Validation of the Decipher genomic classifier in patients receiving salvage radiotherapy without hormone therapy after radical prostatectomy - an ancillary study of the SAKK 09/10 randomized clinical trial.

BACKGROUND: The Decipher genomic classifier (GC) has shown to independently prognosticate outcomes in prostate cancer. The objective of this study was to validate the GC in a randomized phase III trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy. PATIENTS AND METHODS: A clinical-grade whole-transcriptome assay was carried out on radical prostatectomy samples obtained from patients enrolled in Swiss Group for Clinical Cancer Research (SAKK) 09/10, a phase III trial of 350 men with biochemical recurrence after radical prostatectomy randomized to 64 Gy versus 70 Gy without concurrent hormonal therapy or pelvic nodal RT. A prespecified statistical plan was developed to assess the impact of the GC on clinical outcomes. The primary endpoint was biochemical progression; secondary endpoints were clinical progression and time to hormone therapy. Multivariable analyses adjusted for age, T-category, Gleason score, postradical prostatectomy persistent prostate-specific antigen (PSA), PSA at randomization, and randomization arm were conducted, accounting for competing risks. RESULTS: The analytic cohort of 226 patients was representative of the overall trial, with a median follow-up of 6.3 years (interquartile range 6.1-7.2 years). The GC (high versus low-intermediate) was independently associated with biochemical progression [subdistribution hazard ratio (sHR) 2.26, 95% confidence interval (CI) 1.42-3.60; P < 0.001], clinical progression (HR 2.29, 95% CI 1.32-3.98; P = 0.003), and use of hormone therapy (sHR 2.99, 95% CI 1.55-5.76; P = 0.001). GC high patients had a 5-year freedom from biochemical progression of 45% versus 71% for GC low-intermediate. Dose escalation did not benefit the overall cohort, nor patients with lower versus higher GC scores. CONCLUSIONS: This study represents the first contemporary randomized controlled trial in patients treated with early SRT without concurrent hormone therapy or pelvic nodal RT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and RT dose, high-GC patients were more than twice as likely than lower-GC patients to experience biochemical and clinical progression and receive of salvage hormone therapy. These data confirm the clinical value of Decipher GC to personalize the use of concurrent systemic therapy in the postoperative salvage setting.

Integration of radiation oncology teaching in medical studies by German medical faculties due to the new licensing regulations : An overview and recommendations of the consortium academic radiation oncology of the German Society for Radiation Oncology (DEGRO).

The new Medical Licensing Regulations 2025 (Ärztliche Approbationsordnung, ÄApprO) will soon be passed by the Federal Council (Bundesrat) and will be implemented step by step by the individual faculties in the coming months. The further development of medical studies essentially involves an orientation from fact-based to competence-based learning and focuses on practical, longitudinal and interdisciplinary training. Radiation oncology and radiation therapy are important components of therapeutic oncology and are of great importance for public health, both clinically and epidemiologically, and therefore should be given appropriate attention in medical education. This report is based on a recent survey on the current state of radiation therapy teaching at university hospitals in Germany as well as the contents of the National Competence Based Learning Objectives Catalogue for Medicine 2.0 (Nationaler Kompetenzbasierter Lernzielkatalog Medizin 2.0, NKLM) and the closely related Subject Catalogue (Gegenstandskatalog, GK) of the Institute for Medical and Pharmaceutical Examination Questions (Institut für Medizinische und Pharmazeutische Prüfungsfragen, IMPP). The current recommendations of the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) regarding topics, scope and rationale for the establishment of radiation oncology teaching at the respective faculties are also included.

Interleukin-10 suppression enhances T-cell antitumor immunity and responses to checkpoint blockade in chronic lymphocytic leukemia.

