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Spinal muscular atrophy (SMA) is a rare autosomal recessive motor neurodegenerative disease and is the leading genetic cause of death among infants and toddlers.
Department of Radiation Oncology, Radiobiology Section, VU University Medical Center, De Boelelaan 1117, P.O. Malignant gliomas relapse in close proximity to the resection site, which is the postoperatively irradiated volume.
Clinical data on brain re-irradiation by conventional radiotherapy: Physical dose and equivalent total dose in 2 Gy fractions (EQD2), survival and toxicity. Clinical data on brain re-irradiation by fractionated stereotactic radiotherapy: physical dose and equivalent total dose in 2 Gy fractions (EQD2), survival and toxicity.
Clinical data on brain re-irradiation by stereotactic radiosurgery: physical dose and equivalent total dose in 2 Gy fractions (EQD2), survival and toxicity.
Total dose in 2 Gy fractions (EQD2cumulative) as a function of the time interval between initial treatment and conventional re-irradiation (squares), fractionated stereotactic radiotherapy (triangles) and stereotactic radiosurgery (circles).
Data on the correlation between the EQD2 of the initial scheme and of the re-irradiation scheme are presented in Figure 2.
Correlation of the initial dose (EQD2initial) and re-irradiation dose (EQD2reirradiation) for patients re-irradiated with conventional radiotherapy, fractionated stereotactic radiotherapy and stereotactic radiosurgery (see legend to Figure 1 for an explanation of the symbols).
Data on current re-irradiation protocols for the human brain, showing the EQD2cumulative, time interval between the initial radiotherapy course and re-irradiation course, and treatment volume (values are mean ± SD (range); n = 6–17).
How Heterogeneous Cell Populations, Cancer Cell Dormancy, and Minimal Residual Disease Influence the Natural History of CancersUnderstanding the Kinetics of Cancer: Implications from Prevention to PrognosticationCancer Age: Can We Reliably Estimate and Apply This Knowledge? This page is designed to give a general overview of the capabilities of NCSS Statistical Analysis Software for survival analysis. This procedure computes the nonparametric Kaplan-Meier and Nelson-Aalen estimates of survival and associated hazard rates.
A life table presents the proportion surviving, the cumulative hazard function, and the hazard rates of a large group of subjects followed over time. This procedure calculates nonparametric, maximum-likelihood estimates, and confidence limits of the probability of failure (the cumulative incidence) for a particular cause in the presence of other causes. An often used, though incorrect, approach is to treat all failures from causes other than that of interest as censored observations and estimate the cumulative incidence using 1 – KM (Kaplan-Meier estimate). This procedure also calculates Gray’s Test (K groups) and Pepe and Mori’s Test (2 groups) for comparing groups.
The Weibull Distribution Fitting procedure estimates the parameters of the exponential, extreme value, logistic, log-logistic, lognormal, normal, and Weibull probability distributions, using maximum likelihood.
Introduction N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) plasma levels are assessed in patients who present acutely with dyspnoea. Several mouse models have been developed and scientists at PsychoGenics have contributed to the behavioral characterization of several of them. Animals are placed head facing down on an inclined plane and latency to re-orient head up is recorded.
IntroductionGliomas are the most common primary brain tumours, with glioblastoma multiforme (GBM) being the most frequent, aggressive and invasive tumour type. In patients re-irradiated with conventional radiotherapy, the EQD2re-irradiation was always lower than the EQD2initial (squares).In contrast, in FSRT series the EQD2re-irradiation was higher than the EQD2initial in four out of 16 studies (triangles). The symbols match the studies presented in Table 2 and Table 3 (see legend to Figure 1 for an explanation of the symbols). We conducted a systematic review of English medical literature to identify studies reporting LRF rates, over time, following surgery alone for breast, lung, or colorectal cancer.
In many instances, the answer to the question is not particularly relevant since treatment approaches may not be influenced by the “age” of the cancer. When patients are diagnosed with cancer, they often seek to understand “why.” They search for particular events in their lives that may have “caused” the cancer to form.
