Age-adjusted Charlson comorbidity index in recurrent glioblastoma: a new prognostic factor?

BACKGROUND: For recurrent glioblastoma (GB) patients, several therapy options have been established over the last years such as more aggressive surgery, re-irradiation or chemotherapy. Age and the Karnofsky Performance Status Scale (KPSS) are used to make decisions for these patients as these are established as prognostic factors in the initial diagnosis of GB. This study’s aim was to evaluate preoperative patient comorbidities by using the age-adjusted Charlson Comorbidity Index (ACCI) as a prognostic factor for recurrent GB patients. METHODS: In this retrospective analysis we could include 123 patients with surgery for primary recurrence of GB from January 2007 until December 2016 (43 females, 80 males, mean age 57 years (range 21–80 years)). Preoperative age, sex, ACCI, KPSS and adjuvant treatment regimes were recorded for each patient. Extent of resection (EOR) was recorded as a complete/incomplete resection of the contrast-enhancing tumor part. RESULTS: Median overall survival (OS) was 9.0 months (95% CI 7.1–10.9 months) after first re-resection. Preoperative KPSS > 80% (P < 0.001) and EOR (P = 0.013) were associated with significantly improved survival in univariate analysis. Including these factors in multivariate analysis, preoperative KPSS < 80 (HR 2.002 [95% CI: 1.246–3.216], P = 0.004) and EOR are the only significant prognostic factor (HR 1.611 [95% CI: 1.036–2.505], P = 0.034). ACCI was not shown as a prognostic factor in univariate and multivariate analyses. CONCLUSION: For patients with surgery for recurrent glioblastoma, the ACCI does not add further information about patient’s prognosis besides the well-established KPSS and extent of resection

Retrospective Analysis of Radiological Recurrence Patterns in Glioblastoma, Their Prognostic Value And Association to Postoperative Infarct Volume

Recent studies suggested that postoperative hypoxia might trigger invasive tumor growth, resulting in diffuse/multifocal recurrence patterns. Aim of this study was to analyze distinct recurrence patterns and their association to postoperative infarct volume and outcome. 526 consecutive glioblastoma patients were analyzed, of which 129 met our inclusion criteria: initial tumor diagnosis, surgery, postoperative diffusion-weighted imaging and tumor recurrence during follow-up. Distinct patterns of contrast-enhancement at initial diagnosis and at first tumor recurrence (multifocal growth/progression, contact to dura/ventricle, ependymal spread, local/distant recurrence) were recorded by two blinded neuroradiologists. The association of radiological patterns to survival and postoperative infarct volume was analyzed by uni-/multivariate survival analyses and binary logistic regression analysis. With increasing postoperative infarct volume, patients were significantly more likely to develop multifocal recurrence, recurrence with contact to ventricle and contact to dura. Patients with multifocal recurrence (Hazard Ratio (HR) 1.99, P = 0.010) had significantly shorter OS, patients with recurrent tumor with contact to ventricle (HR 1.85, P = 0.036), ependymal spread (HR 2.97, P = 0.004) and distant recurrence (HR 1.75, P = 0.019) significantly shorter post-progression survival in multivariate analyses including well-established prognostic factors like age, Karnofsky Performance Score (KPS), therapy, extent of resection and patterns of primary tumors. Postoperative infarct volume might initiate hypoxia-mediated aggressive tumor growth resulting in multifocal and diffuse recurrence patterns and impaired survival

Prognostic value of tumour volume in patients with a poor Karnofsky performance status scale – a bicentric retrospective study