T-cell dysfunction is a hallmark of B-cell Chronic Lymphocytic Leukemia (CLL), where CLL cells downregulate T-cell responses through regulatory molecules including programmed death ligand-1 (PD-L1) and Interleukin-10 (IL-10). Immune checkpoint blockade (ICB) aims to restore T-cell function by preventing the ligation of inhibitory receptors like PD-1. However, most CLL patients do not respond well to this therapy. Thus, we investigated whether IL-10 suppression could enhance antitumor T-cell activity and responses to ICB. Since CLL IL-10 expression depends on Sp1, we utilized a novel, better tolerated analogue of the Sp1 inhibitor mithramycin (MTMox32E) to suppress CLL IL-10. MTMox32E treatment inhibited mouse and human CLL IL-10 production and maintained T-cell effector function in vitro. In the Eµ-Tcl1 mouse model, treatment reduced plasma IL-10 and CLL burden and increased CD8+ T-cell proliferation, effector and memory cell prevalence, and interferon-γ production. When combined with ICB, suppression of IL-10 improved responses to anti-PD-L1 as shown by a 4.5-fold decrease in CLL cell burden compared to anti-PD-L1 alone. Combination therapy also produced more interferon-γ+, cytotoxic effector KLRG1+, and memory CD8+ T-cells, and fewer exhausted T-cells. Since current therapies for CLL do not target IL-10, this provides a novel strategy to improve immunotherapies.

Screening for irradiation vasculopathy by intima-media thickness sonography in head and neck cancer patients.

PURPOSE: Post-irradiation vasculopathy is a severe form of atherosclerosis and affects the prognosis of head and neck cancer survivors. Sonographic intima-media thickness (IMT) precedes stenosis, plaque formation, and cerebrovascular events. Therefore, IMT may be a valuable screening marker for post-irradiation toxicity. However, the critical irradiation dose and the onset of IMT increase remain unclear. METHODS: The cross-sectional study analysed the carotid artery IMT in 96 irradiated patients and 41 controls regarding irradiation dose, post-irradiation-interval, and cardiovascular risk factors. Distinct irradiation doses to the tumour side and the contralateral hemineck enabled detection of dose depended effects within one patient and control of risk factors. RESULTS: Radiotherapy caused a dose-dependent increase in IMT. The toxicity did not have saturation effects for > 60 Gy. The IMT increase occurred in short-term following radiotherapy and the risk for a pathological value (> 0.9 mm) rose significantly. The correlation between IMT and radiotherapy was comparable to established cardiovascular risk factors. CONCLUSION: Radiotherapists should consider the additional toxicity of high doses for non-metastatic head and neck cancer. If neck metastases require radiotherapy with boost, IMT measurement is suitable for early detection of carotid artery damage.

The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: a combined analysis of 388 patients with 500 metastases.

BACKGROUND: The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. METHODS: The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. RESULTS: Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. CONCLUSION: In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.

Exposure of remote organs and associated cancer risks from tangential and multi-field breast cancer radiotherapy.

PURPOSE: With the ever-increasing cure rates in breast cancer, radiotherapy-induced cancers have become an important issue. This study aimed to estimate secondary cancer risks for different treatment techniques, taking into account organs throughout the body. MATERIAL AND METHODS: Organ doses were evaluated for a tangential three-dimensional conformal (3D-CRT) and a multi-field intensity-modulated radiotherapy (IMRT) plan using a validated, Monte Carlo-based treatment planning system. Effects of wedges and of forward versus inverse planning were systematically investigated on the basis of phantom measurements. Organ-specific cancer risks were estimated using risk coefficients derived from radiotherapy patients or from the atomic bomb survivors. RESULTS: In the 3D-CRT plan, mean organ doses could be kept below 1 Gy for more remote organs than the lung, heart, and contralateral breast, and decreased to a few cGy for organs in the lower torso. Multi-field IMRT led to considerably higher mean doses in organs at risk, the difference being higher than 50% for many organs. Likewise, the peripheral radiation burden was increased by external wedges. No difference was observed for forward versus inverse planning. Despite the lower doses, the total estimated secondary cancer risk in more remote organs was comparable to that in the lung or the contralateral breast. For multi-field IMRT it was 75% higher than for 3D-CRT without external wedges. CONCLUSION: Remote organs are important for assessment of radiation-induced cancer risk. Remote doses can be reduced effectively by application of a tangential field configuration and a linear accelerator set-up with low head scatter radiation.

Repeat epidural steroid injections for radicular pain due to lumbar or cervical disc herniation: what happens after 'salvage treatment'?.

