IMI during/after standard of care should be prospectively explored.

Pycnogenol® supplementation alleviates symptoms of Parkinson's disease with mild cognitive impairment.

The aim of this pilot registry study was to assess the preventive effect of an 8-week Pycnogenol® (French maritime pine bark extract) supplementation on symptoms, such as cognitive and motor aspects, in subjects with Parkinson's disease (PD). The study was based on five types of observations: a. Karnofsky performance scale index; b. oxidative stress markers in plasma (plasma free radicals, PFR); c. the main signs and symptoms, evaluated by a physician; d. face motion and expressions and their symmetry, recorded with a high-speed video camera. A total of 79 patients were included in the study: 39 controls using only standard management (SM) and 40 subjects supplemented with Pycnogenol® 150 mg/day. At inclusion, the two groups (SM and SM+Pycnogenol®) were comparable for age, symptoms, Karnofsky performance scale rating and for the management of PD. Likewise, oxidative stress and the presence of peripheral edema were also comparable between the two groups. No side effects of supplementation were observed. There were no tolerability problems. At the end of the study after 8 weeks, the Karnofsky performance index was significantly (P<0.05) higher with Pycnogenol® compared to controls. Also, the proportion of patients with a clinically visible peripheral edema decreased significantly over 8 weeks with Pycnogenol® compared to controls (P<0.05). Plasma oxidative stress was significantly lower with Pycnogenol® (P<0.05). The scores of PD main signs/symptoms like tremor, bradykinesia, alterations in cognitive functions, rigidity and speech impairment were significantly lower in the Pycnogenol® group compared to controls (P<0.05). Face expression evaluation showed a marked asymmetry at inclusion. Over 8-week supplementation, facial expression scores for visible and subliminal asymmetry, altered facial responses, altered shoulder motion and altered emotional pattern improved significantly in the Pycnogenol® group compared to controls (P<0.05) where the scores did not change significantly. In conclusion, according to this pilot registry study, Pycnogenol® supplementation helps patients with moderate, well-controlled PD - under stable treatment - to attenuate most signs and symptoms and life-relational aspects associated with Parkinson-related cognitive impairment.

Surgical treatment of solitare brain metastases

Background. Brain metastasis occurs in 10–30 % of patients with different malignances. Despite of successes, achieved in the treatment of extracranial malignances in last decade, tendency to increase of the survival and duration of the disease-free period in patients with brain metastasis is absent. Several treatment modalities: chemotherapy, radiation, immune and target therapy, stereotactic radiosurgery, different types of surgical procedures, however, an optimal combination of these methods remain unclear.The aim of the study: to summarize experience of complex treatment of patients with brain metastases in hospital with opportunity of both surgical removal, chemo- and radiotherapy and review literature on the topic.Materials and methods. The retrospective analysis of medical data of patients with brain metastases performed with assessment of most frequent sources of metastases, there value, localization, median survival duration from metastasis revealing due to different types of therapy, main period of recurrences and hospital state duration, early and late complications. Inclusion criteria were: patients with surgical treatment of brain metastases, availability of medical data. Exclusion criteria were: multiple brain metastases, contraindications for surgical treatment, sensitive to chemo- and radiation therapy malignances (leukoses, lymphoma, germinative tumors etc.). The assessment of degree of metastasis resection was made by postop CT and MRI with intravenous enhancement or by operation records. Intraoperative florescence was used for evaluation of tumor borders. In case of localization of metastasis in sensory or motor zones intraoperative electrophysiological monitoring acquired. Few operations for metastasis localized in speech zones were made with «asleep–awake–asleep» method. Follow-up assessed by questioning of patients and their relatives. Statistical analyzes performed in IBM SPSS Statistics 23.Results. 52 patients meet criteria and were included to the study. Male to female ratio was 1 : 1, main age – 60 years. The most common sources of brain metastases were (in decreasing order) melanoma, lung cancer, kidney cancer, breast cancer, rectal cancer, prostate cancer, ovarian cancer and uterus cancer. Two patients had 2 brain metastases at the time of assessment, other 50 – single. Most common localizations of brain metastases (in decreasing order) were: parietal lobe, frontal lobe, cerebellum hemispheres, occipital lobe, temporal lobe, ventricular system and brain meninges. In 46 % of cases metastases involves significant functional areas of brain. Median value of metastasis was 11 cm3; midline dislocation appeared in 65,4 % of cases; 6 patients have hemorrhage in the tumor, 2 – seizures, 2 – occlusive hydrocephalus. Main Karnofsky performance index – 73,8. Total resection performed in 84,6, subtotal resection – in 7,7 % of cases gross. Intraoperative fluorescence used in 73 %. In 10 cases metastasis localized in motor and sensory zones, all these cases were treat with intraoperative neurophysiological monitoring. Postoperative hemiparesis noticed in 1 patient; 3 surgeries performed with awake; no aphasias mentioned. Follow-up was assessed in 44 patients, 20 of them were dead at the time of the study. An assessment of dependence of overall survival median on primary tumor morphology performed. Prognostic factors of brain metastases: its morphology and value, extent of resection, Karnofsky status and early complications.Conclusions. Most patients with brain metastasis are in satisfactory condition. Most frequent tumors which form brain metastasis: melanoma and lung cancer, they are characterized by poorer prognosis. Most metastasis are supratentorial, intracranial hypertension is obvious. Metastasis localization, time from its evaluation to surgery, significant functional areas involvement and primary tumor resection aren’t fluent on survival.