That is, it is the study of the elapsed time between an initiating event (birth, start of treatment, diagnosis, or start of operation) and a terminal event (death, relapse, cure, or machine failure). It can fit complete, right censored, left censored, interval censored (readout), and grouped data values.
The analysis accounts for subjects who die (fail) as well as subjects who are censored (withdrawn).
The problem with this approach is that it makes the incorrect assumption that the probability of failing prior to time t from other causes is zero. Gray’s Test compares the weighted averages of the subdistribution hazards across groups for the event of interest.
Some features available in the Weibull Distribution Fitting procedure include probability plotting, hazard plotting, and reliability plotting for the common life distributions.
NT-pro-BNP plasma levels are related to the severity of congestive heart failure (CHF) [1], and they are evaluated in order to diagnose CHF in older subjects aged 70 years [2]. The studies were analyzed using the linear-quadratic model to express the re-irradiation tolerance in cumulative equivalent total doses when applied in 2 Gy fractions (EQD2cumulative). Postoperative radiotherapy with concomitant temozolomide (TMZ) has become the standard of care for patients with newly diagnosed GBM, based on the results of a large European-Canadian phase III trial [1].
One exception (lowest triangle, Figure 2) is the study [24] using re-irradiation in combination with hyperbaric oxygen therapy, resulting in radionecrosis at a relatively low EQD2re-irradiation. Re-Irradiation Tolerance of the CNSThe different re-irradiation protocols show distinct variability in the tolerance of the human brain with regard to the total irradiation dose when applied in 2 Gy fractions.
However, in some instances the age of a cancer, which implies its natural history, may influence treatment recommendations. To see how these tools can benefit you, we recommend you download and install the free trial of NCSS.
The data values are typically a mixture of complete (terminal event occurred) and censored (terminal event has not occurred) observations. There you will find formulas, references, discussions, and examples or tutorials describing the procedure in detail. It outputs various statistics and graphs that are useful in reliability and survival analysis.
The life-table method competes with the Kaplan-Meier product-limit method as a technique for survival analysis. Pepe and Mori’s Test compares the cumulative incidence functions (CIF’s) directly for the event of interest. The data may be any combination of complete, right censored, left censored, and interval censored data. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.AbstractBackground. Moreover, NT-pro-BNP levels have been found to predict incident disability in older people. The SMNΔ7 neonatal model has been well phenotyped and characterized at PsychoGenics (El-Khodor et. Analysis shows that the EQD2cumulative increases from conventional re-irradiation series to fractionated stereotactic radiotherapy (FSRT) to LINAC-based stereotactic radiosurgery (SRS). In studies using SRS for retreatment of gliomas, the EQD2re-irradiation exceeded the EQD2initial in all but one of the seven series (circles, Figure 2).Figure 3 shows correlations between the EQD2cumulative and the irradiated volume.
They hypothesized that if the change in tumor volume were known for a given time interval, the average growth rate could be calculated and used to estimate the time of inception for a given tumor[5]. From the data values, the survival analyst makes statements about the survival distribution of the failure times. It also performs several logrank tests and provides both the parametric and randomization test significance levels. The life-table method was developed first, but the Kaplan-Meier method has been shown to be superior and with the advent of computers is now the method of choice. This overestimation can be quite substantial if there are many failures from other causes in the data. Maximum likelihood and probability plot estimates of distribution parameters, percentiles, reliability (survival) functions, hazard rates, and hazard functions are also available. We investigated the relationship between NT-pro-BNP, glomerular filtration rate (GFR), and all-cause mortality rates in a cohort of older people discharged from an internal medicine unit after admission for dyspnoea. The mean time interval between primary radiotherapy and the re-irradiation course was shortened from 30 months for conventional re-irradiation to 17 and 10 months for FSRT and SRS, respectively. The figure shows a decrease in treatment volume from FSRT (triangles) re-irradiation series to SRS series (circles). The incidence of radionecrosis increased to approximately 17%, but was independent of the chosen re-irradiation technique and EQD2cumulative. For lung cancer (based on data from 1190 patients from 4 studies), the median time to LRF was 1.5 years. This distribution allows questions about such quantities as survivability, expected life time, and mean time to failure to be answered. However, for large samples, the life-table method is still popular in that it provides a simple summary of a large set of data. You can produce confidence intervals for distribution parameters and percentiles as well as nonparametric estimates of survival using the Kaplan-Meier procedure.
