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In this systematic review and meta-analysis of clinical controlled trials (CCTs) we aimed to investigate the efficacy of KDs as an adjuvant therapy on cardiometabolic outcomes in patient with cancer compared to conventional non-ketogenic diets. Only CCTs involving cancer patients that were assigned to either a KD or a standard diet control group were selected. Two reviewers independently extracted the data, and a meta-analysis was performed using a random effects model to estimate weighted mean differences (WMDs) and confidence intervals (CIs) in body composition, metabolite, lipid profile, liver and kidney function parameters and quality of life. This meta-analysis showed a significant reduction in body weight (WMD= -2.99 kg; 95% CI: -4.67, -1.31; and

Background TheWorld Economic Forum (WEF) has spawned a global network of elites called Young Global Leaders (YGLs) with significant influence on large corporations, politics, academia, and media. This article scrutinizes the idea that through this network, the WEF had a significant influence on the scale and scope of the non-pharmaceutical interventions (NPIs) implemented in response to the COVID-19 crisis. We tested for associations between the country-level distribution of YGLs and the intensity and duration of the implemented NPIs summarized by the Government Response Severity Index (GRSI). Materials and methods The number and category of YGLs per country was extracted from the WEF website. We also extracted the maximum and median GRSI values for three time periods: (i) the beginning of the first wave of the pandemic (March 1, 2020, to April 30, 2020), (ii) the height of the second wave in Europe (December 1, 2020, to January 31, 2021), and (iii) the approximate first year (March 1, 2020, to January 31, 2021). Being a precondition for causality, any association between the total or category-specific number of YGLs and the GRSI values in each time period was evaluated using Spearman's ρ correlation coefficients and polynomial regression, respectively. Results There was a highly significant positive correlation between the total number of YGLs in a country and the median (ρ = 0.36, p = 2.5×10

Vitamin D has been shown to be associated with reduced risk and severity of COVID-19 and exerts regulating effects on all hallmarks of cancer. The goal of this study was to analyze the vitamin D status of a cancer patient cohort from our clinic in the Franconian region, Germany.25-hydroxyvitamin D concentrations were available for 116 patients included in prospective trials in our clinic. Associations of vitamin D with anthropometric and blood parameters were investigated using Kendall's τ correlation coefficients and linear regression.A total of 57 patients (49.1%) were vitamin D deficient (20 ng/mL), and 92.2% did not meet the recommended vitamin D level of 40 ng/mL. There was a strong negative association between vitamin D and leukocyte count (τ = -0.173, p = 0.007) and C-reactive protein concentration (τ = -0.172, p = 0.007). In linear regression, the most important variables for predicting vitamin D levels were (in order of decreasing importance) season, fat mass index, platelet, and leukocyte count.Despite appeals towards medical societies to target widespread vitamin D deficiency in Germany more than 10 years ago, our data indicate that these have been without avail. Low vitamin D levels in cancer patients should be corrected using reasonable sun exposure and supplements.Hintergrund: Es wurde gezeigt, dass Vitamin D mit einem reduzierten Risiko für die Ansteckung mit SARS-CoV-2 und leichteren Verläufen von COVID-19 assoziiert ist; zudem wirkt Vitamin D bei allen kennzeichnenden Merkmalen einer Krebserkrankung mitregulierend. Das Ziel dieser Studie war deshalb, den Vitamin D Status einer Kohorte von Krebspatienten aus unserer Klinik in Unterfranken zu erheben. Methoden: Für 116 Patienten wurde innerhalb prospektiver Studien die 25-Hydroxyvitamin D Konzentration gemessen. Assoziationen zwischen Vitamin D und anthropometrischen sowie Blutparametern wurden mittels Kendall’s Korrelationskoeffizienten τ und linearer Regression untersucht. Ergebnisse: Insgesamt wiesen 57 Patienten (49,1%) einen Vitamin-D Mangel (20 ng/mL) auf, und 92,2% lagen unterhalb des empfohlenen Vitamin D Spiegels von 40 ng/mL. Wir fanden eine starke negative Korrelation zwischen Vitamin D und der Anzahl an Leukozyten (τ = –0.173, p = 0.007) sowie C-reaktivem Protein (τ = –0.172, p = 0.007). Die wichtigsten Variablen zur Vorhersage des Vitamin D Wertes in der linearen Regression waren (der Wichtigkeit nach) die Jahreszeit, der Fettmasseindex, die Thrombozyten- und die Leukozyten-Zahl. Schlussfolgerungen: Trotz dringender Appelle an medizinische Fachgesellschaften vor über 10 Jahren, etwas gegen weitverbreiteten Vitamin D Mangel zu unternehmen, zeigen unsere Daten, dass diesbezüglich immer noch enormer Handlungsbedarf besteht. Niedrige Vitamin D Spiegel von Tumorpatienten sollten mittels vernünftiger Sonnenexposition und Nahrungsergänzungsmitteln behoben werden.