Use of a Chemotherapy Toxicity Prediction Tool to Decrease Risks for Hospitalization in Older Patients.

ObjectivesPerformance status (PS) scales such as the Eastern Cooperative Oncology Group (ECOG) PS and the Karnofsky Performance Index have limited utility in selecting therapies and predicting related adverse events in older patients with cancer. In July 2016, medical oncologists at our institution adopted the Cancer and Aging Research Group toxicity prediction score (CARG), a toxicity prediction tool, to identify patients who are “fit” for chemotherapy versus those who are “frail” and may experience severe complications.MethodsOur retrospective review included referrals of beneficiaries 75 years of age and older who received standard systemic therapy and patients of the same age whose treatment was modified due to CARG. We compared the score’s utilization six months before and after its incorporation and then assessed how its application impacted admissions, emergency department (ED) visits, and medical management.ResultsThirty-eight patients with a mean age of 81 years met the inclusion criteria. Their diagnoses included gastrointestinal (37%), lung (21%), hematologic (18%), breast (10.5%), genitourinary (3%), and other (10.5%) malignancies. CARG was documented for 12.5% of systemic therapy recipients before its adoption and 41% of recipients after adoption. Its use was limited by the reliance on physicians to perform scoring during time-constrained patient encounters. Patients had fewer mean inpatient admissions (0.7 versus 2.3), admission days (4.3 versus 8), and ED visits (1.1 versus 2.5) when management was modified based on the score.ConclusionCARG assessment may facilitate a safer and more tailored approach to cancer care in older patients than conventional PS scales alone. Its integration into patient screening would increase its application and better define its potential predictive capacity to decrease risks for hospitalization.

Breakouts-A Radiological Sign of Poor Prognosis in Patients With Brain Metastases.

PurposeBrain metastases (BM) can present a displacing or infiltrating growth pattern, independent of the primary tumor type. Previous studies have shown that tumor cell infiltration at the macro-metastasis/brain parenchyma interface (MMPI) is correlated with poor outcome. Therefore, a pre-therapeutic, non-invasive detection tool for potential metastatic cell infiltration at the MMPI would be desirable to help identify patients who may benefit from a more aggressive local treatment strategy. The aim of this study was to identify specific magnetic resonance imaging (MRI) patterns at the MMPI in patients with BM and to correlate these patterns with patient outcome.Patients and MethodsIn this retrospective analysis of a prospective BM registry, we categorized preoperative MR images of 261 patients with BM according to a prespecified analysis system, which consisted of four MRI contrast enhancement (CE) patterns: two with apparently regularly shaped borders (termed “rim-enhancing” and “spherical”) and two with irregular delineation (termed “breakout” and “diffuse”). The primary outcome parameter was overall survival (OS). Additionally analyzed prognostic parameters were the Karnofsky Performance Index, tumor size, edema formation, extent of resection, and RPA class.ResultsOS of patients with a breakout pattern was significantly worse than OS of all other groups.ConclusionOur data show that BM with a breakout pattern have a highly aggressive clinical course. Patients with such a pattern potentially require a more aggressive local and systemic treatment strategy.

Tumor characteristics and surgical outcomes of intracranial subependymomas: a systematic review and meta-analysis.