Again, assessment of natriuretic peptide after myocardial infarction is a good indicator of infarct size and left ventricle function [4], probaly due to its overexpression in the ischemic myocardium [5]. Following conventional re-irradiation, radiation-induced normal brain tissue necrosis occurred beyond an EQD2cumulative around 100 Gy. The EQD2 values were calculated according to the linear-quadratic formula, which is the generally accepted standard model for dose-fractionation analyses [7] in clinical radiotherapy. For rectal cancer (based on data from 3334 patients from 10 studies), the median time to LRF was 1.5 years. In a graph (see Appendix) that compared the patients’ age at diagnosis to their age at follow up, he noted that all local recurrences occurred at time intervals that were shorter than the patients’ “gestational age” (ie, their age plus 9 months) at diagnosis. NT-pro-BNP was evaluated in serum samples of 134 patients aged 80 ± 6 years who presented to a single academic centre with worsening dyspnoea.
Nevertheless, not all patients with symptomatic CHF have high NT-pro-BNP plasma concentrations, and not all asymptomatic patients have low NT-pro-BNP values.


By using its in vivo neonatal drug screening platform, PsychoGenics can evaluate new chemical entities, biologics and gene therapies in the SMNΔ7 neonates.
With increasing conformality of therapy, the smaller the treatment volume is, the higher the radiation dose that can be tolerated.
The high recurrence rate of about 100% is due to the infiltrative growth characteristics of this tumour type, with its spread throughout normal brain tissue, and high resistance to both radiotherapy and chemotherapy.
However, in fractionated stereotactic re-irradiation, fraction sizes mostly exceed 5 Gy, and in radiosurgery single-dose fractions as high as 18 Gy are applied. Based on Collins’ law, the distribution of time to LRF suggests that the age of most of the solid tumors studied was 3 to 6 years.
History data and anthropometric, clinical, and biochemical parameters including GFR were collected at the time of admission. Furthermore, plasma NT-pro-BNP provides prognostic information in patients with acute and chronic CHF and, in short-of-breath patients, it may be predictive of 1-year all-cause mortality independently of the baseline diagnosis of acute CHF [6]. Malignant gliomas relapse in up to 90%, in close proximity to the resection site or the initially irradiated volume [3]. The validity of the linear-quadratic model for such high-dose fractions is questionable and estimates should be considered carefully [37,38]. Thus, a patient whose tumor is resected at the age of 3 can be considered cured when he or she reaches the age of 6 years and 9 months. 119 out of 134 were discharged alive from hospital and were included in the follow-up of 779 ± 370 days.
Age, gender, and body mass index (BMI) are known determinants of NT-pro-BNP plasma levels, and the normal values tend to increase with age. On basis of our analysis, the use of particle therapy in the treatment of recurrent gliomas, because of the optimized physical dose distribution in the tumour and surrounding healthy brain tissue, should be considered for future clinical trials. Treatment options for recurrent glioma remain limited and include re-resection, chemotherapy, and a second course of radiotherapy. The model has been described to either overpredict or underestimate the biological effect of high single-dose fractions. We have previously shown that, in older people, diseases different from CHF affect NT-pro-BNP plasma levels [7], so that determination of NT-pro-BNP levels does not seem to help clinicians in definition of dyspnoea. We reviewed the reported pace of local relapse following definitive local therapy as a means of estimating the age of the initial tumor at diagnosis. The limited radiation tolerance of normal brain tissue determines the re-irradiation dose that can be applied in addition to the dose of the initial irradiation course, with an acceptable late morbidity profile. Additional to the fraction size, kinetics of sublethal DNA damage repair, which is considered to be bi-exponential with a fast and a slow repair component, could determine the biological dose to the healthy brain.
