DNA repair biomarkers XPF and phospho-MAPKAP kinase 2 correlate with clinical outcome in advanced head and neck cancer.

BackgroundInduction chemotherapy is a common therapeutic option for patients with locoregionally-advanced head and neck cancer (HNC), but it remains unclear which patients will benefit. In this study, we searched for biomarkers predicting the response of patients with locoregionally-advanced HNC to induction chemotherapy by evaluating the expression pattern of DNA repair proteins.MethodsExpression of a panel of DNA-repair proteins in formalin-fixed paraffin embedded specimens from a cohort of 37 HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation were analyzed using quantitative immunohistochemistry.ResultsWe found that XPF (an ERCC1 binding partner) and phospho-MAPKAP Kinase 2 (pMK2) are novel biomarkers for HNSCC patients undergoing platinum-based induction chemotherapy. Low XPF expression in HNSCC patients is associated with better response to induction chemoradiotherapy, while high XPF expression correlates with a worse response (p = 0.02). Furthermore, low pMK2 expression was found to correlate significantly with overall survival after induction plus chemoradiation therapy (p = 0.01), suggesting that pMK2 may relate to chemoradiation therapy.ConclusionsWe identified XPF and pMK2 as novel DNA-repair biomarkers for locoregionally-advanced HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation. Our study provides insights for the use of DNA repair biomarkers in personalized diagnostics strategies. Further validation in a larger cohort is indicated

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

Role of stereotactic body radiation therapy for unresected pancreatic cancer

Hintergrund Patienten mit einem Pankreaskarzinom haben noch immer eine vergleichsweise schlechte Prognose, auch wenn bei der Erstdiagnose keine Metastasen vorhanden sind. Obwohl das Pankreaskarzinom bei manchen Onkologen als verhältnismäßig radioresistent gilt, haben Studien doch einen Überlebensvorteil durch eine kombinierte Radiochemotherapie (RCT) zeigen können. Allerdings bleibt der Einfluss der verschiedenen Radiotherapietechniken und Fraktionierungsschemata sowie die optimale Einbettung in multimodale Therapiekonzepte weiterhin unklar. Die Autoren der hier zu diskutierenden Studie strebten deshalb eine Aussage über die Rolle verschiedener Bestrahlungstechniken, also externe Strahlentherapie („external-beam radiation therapy“, EBRT), intensitätsmodulierte Strahlentherapie (IMRT) und insbesondere der stereotaktischen Radiotherapie („stereotactic body radiation therapy“, SBRT) in Kombination mit einer Chemotherapie, an. Patienten und Methoden In einer großen retrospektiven Studie durchsuchten die Autoren die Datenbank der National Cancer Data Base nach Patienten mit nichtresezierten und nichtmetastasierten Pankreaskarzinomen der Jahre 2004 bis 2012. Sie analysierten die Behandlungs- und Überlebensdaten für 14.331 Patienten und bildeten vier Behandlungsgruppen: 38,1 % der Patienten erhielten ausschließlich eine Chemotherapie, 44,8 % außerdem eine EBRT, 2,3 % eine IMRT und 14,8 % wurden mittels SBRT radiochemotherapiert. Um eine mögliche Stichprobenverzerrung zu kontrollieren, führten die Autoren ein Propensity Score Matching durch. Ergebnisse Die Patienten, die mittels SBRT radiochemotherapiert wurden, hatten einen Gesamtüberlebensvorteil von 3,7 Monaten im Vergleich zu lediglich chemotherapierten Patienten (13,9 vs. 10,2 Monate). Patienten, die zusätzlich zur Chemotherapie eine SBRT erhielten, profitierten auch im medianen Gesamtüberleben gegenüber solchen, die mit einer EBRT therapiert wurden (13,9 vs. 11,6 Monate). Es zeigte sich hingegen kein signifikanter Unterschied im Gesamtüberleben zwischen Patienten mit SBRT gegenüber solchen mit IMRT. Schlussfolgerung der Autoren Wegen der kurzen Behandlungsdauer, der sicheren Anwendung, der hohen lokalen Kontrolle und des guten Schmerzansprechens sollte eine SBRT als Behandlungsoption in Betracht gezogen werden. Künftig seien weitere Studien dringend erforderlich, um die Rolle der SBRT-Radiochemotherapie bei Pankreaskarzinompatienten weiter untersuchen zu können

Modeling Exposure to Heat Stress with a Simple Urban Model

As a first step in modeling health-related urban well-being (UrbWellth), a mathematical model is constructed that dynamically simulates heat stress exposure of commuters in an idealized city. This is done by coupling the Simple Urban Radiation Model (SURM), which computes the mean radiant temperature ( T m r t ), with a newly developed multi-class multi-mode traffic model. Simulation results with parameters chosen for the city of Hamburg for a hot summer day show that commuters are potentially most exposed to heat stress in the early afternoon when T m r t has its maximum. Varying the morphology with respect to street width and building height shows that a more compact city configuration reduces T m r t and therefore the exposure to heat stress. The impact resulting from changes in the city structure on traffic is simulated to determine the time spent outside during the commute. While the time in traffic jams increases for compact cities, the total commuting time decreases due to shorter distances between home and work place. Concerning adaptation measures, it is shown that increases in the albedo of the urban surfaces lead to an increase in daytime heat stress. Dramatic increases in heat stress exposure are found when both, wall and street albedo, are increased