AIMS: The aim of this study was to determine the efficacy of repeat epidural steroid injections as a form of treatment for patients with insufficiently controlled or recurrent radicular pain due to a lumbar or cervical disc herniation. PATIENTS AND METHODS: A cohort of 102 patients was prospectively followed, after an epidural steroid injection for radicular symptoms due to lumbar disc herniation, in 57 patients, and cervical disc herniation, in 45 patients. Those patients with persistent pain who requested a second injection were prospectively followed for one year. Radicular and local pain were assessed on a visual analogue scale (VAS), functional outcome with the Oswestry Disability Index (ODI) or the Neck Pain and Disability Index (NPAD), as well as health-related quality of life (HRQoL) using the 12-Item Short-Form Health Survey questionnaire (SF-12). RESULTS: A second injection was performed in 17 patients (29.8%) with lumbar herniation and seven (15.6%) with cervical herniation at a mean of 65.3 days (sd 46.5) and 47 days (sd 37.2), respectively, after the initial injection. All but one patient, who underwent lumbar microdiscectomy, responded satisfactorily with a mean VAS for leg pain of 8.8 mm (sd 10.3) and a mean VAS for arm pain of 6.3 mm (sd 9) one year after the second injection, respectively. Similarly, functional outcome and HRQoL were improved significantly from the baseline scores: mean ODI, 12.3 (sd 12.4; p < 0.001); mean NPAD, 19.3 (sd 24.3; p = 0.041); mean SF-12 physical component summary (PCS) in lumbar herniation, 46.8 (sd 7.7; p < 0.001); mean SF-12 PCS in cervical herniation, 43 (sd 6.8; p = 0.103). CONCLUSION: Repeat steroid injections are a justifiable form of treatment in symptomatic patients with lumbar or cervical disc herniation whose symptoms are not satisfactorily relieved after the first injection. Cite this article: Bone Joint J 2018;100-B:1364-71.

Survival of rats bearing advanced intracerebral F 98 tumors after glutathione depletion and microbeam radiation therapy: conclusions from a pilot project.

BACKGROUND: Resistance to radiotherapy is frequently encountered in patients with glioblastoma multiforme. It is caused at least partially by the high glutathione content in the tumour tissue. Therefore, the administration of the glutathione synthesis inhibitor Buthionine-SR-Sulfoximine (BSO) should increase survival time. METHODS: BSO was tested in combination with an experimental synchrotron-based treatment, microbeam radiation therapy (MRT), characterized by spatially and periodically alternating microscopic dose distribution. One hundred thousand F98 glioma cells were injected into the right cerebral hemisphere of adult male Fischer rats to generate an orthotopic small animal model of a highly malignant brain tumour in a very advanced stage. Therapy was scheduled for day 13 after tumour cell implantation. At this time, 12.5% of the animals had already died from their disease. The surviving 24 tumour-bearing animals were randomly distributed in three experimental groups: subjected to MRT alone (Group A), to MRT plus BSO (Group B) and tumour-bearing untreated controls (Group C). Thus, half of the irradiated animals received an injection of 100 µM BSO into the tumour two hours before radiotherapy. Additional tumour-free animals, mirroring the treatment of the tumour-bearing animals, were included in the experiment. MRT was administered in bi-directional mode with arrays of quasi-parallel beams crossing at the tumour location. The width of the microbeams was ≈28 µm with a center-to-center distance of ≈400 µm, a peak dose of 350 Gy, and a valley dose of 9 Gy in the normal tissue and 18 Gy at the tumour location; thus, the peak to valley dose ratio (PVDR) was 31. RESULTS: After tumour-cell implantation, otherwise untreated rats had a mean survival time of 15 days. Twenty days after implantation, 62.5% of the animals receiving MRT alone (group A) and 75% of the rats given MRT + BSO (group B) were still alive. Thirty days after implantation, survival was 12.5% in Group A and 62.5% in Group B. There were no survivors on or beyond day 35 in Group A, but 25% were still alive in Group B. Thus, rats which underwent MRT with adjuvant BSO injection experienced the largest survival gain. CONCLUSIONS: In this pilot project using an orthotopic small animal model of advanced malignant brain tumour, the injection of the glutathione inhibitor BSO with MRT significantly increased mean survival time.

The SBRT database initiative of the German Society for Radiation Oncology (DEGRO): patterns of care and outcome analysis of stereotactic body radiotherapy (SBRT) for liver oligometastases in 474 patients with 623 metastases.