We investigate the epistemological consequences of a positive polymerase chain reaction SARS-CoV test for two relevant hypotheses: (i) V is the hypothesis that an individual has been infected with SARS-CoV-2; (ii) C is the hypothesis that SARS-CoV-2 is the cause of flu-like symptoms in a given patient. We ask two fundamental epistemological questions regarding each hypothesis: First, how much confirmation does a positive test lend to each hypothesis? Second, how much evidence does a positive test provide for each hypothesis against its negation? We respond to each question within a formal Bayesian framework. We construe degree of confirmation as the difference between the posterior probability of the hypothesis and its prior, and the strength of evidence for a hypothesis against its alternative in terms of their likelihood ratio. We find that test specificity—and coinfection probabilities when making inferences about C—were key determinants of confirmation and evidence. Tests with 8) for V against ¬V regardless of sensitivity. Accordingly, low specificity tests could not provide strong evidence in favor of C in all plausible scenarios modeled. We also show how a positive influenza A test disconfirms C and provides weak evidence against C in dependence on the probability that the patient is influenza A infected given that his/her symptoms are not caused by SARS-CoV-2. Our analysis points out some caveats that should be considered when attributing symptoms or death of a positively tested patient to SARS-CoV-2.

Background and aim Ketogenic diets (KDs) have gained interest as a complementary treatment for cancer patients. Here we present first results of our ongoing KETOCOMP study (NCT02516501) concerning body composition changes among rectal, breast and head & neck cancer (HNC) patients who consumed a KD during curative radiotherapy (RT). Experimental procedure Sixty-one patients eating a non-ketogenic diet were compared to 20 patients on a KD supplemented with 10 g essential amino acids on RT days. Body composition was measured prior to and weekly during RT using 8-electrode bioimpedance analysis. Longitudinal body composition data were analyzed using linear mixed effects models. Results and conclusion Patients on the KD exhibited nutritional ketosis, defined as serum β-hydroxybutyrate levels ≥0.5 mmol/l, in a median of 69.0% of blood measurements (range 0–100%) performed in our clinic. In rectal and breast cancer patients, KD was significantly associated with a loss of 0.5 and 0.4 kg fat mass per week (p = 0.00089 and 8.49 × 10−5, respectively), with no significant changes in fat free and skeletal muscle mass. In HNC patients, concurrent chemotherapy was the strongest predictor of body weight, fat free and skeletal muscle mass loss during RT, while consuming a KD was significantly associated with a gain in these measures. These preliminary results confirm prior reports indicating that KDs are safe to consume during standard-of-care therapy. They also provide an important first indication that KDs with ample amino acid intake could improve body composition during RT in curative cancer patients., Graphical abstract Image 1, Highlights • Consumption of a ketogenic diet (KD) during radio(chemo-)therapy is feasible. • In rectal and breast cancer patients, the KD significantly reduced fat mass. • Fat-free mass and skeletal muscle mass were preserved by the KD. • In head and neck cancer patients a KD influenced body composition opposite to chemotherapy.

There is a growing interest in a particular metabolic state and its influence on cancer therapy: ketosis. Ketosis denotes the physiological rise in ketone bodies that is proportional to fat oxidati...

Background High-dose hypofractionated radiotherapy should theoretically result in a deviation from the typical linear-quadratic shape of the cell survival curve beyond a certain threshold dose, yet no evidence for this hypothesis has so far been found in clinical data of stereotactic body radiotherapy treatment (SBRT) for early-stage non-small cell lung cancer (NSCLC). A pragmatic explanation is a larger α/β ratio than the conventionally assumed 10 Gy. We here attempted an estimation of the α/β ratio for NSCLC treated with SBRT using individual patient data. Materials and methods We combined two large retrospective datasets, yielding 1294 SBRTs (≤10 fractions) of early stage NSCLC. Cox proportional hazards regression, a logistic tumor control probability model and a biologically motivated Bayesian cure rate model were used to estimate the α/β ratio based on the observed number of local recurrences and accounting for tumor size. Results A total of 109 local progressions were observed after a median of 17.7 months (range 0.6–76.3 months). Cox regression, logistic regression of 3 year tumor control probability and the cure rate model yielded best-fit estimates of α/β = 12.8 Gy, 14.9 Gy and 12–16 Gy (depending on the prior for α/β), respectively, although with large uncertainties that did not rule out the conventional α/β = 10 Gy. Conclusions Clinicians can continue to use the simple LQ formalism to compare different SBRT treatment schedules for NSCLC. While α/β = 10 Gy is not ruled out by our data, larger values in the range 12–16 Gy are more probable, consistent with recent meta-regression analyses.