The tumor characteristics and surgical outcomes of intracranial subependymomas are poorly defined. In this study the authors aimed to provide a comprehensive review of all clinical, pathological, radiological, and surgical aspects of this important neoplasm to inform future management strategies. A systematic review and meta-analysis of MEDLINE, EMBASE, Cochrane, and Google Scholar databases adherent to PRISMA guidelines was conducted. Of the 1145 articles initially retrieved, 24 studies encompassing 890 cases were included. The authors identified 3 retrospective cohort studies and 21 case series, but no controlled trials. Mean age at presentation was 46.7 ± 18.1 years with a male predominance (70.2%). Common sites of tumor origin were the lateral ventricle (44.5%) and fourth ventricle (43.1%). Cumulative postoperative mortality and morbidity rates were 3.4% and 24.3% respectively. Meta-analysis revealed that male sex (HR 3.15, 95% CI 1.39-7.14, p = 0.006) was associated with poorer 5-year overall mortality rates. All-cause mortality rates were similar when performing subgroup meta-analyses for age (HR 0.50, 95% CI 0.03-7.36, p = 0.61), smaller subependymoma size (HR 1.51, 95% CI 0.78-2.92, p = 0.22), gross-total resection (HR 0.65, 95% CI 0.35-1.23, p = 0.18), and receipt of postoperative radiation therapy (HR 0.88, 95% CI 0.27-2.88, p = 0.84). Postoperative Karnofsky Performance Index scores improved by a mean difference of 1.62 ± 12.14 points (p = 0.42). The pooled overall 5-year survival rate was 89.2%, while the cumulative recurrence rate was 1.3% over a median follow-up ranging from 15.3 to 120.0 months. The pure subependymoma histopathological subtype was most prevalent (85.6%), followed by the mixed subependymoma-ependymoma tumor variant (13.7%). Surgical extirpation without postoperative radiotherapy results in excellent postoperative survival and functional outcomes in the treatment of intracranial subependymomas. Aggressive tumor behavior should prompt histological reevaluation for a mixed subependymoma-ependymoma subtype. Further high-quality controlled trials are still required to investigate this rare tumor.

Fluorescein-guided resection of newly diagnosed high-grade glioma: Impact on extent of resection and outcome

IntroductionMaximal resection of high-grade glioma (HGG) improves progression–free survival (PFS) and overall survival (OS). Fluorescein sodium (FL) in combination with the YELLOW 560 ​nm filter (Carl Zeiss Meditec, Germany) is a safe and feasible method of visualizing residual tumor tissue during brain tumor resection. Research questionWe hypothesized that use of FL positively influenced the volumetric extent of resection (EOR), PFS, and OS in patients undergoing resection of a newly diagnosed HGG. Materials and methodUsing a prospective HGG registry, we identified 347 patients (median age 62.4 years; 141 women) with preoperative high-quality magnetic resonance images for volumetric analysis. Resection was performed under white light in n ​= ​151 (43.5%, white-light group) and under FL-guidance in n ​= ​196 (56.5%, FL group). Sex, age, presurgical Karnofsky Performance Index (KPI), O6-Methylguanin-DNA-Methyltransferase-Gene (MGMT) status, and adjuvant treatment modalities were well balanced between the groups. Volumetric analysis was performed by quantifying pre- and postoperative tumor volume based on gadolinium-enhanced T1 sequences in a blinded fashion. ResultsIn the FL group, postoperative tumor volume was significantly smaller (p ​= ​0.003); accordingly, quantitative EOR was significantly larger (p ​= ​0.003). Significantly more complete resections were achieved in the FL group than in the white-light group (p ​= ​0.003). The FL group showed significantly longer PFS (p ​= ​0.020) and OS (p ​= ​0.015, log rank testing). Multivariate Cox regression modelling showed age, presurgical KPI, MGMT status, and FL-guided resection to be independent prognostic factors for survival. Discussion and conclusionCompared to white-light resection, FL-guided resection of newly diagnosed HGG significantly improved EOR and prolonged OS.

SURG-04. Surgical resection of symptomatic brain metastasis in patients with non-small cell lung cancer irrespective from lesion count