BACKGROUND: The intent of this pooled analysis as part of the German society for radiation oncology (DEGRO) stereotactic body radiotherapy (SBRT) initiative was to analyze the patterns of care of SBRT for liver oligometastases and to derive factors influencing treated metastases control and overall survival in a large patient cohort. METHODS: From 17 German and Swiss centers, data on all patients treated for liver oligometastases with SBRT since its introduction in 1997 has been collected and entered into a centralized database. In addition to patient and tumor characteristics, data on immobilization, image guidance and motion management as well as dose prescription and fractionation has been gathered. Besides dose response and survival statistics, time trends of the aforementioned variables have been investigated. RESULTS: In total, 474 patients with 623 liver oligometastases (median 1 lesion/patient; range 1­4) have been collected from 1997 until 2015. Predominant histologies were colorectal cancer (n = 213 pts.; 300 lesions) and breast cancer (n = 57; 81 lesions). All centers employed an SBRT specific setup. Initially, stereotactic coordinates and CT simulation were used for treatment set-up (55%), but eventually were replaced by CBCT guidance (28%) or more recently robotic tracking (17%). High variance in fraction (fx) number (median 1 fx; range 1­13) and dose per fraction (median: 18.5 Gy; range 3­37.5 Gy) was observed, although median BED remained consistently high after an initial learning curve. Median follow-up time was 15 months; median overall survival after SBRT was 24 months. One- and 2-year treated metastases control rate of treated lesions was 77% and 64%; if maximum isocenter biological equivalent dose (BED) was greater than 150 Gy EQD2Gy, it increased to 83% and 70%, respectively. Besides radiation dose colorectal and breast histology and motion management methods were associated with improved treated metastases control. CONCLUSION: After an initial learning curve with regards to total cumulative doses, consistently high biologically effective doses have been employed translating into high local tumor control at 1 and 2 years. The true impact of histology and motion management method on treated metastases control deserve deeper analysis. Overall survival is mainly influenced by histology and metastatic tumor burden.

Stereotactic body radiotherapy (SBRT) for multiple pulmonary oligometastases: Analysis of number and timing of repeat SBRT as impact factors on treatment safety and efficacy.

BACKGROUND: Stereotactic body radiotherapy (SBRT) for oligometastatic disease is characterized by an excellent safety profile; however, experiences are mostly based on treatment of one single metastasis. It was the aim of this study to evaluate safety and efficacy of SBRT for multiple pulmonary metastases. PATIENTS AND METHODS: This study is based on a retrospective database of the DEGRO stereotactic working group, consisting of 637 patients with 858 treatments. Cox regression and logistic regression were used to analyze the association between the number of SBRT treatments or the number and the timing of repeat SBRT courses with overall survival (OS) and the risk of early death. RESULTS: Out of 637 patients, 145 patients were treated for multiple pulmonary metastases; 88 patients received all SBRT treatments within one month whereas 57 patients were treated with repeat SBRT separated by at least one month. Median OS for the total patient population was 23.5 months and OS was not significantly influenced by the overall number of SBRT treatments or the number and timing of repeat SBRT courses. The risk of early death within 3 and 6 months was not increased in patients treated with multiple SBRT treatments, and no grade 4 or grade 5 toxicity was observed in these patients. CONCLUSIONS: In appropriately selected patients, synchronous SBRT for multiple pulmonary oligometastases and repeat SBRT may have a comparable safety and efficacy profile compared to SBRT for one single oligometastasis.

Early relapse after autologous hematopoietic cell transplantation remains a poor prognostic factor in multiple myeloma but outcomes have improved over time.

Duration of initial disease response remains a strong prognostic factor in multiple myeloma (MM) particularly for upfront autologous hematopoietic cell transplant (AHCT) recipients. We hypothesized that new drug classes and combinations employed prior to AHCT as well as after post-AHCT relapse may have changed the natural history of MM in this population. We analyzed the Center for International Blood and Marrow Transplant Research database to track overall survival (OS) of MM patients receiving single AHCT within 12 months after diagnosis (N=3256) and relapsing early post-AHCT (<24 months), and to identify factors predicting for early vs late relapses (24-48 months post-AHCT). Over three periods (2001-2004, 2005-2008, 2009-2013), patient characteristics were balanced except for lower proportion of Stage III, higher likelihood of one induction therapy with novel triplets and higher rates of planned post-AHCT maintenance over time. The proportion of patients relapsing early was stable over time at 35-38%. Factors reducing risk of early relapse included lower stage, chemosensitivity, transplant after 2008 and post-AHCT maintenance. Shorter post-relapse OS was associated with early relapse, IgA MM, Karnofsky <90, stage III, >1 line of induction and lack of maintenance. Post-AHCT early relapse remains a poor prognostic factor, even though outcomes have improved over time.