ObjectiveTo answer the question: Why do people consent to being vaccinated with novel vaccines against SARS-CoV-2?DesignRepresentative survey.SettingOnline panel.Participants1032 respondents of the general German population.MethodA representative survey among German citizens in November/December 2021 that resulted in 1032 complete responses on vaccination status, sociodemographic parameters and opinions about the COVID-19 situation.ResultsAlmost 83% of the respondents were vaccinated. The major motivation was fear of medical consequences of an infection and the wish to lead a normal life again. The major motivation to be not vaccinated was the fear of side effects and scepticism about long-term effectiveness and safety. Sixteen per cent of vaccinated respondents reported some serious side effect, while more than 30% reported health improvements, mostly due to the relief of psychological stress and social reintegration. We also validated a ‘Corona Orthodoxy Score—COS’ consisting of seven items reflecting opinions on COVID-19. The scale is reliable (alpha=0.76) and unidimensional. The COS was a highly significant predictor of vaccination status and readiness to be vaccinated in a multivariable logistic regression model. Those who were vaccinated were more likely to live in smaller households (OR=0.82, p=0.024), had a higher income (OR=1.27, pConclusionsThe major motives for being vaccinated are fear of medical symptoms and the wish to lead a normal life. Those not wanting to be vaccinated cite a lack of knowledge regarding long-term safety and side effects as reasons. This can likely only be overcome by careful and active long-term efficacy and safety monitoring.

Background and purpose The standard treatment of glioblastoma patients consists of surgery followed by normofractionated radiotherapy (NFRT) with concomitant and adjuvant temozolomide chemotherapy. Whether accelerated hyperfractionated radiotherapy (HFRT) yields comparable results to NFRT in combination with temozolomide has only sparsely been investigated. The objective of this study was to compare NFRT with HFRT in a multicenter analysis. Materials and methods A total of 484 glioblastoma patients from four centers were retrospectively pooled and analyzed. Three-hundred-ten and 174 patients had been treated with NFRT (30 × 1.8 Gy or 30 × 2 Gy) and HFRT (37 × 1.6 Gy or 30 × 1.8 Gy twice/day), respectively. The primary outcome of interest was overall survival (OS) which was correlated with patient-, tumor- and treatment-related variables via univariable and multivariable Cox frailty models. For multivariable modeling, missing covariates were imputed using multiple imputation by chained equations, and a sensitivity analysis was performed on the complete-cases-only dataset. Results After a median follow-up of 15.7 months (range 0.8–88.6 months), median OS was 16.9 months (15.0–18.7 months) in the NFRT group and 14.9 months (13.2–17.3 months) in the HFRT group (p = 0.26). In multivariable frailty regression, better performance status, gross-total versus not gross-total resection, MGMT hypermethylation, IDH mutation, smaller planning target volume and salvage therapy were significantly associated with longer OS (all p Conclusions Since HFRT with temozolomide was not associated with worse OS, we assume HFRT to be a potential option for patients wishing to shorten their treatment time.

Altered glucose metabolism in cancer cells is an almost ubiquitous observation, yet hardly exploited therapeutically. However, ketogenic diets have gained growing attention in recent years as a nontoxic broad-spectrum approach to target this major metabolic difference between normal and cancer cells. Although much research still needs to be done, new knowledge has been gained about the optimal utilization of ketogenic diets for cancer treatment that this review aims to summarize.Although most preclinical studies indicate a therapeutic potential for ketogenic diets in cancer treatment, it is now becoming clear that not all tumors might respond positively. Early clinical trials have investigated ketogenic diets as a monotherapy and - while showing the safety of the approach even in advanced cancer patients - largely failed to prove survival prolonging effects. However, it gradually became clear that the greatest potential for ketogenic diets is as adjuvant treatments combined with pro-oxidative or targeted therapies initiated in early stages of the disease. Beneficial effects on body composition and quality of life have also been found.Ketogenic diets against cancer are worth further exploration, both in the laboratory and clinically. Patients wishing to undertake a ketogenic diet during therapy should receive dietary counselling to avoid common mistakes and optimize compliance. Future research should focus more on important clinical endpoints.

