German Cohort Of Patients Research Articles

Analysis and occurrence of biallelic pathogenic repeat expansions in RFC1 in a German cohort of patients with a main clinical phenotype of motor neuron disease

Biallelic pathogenic repeat expansions in RFC1 were recently identified as molecular origin of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) as well as of one of the most common causes of adult-onset ataxia. In the meantime, the phenotypic spectrum has expanded massively and now includes mimics of multiple system atrophy or parkinsonism. After identifying a patient with a clinical diagnosis of amyotrophic lateral sclerosis (ALS) as a carrier of biallelic pathogenic repeat expansions in RFC1, we studied a cohort of 106 additional patients with a clinical main phenotype of motor neuron disease (MND) to analyze whether such repeat expansions are more common in MND patients. Indeed, two additional MND patients (one also with ALS and one with primary lateral sclerosis/PLS) have been identified as carrier of biallelic pathogenic repeat expansions in RFC1 in the absence of another genetic alteration explaining the phenotype, suggesting motor neuron disease as another extreme phenotype of RFC1 spectrum disorder. Therefore, MND might belong to the expanding phenotypic spectrum of pathogenic RFC1 repeat expansions, particularly in those MND patients with additional features such as sensory and/or autonomic neuropathy, vestibular deficits, or cerebellar signs. By systematically analyzing the RFC1 repeat array using Oxford nanopore technology long-read sequencing, our study highlights the high intra- and interallelic heterogeneity of this locus and allows the identification of the novel repeat motif ‘ACAAG’.

Cost-effectiveness and Quality of Specialized and Routine Care in a German Cohort of Patients with Chronic Pruritus

Chronic pruritus is a prevalent interdisciplinary symptom with a strong influence on health-related quality of life. Patients need extensive diagnostics and long-term treatment. This retrospective and prospective cohort study compared routine and university-based specialized care in terms of cost-effectiveness and patient benefit. Direct medical and non-medical costs and patient-reported outcomes (PRO; pruritus intensity, quality of life, treatment needs and benefits) were assessed. Data analyses were conducted using descriptive methods and non-parametric statistical tests. A total of 300 adult patients (54.3% female) participated in the study. Six months after the treatment start in a specialized German pruritus care unit, the total costs were significantly reduced (mean total costs 686 € vs 433 € per patient per half year (total cohort); p < 0.001; mean out-of-pocket costs 198 € vs 124 € per half year (total cohort), p < 0.001). Pruritus intensity (numerical rating scale 5.3 vs 3.7, p < 0.001), quality of life (Dermatology Life Quality Index 8.9 vs 5.7, p < 0.001) and patient benefit (Patient Benefit Index Pruritus 1.2 vs 2.1, p < 0.001) improved significantly (total cohort). The results of this study show, that treatment of chronic pruritus patients in a specialized itch centre leads to an improvement in patient benefit and reduces the economic burden at the same time.

High prevalence of reduced fertility and use of assisted reproductive technology in a German cohort of patients with peripartum cardiomyopathy

BackgroundOver the past decades the use of assisted reproduction technology (ART) increased worldwide. ARTs are associated with an elevated risk for cardiovascular complications. However, a potential relation between subfertility/ARTs and the heart disease peripartum cardiomyopathy (PPCM) has not been systematically analyzed yet.MethodsA retrospective cohort study was carried out, including n = 111 PPCM patients from the German PPCM registry. Data from PPCM patients were compared to those from postpartum women in the German general population.ResultsThe prevalence of reported subfertility was high among PPCM patients (30%; 33/111). Most of the subfertile PPCM patients (55%; 18/33) obtained vitro fertilizations (IVF) or intracytoplasmic sperm injections (ICSI). PPCM patients were older (p < 0.0001), the percentage of born infants conceived by IVF/ICSI was higher (p < 0.0001) with a higher multiple birth (p < 0.0001), C-section (p < 0.0001) and preeclampsia rate (p < 0.0001), compared to postpartum women. The cardiac outcome was comparable between subfertile and fertile PPCM patients. Whole exome sequencing in a subset of n = 15 subfertile PPCM patients revealed that 33% (5/15) carried pathogenic or likely pathogenic gene variants associated with cardiomyopathies and/or cancer predisposition syndrome.ConclusionsSubfertility occurred frequently among PPCM patients and was associated with increased age, hormonal disorders, higher twin pregnancy rate and high prevalence of pathogenic gene variants suggesting a causal relationship between subfertility and PPCM. Although this study found no evidence that the ART treatment per se increases the risk for PPCM or the risk for an adverse outcome, women with subfertility should be closely monitored for signs of peripartum heart failure.Graphical abstract