We hypothesize that the time of inception for various tumors might be estimated by quantifying the interval between gross total resection and time to local failure.MethodsAssuming that the growth rate of a tumor is constant before diagnosis and after surgery (but before a local recurrence), one can use the time to local recurrence to estimate the tumor’s age. A large variety of palliative re-irradiation treatment schemes are reported, with different total dose, number and size of fractions. Both the number of beams and the time interval between their application and the protracted treatment time might result in a lower biological dose to the normal brain due to fast repair kinetics. MethodsIn the present study we evaluated with a two-year follow-up 134 patients, aged 65 to 90 years, previously enrolled in a cross-sectional study [7]. Retreatment schemes for recurrent gliomas often comprise hypofractionation as well as additional therapy, mostly anti-angiogenic drugs.
A higher biological dose on the normal brain might explain toxicity in the one study using a hyperfractionation regimen, although this was not to be expected because of the time interval of 6 hours between the two daily fractions [12]. All these subjects had been admitted along a complete calendar year to our medical unit because of shortness of breath.
In this latter study, despite an EQD2cumulative of <90 Gy, radionecrosis was reported, while no necrosis was reported in other conventional re-irradiation studies with higher EQD2cumulative. The solid line represents the situation in which only one tumor cell remains in the patient following surgery, and the dotted line represents that in which there are multiple remaining tumor cells. They were suspected of having CHF and were studied with NT-pro-BNP assessment [7]; subjects with pulmonary infections and cancer were also included into the study. Only tumour recurrences that are sufficiently small can be treated with high conformality and allow the use of hypofractionated or single dose treatment; this spares normal tissue, which decreases the risk of volume-dependent late toxicity [4,5]. This observation indicates slow DNA damage repair, which is incomplete in the time interval of 6 hours between the two subsequent daily fractions, resulting in a higher EQD2 than predicted by complete repair model calculations.
If more cells remain in the patient, the cancer will recur faster, thereby reducing the time to local recurrence.
CHF was diagnosed according to the European Society of Cardiology criteria [9], and dyspnoea was assessed on the basis of Medical Research Council (MRC) breathlessness scale [10] plus the objective sign of increased use of respiratory accessory musculature.
This paper presents an overview of current clinical data on re-irradiation of recurrent glioma with respect to the tolerance dose of normal, healthy brain tissue. The repair half-time of normal brain tissue is not known, but long mono-exponential repair half-times in the order of 2.5 to 4 h for late morbidity were estimated from the CHART trial, in which head and neck cancer patients were treated with three fractions per day spaced 6 h apart [39]. A group of patients who experience a local recurrence after surgery likely reflect diversity in the number of cells remaining in the post-operative tumor bed. In particular, the study included only patients in grade 5 of the MRC breathlessness scale and those with evidence of increasing use of respiratory accessory musculature, whereas subjects with pulmonary embolism were excluded. To obtain the cumulative radiation dose from the initial and the re-irradiation protocols and to enable comparison of data between studies, rather than taking the “physical” dose, the tolerance dose of normal brain tissue is presented as a ‘biological’ equivalent total dose when applied in 2 Gy fractions (EQD2), estimated by analysis using the linear quadratic model [6,7,8]. In FSRT and SRT series radionecrosis were reported after a EQD2cumulative of ?96 Gy and >137 Gy, respectively.
Age, sex, body mass index (BMI), and serum creatinine were recorded at the time of admission.
Such analysis provides insight into the re-irradiation tolerance of the normal, healthy brain that might be used as a guideline in clinical practice.
An exception should be made for the study using hyperbaric oxygen as radiosensitizer, where radionecrosis was observed at a EQD2cumulative as low as 86.2 Gy [24]. The search was conducted through several databases, including PubMed, Ovid Medline, and Elsevier, for the years 1956 to 2008, inclusive. Serum creatinine levels assays were all performed with the Jaffe method on a Hitachi Modular (Roche Diagnostics, Mannheim, Germany).
Hoes, “Applicability of current diagnostic algorithms in geriatric patients suspected of new, slow onset heart failure,” Age and Ageing, vol. Particle irradiation has a beneficial dose distribution and should be investigated in the small proportion of patients with small and well described recurrent glioma. In that study, recurrent glioma patients were treated with fractionated gamma knife irradiation within 7 min following hyperbaric oxygen therapy [24]. The systematic review was focused primarily on the identification of prospective randomized controlled trials published in English in which one of the study arms was surgery alone.