Background: COVID-19 vaccines have had expedited reviews without sufficient safety data. We wanted to compare risks and benefits. Method: We calculated the number needed to vaccinate (NNTV) from a large Israeli field study to prevent one death. We accessed the Adverse Drug Reactions (ADR) database of the European Medicines Agency and of the Dutch National Register (lareb.nl) to extract the number of cases reporting severe side effects and the number of cases with fatal side effects. Result: The NNTV is between 200–700 to prevent one case of COVID-19 for the mRNA vaccine marketed by Pfizer, while the NNTV to prevent one death is between 9000 and 50,000 (95% confidence interval), with 16,000 as a point estimate. The number of cases experiencing adverse reactions has been reported to be 700 per 100,000 vaccinations. Currently, we see 16 serious side effects per 100,000 vaccinations, and the number of fatal side effects is at 4.11/100,000 vaccinations. For three deaths prevented by vaccination we have to accept two inflicted by vaccination. Conclusions: This lack of clear benefit should cause governments to rethink their vaccination policy.

Interest in ketogenic diets (KDs) as complementary nutritional treatments for cancer patients is rising, although some skepticism about their safety exists. We, therefore, studied the effects of KDs on quality of life and blood parameters in rectal cancer patients undergoing radio-chemotherapy.EORTC-QLQ30 questionnaire scores and different metabolic and hormonal blood parameters were obtained prior to, in the middle of and at the end of radiotherapy within the KETOCOMP study (ClinicalTrials.gov Identifier: NCT02516501). A total of 18 patients consuming a KD were compared to 23 patients consuming their standard diet (SD). Baseline-end differences were measured using Wilcoxon tests, and repeated measures analysis was performed using linear mixed effects models.Eighty-nine percent of patients on the KD reported subjectively feeling good or very good, but roughly half of them rated the daily routine implementation as difficult. Only the SD group experienced significant declines in physical and role functioning, while the KD group improved in role (p = 0.045), emotional (p = 0.018) and social functioning (p = 0.009).Urinary frequency, buttock pain and fatigue significantly increased in the SD group, but to a much lesser extent in the KD group. Several biomarkers of metabolic health (gamma-glutamyl-transpeptidase, triglyceride-glucose index, HDL cholesterol/triglyceride ratio, and free T3) improved in the KD, but not the SD group.Despite being perceived as difficult to implement by ≈50% of patients, KDs are feasible as complementary therapies alongside radio-chemotherapy and associated with subjective well-being. The hypothesis that they exert beneficial effects on quality of life and metabolic health in rectal cancer patients is supported by our data.ClinicalTrials.gov identifier NCT02516501, registered Aug 6th 2015.

Highlights • Re-irradiation of the brain is feasible with an encouraging overall survival. • Treatment related toxicity was low within the reported dose range. • EQD2 cumulative dose distributions were calculated using rigid registration. • Dose-Response-Modelling with logistic regression showed a correlation of the D1cc brain with any grade of acute toxicity., Introduction The use of cranial re-irradiation is growing with improving overall survival and the advent of high-precision radiotherapy techniques. Still the value of re-irradiation needs careful evaluation regarding safety and efficacy. We analyzed dosimetric and clinical data of patients receiving cranial re-irradiation using EQD2 sum plans. Methods and material We retrospectively analyzed the data of 76 patients who received repeated cranial radiotherapy from 02/2013 to 09/2016. 34 patients suffered from recurrent primary brain tumors, 42 from brain metastases. Dosimetric analysis was performed accumulating EQD2 dose distributions based on rigid image registration. Clinical and radiological data was collected at follow-ups including toxicity, local control and overall survival. Results In total 76 patients had at least 2 courses of intracranial radiotherapy. The median accumulated prescription EQD2 dose was 96.5 Gy2 for all radiation courses combined. The median D(0.1 cc) of the brain for patients receiving more than 100 Gy2 was 114 Gy2 with a highest dose of 161.5 Gy2. 74% of patients suffered from low grade (G1–G2) acute toxicity, only two high grade (>G3) toxicities were recorded. Median overall survival from the time of first re-irradiation was 57 weeks (range 4–186 weeks). The median time to local failure for patients with a primary brain tumor was not reached and 24 weeks (range 1–77 weeks) for patients with brain metastases. Conclusion Repeated radiotherapy appears both safe and efficient in patients with recurrent primary or secondary brain tumors with doses to the brain up to 120 Gy2 EQD2, doses below 100 Gy2 for brainstem and doses below 75 Gy2 EQD2 to chiasm and optic nerves.