One year monitoring of SARS-CoV-2 prevalence in a German cohort of patients with cystic fibrosis

BackgroundIn Germany, the first case of coronavirus disease 2019 (COVID-19) was registered on 28 January 2020. By February 2021, the third wave of the pandemic began. So far, only few data are available on the SARS-CoV-2 prevalence and the clinical impact of an infection in patients with cystic fibrosis (CF).MethodsFrom February 2020 until March 2021, we screened 156 CF patients for anti-SARS-CoV-2 IgG antibodies (serology) and the presence of SARS-CoV-2 in deep throat saliva or nasopharyngeal swabs (molecular testing). From patients with confirmed SARS-CoV-2 infection, we recorded symptoms and collected clinical data.ResultsIn total, 13 patients (8.3%) were tested positive for SARS-CoV-2 infection, most of them during the second and the beginning third wave of the pandemic. Ten positive tested patients described symptoms linked to COVID-19. The most common symptom was cough followed by fatigue and headache. SARS-CoV-2 infection did not impair lung function. No positive tested patient needed to be hospitalized.ConclusionsSARS-CoV-2 infections in patients with CF are not as rare as initially anticipated, as frequent testing revealed. However, infected patients did not experience more severe clinical courses or worse clinical outcome. Our observation is in line with published reports indicating that individuals with CF are not at higher risk for severe COVID-19.

Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors

ObjectiveThe aim of this study was to investigate the prevalence of cancer and associating clinical, immunological, and genetic factors in a German cohort of patients with common variable immunodeficiency (CVID).MethodsIn this retrospective monocenter cohort study, we estimated the standardized incidence ratio (SIR) for different forms of cancer diagnosed in CVID patients. Furthermore, we evaluated the likely association of infectious and non-infectious CVID-related phenotypes with the diagnosis of cancer by calculation of the odds ratio. The genetic background of CVID in patients with cancer was evaluated with sequential targeted next-generation sequencing (tNGS) and whole-exome sequencing (WES). Patients’ family history and WES data were evaluated for genetic predisposition to cancer.ResultsA total of 27/219 patients (12.3%) were diagnosed with at least one type of cancer. Most common types of cancer were gastric cancer (SIR: 16.5), non-melanoma skin cancer (NMSC) (SIR: 12.7), and non-Hodgkin lymphoma (NHL) (SIR: 12.2). Immune dysregulation manifesting as arthritis, atrophic gastritis, or interstitial lung disease (ILD) was associated with the diagnosis of cancer. Furthermore, diagnosis of NMSC associated with the diagnosis of an alternative type of cancer. Studied immunological parameters did not display any significant difference between patients with cancer and those without. tNGS and/or WES yielded a definite or likely genetic diagnosis in 11.1% of CVID patients with cancer. Based on identified variants in cancer-associated genes, the types of diagnosed cancers, and family history data, 14.3% of studied patients may have a likely genetic susceptibility to cancer, falling under a known hereditary cancer syndrome.ConclusionsGastric cancer, NMSC, and NHL are the most frequent CVID-associated types of cancer. Manifestations of immune dysregulation, such as arthritis and ILD, were identified as risk factors of malignancy in CVID, whereas studied immunological parameters or the identification of a monogenic form of CVID appears to have a limited role in the evaluation of cancer risk in CVID.