Backround: Median overall survival (OS) after diagnosis of glioblastoma (GBM) remains 15 months amongst patients receiving aggressive surgical resection, chemotherapy and irradiation. Treatment of patients with a poor preoperative Karnofsky Performance Status Scale (KPSS) is still controversial. Therefore, we retrospectively assessed the outcome after surgical treatment in patients with a KPSS of ≤60%. Methods: We retrospectively included patients with a de-novo glioblastoma WHO °IV and preoperative KPSS ≤60%, who underwent surgery at two neurosurgical centres between September 2006 and March 2016. We recorded pre- and postoperative tumour volume, pre- and postoperative KPSS, OS, age and MGMT promoter status. Results: One hundred twenty-three patients (58 females/65 males, mean age 67.4 ± 13.4 years) met the inclusion criteria. Seventy-five of the 123 patients (61%) underwent surgical resection. 48/123 patients (39%) received a biopsy. The median preoperative and postoperative tumour volume of all patients was 33.0 ± 31.3 cm3 (IR 15.0–56.5cm3) and 3.1 ± 23.8 cm3 (IR 0.2–15.0 cm3), respectively. The median KPSS was 60% (range 20–60%) preoperatively and 50% (range 0–80%) postoperatively. Patients who received a biopsy showed a median OS for patients who received a biopsy only was 3.0 months (95% CI 2.0–4.0 months), compared to patients who had a resection and had a median OS of 8 months (95% CI 3.1–12.9 months). Age (p &lt; 0.001, HR: 1.045 [95% CI 1.022–1.068]), postoperative tumour volume (p = 0.02, HR: 1.016 [95% CI 1.002–1.029]) and MGMT promotor status (p = 0.016, HR: 0.473 [95% CI 0.257–0.871]) were statistically significant in multivariate analysis. In subgroup analyses only age was shown as a significant prognostic factor in multivariate analyses for patients receiving surgery (p &lt; 0.001, HR: 1.046 [95% CI 1.022–1.072]). In the biopsy group no significant prognostic factors were shown in multivariate analysis. Conclusion: GBM patients with a preoperative KPSS of ≤60% might profit from surgical reduction of tumour burden

Organizational Configurations and Performance: A Meta-Analysis

The link between organizational configurations and performance has become a central and somewhat controversial focus of research in the strategic management literature, We statistically aggregated results from 40 original tests of the configurations-performance relationship. In contrast to previous qualitative reviews, this meta-analysis demonstrated that an organization\u27s performance is partially explained by its configuration. Tests of four potential moderators showed that organizations\u27 configurations contributed more to performance explanation to the extent that studies used (1) broad definitions of configurations, (2) single-industry samples, and (3) longitudinal designs, Results highlight the need for programmatic research

Multicentric assessment of safety and efficacy of combinatorial adjuvant brain metastasis treatment by intraoperative radiotherapy and immunotherapy

Purpose Following surgical resection of brain metastases (BMs), intraoperative radiation therapy (IORT) provides a promising alternative to adjuvant external beam radiation therapy (EBRT) by enabling superior organ at risk preservation, reduction of in-hospital times and timely admission to subsequent systemic treatments, which increasingly comprise novel targeted immunotherapeutic approaches. We sought to assess safety and efficacy of IORT in combination with immune checkpoint inhibitors (ICIs) and other targeted therapies (TTs). Methods In a multicentric approach incorporating individual patient data from six international IORT centers, all patients with BMs undergoing IORT were retrospectively assessed for combinatorial treatment with ICIs/TTs and evaluated for toxicity and cumulative rates, including wound dehiscence, radiation necrosis (RN), leptomeningeal spread (LMS), local control (LC), distant brain progression (DBP) and estimated overall survival (OS). Results A total of 103 lesions with a median diameter of 34 mm receiving IORT combined with immunomodulatory systemic treatment or other TTs were included. The median follow up was 13.2 (1.2-102.4) months and the median IORT dose was 25 (18-30) Gy prescribed to the applicator surface. There was one grade 3 adverse event related to IORT recorded (2.2%). A 4.9% cumulative RN rate was observed. The 1-year LCR was 98.0% and the 1-year DBP-free rate 60.0%. Median time to DBP was 5.5 (1.0-18.5) months in the subgroup of patients experiencing DBP and the cumulative LMS rate was 4.9%. The median estimated OS was 26 (1.2-not reached) months with a 1-year survival rate of 74.0%. Early initiation of IT/TT was associated with a non-significant trend towards improved DBP rate and OS. Conclusion The combination of ICIs/TT with IORT for resected BMs does not seem to increase toxicity, while yielding encouraging local control outcomes in the difficult-to-treat subgroup of larger BMs. Time gaps between surgery and systemic treatment could be shortened or avoided. The definitive role of IORT in local control after BM resection will be defined in a prospective trial

Opportunities and Alternatives of Modern Radiation Oncology and Surgery for the Management of Resectable Brain Metastases.