Vitamin D3 (cholecalciferol) is a secosteroid and prohormone which is metabolized in various tissues to the biologically most active vitamin D hormone 1,25(OH)2D3 (calcitriol). 1,25(OH)2D3 has multiple pleiotropic effects, particularly within the immune system, and is increasingly utilized not only within prophylaxis, but also within therapy of various diseases. In this context, the latest research has revealed clinical benefits of high dose vitamin D3 therapy in autoimmune diseases. The necessity of high doses of vitamin D3 for treatment success can be explained by the concept of an acquired form of vitamin D resistance. Its etiology is based on the one hand on polymorphisms within genes affecting the vitamin D system, causing susceptibility towards developing low vitamin D responsiveness and autoimmune diseases; on the other hand it is based on a blockade of vitamin D receptor signaling, e.g. through pathogen infections. In this paper, we review observational and mechanistic evidence for the acquired vitamin D resistance hypothesis. We particularly focus on its clinical confirmation from our experience of treating multiple sclerosis patients with the so-called Coimbra protocol, in which daily doses up to 1000 I.U. vitamin D3 per kg body weight can be administered safely. Parathyroid hormone levels in serum thereby provide the key information for finding the right dose. We argue that acquired vitamin D resistance provides a plausible pathomechanism for the development of autoimmune diseases, which could be treated using high-dose vitamin D3 therapy.

To report outcome (freedom from local progression: FFLP, overall survival: OS, and toxicity) after stereotactic, palliative, or highly conformal fractionated (> 12) radiotherapy (SBRT, Pall-RT, 3DCRT/IMRT) for adrenal metastases in a retrospective multicenter cohort within the framework of the German Society for Radiation Oncology (DEGRO). Adrenal metastases treated with SBRT (≤ 12 fractions, biologically effective dose, (BED10) ≥ 50 Gy), 3DCRT/IMRT (> 12 fractions, BED10 ≥ 50 Gy) or Pall-RT (BED10 < 50 Gy) were eligible for this analysis. In addition to unadjusted FFLP (Kaplan-Meier/Log-rank), we calculated the competing-risk-adjusted local recurrence rate (CRA-LRR). 326 patients with 366 metastases were included by 21 centers (median follow-up: 11.7 months). Treatment was SBRT, 3DCRT/IMRT, and Pall-RT in 260, 27, and 79 cases, respectively. Most frequent primary tumors were non-small-cell lung cancer (NSCLC; 52.5%), SCLC (16.3%), and melanoma (6.7%). Unadjusted FFLP was higher after SBRT v. Pall-RT (p = 0.026) while numerical differences in CRA-LRR between groups did not reach statistical significance (1-year CRA-LRR: 13.8%, 17.4%, and 27.7%). OS was longer after SBRT v. other groups (p < 0.05) and increased in patients with locally-controlled metastases in a landmark analysis (p < 0.0001). Toxicity was mostly mild; notably, 4 cases of adrenal insufficiency occurred, 2 of which were likely caused by immunotherapy or tumor progression. RT for adrenal metastases was associated with a mild toxicity profile in all groups and a favorable 1-year CRA-LRR after SBRT or 3DCRT/IMRT. 1-year FFLP was associated with longer OS. Dose-response analyses for the dataset are underway. This article is protected by copyright. All rights reserved.

Breast cancer (BC) patients often ask for a healthy diet. Here, we investigated a healthy standard diet (SD), a low carb diet (LCD), and a ketogenic diet (KD) for BC patients during the rehabilitation phase. KOLIBRI was an open-label non-randomized one-site nutritional intervention trial, combining inpatient and outpatient phases for 20 weeks. Female BC patients (n = 152, mean age 51.7 years) could select their diet. Data collected were: Quality of life (QoL), spiroergometry, body composition, and blood parameters. In total 30, 92, and 30 patients started the KD, LCD, and SD, respectively. Of those, 20, 76, and 25 completed the final examination. Patients rated all diets as feasible in daily life. All groups enhanced QoL, body composition, and physical performance. LCD participants showed the most impressive improvement in QoL aspects. KD participants finished with a very good physical performance and muscle/fat ratio. Despite increased cholesterol levels, KD patients had the best triglyceride/high-density lipoprotein (HDL) ratio and homeostatic model assessment of insulin resistance index (HOMA-IR). Most metabolic parameters significantly improved in the LCD group. SD participants ended with remarkably low cholesterol levels but did not improve triglyceride/HDL or HOMA-IR. In conclusion, both well-defined KDs and LCDs are safe and beneficial for BC patients and can be recommended during the rehabilitation phase.

Evolutionary principles are rarely considered in clinical oncology. We here aimed to test the feasibility and effects of a dietary and physical activity intervention based on evolutionary considerations in an oncological setting. A total of 13 breast cancer patients referred to our clinic for curative radiotherapy were recruited for this pilot study. The women were supposed to undertake a “Paleolithic lifestyle” (PL) intervention consisting of a Paleolithic diet and daily outdoor activity of at least 30 min duration while undergoing radiotherapy. Body composition was measured weekly by bioimpedance analysis. Blood parameters were assessed before, during, and at the end of radiotherapy. A control group on an unspecified standard diet (SD) was assigned by propensity score matching. A total of eleven patients completed the study. The majority of patients (64%) reported feeling good or very good during the intervention. The intervention group experienced an average decrease of 0.4 kg body weight (p