Renal function was also assessed as GFR evaluated by CKD-EPI formula [11]; patients were classified into the five stages of chronic kidney disease (CKD) [12]. Prospective trials were preferred since in this type of study patients typically have regular follow-up evaluations and data collection is fairly consistent. This effect seems to be due to a radiosensitizing effect of oxygen on the normal nervous tissue, additional to tumour radiosensitization. In some instances in which there were limited prospective data, large retrospective studies were also included. In all instances, only studies that reported the rates of local failure over time were included.
Cases of inhospital death were excluded, and the rate of death from all causes occurring after discharge was determined. The present review on the re-irradiation tolerance of normal, healthy brain indicates that the following issues warrant more attention.
Out of 134 patients, 119 were discharged alive from hospital and were included in the follow-up.The study was approved by the local ethics committee. The applicability of Collins' Law to childhood brain tumors and its usefulness as a predictor of survival.
Data were extracted from patients treated only with surgery, in order to avoid the confounding effects of radiation, hormonal therapy, or chemotherapy.
Statistical AnalysisThe results are presented as mean ± SD or percentage as appropriate.
These therapies may alter the growth kinetics of the tumor after initial surgery.Data were obtained either from statistics listed in the studies or from graphs within the studies. NT-pro-BNP values were log transformed [Ln (NT-pro-BNP)] prior to the analysis, in order to approximate normal distribution. If a graph was used to obtain data, simple measurements with a digital ruler were used to approximate data points (ie, the rates of local failure over time). Medulloblastoma and Collins' law: a critical review of the concept of a period of risk for tumor recurrence and patient survival. Time Interval between Initial Exposure and RetreatmentThe time interval between the initial irradiation and retreatment ranged from 3–55 months (Figure 1; Table 1, Table 2, Table 3). After all tumor types were graphed, the weighted average was calculated for each tumor type, with weight added to the studies with larger cohorts.Data were considered in several ways.
Following the initial exposure tissue recovery will start, which is a time-dependent process. Second, in order to facilitate comparisons between studies, the data were considered as the percents of the LRFs that had manifested over time. The re-irradiation tolerance of the primate spinal cord increases progressively with increasing time interval between initial exposure and re-irradiation [41]. With this approach, we were able to compare the distribution of “time to LRF” between studies even if the absolute magnitude of the LRF rate was different between studies. Rakowski et al., “Predictive utility of NT-pro BNP for infarct size and left ventricle function after acute myocardial infarction in long-term follow-up,” Disease Markers, vol.
For standard fractionation schemes, a dose response relationship for brain necrosis following irradiation has been reported, with an incidence of necrosis of 5% and 10% after 72 Gy and 90 Gy, respectively, in 2 Gy fractions [5]. Third, for each disease site, the percent of the LRFs that had manifested over time was averaged from the individual studies.


Comparison with data from the present analysis, showing ± a 15–40% higher cumulative tolerance dose for brain necrosis, supports long-term recovery from radiation injury for the human brain. This average was weighted based on the total number of patients with an LRF from the study. However, our analysis does not show a correlation between the time interval (range 3–55 months) and tolerance to re-irradiation. The details are given below.Absolute cumulative rates of LRF over timeFor each article considered, the absolute cumulative rate of LRF, at various time intervals, was extracted from the report.
For example, in the study with the shortest time interval of 3 months, an EQD2cumulative of 105 Gy did not result in tissue necrosis [18], while in another report [21] necrosis was found at an even lower EQD2cumulative and longer time elapsed since initial irradiation.
Also, shortening of the mean time interval from 30 months for conventional re-irradiation to 17 and 10 months for FSRT and SRS, respectively, (Table 4) did not increase the probability of radiation-induced brain necrosis. In most of the studies, the LRF rates were recorded annually in the form of text, tables, or graphs.