Evolution of treatment strategies for oligometastatic NSCLC patients - a systematic review of the literature

BACKGROUND: The concept of oligometastatic disease (OMD) has expanded the scope of potentially curative therapy for metastatic NSCLC. However, large uncertainties remain regarding its definition and optimal management strategies. We therefore conducted a systematic review to investigate the value of various multimodality treatment concepts. METHODS: We searched the available literature in Pubmed, Medline and EMBASE using the terms "oligomet*", "synchron*", "oligorec*", "metachr*" "NSCLC", "lung cancer" and "stage IV" and included studies reporting treatment regimens and outcomes on radically treated patients with either "synchronous", "metachronous" or "mixed" OMD. Only de-novo diagnosis of OMD was considered. The impact of patient and treatment characteristics on overall survival (OS) and time trends in patterns of care were investigated. RESULTS: 54 studies published between 1987 and 2018 were included. Despite a wide range of OMD definitions, 90.1% of patients were treated for a single metastasis. Systemic therapy was used as backbone treatment for most patients. Although surgery was the preferred local treatment in earlier studies, the use of stereotactic radiotherapy increased rapidly after 2011. No OS difference was observed between surgery or radiotherapy as the treatment of primary tumor or metastases, respectively. A time trend towards improved OS after 2011 could be detected. CONCLUSIONS: While evidence in favor of radical treatment is emerging, most studies remain retrospective and mainly evaluate patients with singular metastases. While surgery, stereotactic radiotherapy and chemotherapy are the cornerstones of current treatment strategies, future clinical trials need to address the high risk of distant metastases by integrating targeted or immunotherapy

DNA repair biomarkers XPF and phospho-MAPKAP kinase 2 correlate with clinical outcome in advanced head and neck cancer.

BackgroundInduction chemotherapy is a common therapeutic option for patients with locoregionally-advanced head and neck cancer (HNC), but it remains unclear which patients will benefit. In this study, we searched for biomarkers predicting the response of patients with locoregionally-advanced HNC to induction chemotherapy by evaluating the expression pattern of DNA repair proteins.MethodsExpression of a panel of DNA-repair proteins in formalin-fixed paraffin embedded specimens from a cohort of 37 HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation were analyzed using quantitative immunohistochemistry.ResultsWe found that XPF (an ERCC1 binding partner) and phospho-MAPKAP Kinase 2 (pMK2) are novel biomarkers for HNSCC patients undergoing platinum-based induction chemotherapy. Low XPF expression in HNSCC patients is associated with better response to induction chemoradiotherapy, while high XPF expression correlates with a worse response (p = 0.02). Furthermore, low pMK2 expression was found to correlate significantly with overall survival after induction plus chemoradiation therapy (p = 0.01), suggesting that pMK2 may relate to chemoradiation therapy.ConclusionsWe identified XPF and pMK2 as novel DNA-repair biomarkers for locoregionally-advanced HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation. Our study provides insights for the use of DNA repair biomarkers in personalized diagnostics strategies. Further validation in a larger cohort is indicated

DNA Repair Biomarkers XPF and Phospho-MAPKAP Kinase 2 Correlate with Clinical Outcome in Advanced Head and Neck Cancer

Background: Induction chemotherapy is a common therapeutic option for patients with locoregionally-advanced head and neck cancer (HNC), but it remains unclear which patients will benefit. In this study, we searched for biomarkers predicting the response of patients with locoregionally-advanced HNC to induction chemotherapy by evaluating the expression pattern of DNA repair proteins.Methods: Expression of a panel of DNA-repair proteins in formalin-fixed paraffin embedded specimens from a cohort of 37 HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation were analyzed using quantitative immunohistochemistry.Results: We found that XPF (an ERCC1 binding partner) and phospho-MAPKAP Kinase 2 (pMK2) are novel biomarkers for HNSCC patients undergoing platinum-based induction chemotherapy. Low XPF expression in HNSCC patients is associated with better response to induction chemoradiotherapy, while high XPF expression correlates with a worse response (p = 0.02). Furthermore, low pMK2 expression was found to correlate significantly with overall survival after induction plus chemoradiation therapy (p = 0.01), suggesting that pMK2 may relate to chemoradiation therapy.Conclusions: We identified XPF and pMK2 as novel DNA-repair biomarkers for locoregionally-advanced HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation. Our study provides insights for the use of DNA repair biomarkers in personalized diagnostics strategies. Further validation in a larger cohort is indicated.</p