Stereotactic body radiotherapy for oligo-metastatic liver disease - Influence of pre-treatment chemotherapy and histology on local tumor control.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is applied in the oligometastatic setting to treat liver metastases. However, factors influencing tumor control probability (TCP) other than radiation dose have not been thoroughly investigated. Here we set out to investigate such factors with a focus on the influence of histology and chemotherapy prior to SBRT using a large multi-center database from the German Society of Radiation Oncology. METHODS: 452 SBRT treatments in 363 patients were analyzed after collection of patient, tumor and treatment data in a multi-center database. Histology was considered through random effects in semi-parametric and parametric frailty models. Dose prescriptions were parametrized by conversion to the maximum biologically effective dose using alpha/beta of 10Gy (BEDmax). RESULTS: After adjusting for histology, BEDmax was the strongest predictor of TCP. Larger PTV volumes, chemotherapy prior to SBRT and simple motion management techniques predicted significantly lower TCP. The model predicted a BED of 209±67Gy10 necessary for 90% TCP at 2years with no prior chemotherapy, but 286±78Gy10 when chemotherapy had been given. Breast cancer metastases were significantly more responsive to SBRT compared to other histologies with 90% TCP at 2years achievable with BEDmax of 157±80Gy10 or 80±62Gy10 with and without prior chemotherapy, respectively. CONCLUSIONS: Besides dose, histology and pretreatment chemotherapy were important factors influencing local TCP in this large cohort of liver metastases. After adjusting for prior chemotherapy, our data add to the emerging evidence that breast cancer metastases do respond better to hypofractionated SBRT compared to other histologies.

Restricted Axillary Staging in Clinically and Sonographically Node-Negative Early Invasive Breast Cancer (c/iT1-2) in the Context of Breast Conserving Therapy: First Results Following Commencement of the Intergroup-Sentinel-Mamma (INSEMA) Trial.

Axillary lymph node status remains an important prognostic factor in early breast cancer. It is regarded as an indicator for (neo)adjuvant systemic treatment and postoperative radiotherapy of the regional lymphatics. Commenced in September 2015, the INSEMA trial is investigating whether operative determination of nodal status as part of breast conserving therapy (BCT) for early stage breast cancer (c/iT1-2 c/iN0) can be avoided without reducing oncological safety. After inclusion of 1001 patients there was general acceptance of the complex study design by patients and study doctors so that recruitment for the first randomisation (axillary sentinel lymph node biopsy [SLNB]: yes or no) achieved predicted case numbers. The second randomisation however (SLNB alone versus complete axillary dissection when one or two macrometastases are present at SLNB) recruited fewer cases than expected for the following three reasons: a) the 13 % rate of one or two macrometastases after SLNB in the INSEMA trial collective was lower than expected; b) around 20 % of patients refused the second randomisation; c) there was delayed inclusion of the Austrian study centres, which only recruited for the second randomisation. Lack of knowledge of nodal status when SLNB is avoided represents a new challenge for the postoperative tumour board. In particular decisions on chemotherapy for luminal-like tumours and irradiation of the lymphatics (excluding axilla) must be guided by tumour biological parameters. The INSEMA trial does not provide answers to some important questions, e.g. it remains unclear whether patients without SLNB can be offered partial breast irradiation alone in low-risk situations and whether SLNB can also be avoided in patients with stage T1-2 tumours who have a mastectomy indication.

Nomogram based overall survival prediction in stereotactic body radiotherapy for oligo-metastatic lung disease.