Toscana virus encephalitis in Southwest Germany: a retrospective study

BackgroundToscana virus (TOSV) is an arthropod-borne virus transmitted by phlebotomine sandflies (Phlebotomus sp.) widespread throughout the Mediterranean having the potential to cause meningoencephalitis in humans. In Germany, the vectors of TOSV are introduced recently and become endemic especially in Southwestern Germany. As TOSV is not investigated regularly in patients with meningoencephalitis, cases of TOSV-neuroinvasive disease may remain mostly undetected.MethodsWe conducted a retrospective cohort study on patients with meningoencephalitis without identification of a causal pathogen from 2006 to 2016. Serologic assessment for anti-TOSV-IgG and IgM was performed on serum and CSF. Demographic, clinical and CSF data from TOSV-positive patients were compared to a cohort of patients with meningoencephalitis due to enterovirus. Informed consent was obtained from all included patients.ResultsWe found 138 patients with meningoencephalitis without identified causal pathogen. From 98 of these patients CSF and serum was available for further testing. Additionally, we included 27 patients with meningoencephalitis due to enterovirus. We identified two patients with serological confirmed TOSV-neuroinvasive disease (TOSV-IgM and IgG positive, 2%) and two patients with possible TOSV-neuroinvasive disease (isolated TOSV-IgM positive, 2%). Overall, TOSV-neuroinvasive was detected in 4% of our cases with suspected viral meningoencephalitis. None of them had a history of recent travel to an endemic area.ConclusionsWe found cases of TOSV-neuroinvasive disease in our German cohort of patients with meningoencephalitis. As no recent history of travel to an endemic area was reported, it remains probable that these cases resemble autochthonous infections, albeit we cannot draw conclusions regarding the origin of the respective vectors. TOSV could be considered in patients with meningoencephalitis in Germany.

Burden of depression and anxiety disorders per disease codes in patients with lymphoma in Germany

PurposeThe aim of this study was to explore the incidence of depression and anxiety disorder diagnoses in a large German cohort of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) diagnoses in comparison to patients without cancer over a 10-year time frame.MethodsPatients with HL (n=687) and NHL (n=4130) were matched to cohorts without a cancer diagnosis (n=687 and 4130) by age, sex, and yearly consultation frequency. The primary outcome of the study was the incidence of depression and anxiety disorders. The relationship between lymphoma, separated into HL and NHL, and both depression and anxiety disorders was investigated using Cox regression models.ResultsWe compared 687 patients with HL with 687 matched non-cancer individuals and 4130 patients with NHL with 4130 matched non-cancer individuals. Within 10 years of the index date, 24.0% of patients with HL and 22.3% of patients with NHL were diagnosed with depression. Anxiety disorders were diagnosed in 6.7% and 5.3% of patients with HL and NHL, respectively. On regression analyses, HL (HR 2.30, 95% CI 1.65–3.21, p<0.001) and NHL (HR 2.09, 95% CI 1.81–2.41, p<0.001) were positively associated with incident depression. The HR for anxiety disorders was 1.64 (95% CI 1.24–2.16, p<0.001) in patients with NHL, while HL was not associated with incident anxiety disorders (HR 1.21, 95% CI 0.71–2.07, p<0.478).ConclusionLymphoma constitutes a risk factor for emerging depression and anxiety disorders. Following the diagnosis of lymphoma, screening and strategies to prevent the occurrence of these diseases seem warranted.

Hepatitis E seroprevalence in a German cohort of patients with inflammatory bowel diseases.

The incidence of hepatitis E virus (HEV)-infections in industrialized nations has been increasing over the past years. Patients suffering from inflammatory bowel diseases (IBD) may be more prone to transmission. Data on HEV seroprevalence in IBD patients is scarce and has not been reported in German IBD patients. The German Health Examination Survey for Adults 2008-2011, which included 4.422 samples, found a HEV seroprevalence of 16.8%, increasing with age. The aim of the present study was to determine the seroprevalence of anti-HEV IgG in a German cohort of IBD patients, and to explore which parameters have an impact on HEV seroprevalence. This is an uncontrolled, cross-sectional, retrospective monocentric study. Among the patients visiting the IBD outpatient clinic between 25 January, 2019 and 24 September, 2019, 328 patients with Crohn's disease (CD) and 150 patients with ulcerative colitis (UC) were included in the study. IgG antibodies against HEV were determined by enzyme-linked immunosorbent assay. Positive antibody titers were verified using immunoblot analysis. Medical records were reviewed for demographic and clinical parameters to identify potential risk factors for HEV infection. The prevalence of anti-HEV IgG antibodies was 17.4% in CD patients and 24.7% in UC patients. No patient with positive HEV PCR was detected. Greater age of CD und UC patients and longer duration of anti-interleukin 12/23 treatment in CD patients were associated with higher anti-HEV IgG antibody rates. In summary, we conclude that patients with UC have a higher anti-HEV IgG antibody prevalence than the general population in Germany, and that immunosuppressive therapy may carry no higher risk for HEV infection.