These observations suggest a relatively fast process of (partial) long-term recovery, in the order of months rather than of years. Rakowski et al., “Coincidence of moderately elevated N-terminal pro-B-type natriuretic peptide, endothelial progenitor cells deficiency and propensity to exercise-induced myocardial ischemia in stable angina,” Disease Markers, vol. Treatment VolumeThe present analysis shows that the actually prescribed re-irradiation dose increases with a change in irradiation technique from conventional to FSRT to LINAC-based SRS re-treatment (Figure 2). In patients re-irradiated with conventional radiotherapy, the EQD2re-irradiation was always lower than the EQD2initial, whereas it was higher in some of the FSRT series and in 6 out of 7 SRS series. In the SRS studies, re-irradiation dose regimens were used that would likely exceed the tolerance dose of the brain. For lung and rectal cancer, most LRFs occur in the range of 1 to 3 years post-surgery, with a maximum time to LRF of ? 3 to 4 years. An inverse correlation was found between the cumulative radiation dose and treatment volume (Figure 3, Table 4). Using Collins’ law, one would then conclude that the age of most cancers at the time of diagnosis is in the range of 3 to 6 years. Collins' law revisited: can we reliably predict the time to recurrence in common pediatric tumors? This is likely due to the choice for high conformal therapy in case of small tumour recurrence and a consequent decrease in late normal tissue toxicity. The LRFs occurring at shorter time intervals might result from patients with disease burdens greater than one cell after surgery.This analysis is idealized, and several shortcomings arise from the underlying assumptions. First, it is assumed that the tumor growth rates before diagnosis and after resection are relatively similar. Haltmayer, “B-type natriuretic peptide and amino terminal proBNP predict one-year mortality in short of breath patients independently of the baseline diagnosis of acute destabilized heart failure,” Clinica Chimica Acta, vol. In a recent review [5], a clear correlation was reported between the maximal tolerated dose for radiation necrosis and the irradiation volume.
For SRS, the volume of brain receiving ? 12 Gy was found to correlate with both the incidence of radiation necrosis and asymptomatic radiologic changes [5]. If this was the case, the observed times to local failure may underestimate the age of the cancer at diagnosis.
Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: an update. On the other hand, it is often difficult to detect a local recurrence on imaging since post-operative changes often limit the sensitivity of imaging. Similarly, there might have been inter-physician differences in the frequency of follow-up evaluations, and inter-patient variations in the propensity to seek medical attention, which might have influenced the reported pace of local failure. Nevertheless, the logarithmic nature of tumor growth would suggest that these effects are relatively modest.
Furthermore, the preferential use of data from prospective studies was intended to minimize these variations.
Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. However, there appeared to be no systematic differences between the data from the prospective studies and those from retrospective studies with regard to the pace of the recurrences. Portaluppi, “Elevated NT-proBNP levels should be interpreted in elderly patients presenting with dyspnea,” European Journal of Internal Medicine, vol. Thus, combining the data from the prospective and the retrospective series may be reasonableFourth, two of the studies reported local-regional recurrence, rather than “local only” recurrences. Randomised controlled trial of conservation therapy for breast cancer: 6-year analysis of the Scottish trial.
Thus, the data from these studies appear very similar to data from studies that reported specifically local failures.The information presented regarding the pace of local failure is likely not particularly relevant to treatment decisions. However, it might be helpful for patients to understand the natural history of their cancer. While this is understandable, the new information regarding the typical ages of cancers may help patients keep this time element in perspective.The data presented here are from only three specific diseases and may not be applicable to other cancer types. 10-Year results after sector resection with or without postoperative radiotherapy for stage I breast cancer: a randomized trial. Degryse, “The accuracy of plasma natriuretic peptide levels for diagnosis of cardiac dysfunction and chronic heart failure in community-dwelling elderly: a systematic review,” Age and Ageing, vol. Marks receives research funds from the National Institutes of Health and the Lance Armstrong Foundation, and he is an unpaid advisor to Siemens. Neurocognitive Function after Re-IrradiationWith improving survival of glioma patients, focus on long-term treatment-related morbidity has increased, with the effect of brain (re-)irradiation on cognitive performance as major concern. Radiotherapy after breast-conserving surgery in small breast carcinoma: long-term results of a randomized trial. Establishing the effect of radiation on patients’ neurocognitive impairment is difficult because of confounding factors like the tumour itself, surgery, chemotherapy, concurrent illnesses, neurologic co-morbidity and medications [47]. In their review, Laack and Brown conclude that high total dose, large fraction size and large brain volumes are associated with increased risk of neurocognitive decline after radiotherapy. Overall survival and local recurrence of 406 completely resected stage IIIa-N2 non-small cell lung cancer patients: questionnaire survey of the Japan Clinical Oncology Group to plan for clinical trials. Filippatos et al., “ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008,” European Heart Journal, vol. Local failure after complete resection of “early-stage” non-small cell lung cancer: the potential role of post-operative radiation therapy.