BACKGROUND: Radical local treatment of pulmonary metastases is practiced with increasing frequency due to acknowledgment and better understanding of oligo-metastatic disease. This study aimed to develop a nomogram predicting overall survival (OS) after stereotactic body radiotherapy (SBRT) for pulmonary metastases. PATIENTS AND METHODS: A multi-institutional database of 670 patients treated with SBRT for pulmonary metastases was used as training cohort. Cox regression analysis with bidirectional variable elimination was performed to identify factors to be included into the nomogram model to predict 2-year OS. The calibration rate of the nomogram was assessed by plotting the actual Kaplan-Meier 2-year OS against the nomogram predicted survival. The nomogram was externally validated using two separate monocentric databases of 145 and 92 patients treated with SBRT for pulmonary metastases. RESULTS: The median follow up of the trainings cohort was 14.3months, the 2-year and 5-year OS was 52.6% and 23.7%, respectively. Karnofsky performance index, type of the primary tumor, control of the primary tumor, maximum diameter of the largest treated metastasis and number of metastases (1 versus >1) were significant prognostic factors in the Cox model (all p<0.05). The calculated concordance-index for the nomogram was 0.73 (concordance indexes of all prognostic factors between 0.54 and 0.6). Based on the nomogram the training cohort was divided into 4 groups and 2-year OS ranged between 24.2% and 76.1% (predicted OS between 30.2% and 78.4%). The nomogram discriminated between risk groups in the two validation cohorts (concordance index 0.68 and 0.67). CONCLUSIONS: A nomogram for prediction of OS after SBRT for pulmonary metastases was generated and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting. KEY MESSAGE: A nomogram for prediction of overall survival after stereotactic body radiotherapy (SBRT) for pulmonary metastases was developed and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting.

Correlation of pain, functional impairment, and health-related quality of life with radiological grading scales of lumbar degenerative disc disease.

BACKGROUND: It is generally believed that radiological signs of lumbar degenerative disc disease (DDD) are associated with increased pain and functional impairment as well as lower health-related quality of life (HRQoL). Our aim was to assess the association of the Modic and Pfirrmann grading scales with established outcome questionnaires and the timed-up-and-go (TUG) test. METHODS: In a prospective two-center study with patients scheduled for lumbar spine surgery, visual analogue scale (VAS) for back and leg pain, Roland-Morris Disability Index, Oswestry Disability Index and HRQoL, as determined by the Short-Form (SF)-12 and the Euro-Qol, were recorded. Functional mobility was measured with the TUG test. Modic type (MOD) and Pfirrmann grade (PFI) of the affected lumbar segment were assessed with preoperative imaging. Uni- and multivariate logistic regression analysis was performed to estimate the effect size of the relationship between clinical and radiological findings. RESULTS: Two hundred eighty-four patients (mean age 58.5, 119 (42 %) females) were enrolled. None of the radiological grading scales were significantly associated with any of the subjective or objective clinical tests. There was a tendency for higher VAS back pain (3.48 vs. 4.14, p = 0.096) and lower SF-12 physical component scale (31.2 vs. 29.4, p = 0.065) in patients with high PFI (4-5) as compared to patients with low PFI (0-3). In the multivariate analysis, patients with MOD changes of the vertebral endplates were 100 % as likely as patients without changes to show an impaired TUG test performance (odds ratio (OR) 1.00, 95 % confidence interval (CI) 0.56-1.80, p = 0.982). Patients with high PFI were 145 % as likely as those with low PFI to show an impaired TUG test performance (OR 1.45, 95 % CI 0.79-2.66, p = 0.230). CONCLUSIONS: There was no association between established outcome questionnaires of symptom severity and two widely used radiological classifications in patients undergoing surgery for lumbar DDD.

[The parameter "relative survival": Analysis of regional cancer registry data for prostate cancer]. / Der Parameter "Relatives Überleben" : Analyse regionaler Krebsregisterdaten beim Prostatakarzinom.