Postsurgical radiotherapy (RT) has been early proven to prevent local tumor recurrence, initially performed with whole brain RT (WBRT). Subsequent to disadvantageous cognitive sequalae for the patient and the broad distribution of modern linear accelerators, focal irradiation of the tumor has omitted WBRT in most cases. In many studies, the effectiveness of local RT of the resection cavity, either as single-fraction stereotactic radiosurgery (SRS) or hypo-fractionated stereotactic RT (hFSRT), has been demonstrated to be effective and safe. However, whereas prospective high-level incidence is still lacking on which dose and fractionation scheme is the best choice for the patient, further ablative techniques have come into play. Neoadjuvant SRS (N-SRS) prior to resection combines straightforward target delineation with an accelerated post-surgical phase, allowing an earlier start of systemic treatment or rehabilitation as indicated. In addition, low-energy intraoperative RT (IORT) on the surgical bed has been introduced as another alternative to external beam RT, offering sterilization of the cavity surface with steep dose gradients towards the healthy brain. This consensus paper summarizes current local treatment strategies for resectable brain metastases regarding available data and patient-centered decision-making

Measures of infection prevention and incidence of SARS-CoV-2 infections in cancer patients undergoing radiotherapy in Germany, Austria and Switzerland

Abstract Purpose COVID-19 infection has manifested as a major threat to both patients and healthcare providers around the world. Radiation oncology institutions (ROI) deliver a major component of cancer treatment, with protocols that might span over several weeks, with the result of increasing susceptibility to COVID-19 infection and presenting with a more severe clinical course when compared with the general population. The aim of this manuscript is to investigate the impact of ROI protocols and performance on daily practice in the high-risk cancer patients during this pandemic. Methods We addressed the incidence of positive COVID-19 cases in both patients and health care workers (HCW), in addition to the protective measures adopted in ROIs in Germany, Austria and Switzerland using a specific questionnaire. Results The results of the questionnaire showed that a noteworthy number of ROIs were able to complete treatment in SARS-CoV‑2 positive cancer patients, with only a short interruption. The ROIs reported a significant decrease in patient volume that was not impacted by the circumambient disease incidence, the type of ROI or the occurrence of positive cases. Of the ROIs 16.5% also reported infected HCWs. About half of the ROIs (50.5%) adopted a screening program for patients whereas only 23.3% also screened their HCWs. The range of protective measures included the creation of working groups, instituting home office work and protection with face masks. Regarding the therapeutic options offered, curative procedures were performed with either unchanged or moderately decreased schedules, whereas palliative or benign radiotherapy procedures were more often shortened. Most ROIs postponed or cancelled radiation treatment for benign indications (88.1%). The occurrence of SARS-CoV‑2 infections did not affect the treatment options for curative procedures. Non-university-based ROIs seemed to be more willing to change their treatment options for curative and palliative cases than university-based ROIs. Conclusion Most ROIs reported a deep impact of SARS-CoV‑2 infections on their work routine. Modification and prioritization of treatment regimens and the application of protective measures preserved a well-functioning radiation oncology service and patient care

First statement on preparation for the COVID-19 pandemic in large German speaking University-based radiation oncology departments

The COVID-19 pandemic is challenging modern radiation oncology. At University Hospitals, we have a mandate to offer high-end treatments to all cancer patients. However, in times of crisis we must learn to prioritize resources, especially personnel. Compromising oncological outcome will blur all statistics, therefore all measures must be taken with great caution. Communication with our neighboring countries, within societies and between departments can help meet the challenge. Here, we report on our learning system and preparation measures to effectively tackle the COVID-19 challenge in University-Based Radiation Oncology Departments

Maternal trauma and fear history predict BDNF methylation and gene expression in newborns

Trauma and related fear exert significant influence on mental and physical health throughout the lifespan and are associated with intergenerational patterns of development, health, and behavior. DNA methylation and gene expression are involved in our developmental adaptations to our experiences and can be influenced by social interventions. Patterns of DNA methylation and expression of a gene involved in neurodevelopment and psychiatric risk (BDNF) have been linked with childhood trauma. Given the intergenerational patterns of health and behavior, and previous links between childhood trauma and BDNF methylation and expression, this study investigated the potential for maternal history of traumatic experiences to influence development in her newborn, via changes in her newborn's BDNF methylation and expression. We found that mothers' trauma history was associated with epigenetic regulation of BDNF in their newborns. Moreover, the association between maternal trauma and BDNF methylation and expression patterns were moderated by newborn sex. Male newborns showed increased BDNF expression with maternal exposure to child abuse (p&nbsp;=&nbsp;.001), and increased BDNF methylation with greater maternal fear (p&nbsp;=&nbsp;.001). Female newborns showed reduced BDNF expression with greater maternal fear (p&nbsp;=&nbsp;.004). Practitioners strive to identify prevention and intervention avenues that will reduce the harmful effects of trauma. Future research should consider the potential for maternal historical trauma experiences to influence offspring DNA methylation and gene expression in a manner that could alter development and inform novel prevention strategies