Imaging revealed a maximum of two patients with changes compatible with radiation necrosis, no histological confirmation was established, nor was the use of bevacizumab in these two patients clearly stated. Clinical side-effects of bevacizumab, according to Common Toxicity Criteria, were wound healing complications grade 4 (n = 1), deep vein thrombosis grade 3 (n = 1) and hypertension grade 2 (n = 1). The role of post-operative radiotherapy in non-small-cell lung cancer: a multicentre randomised trial in patients with pathologically staged T1-2, N1-2, M0 disease. Factors associated with local and distant recurrence and survival in patients with resected non–small cell lung cancer. Schmid et al., “A new equation to estimate glomerular filtration rate,” Annals of Internal Medicine, vol. Final results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC). Schneider, “NT-pro-BNP measured at discharge predicts outcome in multimorbid diabetic inpatients with a broad spectrum of cardiovascular disease,” Acta Diabetologica, vol.
Patients Re-Irradiated with Stereotactic RadiosurgeryIn three of seven studies in this group (Table 3), chemotherapy of various regimens was used at the initial treatment course [31,32,35]. Laule et al., “Long-term prognostic value of B-type natriuretic peptide in cardiac and non-cardiac causes of acute dyspnoea,” European Journal of Clinical Investigation, vol.
VonScheidt, “Role of brain natriuretic peptide in risk stratification of patients with congestive heart failure,” Journal of the American College of Cardiology, vol.
Strecker et al., “B-type natriuretic peptide predicts sudden death in patients with chronic heart failure,” Circulation, vol. Sharma, “N-terminal probrain natriuretic peptide predicts 1-year mortality following acute stroke: possible evidence of occult cardiac dysfunction among patients with acute stroke,” Age and Ageing, vol. Glasziou, “How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review,” British Medical Journal, vol. Results from an epidemiological study of elderly patients with symptoms of heart failure,” International Journal of Cardiology, vol. Lowe et al., “N-terminal pro-brain natriuretic peptide is a more useful predictor of cardiovascular disease risk than C-reactive protein in older men with and without pre-existing cardiovascular disease,” Journal of the American College of Cardiology, vol.
Vanderecamer et al., “Admission NT-proBNP levels, renal insufficiency and age as predictors of mortality in elderly patients hospitalized for acute dyspnea,” European Journal of Internal Medicine, vol. Christensen, “NT-pro-BNP is an independent predictor of mortality in patients with end-stage renal disease,” Clinical Nephrology, vol. Huh et al., “N-terminal pro-brain natriuretic peptide levels predict left ventricular systolic function in patients with chronic kidney disease,” Journal of Korean Medical Science, vol. Manfredini, “Intensive therapy and GFR in type 1 diabetes,” The New England Journal of Medicine, vol. Senthilselvan, “Comparison of chronic kidney disease (CKD) epidemiology formula with other calculated creatinine formulas for the determination of CKD in cognitively intact and impaired elderly outpatients,” Journal of the American Geriatrics Society, vol. Uhlig, “Estimating equations for glomerular filtration rate in the era of creatinine standardization.
Antonelli Incalzi, “Association between glomerular filtration rate and adverse drug reactions in elderly hospitalized patients: the role of the estimating equation,” Drugs and Aging, vol. Zuliani, “Relationship between N-terminal pro-B-type natriuretic peptide plasma levels and renal function evaluated with different formulae in older adult subjects admitted because of dyspnea,” Gerontology, vol.



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