Background Obesity and low muscle mass are associated with worse outcomes of breast cancer patients. We conducted a controlled trial to study the impact of a ketogenic diet (KD) based on natural foods versus an unspecified standard diet (SD) on body composition in breast cancer patients undergoing radiotherapy. Methods Patients with non-metastasized breast cancer were allocated to either the KD (N = 32) or the SD (N = 31) during radiotherapy. Body composition was measured weekly by bioimpedance analysis. Blood parameters and quality of life were assessed before, during, and at the end of radiotherapy. Results A total of 29 KD and 30 SD patients completed the study. During radiotherapy, mean and median fasting BHB concentrations in the KD group were 0.72 and 0.49 mmol/l (range 0.06–4.9) which was significantly higher than those in the SD group (p −16). There was a very small and insignificant increase in body weight and fat mass in the SD group, as well as a decrease of fat free mass. In contrast, patients in the KD group lost body weight and fat free and skeletal muscle mass quickly after diet onset, which for the most part was related to water losses. The KD did not cause further substantial changes in fat free or skeletal muscle mass, but was associated with a gradual decrease of 0.4 kg body weight and fat mass per week (p p = 6.3 × 10−5). Global quality of life remained stable in the SD group but increased in the KD group from a score of 66.7 to 75.0 (p = 0.20). Conclusions In breast cancer patients undergoing curative radiotherapy, a KD based on natural foods is feasible. After initial water losses, the KD tends to reduce body weight and fat mass while preserving fat free and skeletal muscle mass. Trial registration ClinicalTrials.gov identifier: NCT02516501, registered on August 06, 2015.

We here express our concern about a general decree to let patients wear face masks in radiation oncology clinics. We believe that potential risks associated with wearing masks, such as the risk of confounding patients, outweigh any benefits of such a policy for which evidence of protection from COVID-19 is generally weak. For asymptomatic patients, wearing masks in addition to hygiene standards will not provide additional protection of others and should be cautioned against.

Background Large variation regarding prescription and dose inhomogeneity exists in stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer. The aim of this modeling study was to identify which dose metric correlates best with local tumor control probability to make recommendations regarding SBRT prescription. Methods and Materials We combined 2 retrospective databases of patients with non-small cell lung cancer, yielding 1500 SBRT treatments for analysis. Three dose parameters were converted to biologically effective doses (BEDs): (1) the (near-minimum) dose prescribed to the planning target volume (PTV) periphery (yielding BEDmin); (2) the (near-maximum) dose absorbed by 1% of the PTV (yielding BEDmax); and (3) the average between near-minimum and near-maximum doses (yielding BEDave). These BED parameters were then correlated to the risk of local recurrence through Cox regression. Furthermore, BED-based prediction of local recurrence was attempted by logistic regression and fast and frugal trees. Models were compared using the Akaike information criterion. Results There were 1500 treatments in 1434 patients; 117 tumors recurred locally. Actuarial local control rates at 12 and 36 months were 96.8% (95% confidence interval, 95.8%-97.8%) and 89.0% (87.0%-91.1%), respectively. In univariable Cox regression, BEDave was the best predictor of risk of local recurrence, and a model based on BEDmin had substantially less evidential support. In univariable logistic regression, the model based on BEDave also performed best. Multivariable classification using fast and frugal trees revealed BEDmax to be the most important predictor, followed by BEDave. Conclusions BEDave was generally better correlated with tumor control probability than either BEDmax or BEDmin. Because the average between near-minimum and near-maximum doses was highly correlated to the mean gross tumor volume dose, the latter may be used as a prescription target. More emphasis could be placed on achieving sufficiently high mean doses within the gross tumor volume rather than the PTV covering dose, a concept needing further validation.

Background: Breast Cancer (BC) patients often ask for a healthy diet. Here, we compared three different diets which could support BC patients during the rehabilitation process: a healthy standard diet (SD), a low carb diet (LCD) and a ketogenic diet (KD).Patients and Methods:KOLIBRI was a one-site nutritional intervention trial, combining inpatient and outhouse phases for 20 weeks. Female BC patients (n=152; mean age 51.7 years) could select their diet. Data collected were: quality of life (QoL), spiroergometry, body composition, blood biochemistry. 30, 92 and 30 patients started the KD, LCD and SD, respectively. Of those, 20, 72 and 25 completed the final examination.Results:Patients rated all diets as feasible in daily life. No adverse effects occurred in any diet group. KD offered the highest amount of energy and protein. All groups improved in QoL, body composition and physical performance. KD was superior in improving fatigue, insomnia and physical functioning. KD participants finished with the best physical performance and the highest muscle/fat ratio. Despite their increased cholesterol, KD patients had the best triglyceride/HDL ratio and HOMA-IR. Most metabolic parameters significantly improved in the LCD group. SD participants ended with remarkably low cholesterol levels, but did not improve triglyceride/HDL or HOMA-IR.Conclusions:A well-defined KD and LCD are safe and beneficial for BC. Both diets could thus be recommended for patients wanting to self-support their rehabilitation process.Trial registration IDNCT02092753 Protocol Registration date:02/26/2014Ketogenic Or LOGI Diet In a Breast Cancer Rehabilitation Intervention (KOLIBRI)URL: https://clinicaltrials.gov/ct2/show/NCT02092753?cond=KOLIBRI&draw=2&rank=1