CAH-X Syndrome in a german cohort of patients with 21--hydroxylase deficiency

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

MON-177 CAH-X Syndrome in a German Cohort of Patients with Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is encoded by the CYP21A2 gene. The CYP21A2 gene is flanked and partially overlapped by the TNXB gene encoding an extracellular matrix protein called Tenascin-X. Deficiency of Tenascin X can cause the Ehlers-Danlos Syndrome (EDS). Deletions of CYP21A2 extending into TNXB rarely cause CAH combined with EDS. Heterozygosity of TNXB mutations causing haploinsufficiency of TNX, however, have been described in about 5-7% in a patient cohort from the US and has been named CAH-X syndrome, CAH associated with mild hypermobility form of EDS.We genetically investigated a cohort of 81 adult patients (31 males, mean age 37,8 years +/- 9,8) with classic CAH for CAH-X. Patients genetically positive for CAH-X and unaffected CAH control patients matched for sex, age and BMI underwent a thorough clinical investigation including joint examination by Beighton 9-point scale, skin and neurological examination, by a standardised protocol of thransthoracic echocardiography and muscle ultrasound. In addition serum tenascin-X has been measured.In our cohort we identified one patient with CAH and EDS and 4 patients with CAH-X syndrome. All CAH-X patients had serum concentrations of tenascin-X below the normal range, however, not different from 35 unaffected CAH patients with regard to serum concentration. All 4 patients with CAH-X syndrome showed some associated clinical symptoms. Two had joint hypermobility detected by Beighton 9-point score. Two of four CAH-X patients showed cardiac abnormalities (mild mitral regurgitation in one patient and a surgically corrected common arterial trunk type I A in the other patient). The patient with CAH and EDS showed cardiac abnormalities in addition to typical EDS symptomatology. All 5 affected patients complained about back pain and showed foot malposition. Profound changes in muscle ultrasound were found in 60 % of patients with CAH-X syndrome (3/5) and in none of the controls (0/5).In conclusion, our data confirm the previously described prevalence of CAH-X. Beighton-score seems to be a quick and cheap screening instrument for CAH-X and should be performed in all patients with classic CAH, since protein level in serum cannot be used for screening for CAH-X-Syndrome. A stronger focus needs to be made on back pain and foot malposition as symptoms of CAH-X and echocardiography should be performed in all CAH-X patients. Therapy should depend on clinical symptoms in patients.

26-Year-Old Woman With Shortness of Breath and Chest Pain

26-Year-Old Woman With Shortness of Breath and Chest Pain

Su1084 – No Significant Impact of Fructose Consumption on Gut Microbiota Composition in a German Cohort of Patients with Biopsy-Proven Nonalcoholic Fatty Liver Disease (NAFLD)

Su1084 – No Significant Impact of Fructose Consumption on Gut Microbiota Composition in a German Cohort of Patients with Biopsy-Proven Nonalcoholic Fatty Liver Disease (NAFLD)

Antidepressant medication in a German cohort of patients with Alzheimer's disease .

The use of antidepressant drugs in dementia patients is associated with the risk of adverse events, and the evidence for relevant effects is scarce. We aimed to determine the associations between the prescription of antidepressants and patients' sociodemographic (e.g., age, gender, living situation) and clinical characteristics (e.g., disease severity, neuropsychiatric symptoms). We included 395 institutionalized and community-dwelling patients with Alzheimer's disease (AD) across all severity stages of dementia in a cross-sectional study design. The patients' clinical characteristics comprised of cognitive status, daily activities, depressive symptoms, further neuropsychiatric symptoms, and health-related quality of life (HrQoL). We conducted multiple logistic regression analyses for the association between the use of antidepressant drugs and the covariates. Approximately 31% of the participants were treated with antidepressant drugs, with a higher chance of being medicated for institutionalized patients (χ2-test: p=0.010). In the bivariate analyses, the use of antidepressants was significantly associated with higher levels of care, lower cognitive and daily life capacity, higher extent of neuropsychiatric symptoms, and a lower proxy-reported HrQoL. Finally, multiple logistic regression models showed a significantly higher use of antidepressants in patients treated by psychiatrists and neurologists (OR 2.852, 95% CI: 1.223-6.652). The use of antidepressant drugs in the study population was high, and the suitability of the treatment with antidepressants remains unclear. Participants with diminished cognitive and functional capacity, higher extent of neuropsychiatric symptoms, and those treated by neuropsychiatric specialists were more likely to be treated with antidepressants. The pharmaceutical treatment of patients with these clinical characteristics should be particularly considered in the daily care for dementia patients. Further longitudinal studies should evaluate the appropriateness of indications for antidepressants and the causative direction of correlations with the patients' clinical characteristics. .