BACKGROUND: There is a lack of comparability of relative survival rates due to differences in regional mortality. OBJECTIVE: How should relative survival be calculated to be able to compare regional cancer mortality? MATERIALS AND METHODS: Calculation of relative survival rates of prostate cancer patients from a regional cancer registry using diagnosis year and stage, based on differential mortality tables. RESULTS: Calculation of relative survival for all prostate cancer patients shows a very slight excess mortality after 5 years compared to a matched general population. Introduction of new imaging techniques and PSA screening led to a change in the distribution of diagnosed stages. Differentiation by stage is therefore essential. Thus, patients with UICC stage I, II, and III have a very low excess mortality, while patients with a UICC stage IV have a significantly higher excess mortality; however, it is very surprising that the excess mortality of patients without specification of the UICC stage is similarly unfavorable as in the case of patients with UICC stage IV. CONCLUSION: If data from a regional cancer registry are used, adequate mortality tables from the catchment area of the registry should be used as a reference due to regional mortality differences. Thus, progress in patient survival can be more precisely mapped. With respect to prostate cancer patients, differential consideration by stage is also necessary because improved early detection methods has led to a change in the stage distribution and, thus, survival.

[Perampanel in the treatment of a patient with glioblastoma multiforme without IDH1 mutation and without MGMT promotor methylation]. / Perampanel in der Behandlung eines Patienten mit Glioblastoma multiforme ohne IHD-1-Mutation und ohne MGMT-Promotor-Methylierung.

Malignant gliomas like glioblastoma multiforme (GBM) release glutamate which causes excitotoxic death to surrounding neurons, thereby vacating room for tumor expansion. We report the case of a patient with GBM treated with the AMPA receptor blocker Perampanel (PER) in combination therapy for partial seizures. Histological work-up of a biopsy showed the tissue of a GBM without mutation of the isocitrate dehydrogenase 1 (IDH1) and without promotor methylation of the O6-methylguanine-DNA methyltransferase (MGMT). In a group of patients with IDH 1 wild type and non-methylated MGMT a median survival of 199 days after surgery (i. e. 6.5 months) was described. Our patient lived about one year longer. PER rendered our patient seizure-free for at least the last seven months of his life. It was well tolerated and did not increase the toxicity of temozolomide. When choosing an antiepileptic drug (AED) for the treatment of seizures in patients with malignant brain tumors, the efficacy, the tolerability and perhaps possible effects on tumor progression of the AED should be taken into account.

Late inflammatory and thrombotic changes in irradiated hearts of C57BL/6 wild-type and atherosclerosis-prone ApoE-deficient mice.

BACKGROUND AND PURPOSE: Radiation-induced heart disease represents a late complication of thoracic radiotherapy. We investigated the inflammatory and thrombotic response after local heart irradiation in wild-type and atherosclerosis-prone mice. MATERIAL AND METHODS: Atherosclerosis-prone ApoE(-/-) and C57BL/6 wild-type mice were sacrificed 20, 40, and 60 weeks after irradiation with 0.2, 2, 8, or 16 Gy. The expression of CD31, vascular cell adhesion molecule-1 (VCAM-1), thrombomodulin (TM), and CD45 were quantified by immunofluorescence staining of heart tissue sections. RESULTS: Microvascular density decreased at 40 weeks after 16 Gy in C57BL/6 but not in ApoE(-/-) mice. CD31 expression declined in C57BL/6 mice at 40 weeks (8 Gy), but increased in ApoE(-/-) mice at 20 (2/8/16 Gy) and 60 weeks (16 Gy). Capillary area decreased in C57BL/6 at 40 weeks (8/16 Gy) but increased in ApoE(-/-) mice at 20 weeks (16 Gy). Endocardial VCAM-1 expression remained unchanged. TM-positive capillaries decreased at 40 weeks (8/16 Gy) in C57BL/6 and at 60 weeks (2/16 Gy) in ApoE(-/-) mice. Leukocyte infiltration transiently rose 40 weeks after 8 Gy (only ApoE(-/-)) and 16 Gy. After receiving a low irradiation dose of 0.2 Gy, no significant changes were observed in any of the mouse models. CONCLUSION: This study demonstrated that local heart irradiation affects microvascular structure and induces inflammatory/thrombotic responses in mice in a dose- and time-dependent manner. Thereby, significant prothrombotic changes were found in both strains, although they were progressive in ApoE(-/-) mice only. Proinflammatory responses, like the increase of adhesion molecules and leukocyte infiltration, were more pronounced and occurred at lower doses in ApoE(-/-) vs. C57BL/6 mice. These findings indicate that metabolic risk factors, such as decreased ApoE lipoproteins, may lead to an enhanced proinflammatory and prothrombotic late response in locally irradiated hearts.