We investigate the epistemological consequences of a positive SARS-CoV-2 test for two relevant hypotheses: (i) V is the hypothesis that an individual has been infected with SARS-CoV-2; (ii) C is the hypothesis that SARS-CoV-2 is the sole cause of flu-like symptoms in a given patient. We ask two fundamental epistemological questions regarding each hypothesis: First, given a positive SARS-CoV-2 test, what should we believe about the hypothesis and to what degree? Second, how much evidence does a positive test provide for a hypothesis against its negation? We respond to each question within a formal Bayesian framework. We construe degree of confirmation as the difference between the posterior probability of the hypothesis and its prior, and the strength of evidence for a hypothesis against its alternative in terms of their likelihood ratio. We find that for realistic assumptions about the base rate of infected individuals, P(V)≲20%, positive tests having low specificity (75%) would not raise the posterior probability for V to more than 50%. Furthermore, if the test specificity is less than 88.1%, even a positive test having 95% sensitivity would only yield weak to moderate evidence for V against ¬V. We also find that in plausible scenarios, positive tests would only provide weak to moderate evidence for C unless the tests have a high specificity. One has thus to be careful in ascribing the symptoms or death of a positively tested patient to SARS-CoV-2, if the possibility exists that the disease has been caused by another pathogen.

Preclinical data provide evidence for synergism between ketogenic diets (KDs) and other oncological therapies. The aim of this systematic review was to summarize data from clinical studies that have tested KDs along with other treatments used within medical oncology. The PubMed database was searched using the key words "ketogenic" AND ("cancer" OR "glioblastoma"). A secondary search was conducted by screening the reference lists of relevant articles on this topic. Relevant studies for this review were defined as studies in which KDs were used complementary to surgery, radio-, chemo-, or targeted therapy and at least one of the following four outcomes were reported: (i) Overall survival (OS); (ii) progression-free survival (PFS); (iii) local control rate; (iv) body composition changes. Twelve papers reporting on 13 clinical studies were identified. Nine studies were prospective and six had a control group, but only two were randomized. KD prescription varied widely between studies and was described only rudimentarily in most papers. Adverse events attributed to the diet were rare and only minor (grade 1-2) except for one possibly diet-related grade 4 event. Studies reporting body composition changes found beneficial effects of KDs in both overweight and frail patient populations. Beneficial effects of KDs on OS and/or PFS were found in four studies including one randomized controlled trial. Studies in high-grade glioma patients were not sufficiently powered to prove efficacy. Evidence for beneficial effects of KDs during cancer therapy is accumulating, but more high-quality studies are needed to assess the overall strength of evidence.

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.

Radiation therapy (RT) is often delivered after lumpectomy for women with breast cancer. A common perceived side effect of RT is fatigue, yet its exact effect on activity levels and sleep is unknown. In this study we analyzed the change in activity levels and sleep using an activity tracking device before, during, and after RT for women with early stage breast cancer and ductal carcinoma in situ who underwent adjuvant RT.After institutional review board approval, activity levels were quantified before, during, and after RT with measurements of steps, miles walked, calories burned, and sleep metrics in 10 women fitted with activity trackers. All data were uploaded and tabulated on a secure database. Multivariable linear regressions were used to evaluate changes in these variables over time during the RT course.Median step count was 5047 per day (range, 2741-15,508) and distance traveled was 1.6 miles per day (range, 0.9-5.3). Step count, distance, and calories decreased by an average of 54 steps per day, 0.02 miles per day, and 3 calories per day (median calories 1822; range, 1461-2712) during RT, respectively. These changes were statistically significant (P .001), but not clinically relevant. There was no significant change in sleep (average 6.8 hours per night; range, 5.5-8.3).RT has a minimal effect on activity or sleep in women undergoing treatment for breast cancer. Activity levels varied greatly between patients in a population of women undergoing hypofractionated RT. Because increased activity levels correlate with improved outcomes, further studies evaluating attempts to increase physical activity during as well as after treatment with radiation are warranted.