Stroke in Duchenne Muscular Dystrophy: A Retrospective Longitudinal Study in 54 Patients.

Duchenne muscular dystrophy (DMD) is the most frequent skeletal muscle myopathy. Nearly all patients develop cardiomyopathy in their second decade of life. The purpose of this study was to evaluate the frequency, cause, and outcome of stroke in a German cohort of patients with DMD. Retrospective analysis of medical records of 54 DMD patients, who lived in a regional facility for handicapped people (Wichernhaus Altdorf, Germany) between 1963 and 2013. Fifty-four DMD patients were followed up for 7.4 years on average. Mean age at admission and discharge from the long-term care facility or death were 11.4 and 18.8 years, respectively. Covering a total observation period of 400 patient-years, we identified 4 DMD patients with juvenile arterial ischemic strokes. Off-label systemic thrombolysis in 2 patients resulted in a nearly complete regression of stroke-related symptoms, but 1 patient died of septic pneumonia and cardiac failure 24 days after thrombolysis therapy. In the other 2 patients, who had their ischemic strokes in 1994 and 1998, severe infarction-related symptoms persisted, and 1 patient died 13 days later. DMD-associated cardiomyopathy without evidence of atrial fibrillation was the only risk factor for ischemic stroke in all patients. This study indicates an increased risk for ischemic strokes in DMD patients. Regular cardiological assessment of all DMD patients is mandatory to evaluate the individual risk profile for cardioembolic events and to adapt therapeutic strategies.

SAT-030 - Frequency of Resistance to Commonly used Antibiotics among A German Cohort of Patients with Spontaneous Bacterial Peritonitis Challenges Current Treatment Recommendations

SAT-030 - Frequency of Resistance to Commonly used Antibiotics among A German Cohort of Patients with Spontaneous Bacterial Peritonitis Challenges Current Treatment Recommendations

Vitamin D controls apoptosis and proliferation of cutaneous T‐cell lymphoma cells

Vitamin D controls apoptosis and proliferation of cutaneous T‐cell lymphoma cells

Restless legs syndrome in psoriasis: an unexpected comorbidity.

Restless legs syndrome (RLS) is characterized by unpleasant sensations in the legs and an uncontrollable urge to move them in order to gain relief. Higher frequencies of RLS have been reported in systemic lupus, multiple sclerosis, rheumatoid arthritis and atopic dermatitis. Since the disease-related stress present in psoriasis is similar to the stress of those diseases, we aimed to study the frequency of RLS in a German cohort of patients with psoriasis. 300 patients with psoriasis and 300 healthy controls were evaluated for RLS symptoms in this study. While 17% (n = 51) of patients with psoriasis reported symptoms of RLS, only 4% (n = 12) of individuals without psoriasis suffered from RLS symptoms (95% confidence interval: 0.08 - 0.18, p<0.01). In patients with psoriasis and RLS the average RLS score was 16.0 ± 9.2 whereas individuals with RLS in the control group had an average RLS score of 13.5 ± 7.1. Our findings indicate an increased frequency of RLS in patients with psoriasis, suggesting screening patients with psoriasis for the presence of RLS as a well-treatable co-morbidity.