Background and PurposeCurrent guidelines primarily suggest the resection in case of a limited number of brain metastases (BM). With an increasing number of local and systemic treatment options this approach needs reconsideration. Therefore, we aimed to evaluate the role of metastectomy in patients with non-small cell lung cancer (NSCLC) treated in a comprehensive setting disregarding lesion count.Patients and MethodsIn this monocentric retrospective analysis, patients receiving surgery for 1–3 BM with available demographic, clinical, and tumor-associated parameters were included. Prognostic factors for local control (LC) and overall survival (OS) were analyzed by Log rank test and Cox proportional hazards.ResultsTwo-hundred-sixteen patients were included: 129 (59.7%) with single/solitary, 64 (29.6%) with 2–3, and 23 (10.6%) with more than three BM. Resection of the symptomatic BM(s) improved the patients’ Karnofsky performance index (KPI) significantly (p<0.001), enabling adjuvant radiotherapy in 199 (92.1%) and systemic treatment in 119 (55.1%) patients.After a mean radiological follow-up of eight (1–79) months, LC was observed in 83 (38.4%) patients and was not significantly influenced by BM count (p=0.064). After a mean OS after surgery of 12.7 (0–88) months, 120 (55.6%) patients had died.In univariate analysis, BM count showed no impact on OS (p=0.844), while age ≥/< 65 years (p=0.007), pre- and postoperative KPI ≥70 (p=0.002 and p=0.005, respectively), extra-cranial metastases (p=0.004), adjuvant radiation therapy (p<0.001), and adjuvant systemic treatment (p<0.001) did. In regression analysis the presence of extra-cranial metastases (HR 2.30 95%CI 1.53–3.48; p<0.001), adjuvant radiation therapy (HR 0.97 95%CI 0.23–0.86; p=0.016), and adjuvant systemic treatment (HR 0.37 95%CI 0.25–0.55; p<0.001) remained independent factors for survival.ConclusionsThe indication for resection of symptomatic BM in patients with NSCLC is justified even in case of multiple lesions to alleviate their neurological symptoms and to enable further treatment.

Prognostic Value of microRNA-221/2 and 17-92 Families in Primary Glioblastoma Patients Treated with Postoperative Radiotherapy.

MicroRNAs (miRs) are non-coding master regulators of transcriptome that could act as tumor suppressors (TSs) or oncogenes (oncomiRs). We aimed to systematically investigate the relevance of miRs as prognostic biomarkers in primary glioblastoma multiforme (GBM) treated with postoperative radio(chemo)therapy (PORT). For hypothesis generation, tumor miR expression by Agilent 8x15K human microRNA microarrays and survival data from 482 GBM patients of The Cancer Genome Atlas (TCGA cohort) were analyzed using Cox-PH models. Expression of candidate miRs with prognostic relevance (miR-221/222; miR-17-5p, miR-18a, miR-19b) was validated by qRT-PCR using Taqman technology on an independent validation cohort of GBM patients (n = 109) treated at Heidelberg University Hospital (HD cohort). In TCGA, 50 miRs showed significant association with survival. Among the top ranked prognostic miRs were members of the two miR families miR-221/222 and miR-17-92. Loss of miR-221/222 was correlated with improved prognosis in both cohorts (TCGA, HD) and was an independent prognostic marker in a multivariate analysis considering demographic characteristics (age, sex, Karnofsky performance index (KPI)), molecular markers (O-6-methylguanine-DNA methyltransferase (MGMT) methylation, IDH mutation status) and PORT as co-variables. The prognostic value of miR-17-92 family members was ambiguous and in part contradictory by direct comparison of the two cohorts, thus warranting further validation in larger prospective trials.

Integrating Conservative kidney management Options and advance care Planning Education (COPE) into routine CKD care: a protocol for a pilot randomised controlled trial

IntroductionPredialysis education for patients with advanced chronic kidney disease (CKD) typically focuses narrowly on haemodialysis and peritoneal dialysis as future treatment options. However, patients who are older or seriously ill...

Quality of life and burden in family caregivers of patients with advanced cancer receiving specialized palliative care.

The caregivers of advanced cancer patients face many physical, psychological, social, and economic problems. In this study, the quality of life and burden in the primary family caregiver of patients with advanced cancer receiving inpatient palliative care were investigated. A total of 200 patients with advanced cancer hospitalized at palliative care center and primary caregivers were included. Functional capacities of patients were evaluated with Karnofsky Performance Scale and need of care with Katz index. The Turkish version of World Health Organization Quality of Life Instrument, Short Form (WHOQOL-BREF TR) was used to assess the quality of life of caregivers. The median Karnofsky Performance score of patients was found to be 30% and Katz Index score to be 2. The mean WHOQOL-BREF TR domain scores of family caregivers were 48.96 (Standard deviation (SD) =12.67) for physical health, 59.21 (SD=14.09) for psychological status, 56.83 (SD=20.91) for social relations, and 55.67 (SD=14.13) for environmental domain. Scores of psychological and environmental subscales were lower in women caregivers. The environmental subscale showed a significant difference in terms of education. The score of social relations subscale of the care giving spouse was lower than caregiving children and siblings. The score of environmental subscale of caregivers with insufficient income was found to be lower than caregivers with sufficient income. Karnofsky Performance and Katz Index scores and subscales of WHOQOL-BREF TR did not reveal any significant relation. This study showed that all subscales of quality of life are impaired in caregivers of advanced cancer patients, physical health being the most prominent.