Purpose/Objective(s) Recent studies suggest improved local control (LC) of early-stage non-small cell lung cancer (NSCLC) treated with SBRT regimens with biologically equivalent dose (BED10) > 150 Gy. It is unclear if this association is histology dependent. Multiple groups have shown lower LC rates after SBRT for squamous cell carcinoma (SCC), compared to non-SCC NSCLC. We compared LC between BEDlow and BEDhigh SBRT schemes, stratified by histology. Materials/Methods As part of an IRB approved collaborative, we retrospectively analyzed 684 patients with cT1-2, cN0, cM0 NSCLC, treated with definitive SBRT to a minimum BED of 100 Gy at five international centers. Patients were grouped into SCC and non-SCC, then divided into BEDhigh (BED10 ≥150 Gy) or BEDlow (BED10 Results Of 684 eligible tumors, 457 were non-SCC and 227 SCC. Median follow-up was 30 months. Of non-SCC patients, 262 (57%) were BEDlow and 195 (43%) BEDhigh. Of SCC patients, 144 (63%) were BEDlow and 83 (37%) BEDhigh. BEDhigh SBRT included those treated with 54 Gy in 3 fractions (54/3). BEDlow included 60/5, 50/5, 48/4, or 60/8. Baseline characteristics, including T-stage and max tumor dimension, were similar between BED groups after matching. MVA including T-stage, tumor grade, and tumor location, showed BEDlow regimens were associated with higher rates of local failure for SCC (HR 9.8, 95% CI 1.9-25.1, P = 0.007), but not for non-SCC (HR 1.2, 95% CI 0.6-2.5, P = 0.6). Three-year LC rates for BEDlow and BEDhigh were 70% and 97%, respectively for SCC, and 91% and 92%, respectively, for non-SCC. Similarly, there were higher rates of failure with BEDlow PTVmean (3 yr LC 94 vs 69%, MVA HR 6.4, 95% CI 1.9-22.2, P = 0.003) and BEDlow GTVmean (3 yr LC 87 vs 68%, MVA HR 7.6, 95% CI 2.7-21.6, P = 0.001) in SCC patients. In non-SCC patients, LC was similar between BED groups for PTVmean (3 yr LC 92% vs 93%, MVA HR 1.1, 95% CI 0.5-2.8, P = 0.8) and GTVmean (3 yr LC 94 vs 90%, MVA HR 0.8, 95% CI 0.3-2.6, P = 0.8). There was a trend of worse survival in BEDlow SCC patients (MVA HR 1.3, 95% CI 0.9-1.9, P = 0.1), but survival was similar in non-SCC patients (MVA HR 1.02, 95% CI 0.8-1.3, P = 0.9). There were no differences in regional recurrence or distant metastases between BED groups in either histology. Conclusion This multi-institutional analysis shows improved LC in early-stage SCC NSCLC treated with SBRT regimens with BED10 > 150 Gy. No difference was observed in LC between BED groups for non-SCC patients. Our results suggest BEDhigh SBRT should be strongly considered for early-stage non-central SCC NSCLC.

Radiotherapy (RT) is a mainstay in the treatment of solid tumors and works by physicochemical reactions inducing oxidative stress in cells. Because in practice the efficacy of RT is limited by its toxicity to normal tissues, any strategy that selectively increases the radiosensitivity of tumor cells or boosts the radioresistance of normal cells is a valuable adjunct to RT. In this review, I summarize preclinical and clinical data supporting the hypothesis that ketogenic therapy through fasting and/or ketogenic diets can be utilized as such an adjunct in order to improve the outcome after RT, in terms of both higher tumor control and lower normal-tissue complication probability. The first effect relates to the metabolic shift from glycolysis towards mitochondrial metabolism, which selectively increases reactive oxygen species (ROS) production and impairs adenoside triphosphate (ATP) production in tumor cells. The second effect is based on the differential stress resistance phenomenon describing the reprogramming of normal cells, but not tumor cells, from proliferation towards maintenance and stress resistance when glucose and growth factor levels are decreased and ketone body levels are elevated. Underlying both effects are metabolic differences between normal and tumor cells. Ketogenic therapy is a non-toxic and cost-effective complementary treatment option that exploits these differences and deserves further clinical investigation.

SummaryDie Ernährung ist ein wichtiger Bestandteil der integrativen Krebstherapie. Doch welche ist die richtige? Sollten Krebspatienten lieber vegetarisch essen oder eher Fleisch? Oder ist viel Fett bei dieser zehrenden Erkrankung das Beste für den Körper? Unsere Ernährungsexperten erklären, welche Vorteile die vegetarische Kost, die Paläo-Diät und die ketogene Diät bei Krebs haben.