To biopsy or not to biopsy: Evaluation of a large German cohort of patients with unclear hepatopathy and negative for viral hepatitis A, B, or C

To biopsy or not to biopsy: Evaluation of a large German cohort of patients with unclear hepatopathy and negative for viral hepatitis A, B, or C

Phenotyping and outcome on contemporary management in a German cohort of patients with peripartum cardiomyopathy

Peripartum cardiomyopathy (PPCM) is a life-threatening heart disease developing towards the end of pregnancy or in the months following delivery in previously healthy women in terms of cardiac disease. Enhanced oxidative stress and the subsequent cleavage of the nursing hormone Prolactin into an anti-angiogenic 16 kDa subfragment emerged as a potential causal factor of the disease. We established a prospective registry with confirmed PPCM present in 115 patients (mean baseline left ventricular ejection fraction, LVEF: 27 ± 9 %). Follow-up data (6 ± 3 months) showed LVEF improvement in 85 % and full recovery in 47 % while 15 % failed to recover with death in 2 % of patients. A positive family history of cardiomyopathy was present in 16.5 %. Pregnancy-associated hypertension was associated with a better outcome while a baseline LVEF ≤ 25 % was associated with a worse outcome. A high recovery rate (96 %) was observed in patients obtaining combination therapy with beta-blocker, angiotensin-converting enzyme (ACE) inhibitors/angiotensin-receptor-blockers (ARBs) and bromocriptine. Increased serum levels of Cathepsin D, the enzyme that generates 16 kDa Prolactin, miR-146a, a direct target of 16 kDa Prolactin, N-terminal-pro-brain-natriuretic peptide (NT-proBNP) and asymmetric dimethylarginine (ADMA) emerged as biomarkers for PPCM. In conclusion, low baseline LVEF is a predictor for poor outcome while pregnancy-induced hypertensive disorders are associated with a better outcome in this European PPCM cohort. The high recovery rate in this collective is associated with a treatment concept using beta-blockers, ACE inhibitors/ARBs and bromocriptine. Increased levels of Cathepsin D activity, miR-146a and ADMA in serum of PPCM patients support the pathophysiological role of 16 kDa Prolactin for PPCM and may be used as a specific diagnostic marker profile.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-013-0366-9) contains supplementary material, which is available to authorized users.

TARGIT-A trial: Updated results for local recurrence and survival for the German centers.

1121 Background: In 2010, we reported data on local control and early toxicity for the TARGIT-A trial of intraoperative radiotherapy after lumpectomy for early breast cancer. The updated results and first analysis of survival of the whole cohort (n = 3,451) were presented at San Antonio Breast Cancer Symposium in December 2012. We analysed the German cohort of patients, which was supposed to be more homogeneous (prepathology IORT only, homogeneous treatment in EBRT arm) and lower risk (older, smaller tumors, larger margin) than the international cohort of patients due to legal restrictions for radiotherapy studies in Germany. Methods: TARGIT-A was a randomised trial in patients &gt;=50 years with invasive ductal carcinoma (&lt;= 2cm) undergoing breast conserving surgery comparing standard fractionated whole breast EBRT (56 Gy) with single dose TARGIT (20 Gy) immediately after tumor excision / at the time of the primary operation. The experimental arm mandated additional EBRT (46 Gy, excluding a boost, n = 126) if adverse features were detected on final pathology (EIC, N+, margin &lt; 1 cm) making this a “risk-adapted policy”. Median follow-up was 2 years and 5 months. Results: 734 patients recruited from 7 centres in Germany. Patient’s ages were &lt;=50y 3%, 51-60y 33%, 61-70y 51%, &gt;70y 12%. Tumour sizes were 0-1cm 35%, 1.1-2cm 55% and &gt;2cm 11%. Grade I 29%, II 59%, III 12% and nodes negative 81%, 1-3 nodes 16%, &gt;3 nodes 3%. At 5-years, the absolute number of events in TARGIT vs. EBRT were as follows: Primary outcome: IBR 4 vs. 1, Exploratory outcome: All recurrences (breast +axilla+contralateral+distant recurrence) 11 vs. 7, Secondary outcome: All deaths 6 vs. 12, Breast Cancer deaths 3 vs. 5, Non-Breast Cancer deaths 3 vs. 7. Conclusions: Patients in the TARGIT-A trial have excellent 5 year outcomes (local control &gt; 97%, overall survival &gt;= 94%) in both arms of the trial. Clinical trial information: protocol 99PRT/47.